Term
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Definition
| a chemical entity of a known structure, other than a nutrient/dietry supplement, which causes biological effect in a living organism. |
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Term
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Definition
| a preparation of one or more drug, alongside other substances (stabilisers, solvents etc), which is used therapeutically. |
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Term
| How are drugs classified? (3) |
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Definition
Molecular Structure
Mode of action
Therapeutic use |
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Term
| Give 3 examples of molecular structure classes |
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Definition
catecholamines (eg noradrenaline, adrenaline and dopamine)
opiods (relieve pain)
tricyclic antidepressents (TCA) |
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Term
| Give 4 examples of mode of action classes |
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Definition
muscarinic antagonists (block Ach receptors)
beta blockers (control heart rhythm, treat angina and reduce HBP)
calcium channel blockers (high blood pressure)
SSRIs |
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Term
| Give 4 examples of therapeutic use classes |
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Definition
antihypertensives (reduce blood pressure)
bronchidilators (causes widening of the bronchi)
diuretics (increase excretion of water from the body)
antidepressants |
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Term
| What are the 3 names a drug will have? |
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Definition
Chemical name
General name (lowercase)
Proprietary/trade name (uppercase) |
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Term
| What are the uses of ibuprofen |
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Definition
-eases moderate/mild pain
-controls fever
-eases pain and inflammation
-eases pain and swelling |
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Term
| What are the uses of aspirin |
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Definition
| antiplatelet which reduces the risk of clots forming in blood therefore reduces the risk of having stroke/heart attack. |
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Term
| What are the uses of paracetamol |
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Definition
-ease mold/moderate pain
-control fever
-blocks the production of prostaglandins |
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Term
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Definition
| the science-orientated study of drug action |
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Term
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Definition
| the study of adverse effects of chemicals on living organisms |
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Term
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Definition
| patient-orientated health service profession, licensed dispensing of medicine, patient monitoring, medicine composition/manufacturing. |
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Term
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Definition
| what a drug does to the body |
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Term
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Definition
| what the body does to the drug (COK = BODY) |
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Term
| Which acronym determines the concentration of a drug at the target site? |
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Definition
ADME
Absorption
Delivery (to the correct tissue)
Metabolism
Elimination |
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Term
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Definition
| movement of a drug from the site of administration to the systematic circulation (not the site of action) |
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Term
| What are the pro's and con's of IV infusion |
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Definition
-all drugs reach the systematic circulation (100% bioavailable)
-unpleasant and requires supervised in-patient care |
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Term
| What are the 2 routes of drug administration |
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Definition
1. Enteral (via GI tract): drugs must cross a tight barrier composed of the epithelial cells of the CI tract (oral, sublingual and rectal)
2. Parenteral (not via GI tract) |
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Term
| Why is oral administration used? |
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Definition
most common route because its good for self dosing, it's cost effective and easy to dose.
rapid onset (10-20 mins once dissolved) |
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Term
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Definition
| the ability of a drug to dissolve in the fluid at the site of drug absorption |
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Term
| Why is dissolution often the rate determining step |
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Definition
| Absorption will only occur after the solid drug is in solution so that the drug must dissolve in the gut fluids. |
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Term
| What is the major site for absorption from the GI tract? |
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Definition
| the small intestine by passive diffusion because of its huge surface area which is about 200m^2 and one cell thick membrane |
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Term
| What is the small intestines blood supply like? |
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Definition
| high blood flow relative to other areas of the GI tract. This helps to maintain the concentration gradient between the drug in the lumen and the drug in the blood (diffuses into the blood). |
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Term
| What must a drug overcome when administered orally? (4) |
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Definition
1. survive gastric acid
2. survive gastric enzymes
3. co-exist with or need to avoid, food
4. cope with gut bacteria-metabolism and metabolites |
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Term
| Give 2 examples of drugs that overcome gastric acid |
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Definition
- Penicillin G is hydrolysed by gastric acid and hence usually given by IV route
- Penicillin V is taken on an empty stomach. some drugs have an enteric coat for protection. |
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Term
| Which drugs cannot be given orally? |
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Definition
| insulin and other peptides due to gastric enzymes |
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Term
| Give an example of a drug that cannot exist with food |
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Definition
| Tetracycline antibiotics bind to Ca^2+ in food, become insoluble and are not absorbed. |
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Term
| What is an enteric coated tablet? |
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Definition
| special coating that prevents the tablet disentigrating and releasing the drug into the acid environment of the stomach. Used to protect the drug from gastric acid or protect the stomach lining from any damaging effects (eg aspirin) |
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Term
| What must a drug be to be absorbed (which is mainly via transcellular passive diffusion)? |
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Definition
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Term
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Definition
| rate = (conc gradient X area X lipid solubility) / membrane thickness |
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Term
| What are most drugs and which form is absorbed |
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Definition
| weak acids or weak bases (HA) or (B) the unionised |
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Term
| What is the pH of the stomach |
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Definition
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Term
| What is the pH of the small intestine |
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Definition
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Term
| What is the pH of the large intestine |
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Definition
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Term
| Why is the unionised form preferentially absorbed? |
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Definition
-more lipophilic than the ionised form
-therefore ionised form are more hydrophilic |
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Term
| What is the extent of ionisation dependent on? |
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Definition
the pH of the solution the acid/base is dissolved in
strength of the weak acid/base (ability to lose H+ measured in pKa) |
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Term
| How is % ionised measured of weak acids? |
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Definition
| 100/(1 + antilog (pKa-pH) |
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Term
| How is % ionised measured of weak base? |
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Definition
| 100/(1 + antilog (ph-pKa) |
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Term
| How do weak acids exist largely as in the stomach? |
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Definition
| unionised form and will be absorbed in an acidic environment |
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Term
| How do weak bases exist largely as in the stomach? |
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Definition
| ionised form and will be absorbed in an alkaline environment |
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Term
| What are P-glycoproteins? |
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Definition
| an ATP powered drug efflux pump which removes a wide range of substrates from the cell interior back into the gut lumen. |
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Term
| Where is P-glycoprotein expressed? |
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Definition
| by the pithelial cells of the small intestine and is embedded in the apical surface of the cells, it pumps drug subtrates out of the cell into the gut lumen. |
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Term
| What effect does P-glycoprotein have on the permeability? |
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Definition
| permeability of the gut mucosa to its substrates drugs in reduced. |
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Term
| How are drugs absorbed from the GI tract? |
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Definition
Transcellular passive diffusion
Carrier-mediated transcellular transport |
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Term
| Describe transcellular passive diffusion |
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Definition
drugs must be lipophilic to diffuse over two plasma membranes
goes with concentration gradient
not saturable |
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Term
| Describe carrier mediated transcellular transport |
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Definition
-requires a specific transport
-energy dependent
-can go against conc gradient
-can be saturated |
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Term
| Give 4 examples of drugs transported across the GI epithelium and their transporters |
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Definition
- L-DOPA and large neutral amino acid transporter
- Penicillins andcephalosporins and digopeptide transporters
- Privastatin and monocarboxylic acid transporters
- Iron (Fe II) and divalent metal transporters-1 and bound to heme by the heme carrier protein |
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Term
| Where does most of the GI's venous drainage enter |
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Definition
| The hepatic portal vein and hence the liver and then the inferior vena cava |
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Term
| What is the fate of drugs absorbed by the small intestine |
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Definition
| delivered directly to the liver before they enter the systematic circulation |
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Term
| What are the 3 major metabolic barrier drugs taken orally have to pass before they can reach circulation |
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Definition
The intestinal lumen
Intestinal wall
The liver |
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Term
| What makes the intestinal lumen a barrier for oral drugs |
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Definition
- digestive enzymes can destroy drugs (eg insulin by peptidases)
- large amount of bacteria capable of metabolism |
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Term
| What makes the intestinal wall a barrier for oral drugs |
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Definition
| the cells of the intestinal wall are able to perform a range of metabolic reactions on drugs (intestinal first pass metabolism) |
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Term
| What makes the liver a barrier for oral drugs |
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Definition
| the liver is the major site for drug metabolism (hepatic first pass metabolism) (eg glyceryl trinitrate used to treat angina) |
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Term
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Definition
| metabolism at any of the above sites may result in loss of drug so only a fraction of the original dose reaches the systematic circulation. |
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Term
| Describe sublingual drug administration |
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Definition
| drug is placed under tongue and sucked and is rapidly absorbed due to good blood supply under tongue. Transcellular diffusion (lipophilic drugs). |
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Term
| Does sublingual drug administration have first pass effect |
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Definition
| no because it drains into jugular vein and then into the heart |
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Term
| What is the negative of sublingual drug administration? |
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Definition
| quantity is limited due to small surface area |
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Term
| Give an example of sublingual drug administration |
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Definition
| glyceryl trinitrate for agina |
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Term
| Describe rectal drug administration |
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Definition
| (lipophilic) drug placed into the rectum via the anus and is absorbed via transellular diffusion. |
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Term
| When is rectal drug administration useful? |
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Definition
- when oral route is compromised (eg vomitting or gastric acid sensitivity)
- when a drug can damage stomach lining (eg NSAIDs)
- no pH effect, no food complications and ease of use. |
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Term
| Where does rectal drug administration drain? |
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Definition
| from upper 1/3 of the rectum into the hepatic portal vein and remaining 2/3 bypass the liver and enter IVC vis hypogastric vein |
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Term
| Does rectal drug administration have first pass effect |
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Definition
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Term
| What are the parenteral routes of drug delivery |
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Definition
Injection (intravenous, intramuscular, subcataneous)
Inhalation
Transdermal (lipid soluble) |
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Term
| Describe intravenous injection |
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Definition
100% bioavailable
High risk of infection and overdose
Used in emergency situations |
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Term
| Describe intramuscular and subcataneous injection |
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Definition
| placed into connective tissue matrix of skeletal muscle and skin. There are very porous blood vessels surrounding these sites. Paracellular diffusion occurs. |
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Term
| Which drugs can be delivered by intramuscular and subcataneous injection |
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Definition
| Hydrophilic (gentamicin), large molecular mass drugs (insulin) and poorly soluble drugs (in suspension) |
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Term
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Definition
| gaseous anaesthetics (small lipid molecules) are inhaled and rapidly absorbed by the lung |
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Term
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Definition
lipid soluble
applied to skin for a local effect (eg anti inflammatory agents steroid cream)
systematic effect via transdermal patches (oestrogen patches) |
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Term
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Definition
trancellular passive diffusion
drugs must be lipophilic |
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Term
| Describe blood/lymphatic absorption |
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Definition
paracellular passive diffusion
hydrophilic drugs can enter circulation |
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Term
| Describe intranasal administration |
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Definition
nasal mucosa enables direct absorption into systematic circulation via the jugular vein
enables peptides to be absorbed |
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Term
| describe topical administration |
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Definition
| drug delivery to the eye, vagina and skin |
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Term
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Definition
| the reversible movement of drug from the systematic circulation to the cells and interstitium of tissues |
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Term
| How are drugs distributed in intramuscular and subcataneous injections? |
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Definition
the drug is placed into the CT matrix and absorbed into local vessels
blood vessels and lymphatic vessels have low impedence which allows for paracellular diffusion |
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Term
| What kind of drugs can be absorbed via intramuscular and subcataneous injections |
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Definition
| hydrophilic drugs and large drugs |
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Term
| What distribution interactions can hydrophilic drugs do? |
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Definition
limited distribution
cannot cross plasma membrane
can only access exposed drug targets (extracellular and membrane proteins) |
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Term
| What distribution interactions can lipophilic drugs do? |
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Definition
cross all blood-tissue boundaries therefore extensive diffusion
across cell membrane
access intracellular drug targets |
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Term
| Why is drug distribution to different tissues non-uniform |
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Definition
-blood flow (perfusion) to certain tissues are faster than others
-blood tissue boundaries vary in different tissues |
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Term
| What are the 3 types of capillary and where are they found? |
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Definition
continuous capillary (low permeability) eg CNS
fenstrated capillary
discontinuous capillary (high permeability) eg liver |
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Term
| What are the rate determining steps of drug distribution |
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Definition
lipid soluble drugs -> perfusion
hydrophilic/large drugs -> permeability of the blood-brain barrier |
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Term
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Definition
| transfer from the brain back into blood and then into peripheral organs |
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Term
| Describe the blood-brain barrier |
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Definition
| most of the CNS is surrounded by a specialised barrier that makes it difficult for hydrophilic substances to cross and penetrate organs. capillary cells in the brain have tight junctions and therefore do not allow paracellular diffusion |
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Term
| What kind of drugs are able to take the transcellular route to the brain |
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Definition
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Term
| Why are CNS related diseases difficult to treat |
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Definition
| many drugs are hydrophilic |
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Term
| Describe the role of P-glycoproteins |
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Definition
| pump toxic material out of the brain, back into the blood. |
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Term
| How do polar drugs get into the brain? |
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Definition
| they must be carrier (eg L-DOPA) |
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Term
| Describe the L_DOPA reaction |
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Definition
| L-DOPA becomes dopamine catalysed by DOPA decarboxylase |
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Term
| What are the issues with administering L-DOPA |
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Definition
| drug goes allow over the body, rather than just the brain which means more drug has to be administered which causes waste and adverse effects. |
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Term
| How are the issues with L-DOPA overcome? |
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Definition
| the drug carbidopa is administered which blocks DOPA decarboxylase. carbidopa cannot cross the BBB therefore dopamine is only in the brain. |
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Term
| Describe the placenta membrane barrier |
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Definition
| controls the exchange of many substances between the foetal and maternal blood. |
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Term
| What drugs can cross the placenta membrane barrier and how are they monitored |
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Definition
| only lipophilic drugs can cross the barrier and p-glycoprotein pumps molecules back into the mothers blood. |
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Term
| Describe blood testes barrier |
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Definition
| has tight junctions and highly expressed p-glycoproteins |
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Term
| What is the fate of drugs bound to proteins |
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Definition
| they do not exit bloodstream due to the high molecular mass f the protein drug complex and cannot pass by diffusion |
|
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Term
| where do large drugs end up |
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Definition
| cannot leave capillaries so remain in blood |
|
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Term
| where do polar drugs end up |
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Definition
| cannot enter cells so remain in ECF |
|
|
Term
| where do lipid soluble drugs end up |
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Definition
| can distribute into total body water |
|
|
Term
| what does distribution between compartments depend on? |
|
Definition
- permeability across tissue barrier
- binding within compartments
- fat water partition
-pH partition |
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Term
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Definition
| sum of metabolism and excretion |
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Term
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Definition
| the chemical modification of a drug and other foreign compounds (xendiotics) |
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Term
| What is the main site of metabolism |
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Definition
| the liver and it occurs in the liver cells (hepatocytes) |
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Term
|
Definition
| converts drugs into a more excretable form (most drugs require it). Usually metabolites are less active/toxic. |
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Term
| What are the other metabolism sites? |
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Definition
kidney
epithelial cells of th GIT and skin |
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Term
| Where are drug metabolising enzymes found? |
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Definition
| either membrane bound (ER) or are freely soluble in the cytoplasm |
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Term
|
Definition
| the primary metabolic pathway for paracetamol |
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Term
| How can paracetamol be toxic? |
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Definition
| 10% of the dose is metabolised by the CIT P450 pathway into NAPQI, a toxic compound that destroys hepatocytes. |
|
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Term
|
Definition
| the majority of NAPQI is inactivated by conjugation with gluthathione, therefore an overdose is caused by not enough gluthathione. |
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Term
| What happens in a Phase I reaction? and which is the most important? |
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Definition
| drug is modified by oxidation, reduction or hydrolysis. Oxidation. |
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Term
| Describe a Phase Oxidation reaction? |
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Definition
-liver
-catalysed by cytochrome P450s (CYPs)
-often result in addition of a hydroxyl group
-ether become hydroxyl |
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Term
| What are the metabolites produced from oxidation reactions like? |
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Definition
| more polar and therefore more excretable |
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Term
| Describe a reduction reaction |
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Definition
| occur for drugs that either contain a nitro or azo group and are catalysed by CYPs |
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Term
| Describe a hydrolysis reaction |
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Definition
many drugs either contrain ester or amide bonds
catalysed by esterases and are found in the liver, plasma and GI flora. |
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Term
| What are the 3 Phase II reactions and which is the most important |
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Definition
Glucuronidation (most important)
Sulphination
N-Acetylation |
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Term
| Which enzymes and cofactors are used in glucuronidation |
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Definition
| UGTS and UDP-glucuronic acid |
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|
Term
| Which compounds undergo glucuronidation |
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Definition
| that contain -OH, -COOH or amine |
|
|
Term
| Which metabolites does glucuronidation produce |
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Definition
| more polar and less lipid soluble and therefore more readily excreted |
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|
Term
| Which enzymes are used in sulphination and what is the sulphate source |
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Definition
|
|
Term
| Which compounds undergo sulphination |
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Definition
| those that contain -OH and -NH2 |
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Term
| Which enzymes are used in n-acetylation and what is the acetyl source |
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Definition
|
|
Term
| Which metabolites does n-acetylation produce |
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Definition
|
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Term
|
Definition
| when exposure of the body to certain drugs results in the induction of enzymes involved in metabolism |
|
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Term
| What can lead to enzyme induction? |
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Definition
Drugs
Alcohol consumption
Smoking
Rich diet in cruciferous vegetables |
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Term
| Which drugs can lead to enzyme induction (with examples) |
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Definition
Anticovulants (e.g. carbamazepine and phenytonin)
Antimicrobial agents (eg ridampicin and isoniazid)
Steroids (eg dexametharane and predisolone) |
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|
Term
| What are the clinical consequences of enzyme induction (4) |
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Definition
drug-drug interactions
tolerance
toxicity
increased variability in a drug response |
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Term
| Give an example of the clinical consequences of drug-drug interactions of enzyme induction |
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Definition
| failure of oral contraceptive and loss of anticogulant control |
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|
Term
| Give an example of the clinical consequences of tolerancee of enzyme induction |
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Definition
| anticovulants induce their own metabolism |
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|
Term
| Give an example of the clinical consequences of toxicity of enzyme induction |
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Definition
| increased conversion of drug to toxic metabolites and enhanced metabolism of endogenous substances |
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|
Term
| What causes increased variability of drug response in enzyme induction |
|
Definition
|
|
Term
| How does infancy affect metabolism |
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Definition
| they have immature lives and hence inefficient metabolism of drugs |
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|
Term
| How does being old/ill affect metabolism |
|
Definition
| impaired liver function therefore dosage must be adjusted to account for slow metabolism otherwise overdose. |
|
|
Term
| What excretion is the most important pathway for drug and metabolite excretion? |
|
Definition
|
|
Term
|
Definition
| the removal of drugs and their metabolites from the body |
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|
Term
| What are the other/minor ways to excrete drugs? |
|
Definition
-bile/faeces
-lungs
-saliva
-sweat
-tears
-breast milk |
|
|
Term
| Give the equation used to express renal excretion |
|
Definition
| = (filatration + secretion) - reabsorption |
|
|
Term
| Which arteriole is before the glomerular capillary and which is after? |
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Definition
| afferant towards and efferent away (A before E) |
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|
Term
Put these in the correct chronological order and where they occur:
Excretion
filatration
reabsorption
secretion |
|
Definition
1. filtration (between glomerular cappilaries and Bowmans capsule)
2. reabsorption (tubule into blood)
3.secretion (blood to tubule)
4.urinary excretion out of tubule |
|
|
Term
| How much cardiac output do the kidneys receive? |
|
Definition
| 25% (1.2-1.5L of blood per minute) |
|
|
Term
| Describe the filtrate that is passed from the glomerular capillaries to the Bowmans capsule |
|
Definition
| almost protein free ultrafiltrate |
|
|
Term
| What is the main driving force for filtration? |
|
Definition
| hydrostatic pressure in glomerular capillaries |
|
|
Term
| Describe glomerular filtration |
|
Definition
| Blood vessels and supporting membrane is highly porous which alllows small molecule drugs and metabolites to be filtered. Protein bound drugs are not. |
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|
Term
| What is the main determinant of glomerular filtration? |
|
Definition
| the substances molecule weight (cut off is 70kDa) |
|
|
Term
|
Definition
| the diffusion and active transport of molecules from the capillaries across the interstitial space and into the lumen of tubules |
|
|
Term
| How do hydrophilic/phobic drugs access the tubular lumen from the blood? |
|
Definition
Hydrophobic drugs pass easily into the lumen.
Hydrophilic drugs must be actively transported by transported: either organic anion transporters (OAT) or organic cation transporters (OCT) |
|
|
Term
| What do OCTs and OATs do? |
|
Definition
| carry out cellular uptake across the basolateral cell surface and then efflux into the tubule lumen across the apical membrane |
|
|
Term
| What supplies OCT and OAT energy? |
|
Definition
| various ion gradients across the cell surface (eg Na+ gradient) |
|
|
Term
| What else is the OAT system responsible for? |
|
Definition
| secretion of anionic drugs, glucuonide, sulphate and amino acid metabolites |
|
|
Term
| Describe benzylpenicillin excretion |
|
Definition
| Rapidly excreted without metabolism and has a v short half life (40mins) so must be constantly re-administered. |
|
|
Term
| What is the relevance of probenecid? |
|
Definition
| Blocks OATs therefore increases the half life of benzylpenecillin (and other drugs) |
|
|
Term
| What other transporters are there? |
|
Definition
| P-glycoproteins and other multi-drug resistance proteins actively pump drugs into the lumen of the proximal tubule |
|
|
Term
| What is the rate of blood filtraion in the kidney? |
|
Definition
|
|
Term
| At what rate is urine produced? |
|
Definition
|
|
Term
| Describe the tubule fluid |
|
Definition
|
|
Term
| Can lipophilic or hydrophilic molecules be reabsorbed in the blood? |
|
Definition
Lipo can easily.
Hydro are trapped and excreted (they follow water and go into wee) unless there is a carrier-mediated mechanism |
|
|
Term
|
Definition
|
|
Term
| What effect does alkaline urine have? |
|
Definition
| accelerates the excretion of weak acid drugs |
|
|
Term
| What is the treatment of an aspirin overdose? |
|
Definition
| alkaline diuresis (IV bicarbonate) |
|
|
Term
| What is the treatment of an amphetamine overdose? |
|
Definition
| acidic diuresis (ascrobic acid or ammonium chloride) this is rare unless urine is already acidic |
|
|
Term
|
Definition
| a number of drugs and their metabolites are actively transported by liver cells into the bile and therefore excretion occurs in the faeces. |
|
|
Term
| Describe bilary excretion via the liver |
|
Definition
-porous capillaries in the liver (sinusoids) which are v leaky
- tight junctions between hepatocytes
-polar drugs and metabolites enter the cells via OCTs and OATs
-some drugs enter the bile conaliculi and then the gut to be excreted |
|
|
Term
| What can bilary excretion lead to |
|
Definition
|
|
Term
| Describe eneterohepatic cycling |
|
Definition
eg methadone is used to treat heroin dependance and is excreted into the bile
bile is delivered to the small intestine where some drug is reabsorbed and is therefore available for excretion into the bile again
slows down elimination and prolongs drug action duration |
|
|
Term
| What are the 4 classes of drug targets? |
|
Definition
Enzymes
Plasma membrane bound receptors (GPCRs)
Transporters
Ion channels |
|
|
Term
| What are nuclear receptors? |
|
Definition
| bind to DNA and regulate transcription |
|
|
Term
| Describe transporter drug targets |
|
Definition
| many neurotransmitters are transported back into their nerve terminals from which they were released. Their transporters can be blocked by drugs |
|
|
Term
| What is X-ray crystallography used for and how? |
|
Definition
1. drug target complex is highly purified and made into crystals
2. xray beams can be fired through the crystal to obtain a diffraction pattern
3. this can be interpreted to give a molecular structure |
|
|
Term
| How is selectivity of action obtained? |
|
Definition
1. modification of drug structure - minimises the chance of the drug interacting with a target other than the desired one
2. selective delivery - takes the drug directly to target site. |
|
|
Term
| What effect does concentration have on selectivity? |
|
Definition
| as concentration increases, selectivity decreases. |
|
|
Term
| What causes good selectivity? |
|
Definition
| good drug affinity (so lower dose can be used) |
|
|
Term
| What bonds are formed in irreversible reactions and give examples |
|
Definition
covalent chemical bonds (eg acetylation and carbamylation)
aspirin and neostigmine |
|
|
Term
| What bonds are formed in reversible reactions |
|
Definition
ionic bonds
hydrogen bonds
van der waals interactions |
|
|
Term
| What are Van der waals interactions |
|
Definition
random asymetric distribution of the electron cloud in molecules results in the formation of temporary dipoles
weak
narrow distance range |
|
|
Term
|
Definition
involve highly electronegative atoms (FON) and a hydrogen atom
electrons move towards the electronegative atom
stronger than VdW but weaker than ionic |
|
|
Term
| what are electrostatic interactions (ionic interactions or salt bridges) |
|
Definition
| positive or negative groups in a drug can interact strongly with the opposite charge on a target |
|
|
Term
| What does drug concentration determine? |
|
Definition
| the percentage of target sites occupied |
|
|
Term
| How is strength measured? |
|
Definition
1. measure a drugs occupancy at a known conc
2. use a ligand with a greater affinity at the same conc (increase occupancy)
3. by comparing the conc required to achieve equivalent occupancy, we have a direct comparison of affinity |
|
|
Term
| How do we measure affinity? |
|
Definition
| Equilibrium dissociation constant (Kd) = the conc of the drug that is required to occupy 50% of the receptors. The lower the Kd the higher the affinity |
|
|
Term
| How do you find the conc of a drug that is required to occupy 50% of the receptors? |
|
Definition
1. incubate a radioligand with the target
2. wash/filter away the free ligand
3. what remains is "total binding" a combination of non-specific binding
4. the number of nonspecific sites is considered infinite and non saturable (linear) |
|
|
Term
|
Definition
| conc of a substrate that produces 50% of the maximal rate |
|
|
Term
|
Definition
|
|
Term
|
Definition
| total density (concentration) of receptors in a sample tissue |
|
|
Term
|
Definition
| conc of an inhibitor where the binding is reduced by half |
|
|
Term
|
Definition
| drugs that bind to a receptor and produce a biological response |
|
|
Term
|
Definition
| drugs that decrease the biological response to an agonist drug or endogenous ligand. |
|
|
Term
| Which is the most common form of antagonism |
|
Definition
| Reversible competitive antagonism |
|
|
Term
|
Definition
Carbachol
Phenylephrine
Heroin |
|
|
Term
| What does it mean if something is cholinergic |
|
Definition
|
|
Term
| Give 2 antagonist examples |
|
Definition
|
|
Term
| What does acetylcholine esterase do on the post-synaptic membrane? |
|
Definition
| degrades Ach into choline acetate to prevent builld up |
|
|
Term
| Describe the pre-synaptic membrane (neuromuscular junction) |
|
Definition
| Ca2+ enters and changes the voltage so Ach vesicles are released across the synapse |
|
|
Term
| Describe the post-synaptic membrane (neuromuscular junction) |
|
Definition
| Sodium cross the nicotinic Ach receptor and causes contraction |
|
|
Term
|
Definition
- agonist
- substrate for acetylcholine esterase which can be antagonised by neostigmine |
|
|
Term
| What do long pre-ganglionic fibres in the parasympathetic NS release? and what do they bind to? |
|
Definition
| Ach binds to nicotonic receptors |
|
|
Term
| What do short post-ganglionic fibres in the parasympathetic NS release? and what do they bind to? |
|
Definition
| Ach binds to muscarinic Ach receptors |
|
|
Term
| What does this cause contraction of? |
|
Definition
- ileal smooth muscle
- tracheal smooth muscle |
|
|
Term
| What are muscarinic and nicotinic receptors both activated by? |
|
Definition
|
|
Term
| Where is noradrenaline released and what does it bind to? |
|
Definition
predominant neurotransmitter released at target tissues in sympathetic NS
acts on adrenoreceptors (alpha and beta) |
|
|
Term
|
Definition
| where postganglionic sympathetic fibres terminate in the target tissues via a series of 'synapse-like' structures |
|
|
Term
| What causes adrenaline release? |
|
Definition
| sympathetic stimulation of the adrenal gland |
|
|
Term
| What are the cells of adrenal medulla modified versions of? |
|
Definition
|
|
Term
| What is the difference between adrenaline and noradrenaline? |
|
Definition
adrenaline is released and enters the circulation
noradrenaline enters an innervated tissue |
|
|
Term
|
Definition
adrenaline and noradrenaline targets
GPCRs |
|
|
Term
| What are the effects of adrenaline? |
|
Definition
contracts cardiac muscle, smooth muscle of aorta and vas deferens
relaxes tracheal and ileal smooth muscle |
|
|
Term
| What are the effects of noradrenaline |
|
Definition
contracts aortic smooth muscle, vas deferens smooth muscle and ventricular muscle
dilation of tracheal smooth muscle |
|
|
Term
| What is the agonist of alpha-1-adrenoceptors and what is the outcome? |
|
Definition
| phenylephrine causes contraction of vascular smooth muscle |
|
|
Term
| What are the antagonists of alpha-1-adrenoceptors? |
|
Definition
| prazosin and phentolamine |
|
|
Term
| What is the agonist of alpha-2-adrenoceptors and what is the outcome? |
|
Definition
clonidine
activation on presynaptic receptors results in reduced release of neurotransmitter |
|
|
Term
| What are the antagonists of alpha-2-adrenoceptors? |
|
Definition
|
|
Term
| What is the agonist of beta-adrenoceptors and what is the outcome? |
|
Definition
isoprenaline and salbutamol
contraction of cardiac muscle
relaxation of smooth muscle |
|
|
Term
| What are the antagonists of beta-adrenoceptors? |
|
Definition
| propanolol (beta blocker) |
|
|
Term
|
Definition
|
|
Term
| What does a high affinity mean? |
|
Definition
| less tendency for the drug to dissociate from the binding site |
|
|
Term
|
Definition
| the ability to produce a desired/intended response |
|
|
Term
| How is a response of a tissue measured? |
|
Definition
1. organ bath with tissue
2. graded conc/dose-response relationship
3. log of conc vs response |
|
|
Term
| What does the log of conc vs response show |
|
Definition
| potency and intrinsic activity |
|
|
Term
|
Definition
| measure of the concentration of drug need to elicit a given effect |
|
|
Term
|
Definition
| conc which produced 50% of the max response |
|
|
Term
| Describe Ahlquist experiment |
|
Definition
| used relative potency to propose the alpha/beta hypothesis for adrenoceptors. Cardiac, aortic and lungs have different receptors. |
|
|
Term
|
Definition
| elicit a max response from the system when even only a small fraction of the receptors population is occupied (IE = 1) |
|
|
Term
|
Definition
| cannot induce a max response even when all receptors are occupied |
|
|
Term
| Define intrinsic activity |
|
Definition
| the ability of the drug receptor complex to evoke a response when it occupies a receptor |
|
|
Term
| Define competitive antagonism |
|
Definition
| agonist and antagonist compete for the same receptor site |
|
|
Term
| Define summountable competitive antagonism |
|
Definition
increasing agonist conc will overcome the block (aka reversible)
dynamic process with rapid association and dissociation |
|
|
Term
| What are the ffects on the dose-response curve when agonist conc increases? |
|
Definition
shifts to the right
response increases |
|
|
Term
| How can competitive antagonism be reversed? |
|
Definition
|
|
Term
| What is the Sheilb analysis used for? |
|
Definition
to obtain affinity data of an antagonist
produces Kb and pA2 |
|
|
Term
|
Definition
| affinity of antagonist (equivalent to Kd at this point) |
|
|
Term
| Define insummountable competitive antagonism |
|
Definition
| increasing agonist conc will not restore maximum response therefore block cannot be totally reversed by the agonist. |
|
|
Term
| Define physiological antagonism |
|
Definition
'functional antagonism'
different receptors produce opposing effects |
|
|
Term
| Give an example of physiological antagonism |
|
Definition
histamine binds to H1 receptors on bronchial smooth muscle which causes contraction
noradrenaline/salbutamol bind to beta-2-adrenoreceptors on SMCs which causes relaxation. |
|
|
Term
| How else can you screen a drug target for many compounds for potency and efficacy and intrinsic activity? |
|
Definition
1. DNA encoding our drug target placed in a vector (plasmid)
2. construct is placed in a cell line by tranfection
3. useful signals in the vector tell the cell to transcribe and translate the genetic information of the gene of interest and so express the recombinant protein which can be pharmalogically analysed |
|
|
Term
| Describe the events that follow G protein activation |
|
Definition
1. G protein undergoes conformation change
2. GDP released from alpha subunit
3. GTP binds to empty alpha subunit, releasing receptor and beta-gamma dimer
4. initiates downstream signaling
5. hydrolysis of GTP by alpha subunit results in G protein reformation |
|
|
Term
| In the cAMP cycle, what it monitored? |
|
Definition
|
|
Term
| In phospholipase C cycle, what is monitored? |
|
Definition
|
|
Term
| What binds to Gs and what cycle follows? |
|
Definition
|
|
Term
| What binds to Gi and what cycle follows? |
|
Definition
|
|
Term
| What binds to Gq and what cycle follows? |
|
Definition
alpha 1
stimulatory
phospholipase C |
|
|
Term
|
Definition
| measure of affinity generated from saturation binding |
|
|
Term
|
Definition
| measure of affinity generated from competition binding |
|
|
Term
|
Definition
| measure of affinity generated from Scheilb analysis |
|
|
Term
|
Definition
| measure of number of receptors you have in your system |
|
|
Term
| Define inflammatory response |
|
Definition
| events in the tissues in response to pathogen and noxious substances. There are 2 components: innate and specific. |
|
|
Term
|
Definition
| no immunological response |
|
|
Term
| What are the events of the innate response |
|
Definition
1. tissue macrophages/APCs recognise PAMPs on invader via surface receptor
2. APCs release pro-inflammatory cytokines (IL-1; TNF-alpha)
3. leads to vascular dilation and exudation of fluid containing enzyme cascades |
|
|
Term
| Describe the vascular events of the innate response |
|
Definition
1. small arterioles dilate which increase blood flow to area (then slows then stasis)
2. post capillary venule increase permeability
3. exudation of fluid taken to lymph nodes |
|
|
Term
| When does the specific immune response occur? |
|
Definition
| when a pathogen has been recognised by the innate system and the antigen is carried to lymph nodes via lymphocytes |
|
|
Term
| What are antigens present to and by who? |
|
Definition
| Antigens are presented to T cells by APCs |
|
|
Term
| What are the 3 types of effector cells? |
|
Definition
1. plasma antibodies (B cells)
2. cell mediated immune response (T cells)
3. antigen sensitive memory cells |
|
|
Term
| Antibodies: what does the Fab portion do? |
|
Definition
|
|
Term
| Antibodies: what does the Fc portion do? |
|
Definition
1. activates the compliment cascade
2. forms links to attach to neutrophils and macrophages |
|
|
Term
| What does the Fc portion of IgE bind to? |
|
Definition
|
|
Term
| Where can antibodies not reach? |
|
Definition
|
|
Term
| What do Tc cells do and what is its co-receptor? |
|
Definition
kill virally infected cells
CD8 |
|
|
Term
| What do Th1 cells do and what is its co-receptor? |
|
Definition
-secrete cytokines
-activate macrophages
-stimulate proliferation of Th1 lymphocytes
-stimulate prliferation of Tc cells
CD4 co-receptor |
|
|
Term
| Describe a Type I immune response |
|
Definition
-immediate
-anaphylactic hypersensitivity
-release of histamine
-IgE produced and bound to mast cells and basophils
-triggered by pollen, dust and drugs |
|
|
Term
| What are the consequences of Type I immune response |
|
Definition
hayfever
urticaria
anaphylactic shock |
|
|
Term
| Describe a Type II immune response |
|
Definition
-antibody mediated cytotoxic hypersensitivity
-IgG, IgM, IgA directed against foreign cells
-can either decrease erythrocytes or platelets |
|
|
Term
| Describe a Type III immune response |
|
Definition
-complex mediated hypersensitivity
-antibodies react with soluble antigens, activating complement C3a and C5
-attach to mast cells |
|
|
Term
| What are the consequences of Type III immune response |
|
Definition
lupus erythematosis (farmers lung)
skin rash
swollen joints
pyrexia |
|
|
Term
| Describe a Type IV immune response |
|
Definition
cell mediated hypersensitivity
involves T cells |
|
|
Term
| What is Type III immune response involved with |
|
Definition
transplant rejection and autoimmune disease
skin reactions to drugs, metals and chemicals |
|
|
Term
| Describe histamine synthesis |
|
Definition
| synthesised from histidine by histidine decarboxylase |
|
|
Term
|
Definition
most tissues (high in lungs, skin and GIT)
high conc in mast cells and basophils (stored in herapin complex in granules) |
|
|
Term
| How is histamine released? |
|
Definition
| from mast cells by exocytosis during inflamatory/allergen reactions via... |
|
|
Term
| What causes histamine release? |
|
Definition
- receptor mediated interaction with C3a/C5 of complement system
- interaction of antigen and IgE antibody
- triggered by rise in intracellular Ca2+
- basic drugs can cause release (eg morphine and tubocurarine) |
|
|
Term
| What can inhibit histamine release? |
|
Definition
| a rise in cAMP (eg beta-adrenoreceptor agonists) |
|
|
Term
| What occurs when histamine binds to H1 receptor? |
|
Definition
vascular permeability
vasodilation
contraction of smooth muscle |
|
|
Term
| What does an intradermal injection of histamine cause? |
|
Definition
the triple response in skin:
redding (local vasodilation)
wheal (permability)
flare (axon reflex) |
|
|
Term
| What occurs when histamine binds to H2 receptor? |
|
Definition
stimulation of gastric acid secretion
increases cardiac rate and force |
|
|
Term
| What occurs when histamine binds to H3 receptor? |
|
Definition
presynaptic sites
inhibits neurotrans release |
|
|
Term
| Name histamine antagonists: |
|
Definition
diphenhydranine
promethanine
cetrizine
terfendodine
fexofenadine |
|
|
Term
| What do diphenhydranine and promethanine have in common? |
|
Definition
| muscarinic antagonist and sedative |
|
|
Term
|
Definition
| most important inflammatory mediator eg prostanoids and leukotrienes |
|
|
Term
|
Definition
| prostaglandins, thromboxane and prostacyclin |
|
|
Term
|
Definition
| found in WBCs formed from arachidonic |
|
|
Term
| How are prostanoids mediated? |
|
Definition
5 main classes of receptors
PGE2 plays a major role |
|
|
Term
| List the platelet aggregation factors: |
|
Definition
- vasodilation
- hyperalgesia
- increase in vascular permeability
- chemotaxis
- bronchiolar spasmogen
- stimulation of phospholipase A2
- platelet aggregation, shape change |
|
|
Term
|
Definition
| peptides released from immune system cells that act by autocrine and paracrine mechanisms on kinase-linked receptors that regulate phosphorylation cascades and therefore gene expression. |
|
|
Term
| What belongs in the cytokine superfamily? |
|
Definition
- numerous interleukins
- tumour necrosis factors
- growth factors
- interferons |
|
|
Term
| List the 5 major actions of NSAIDs |
|
Definition
1. inhibition of COX-1 and 2
2. decrease in prostanoid (PG) synthesis
3. analgesic
4. antipyretic
5. anti-inflammatory |
|
|
Term
| Describe how NSAIDs give an analgesic effect |
|
Definition
several PGs sensitise nociceptors (which respond to mediators).
Therefore NSAIDs are effective against pain involving PGs.
Peripheral action. |
|
|
Term
| What pain are NSAIDs effective in treating? |
|
Definition
mild to moderate
localised or widespread
integumentary rather than visceral
eg postoperative, joints, toothaches and headaches |
|
|
Term
| How does infection cause a raised temperature? |
|
Definition
1. infection leads to the introduction of bacterial toxins
2. causes the release of interleukins 1 from macrophages
3. IL-1 causes PGE2 synthesis in the hypothalamus
4. this induces a fever as a regulation is upset |
|
|
Term
| How do NSAIDs lower body temperature? |
|
Definition
they prevent PG synthesis
normal temp is not affected (only overly high temp is) |
|
|
Term
| Which cyclo-oxygenase is blocked to bring about anti-inflammatory effects and how does it do so? |
|
Definition
COX-2
decreased PGE2 leads to
- reduced vasodilation
- reduced erythema (redness)
- reduced local oedema |
|
|
Term
| How can NSAIDs affect cellular accumulation? |
|
Definition
- some cells (eg phagocytes) increase at site because of increased leuktriene production
- some PGs decrease lysosome and lymphocyte activity
- blocking PG synthesis leads to more tissue damage and could be a problem in arthritis and rheumatism |
|
|
Term
| Where is COX-1 expressed? |
|
Definition
| many tissues (kidneys, blood vessels, stomach and platelets) |
|
|
Term
| Where is COX-2 expressed? |
|
Definition
| induced in inflammatory cells |
|
|
Term
| What effect do NSAIDs have on the GIT? |
|
Definition
damage to GI mucosa
mainly from COX-1 inhibition
direct irritant action |
|
|
Term
| Why are PGs essential for the GIT? |
|
Definition
| PGs protect gastric mucosa, causing decreased acid secretion and increased mucous secretion. NSAIDs disrupt mucosal gel layer of the GIT, letting in acid. |
|
|
Term
| What effect do NSAIDs have on the kidneys? Why? |
|
Definition
- renal disease
- chronic use = 'analgesic nephropathy' nephritis and papillary necrosis
- due to PG mediated control of blood flow |
|
|
Term
| What effect does NSAIDs have on the uterus and what does this mean for labour? |
|
Definition
- decreased actiivty
- PGE and PGFs increase during labour, therefore NSAIDs prolong labour |
|
|
Term
| Describe the major effects and positives of salicylates and give an example |
|
Definition
aspirin
equal major effects (AAA)
cheap, effective and common |
|
|
Term
| What is significant about COX inhibition by salicylates? |
|
Definition
Irreversible
Therefore action outlasts presence of drug |
|
|
Term
| What is the pKa of salicylates and what does this mean? |
|
Definition
3.5
well absorbed in the stomach |
|
|
Term
| What are the unwanted effects of aspirin? |
|
Definition
1. irritation of gastric mucosa
2. ulcer formation and aggregation of existing ones
3. bleedings
4. GIT haemorrhage |
|
|
Term
| What are GIT haemorrhage exacerbated by? |
|
Definition
- inhibition of platelet aggregation
- TXA2 synthesis inhibited
- more with aspirin than other NSAIDs |
|
|
Term
| How can the unwanted effects of salicylates be used as an advantage? |
|
Definition
- given prophylactically to patients at risk of occlusive CVS disease
- may be useful in reducing risk of myocardial infarction in normals |
|
|
Term
| What are the consequences of large doses of salicylates? (3) |
|
Definition
1. uncoupled oxidative phosphorylation
2. salicylism
3. Reye's syndrome in children |
|
|
Term
| Explain uncoupled oxidative phosphorylation and its consequences |
|
Definition
causes increased o2 consumption and co2 production
this causes respiratory alkalosis
this cannot be compensated for by bicarbonate due to dehydration |
|
|
Term
|
Definition
central effect
nausea, dizzinesss and tinnitus |
|
|
Term
|
Definition
liver disease with CNS disorders
can follow viral infection |
|
|
Term
| Describe the effects of paracetamol |
|
Definition
analgesic and antipyretic
less anti-inflammatory, less effect of an effect of GIT and less anticlotting |
|
|
Term
| Describe paracetamols COX inhibition |
|
Definition
| reversible and non competitive |
|
|
Term
| What are the unwanted effects of paracetamol? |
|
Definition
- causes liver at 2-3x the therapeutic dose (>10-15g)
- can be fatal and delayed (long slow suicide) |
|
|
Term
| Describe and explain the toxicity of paracetamol |
|
Definition
produced toxic metabolite (N-acetyl-p-benzoquinoneimine) normally conjugated with glutathione
toxicity can be caught by using glutathione precursors acetyl-cysteine or methionine |
|
|
Term
| Describe the effects of propionic acids and give examples |
|
Definition
ibuprofen and naproxen
equal major effects (AAA)
typical NSAID side effects (yet generally lowest level) |
|
|
Term
| Describe propionic acid COX inhibition and what this means for duration of drug effects |
|
Definition
reversible and competitive
half life determines duration |
|
|
Term
| Describe the effects of COX-2 drugs and give examples |
|
Definition
celecoxib
anti-arthritis
effective as analgesic for dental, orthopaedic and dysmenorrhoea
causes hypertension in association with antihypertensive drugs
reduces renal filtration in elderly |
|
|
Term
| What are adrenal steroids and give examples |
|
Definition
mineralocorticoids or glucocorticoids
- activated by HPA axis
- facilitate hormonal actions
- fight or flight response |
|
|
Term
| What are the effects of mineralocorticoids and give an example |
|
Definition
aldosterones
water and electrolyte balance (sodium retention)
potassium depletion |
|
|
Term
| What are the effects f glucocorticoids and give an example |
|
Definition
hydrocortisome and corticosterones
carbohydrates and protein metabolism
anti-inflammatory
immunosuppressive |
|
|
Term
| Why use adrenal steroids? |
|
Definition
powerful anti-inflammatory and immunosuppressive effects
inhibits early AND late inflammation
steroidal deficient stages (Addison disease) |
|
|
Term
| Describe adrenal steroid anti-inflammatory effects |
|
Definition
1. reduce early effects (erythema, pain, odema)
2. reduce cell proliferation, repair processes, wound healing
useful for all types of inflammation |
|
|
Term
| What are the negatives of adrenal steroid anti-inflammatory effects? |
|
Definition
| hazardous because protective responses are suppressed |
|
|
Term
| What are the unwanted effects of adrenal steroids? |
|
Definition
1. suppression of response to infection (treat with anti-microbials)
2. supression of natural corticosteroid synthesis by mimicry of feedback
3. patients must carry card |
|
|
Term
|
Definition
| when the body is no longer able to respond to signals that control cell survival, proliferation and differentiation. A small population of tumour cells are able to divide repeatedly and invade neighbouring cells. |
|
|
Term
|
Definition
slow growth
remains localised
compresses normal tissue |
|
|
Term
|
Definition
rapid growth
invades and destroys local tissues
metastsis |
|
|
Term
| What tissue is affected by carcinoma cancer? |
|
Definition
|
|
Term
| What tissue is affected by sarcoma cancer? |
|
Definition
|
|
Term
| What tissue is affected by leukemia cancer? |
|
Definition
|
|
Term
| What are the effects of leukemia |
|
Definition
malignant cells replace healthy bone amrrow leading to:
- deficiency or RBCs
- loss of platelets
- deficiency of WBCs |
|
|
Term
| When is chemotherapy used? |
|
Definition
| normally sed alone when the cancer is not treatable with surgery and/or radiation |
|
|
Term
| Define adjuvant chemotherapy |
|
Definition
| anticancer drugs are used to attack mestases following surgery or radiotherapy |
|
|
Term
| Define neo-adjuvant chemotherapy |
|
Definition
| anticancer drugs are given prior to surgery or radiation to shrink tumour bulk |
|
|
Term
| Define maintenance chemotherapy |
|
Definition
| lower doses used to prolong remission |
|
|
Term
| What is the aim of chemotherapy? |
|
Definition
| eradicate all tumour cells |
|
|
Term
| What do anticancer drugs do? |
|
Definition
cytotoxic and/or induce apoptosis
some are only effective against actively dividing cells |
|
|
Term
|
Definition
cells that are less sensitive to anticancer drugs than dividing ones
can be stimulated to divide with surgery/radiation (whilst trying to reduce tumour mass) |
|
|
Term
| What are cell cycle specific anticancer agents and what are they effective for? |
|
Definition
metabolites
high growth fraction tumours (leukemias) |
|
|
Term
| What are cell cycle non specific anticancer agents and what are they effective for? |
|
Definition
alkylating agents
low growth fraction tumours (solid tumours) |
|
|
Term
| What 3 parts make up a tumour? |
|
Definition
a) dividing cells (5%)
b) resting cells
c) cannot divide |
|
|
Term
| Describe tumour growth rate |
|
Definition
| initially rapid but slows as tumour size increases |
|
|
Term
| When do symptoms normally appear? |
|
Definition
| when the tumour contains 10^9 cells (1cm) |
|
|
Term
|
Definition
exponential
a constant % of cell population is killed on exposure to the drug(s) |
|
|
Term
| What are the 3 problems with chemotherapy |
|
Definition
1.Pharmacological sanctuaries (some tumour cells hide behind blood brain barrier)
2.resistance (some tumours are inherently resistant but others require it through selection)
3. adverse effects |
|
|
Term
| What is multi-drug resistance caused by? |
|
Definition
| enhances P-glycoprotein activity |
|
|
Term
|
Definition
| combinations of drugs with different modes of action |
|
|
Term
| What are the 6 hallmarks of cancer? |
|
Definition
1. self sufficient in growth signals
2. insensitive to anti-growth signals
3. tissue invasion and metastasis
4. unlimited replicative potential
5. sustained angiogenesis
6. evasion of apoptosis |
|
|
Term
| What are the two main events that lead to cancer? |
|
Definition
1. proto-oncogenes are converted to oncogenes
2. inactivation of tumour suppressor genes |
|
|
Term
| Name the 3 types of anticancer drugs |
|
Definition
1. cytotoxic drugs
2. hormones (suppression of hormone secretion)
3. other (eg herceptin) |
|
|
Term
| Name the 4 types of cytotoxic drugs and how they work |
|
Definition
1. alkylating agents (form covalent bonds with DNA)
2. antimetabolites (block metabolic pathways of DNA synthesis)
3. cytotoxic antibodies (prevent cell division)
4. plant derivatives (affect cell cycle - mitosis) |
|
|
Term
| How do alkylating agents work? |
|
Definition
form covalent bonds with nucleophilic substances in the cell
forms a carbonium ion (carbon with 6 electrons) thats highly reactive with electron donors |
|
|
Term
| Give examples of electron donors |
|
Definition
amine groups
hydroxyl groups
sulfhydryl groups |
|
|
Term
| What can bifunctional alkylating agents cause? |
|
Definition
| intrastrand linking and cross-linking |
|
|
Term
| What is the main molecular target for alkylating agent? |
|
Definition
| binding guanine (via nitrogen site 7-N7) |
|
|
Term
| What effects do alkylating agents have? |
|
Definition
interfere with transcription and replication
mainly during replication (S phase) and block at G2 (leading to apoptosis) |
|
|
Term
| What are the general unwanted effects of alkylating agents? |
|
Definition
depression of bone marrow
gastrointestinal disturbances (nausea, vomitting) |
|
|
Term
| What are the unwanted effects of prolonged use of alkylating agents? |
|
Definition
depression of gametogenesis (particularly in males, leading to sterility)
increased risk of acute non-lymphocytic Leukemia and other malignancies |
|
|
Term
| What are nitrogen mustards inactive until? |
|
Definition
eg cyclophosphamide
inactive until metabolised by liver P450 oxidases = ethylene immorsism derivatives |
|
|
Term
| WHat do nitrogen mustards affect? |
|
Definition
| lymphocytes and can be used as an immunosuppressant |
|
|
Term
| How are nitrogen mustards administered and what are the effects? |
|
Definition
oral or IV administration
usual unwanted effects |
|
|
Term
|
Definition
| folate antagonists and 'fraudulent' nucleotides |
|
|
Term
| What is the main folate antagonist? |
|
Definition
| methotrexate (also because its an immunosuppressant) |
|
|
Term
| What are folates essential for? |
|
Definition
- synthesis of purine nucleotides and thymidylate (which is essential for DNA synthesis and cell division)
- mainly used to interfere with thymidylate synthesis |
|
|
Term
| Describe folate metabolism |
|
Definition
1. folate is actively taken up by cell
2. converted into various polyglutamates
3. dihydrofolate reductase acts on di and tetrahydrofolate
4. they become purines/DNA |
|
|
Term
| What are the effects of methotrexate on folate metabolism? |
|
Definition
1. causes less tetrahydrofolate made
2. therefore less purines made
3. affects normal DNA synthesis
4. eventually causes apoptosis of entire cell |
|
|
Term
| How is methotrexate administered? |
|
Definition
usually orally
can be IV or IM |
|
|
Term
| Describe methotrexate lipid solubility and the significance of this |
|
Definition
low
therefore little CNS activity
but readily taken up into cells by the folate transport system
stays in cells for weeks/months |
|
|
Term
| What are the problems with methotrexate |
|
Definition
1. resistance (prolonged used can lead to decreased uptake)
2. depression of bone marrow
3. damage to GIT |
|
|
Term
| How can high dose regiments of methotrexate (x10 standard doses) be rescued? |
|
Definition
| folanic acid (form of FH4) |
|
|
Term
| Define psychopharmacology |
|
Definition
| drug treatment of psychiatric disorders |
|
|
Term
| What drugs are used to treat depression? |
|
Definition
antidepressants:
- SSRIs
- TCAs
- MAOIs |
|
|
Term
| What drugs are used to treat schizophrenia? |
|
Definition
| antipsychotics (DA antagonists) |
|
|
Term
| What drugs are used to treat anxiety? |
|
Definition
anxiolytics:
- SSRIs
- benzodiazepines |
|
|
Term
|
Definition
| exaggerated or inappropriate version of a natural response |
|
|
Term
| What disorders are related to anxiety? |
|
Definition
panic disorder
OCD
generalised anxiety disorders (GAD)
society anxiety disorder
phobias
depression |
|
|
Term
| What are the psychological effects of anxiety? |
|
Definition
feeling worried, nervous, agitated
may be associated with aggression |
|
|
Term
| What are the somatic and autonomic effects of anxiety? |
|
Definition
tachycardia
sweating
sleep disorder
tense muscles |
|
|
Term
| What are anti-convulsants? |
|
Definition
| drugs used to prevent/reduce the severity of epileptic fits |
|
|
Term
|
Definition
benzodiazepines
buspirone
beta-adrenoreceptor antagonists
SSRIs |
|
|
Term
| What are benzodiazepines used for and give an example |
|
Definition
as an anxiolytic and hypnotic for insomnia
anticonvulsant activity
eg diazepam |
|
|
Term
|
Definition
|
|
Term
| What are beta-adrenoreceptors antagonists used for and give an example |
|
Definition
beta blocker used in CV diseases and used for panic attacks (tachycardia)
eg pronanolol |
|
|
Term
| Compare the use of SSRI's and benzodiazepines in treating anxiety |
|
Definition
| SSRI's less effective but safer |
|
|
Term
| What receptors do benzodiazepines have an effect on? and have no effect on? |
|
Definition
they selectively act on GABAa receptors and mediate fast inhibitory synaptic transmission
no effect on glycine or glutamate receptors |
|
|
Term
| How do benzodiazepines enhance GABA response? |
|
Definition
| by facilitation of opening of GABA-activated Cl- channels (enhance frequency of opening) |
|
|
Term
| What are the effects of benzodiazepines? |
|
Definition
- reduce anxiety (acute anxiety state)
- sedation (decrease REM sleep)
- reduce muscle tone and coordination
- anticonvulsant (epilepsy)
- anterograde amnesia (minor surgical procedures) |
|
|
Term
| what are the unwanted effects of benzodiazepines? |
|
Definition
- overdose = prolonged sleep
- drowsiness, confusion, amnesia, impaired coordination
- tolerance and dependence (severe with withdrawal) which causes increased anxiety, tremors and dizziness |
|
|
Term
| What occurs if a benzodiazepine overdose is paired with alcohol? |
|
Definition
| servere respiratory depression |
|
|
Term
| What can be given in the case of a benzodiazepine overdose? |
|
Definition
flumazenil
(competitive antagonist) |
|
|
Term
|
Definition
feelings of severe despondency and dejection. (Every day/minimum 2 weeks).
Anhedonia (loss of 'pleasure') |
|
|
Term
| What are the other symptoms needed to be defined as depressed? (minimum 4) |
|
Definition
- disruption of appetite, sleep, concentration
- loss of energy, fatigue
- negative self-concept
- recurrent thoughts of death and suicide
- reactive/endogenous (not clear distinction and not recognised) |
|
|
Term
| Describe the "biogenic amine" hypothesis |
|
Definition
-depression is a result of decreased amine levels in the brain (NA, 5-HT and DA)
-poor evidence
-good supporting evidence from drug effects
-generally not considered true |
|
|
Term
| What drugs are used to treat depression? |
|
Definition
TCAs
MAOIs
SSRIs
Also:
Lithium
Atypical antidepressants
Antipsycotics |
|
|
Term
| Give some examples of SSRIs |
|
Definition
fluoxetine (Prozac)
citalopram (most UK prescribed)
also paroxetine and seratraline |
|
|
Term
| How do SSRIs compare to TCAs? |
|
Definition
- lower autonomic (atropinic/little antimuscarinic)
- lower CV effects
- lower acute toxicity
- less sedation |
|
|
Term
| Give some examples of TCAs |
|
Definition
|
|
Term
| What is the main risk with TCAs? |
|
Definition
| TCAs effects can be used to commit suicide |
|
|
Term
| What is the main issue with all antidepressants? |
|
Definition
| 2+ week delay but re-uptake is blocked immediately |
|
|
Term
| What is thought to cause the delay? |
|
Definition
| disconnect between biochemical and therapeutic effects |
|
|
Term
| Describe the SSRI mechanism |
|
Definition
1. SSRI blocks reuptake pump, increasing 5HT in somatodentritic area
2. 5HT(IA) autoreceptors desensitise
3. Lack of inhibition of impulse flow
4. Increase 5HT from axon terminal
5. post synaptic receptors desensitise (reduction in side effects) |
|
|
Term
| Unwanted effects of SSRIs: |
|
Definition
-nausea, anorexia
-insomnia rather than sedation
-aggression/violence
-sexual dysfunction
-loss of libido
-orgasm failure |
|
|
Term
| Why would SSRI's be used over MAOIs? |
|
Definition
| no more effective but cannot be used for suicide |
|
|
Term
|
Definition
split of the mind (severe and least understood).
symptomatic onset in early adulthood and persists throughout life |
|
|
Term
| Describe the positive/type 1 symptoms of schizophrenia and when they occur |
|
Definition
visual/auditory hallucinations, delusions
younger |
|
|
Term
| Describe the negative/type 2 symptoms of schizophrenia and when they occur |
|
Definition
apathy, lack of emotion, poor or non-existent social functioning
older |
|
|
Term
| Describe the cognitive symptoms of schizophrenia |
|
Definition
| difficulty concentration, following instructions and memory failure |
|
|
Term
| Describe the dopamine hypothesis of schizophrenia |
|
Definition
| dysregulation of dopamine neurotransmission caused by stimulant abuse and produces schizophrenic-like psychosis via release of dopamine |
|
|
Term
| What other drug acts along the dopamine hypothesis of schizophrenia? |
|
Definition
| D2 receptor agonists eg bromocriptine and apomorphine |
|
|
Term
| What are all clinically used antipsychotics? and what correlates with clinical efficacy? |
|
Definition
dopamine antagonists
affinities and occupancy for D2 and D3 receptors |
|
|
Term
| Give examples of typical antipsychotics |
|
Definition
| haloperidol and cherpromazine |
|
|
Term
| Give examples of atypical antipsychotics |
|
Definition
|
|
Term
| What are some of the issues with antipsychotics? |
|
Definition
1. high d1/2 receptor occupancy leads to unwanted effects
2. limited/no effects on negative symptoms and cognition
3. >30% poor responders
4. relatively 50% out patients non compliant |
|
|
Term
| What are some of the unwanted effects of antipsychotic problems? (related to DA antagonism) |
|
Definition
extrapyramidal syndrome (EPS): parkinson-like symptoms
tardive dyskinesia |
|
|
Term
| What does DA in hypothalamus act as? |
|
Definition
release inhibiting factor for prolactin.
AP therefore increase prolactin
causes galactorrhea in fertility, gynacomastia in men |
|
|
Term
| What other endocrine effects are related to antipsychotics? |
|
Definition
| DA controls other hormones, APs cause decrease in growth hormone |
|
|
Term
| What are the unwanted effects of antipsychotics that aren't related to DA |
|
Definition
blockade of muscarinic receptors
-dry mouth/blurred visions
-subject to tolerance
-may be beneficial in EPS as less inhibitory/excitation disturbance
-effective atropinic, causes little EPS |
|
|
Term
| What are the two types of diabetes? |
|
Definition
insipidus (tasteless)
mellitus (honey) |
|
|
Term
| What are the two types of diabetes insipidus? |
|
Definition
neurogenic/central -> deficient vasopressin secretion
nephrogenic -> lack of response to vasopressin |
|
|
Term
| What are the two types of diabetes mellitus? |
|
Definition
Type 1: lack of insulin producing cells and therefore takes insulin via injection
Type 2: glucose intolerant or glucose resistant (either pancreatic beta cells do not release or insulin is released but does not have its effects) |
|
|
Term
| What other names does vasopressin have? |
|
Definition
|
|
Term
| Where is vasopressin synthesised? |
|
Definition
| in neurones of the supraoptic nucleus of the hypothalamus |
|
|
Term
| What is vasopressin released in response to? |
|
Definition
|
|
Term
| What are the effects of vasopressin? |
|
Definition
- they act on vasopressin GPCRs in the kidney to increase water permeability of the collecting duct
- increase permeability of the nephrons to water so water that has been filtered from the glomerulus is reabsorbed back into the body (retention via osmosis) |
|
|
Term
| What is the half life of vasopressin and why? |
|
Definition
<30mins (relatively short)
peptides in the bloodstream are quickly broken down by enzymes (serum peptidases) |
|
|
Term
|
Definition
| synthetic analogue of vasopressin with a longer half life (3.5 hours) |
|
|
Term
| Give examples of desmopressin drugs: |
|
Definition
DDAVP
Desmomelt
Stimate
Minirin |
|
|
Term
| How is desmopressin administered? |
|
Definition
orally, intranasally or parentally
intranasally/orally: max plasma conc achieved 40-50mins |
|
|
Term
| What are the effects of desmopressin? |
|
Definition
urine output will decrease 1-2 hours after admin
effects last 6-18hours |
|
|
Term
|
Definition
| high blood glucose (>11,1mM under normal conditions) causes frequent urination and thirst |
|
|
Term
| What causes type I diabetes millitus |
|
Definition
| autoimmune destruction of pancreatic beta cells |
|
|
Term
| What causes type II diabetes millitus |
|
Definition
insulin is synthesised in pancreatic beta cells but secretion is impaired (glucose intolerance)
OR
insulin released but has little effect in the periphery (insulin resistance) |
|
|
Term
| What influences type II diabetes millitus |
|
Definition
|
|
Term
|
Definition
- peptide hormone expressed only in pancreatic beta cells
- stored in secretory vesicles
- zinc ions help to cluster 6 insulin molecules together as a complex |
|
|
Term
|
Definition
- preproinsulin is cleaved to form insulin
-A chain (21aa) and B chain (30aa) connected by disulphide bonds |
|
|
Term
| Where are insulin receptors expressed? |
|
Definition
| liver, muscle and fat cells |
|
|
Term
| What are the effects of insulin? |
|
Definition
- glucose uptake is increased in muscle and fat cells (from blood)
- increased glycolysis and glycogenesis in liver and muscle |
|
|
Term
| What does insulin help cells to do? |
|
Definition
| take in glucose to be used for energy (glycogen) |
|
|
Term
| How does glucose cross the membrane? |
|
Definition
1. GLUT4 (transporter) reside in vesicles inside the cell at rest
2. when insulin binds to receptor and send off signalling cascades which cause these vesicles to exocytose
3. GLUT4 is moved to the plasma membrane of the cell
Glucose pass down its conc gradient from the blood into the cell |
|
|
Term
| How is diabetes mellitus treated? and what is its significance? |
|
Definition
insulin administered parentally, usually as a subcatnenous injection, otherwise its broken down in the stomach.
this is the only way to treat type 1 |
|
|
Term
| How was insulin harvested in the past? |
|
Definition
| used to be purified from animals for human use (which would trigger an immune response) |
|
|
Term
| How is insulin harvested now? |
|
Definition
| made from human DNA use recombinant technology |
|
|
Term
| Describe long acting insulin |
|
Definition
hour to hour insulin released (between meals)
insulin precipitated with zinc (or protamine) injected as a suspension is slowly released |
|
|
Term
| Describe fast acting insulin |
|
Definition
immediately after a meal when glucose levels are high and quick spike of insulin is needed
soluble monomeric insulin is fast acting |
|
|
Term
| insulin lispro and glargine |
|
Definition
|
|
Term
| Half life of soluble insulin... |
|
Definition
|
|
Term
| What could diabetes mellitus treatment cause? |
|
Definition
hypoglycemia if too much glucose is removed from the blood
<3mM |
|
|
Term
| What is insulin resistance associated with? |
|
Definition
| high levels of circulating triglycerides and free fatty acids |
|
|
Term
| What are some risk factors of insulin resistance? |
|
Definition
| obesity and sedentary lifestyle |
|
|
Term
| What is insulin resistance usually treated with? |
|
Definition
|
|
Term
| What are the effects of metaformin? |
|
Definition
liver: reduce glucose production (gluconeogenesis)
Periphery (muscle/fat): increase glucose uptake and utilisation |
|
|
Term
| What are most of the effects of metaformin caused by? |
|
Definition
stimulation of AMP-activated protein kinase (AMPK)
weak inhibition of mitochondrial complex I (increase cAMP) |
|
|
Term
| What are some of the extra benefits of metaformin? |
|
Definition
- does not cause hypoglycaemia
- enhances effects of insulin when taken with other anti-diabetic therapies |
|
|
Term
| What is the half life of metaformin? |
|
Definition
| 3-6 hours and is excreted unchanged in urine (not metabolised) |
|
|
Term
| What are sulphonylureas and glinides? |
|
Definition
- used to treat type II diabetes by directly stimulating insulin secretion
- risk of hypoglycaemia (less so with glinides) |
|
|
Term
| Describe the mechanism of action for sulphonylureas and glinides |
|
Definition
taken orally as tablets
1. inhibition of the ATP-dependent potassium channcel found in the plasma membrane of pancreatic beta cells
2. bind to serum albumin and so compete with other drugs that bind |
|
|
Term
| How are sulphonylureas and glinides metabolised? |
|
Definition
- by the liver (into active and/or inactive products)
- excreted into urine/faeces |
|
|
Term
| How long acting are sulphonylureas and glinides? |
|
Definition
sulphonylureas: long lasting (1 tablet a day)
glinides: rapid and short acting (taken with meals) |
|
|
Term
| Describe the events that occur in low plasma glucose |
|
Definition
1. High ADP levels, low ATP levels
2. (Katp channels are activated by ADP) therefore membrane hyperpolarised
3. voltage-gated Ca2+ channels closed
4. insulin is not released |
|
|
Term
| Describe the events that occur in high plasma glucose |
|
Definition
1. low ADP levels, high ATP levels
2. (Katp channels are inhibited by ATP) therefore membrane depolarised
3. voltage-gated Ca2+ channels open
4. Ca2+ induced insulin secretion |
|
|
Term
| How does glucose intolerance affect metabolism? |
|
Definition
low metabolism
this prevents generation of sufficient ATP to close Katp channels |
|
|
Term
| How does neonatal diabetes affect metabolism? |
|
Definition
high metabolism
defects in Katp channels prevent closure by ATP |
|
|
Term
| What can Katp inhibitors be used to treat? |
|
Definition
both!
cause closure of Katp channels, membrane depolarisation, ca2+ influc and insulin secretion |
|
|
Term
|
Definition
| group of drugs that inhibit the growth of pathogens without causing serious damage to the host |
|
|
Term
|
Definition
| kill bacteria by disrupting cell wall synthesis (eg penicillin and streptomycin). They do not rely on host defence and are faster acting |
|
|
Term
|
Definition
| stop the growth of bacteria by interfering with DNA synthesis, protein production or metabolites (eg sulphonamides and tetracycline). The host defence removes static bacteria. |
|
|
Term
| How are antibiotics classified? |
|
Definition
| by a spectrum of activity: narrow, moderately broad, broad, very broad |
|
|
Term
| What is folic acid required for? |
|
Definition
- synthesis of DNA and RNA nucleic acids
- step before this is synthesis of purines (which become DNA etc..) |
|
|
Term
|
Definition
| components of DNA and RNA |
|
|
Term
| How do folic acid inhibitors compare to folic acid? |
|
Definition
sulphonamide: resembles p-aminobenzoic acid
trimethoprim: resembles pteridine ring |
|
|
Term
| What does sulphonamide inhibit? |
|
Definition
| dihydropteroate synthase from converting p-aminobenzoic acid into dihydrofolic acid |
|
|
Term
| What does trimethoprim inhibit? |
|
Definition
| ihyfrofolate reductase from converting dihydrofolic acid into tetrafolic acid |
|
|
Term
| How do we obtain folic acid? |
|
Definition
| bacteria synthesises it and we take it whole |
|
|
Term
|
Definition
bacteriostatic
action negated by pus which supplies precursors of nucleic acids |
|
|
Term
| Describe the pharmacokinetics of sulphonamides |
|
Definition
- taken orally
- readily absorbed in the GI tract
- inactivated by the liver by acetylation |
|
|
Term
| What are the unwanted effects of sulphonamides? |
|
Definition
- mild to moderate
- nausea and vomitting
- hepatitis
- hypersensitivity (eg rashes)
- crystalluria |
|
|
Term
| What are the uses of sulphonamide? |
|
Definition
- combined with trimethoprim for pneumocystis carinii
- inflammatory bowel disease
- infectious burns
- some STIs (eg chlamydia) |
|
|
Term
| Describe the pharmacokinetics of trimethoprim |
|
Definition
| given orally and fully absorbed in the GI tract |
|
|
Term
| What are the unwanted effects of trimethoprim? |
|
Definition
- nausea and vomitting
- skin rashes
- blood disorders
- folate deficiency which results in megaloblastic anaemia (can be prevented by folinic acid) |
|
|
Term
| Describe Gram-positive bacteria and give examples |
|
Definition
eg E.coli and H pylori
contain outer membrane which creates an additional compartment (the periplasmic space) this makes them more protected from penicillins |
|
|
Term
| Describe Gram-negative bacteria and give examples |
|
Definition
eg S aureus
do not contain an outer membrane and this makes them less protected from penicillins |
|
|
Term
| Which are more protected from penicillins, gram positive or negative? |
|
Definition
|
|
Term
| Describe the structure of peptidoglycan |
|
Definition
- N-acetylglucosamine (GlcNAc) joined to N-acetylmuranic acid (MurNAc) forming linear chains
- these chains are crosslinked by oligopeptides |
|
|
Term
| How is a peptidoglycan synthesised? |
|
Definition
Transglycosylase: between 2 sugar residues
Transpeptidase: forms peptide bond between 2 amino acids |
|
|
Term
| What drug works on both transglycosylase and transpeptidase? |
|
Definition
| penicillins (beta-lactam antibiotics) |
|
|
Term
|
Definition
| a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of most bacteria, forming the cell wall. |
|
|
Term
| What inhibits many beta-lactamases? |
|
Definition
|
|
Term
| What effect does B-lactam have on bacteria? |
|
Definition
|
|
Term
| What effect does B-lactam + B-lactamase have on bacteria? |
|
Definition
| inactivates B-lactam therefore no effect on bacteria |
|
|
Term
| What effect does B-lactam + B-lactamase + clavulanic acid have on bacteria? |
|
Definition
|
|
Term
| Describe naturally occurring penicillin |
|
Definition
| benzylpenicillin isolated from penicillium mould |
|
|
Term
| Describe semi-synthetic occurring penicillin |
|
Definition
ampicillin and amoxicillin (broad spectrum)
flucoxacillin (b-lacatamase resistant)
carbenicillin (extended spectrum) |
|
|
Term
| Describe the pharmacokinetics of penicillins |
|
Definition
- oral, IV or IM
- intrathecal not advisable
- lipid insolbule therefore does not cross BBB except in meningitis
- short half life and eliminated in urine |
|
|
Term
| Describe the effects of penicillin |
|
Definition
- relatively safe
- hypersensitivity reactions in some
- acute anaphylactic shock
- GI tract disturbance
- superinfection by bacteria insensitive to penicillin |
|
|
Term
| What are the clinical uses of penicillin? |
|
Definition
first choice for many infections:
- bacterial meningitis
- pneumonia
- bone and joint infections
- skin and soft tissues infections
- pharyngitis
- urinary tract infections
- gonorrhoea and syphilis |
|
|
Term
| What forms do cephalosporins come in? |
|
Definition
naturally occuring: cephalosporins isolated from fungus
semisynthetic:
1st gen: cefalexin
2nd gen: cefuroxime
3rd gen: cefotaxim
4th gen: cefepime |
|
|
Term
| How are cephalosporins administered? |
|
Definition
| - mostly parenterally but some may be orally |
|
|
Term
| can cephalosporins cross the BBB? |
|
Definition
| - some lipid soluble cross the BBB |
|
|
Term
| Describe the half life of cephalosporins |
|
Definition
| - short half life, eliminated via kidney and bile |
|
|
Term
| What are the unwanted effects of cephalosporins |
|
Definition
relatively safe
hypersensitivity reactions similar to penicillin |
|
|
Term
| What are the clinical uses of cephalosporin? |
|
Definition
broad spectrum, second choice for many infections:
-septicaemia
-meningitis
-pneumonia
-billary tract infections
-pharyngitis
-sinusitis |
|
|
Term
| Name some B-lactamase resistant B-lactam antibiotics |
|
Definition
Carbapenem (imipenem)
Monolactam (aztreonam) |
|
|
Term
| Describe Carbapenem (imipenem) |
|
Definition
B-lactamase resistant but some organisms have developed resistance
broad spectrum |
|
|
Term
| Describe Monolactam (aztreonam) |
|
Definition
B-lactamase resistant but some organisms have developed resistance
only active against gram negative aerobic rods |
|
|
Term
What are the unwanted effects of Carbapenem (imipenem) and
Monolactam (aztreonam)? |
|
Definition
| similar to other B-lactam antibiotics: nausea and vomiting |
|
|
Term
| What other antibiotics inhibit bacterial cell wall synthesis? |
|
Definition
non-B lactam
Bacitracin
cycloserine
vancomycin |
|
|
Term
| Describe bacitracin (structure and effects) |
|
Definition
cyclic polypeptide isolated from Bacillus subtlis
effective against gram+ and gram- bacteria
streptococcus |
|
|
Term
| Describe cycloserine (structure and effects) |
|
Definition
synthetic
4-amino-3-isoxazolidinone (cycling analogue of D-alanine)
active against Mycobacterium tuberculosis |
|
|
Term
| Describe vancomycin (structure and effects) |
|
Definition
glycopeptide isolated from actinomycetes
active against gram+ bacteria, straphylococcus aureus
reserved for very serious penicillin resistant infections |
|
|
Term
| Where does protein synthesis occur |
|
Definition
made on the ribosomes on the endoplasmic reticulum
small subunit (30s) and large subunit (50s) |
|
|
Term
| Describe the sites involved in protein synthesis |
|
Definition
A site: aminoacyl trna binds
P site: peptidyl-trna binds
E site: exit site for outgoing trna |
|
|
Term
| How does tetracycline inhibit bacterial protein synthesis? |
|
Definition
| competes with aminoacyl-tRNA for the A site on ribosomes |
|
|
Term
| How does chloramphenicol inhibit bacterial protein synthesis? |
|
Definition
| blocks peptidyl transferase |
|
|
Term
| How does aminoglycosides inhibit bacterial protein synthesis? |
|
Definition
| abnormal codon:anticodon recognition leading to misreading of the message |
|
|
Term
| How does erythromycin inhibit bacterial protein synthesis? |
|
Definition
| inhibits translocation of tRNA from Asite to Psite |
|
|
Term
| What forms of tetracyclines are there |
|
Definition
naturally occuring: tetracycline and oxytetracycline: chemically polyketides isolated from actinomycetes
semisynthetic: doxycycline: actively taken by bacteria (bacteriostatic) |
|
|
Term
| How are tetracyclines administered? |
|
Definition
|
|
Term
| Describe the pharmcokinetics of tetracyclines |
|
Definition
some are incompletely absorbed, complex with calcium in food (milk) which further reduce absorption
doxycycline can cross the BBB |
|
|
Term
| What are the unwanted effects of tetracyclines |
|
Definition
relatively safe
GI tract disturbance (direct irritation)
staining of teeth (due to calcium chelation) |
|
|
Term
| What are the clinical uses of tetramycin? |
|
Definition
broad spectrum
first choice for rickettsial, mycoplasma and chlamydial infections, cholera plague |
|
|
Term
| What form is chloramphenicol found in? |
|
Definition
| naturally occuring isolated from streptomycers (bacteriostatic) |
|
|
Term
| Describe the pharmacokinetics of chloraphenicol |
|
Definition
oral rapidly absorbed
can cross BBB |
|
|
Term
| what are the unwanted effects of chloraphenicol? |
|
Definition
severe, idiosyncratic depression of bone marrow, resulting in pancytoperia (decrease in all blood cell elements) RARE
'grey baby syndrome'
GI tract disturbance, hypersensitivity |
|
|
Term
| What are the clinical uses of chloramphenicol |
|
Definition
- broad spectrum
- no longer first choice, should be reserved for serious infections
- meningitis resistant to penicillin
- bacterial conjunctivitis
- originally used in typhoid fever |
|
|
Term
| what forms are aminoglycosides found as? |
|
Definition
naturally occuring
isolated from streptomyces (drugs end in -mycin) and micromonospora (drugs end in -micin) |
|
|
Term
| Describe the pharmacokinetics of aminoglycosides |
|
Definition
water soluble therefore administered by IV or IM
half life is 2-3 hours
cannot cross the BBB |
|
|
Term
| What are the unwanted effects of aminoglycosides |
|
Definition
-ototxicity (damage to sensory cells of cochlea and vestibular organ of the ear)
-nephrotoxicity (damage to kidney tubules) |
|
|
Term
| What are the clinical uses of aminoglycosides |
|
Definition
broad spectrum
serious infections caused by aerobic gram negative bacilli |
|
|
Term
|
Definition
| antibiotics that act on nucleic acids |
|
|
Term
| Describe the pharmacokinetics of quinolones |
|
Definition
selective toxicity based on structural differences in pro and eukaryotes
oral
broad spectrum (antibiotic and bactericidal) |
|
|
Term
| What are the unwanted effects of quinolones |
|
Definition
| GI tract disturbances and hypersensitivity |
|
|
Term
| What are the clinical uses of quinolones? |
|
Definition
UTIs
respiratory infections
eradication of salmonella typhi |
|
|
Term
|
Definition
| semisynthetic derived from amyedotoporis rifamycinia |
|
|
Term
| Describe the pharmacokinetics of rifamicin |
|
Definition
oral
half life 1-5 hours
resistance can be developed quickly |
|
|
Term
|
Definition
bactericidal
inhibits DNA dependent RNA polymerase
selective toxicity based on structural differences between RNA polymerase in pro and eukaryotes |
|
|
Term
| What are the unwanted effects of rifamicin |
|
Definition
relatively infrequent
skin eruptions, fever, GI tract disturbances
hepatotoxicity |
|
|
Term
| what are the clinical uses of rifamicin |
|
Definition
broad spectrum
tuberculosis and leprosy |
|
|
Term
| What carries antibiotic resistance genes |
|
Definition
|
|
Term
| Name 6 drugs that cause resistance via plasmid encoded genes |
|
Definition
b-lactams
chloramphenicol
aminoglycosides
tetracycline
erythromycin
trimethoprim |
|
|
Term
| How do b-lactams cause resistance |
|
Definition
| produce b-lactamases that hydrolyse the lactam ring |
|
|
Term
| How do chloramphenicol cause resistance |
|
Definition
| produce enzymes that acetylate the drug |
|
|
Term
| How do aminoglycosides cause resistance |
|
Definition
| produce enzymes that acetylate, phosphorylate or adenylate the drug |
|
|
Term
| How do tetracycline cause resistance |
|
Definition
| produce a membrane transporter that pumps the antibiotic out |
|
|
Term
| How do erythromycin cause resistance |
|
Definition
| produce an enzyme that methylates the 26s rRNA thereby preventing the binding of the antibiotic |
|
|
Term
| How do trimethoprim cause resistance |
|
Definition
| produce a mutant form of dihydrofolate reductase that is insensitive to the drug |
|
|
Term
| Name 3 manifestations of CV |
|
Definition
heart attach
stroke
gangrene |
|
|
Term
|
Definition
| a disease of the arteries characterised by the deposition of fatty material on the inner walls |
|
|
Term
| What leads to atherosclerosis? |
|
Definition
obesity
smoking
inactivity
hypertension
diabetes |
|
|
Term
| What does atherosclerosis lead to? |
|
Definition
stroke
myocardial infarction (and then heart failure) |
|
|
Term
| What are the two types of CV disease treatment? |
|
Definition
1. prevention/progression
2. reduce mortality |
|
|
Term
| Describe the aims of primary prevention |
|
Definition
| keeps the disease process from being established |
|
|
Term
| Describe the aims of secondary prevention |
|
Definition
| interrupts the disease process before it becomes symptomatic |
|
|
Term
| Describe the aims of tertiary prevention |
|
Definition
| limits the physical and social consequences of symptomatic disease |
|
|
Term
| What drugs are used as primary prevention? |
|
Definition
|
|
Term
|
Definition
| the primary effect is a reduction in serum cholesterol to slow the development of atherosclerosis |
|
|
Term
| What is the role of LDL receptors and what do low levels indicate |
|
Definition
| they take up cholesterol into the cells, low receptor levels lead to familial hypercholesteraemia |
|
|
Term
| How do statins reduce serum cholesterol? 5 steps |
|
Definition
1. reduced hepatic cholesterol synthesis
2. reduced serum cholesterol
3. compensatory increase in LDL receptors
4. increased cholesterol cleared from serum
5. serum cholesterol maintained at lower level |
|
|
Term
| What else do statins do that contribute to beneficial effects? |
|
Definition
| they are anti-thrombotic and improve endothelial function |
|
|
Term
| What drugs are used as secondary prevention? |
|
Definition
|
|
Term
| How does aspirin prevent CV disease? |
|
Definition
1. limits thrombus formation and so reduces the incidence of heart attach/stroke in those with atherosclerosis
2. irreversible inhibitor of the COX-1 enzyme |
|
|
Term
| By inhibiting COX-1, what does aspirin prevent? |
|
Definition
aspirin irreversibly acetylates COX1
arachidonic acid becoming PGI2 and TXA2 |
|
|
Term
| What role do platelets have? |
|
Definition
they aggregate to form thrombus
they have no nucleus |
|
|
Term
|
Definition
|
|
Term
| What effect does aspirin have if it acetylates a COX-1 in an endothelial cell and why? |
|
Definition
1.endothelial cells contain a nucleus and can therefore create new COX-1 enzymes once the original has been acetylated
2.generates anti-aggregation factors
3.PGI2 is anti-aggregation |
|
|
Term
| Why is aspirin often used in conjunction with clopidogrel? |
|
Definition
works on platelets and prevents formation of ADP (rather than TXA2)
works as an antagonist |
|
|
Term
| What role does ADP have in aggregation? |
|
Definition
ADP is a pro-aggregatory molecule
ADP binds to P2gamma receptors and causes aggregation |
|
|
Term
| What else is clopidogrel used as? |
|
Definition
clot buster
used to dispense a clot after its formed to return blood flow |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What drugs are used in primary, secondary and tertiary prevention? |
|
Definition
| ACE inhibitors (angiotensin converting enzyme eg captopril) |
|
|
Term
| What are ACE inhibitors used to treat? |
|
Definition
| hypertension and heart failure (reduce blood pressure) |
|
|
Term
| How and where is blood pressure controlled? |
|
Definition
kidney: controls fluid retention
Blood vessels: resistance to flow |
|
|
Term
| Where does angiotensin II bind and what are the effects? |
|
Definition
ATI receptor
1. increases fluid retention (blood volume)
2. vasoconstriction (resistance)
Angiotensin II is a potent vaso-active peptide that causes blood vessels to constrict, resulting in increased blood pressure. |
|
|
Term
| What conversion do ACE inhibitors prevent? |
|
Definition
| they prevent ACE catalysing the conversion of angiotensin I to angiotensin II |
|
|
Term
| When is renin released and what does it do? |
|
Definition
| When renal blood flow is reduced, juxtaglomerular cells in the kidneys convert the prorenin already present in the blood into renin and secrete it directly into the circulation. Plasma renin then carries out the conversion of angiotensinogen, released by the liver, to angiotensin I. |
|
|
Term
| What are the effects of ACE inhibitors? (4) |
|
Definition
- reduces blood pressure
- reduces incidence of strokes/heart failure
- provides symptomatic relief in heart failure (breathlessness)
- produces dry cough (ACE in lungs - bradykinin) |
|
|
Term
| How else can the effects of angiotensin II be limited and what are the benefits? |
|
Definition
- angiotensin receptors blocks (ARBS)
- fewer side effects than ACE inhibitors |
|
|
Term
| Define what a drug of abuse is |
|
Definition
| a drug that is taken out of choice, not for medical need |
|
|
Term
| When does a drug of abuse become illegal? |
|
Definition
| when society determines social cost is more than the individual benefit |
|
|
Term
| What is the mesolimbic pathway? |
|
Definition
the dopaminergic reward pathway in the brain
the pathway connects the ventral tegmental area (midbrain) to the nucleus accumbens |
|
|
Term
| What are the 5 main drug types of abuse |
|
Definition
1. narcotic analgesics
2. general CNS depressents
3. anxiolytics
4. psychomotor stimulants
5. psychomimetics |
|
|
Term
| What type does ethanol belong to and what is its dependence reliability? |
|
Definition
General CNS depressants
Strong |
|
|
Term
| What type does nicotine belong to and what is its dependence reliability? |
|
Definition
Psychomotor stimulants
Very strong |
|
|
Term
|
Definition
| pharmacologically the active substance in tobacco smoke that acts on nACHRs |
|
|
Term
| Where does nicotine have effects |
|
Definition
-cortex and hippocampus (role in cognitive function)
-ventral tegmental area (DA neurones to nucleus accumbens) |
|
|
Term
| Does nicotine have pre or post-synaptic effects? |
|
Definition
both
causing increased transmitter release and neuronal excitation |
|
|
Term
| What effect does nicotine have on receptors? |
|
Definition
desensitisation
receptor increase |
|
|
Term
| What are the spinal effects of nicotine? |
|
Definition
- inhibition of spinal reflexes
- skeletal muscle relaxes (shown on EMG)
- stimulation of inhibitory Renshaw cells |
|
|
Term
| How does nicotine affect brain function? |
|
Definition
-higher level brain function altered by dose and situation (wake up vs calm down)
-EEG studies support claims |
|
|
Term
| The peripheral effects of nicotine are caused via... |
|
Definition
| ...stimulation of autonomic ganglia and sensory receptors |
|
|
Term
| What are the peripheral effects of nicotine? |
|
Definition
1. tachycardia, increased CO and arterial pressure, reduced GI motility and sweating
2. reduced appetite |
|
|
Term
| How much nicotine does a cigarette contain? |
|
Definition
| 9-17mg and 10% is absorbed |
|
|
Term
| Describe the pharmacokinetics of nicotine |
|
Definition
rapidly absorbed from lungs
poorly from the mouth and nasopharynx therefore inhalation is required |
|
|
Term
| Describe the changes in plasma concentration of nicotine over the smoking of a fag over 10 mins |
|
Definition
1. rises to 100-200nmol/L
2. falls to about half within 10 mins (due to distribution to other tissues)
3. falls slower over next 1-2 hours
4.30nmol/L after 90mins |
|
|
Term
| What causes the slow decline? |
|
Definition
| hepatic metabolism (oxidative) into inactive ketone metabolite cotinine which has a very long plasma half life |
|
|
Term
| Describe the nicotine plasma concentration for a (24hour) nicotine patch |
|
Definition
| plasma concentration rises to 75-150nmol/L and remains constant |
|
|
Term
| Describe the nicotine plasma concentration for a gum/nasal spray |
|
Definition
| cause plasma concentration intermediate between actual smoking and patch |
|
|
Term
| The physical withdrawal syndrome passes after 2-3 weeks, what symptoms are no longer experienced? |
|
Definition
- irritability
- impaired psychomotor performance
- alleviated by nicotine and amphetamines
- aggression
- sleep disturbances |
|
|
Term
| What are the harmful effects of smoking? 7 |
|
Definition
1. cancer
2. CHD and vascular disease
3. chronic bronchitis
4. harmful effects in pregnancy
5. tar and irritants
6. carbon monoxide
7. increased oxidative stress |
|
|
Term
| What are the harmful effects associated with nicotine and pregnancy? |
|
Definition
1. reduced birth weight
2. increased perinatal mortality
3. spontaneous abortion
4. premature delivery
5. nicotine excreted in breast milk enough to cause tachycardia in infant |
|
|
Term
| How is nicotine dependence treated? 2 |
|
Definition
1. nicotine replacement therapy (with psychotherapy)
2. buproprion NA/DA reuptake blocker |
|
|
Term
| What is one unit of alcohol in ethanol and how many units is max? |
|
Definition
1 unit = 8g (10ml)
21 units/week men
14 women |
|
|
Term
| What effect does ethanol have on the CNS |
|
Definition
similar depressant effects to volatile anaesthetics
increases neuronal activity by distribution in reward pathways |
|
|
Term
| What are the main theories of ethanol action? 5 |
|
Definition
1. enhancement of GABA-mediated inhibition on GABAa (like benzodiazepines)
2. inhibition of Ca2+ entry (inhibits NT release)
3. inhibition of NMDAR function
4. inhibition of adenosine transport
5.endogenous opiods due to action of naltrexone reducing the rewarding effects |
|
|
Term
| What are the acute effects of ethanol on the CNS? 4 |
|
Definition
- slurred speech, motor incoordination, increased self confidence, euphoria, new ability to dance
- large mood swings
- failed judgement
- coma and death |
|
|
Term
| What are peripheral effects of ethanol? 4 |
|
Definition
- cutaneous vasodilation
- salivary and gastric secretion
- endocrine effects
- duiresis caused by ADH secretion inhibition |
|
|
Term
| What are the chronic effects of ethanol? 5 |
|
Definition
- hypertension
- irreversible neurological effects
- irreversible dementia
- significant enhancements of other CNS depressents
- feminisation in males |
|
|
Term
| How does ethanol affect the liver? 5 |
|
Definition
1. increased fat accumulation (fatty liver)
2. hepatitis (inflammation of liver)
3. irreversible hepatic necrosis
4. malnutrition via thiamine deficiency
5. varicose veins around the liver can bleed suddenly (internal haemorrhage) |
|
|
Term
| What two disorders can be caused by ethanol in foetal development? |
|
Definition
1. fetal alcohol syndrome (FAS)
2. alcohol related neuro-developmental disorder (ARND) |
|
|
Term
| What are the symptoms of FAS? |
|
Definition
- abnormal facial development and reduced cranial circumference
- mental and growth retardation
- cardiac abnormalities
- malformation of eyes and ears |
|
|
Term
| What are the symptoms of ARND? |
|
Definition
- behavioural problems
- cognitive and motor deficits |
|
|
Term
| When are physical abnormalities caused? |
|
Definition
|
|
Term
| When are brain abnormalities caused? |
|
Definition
|
|
Term
| Describe the pharmacokinetics of ethanol |
|
Definition
- rapidly absorbed by the stomach
- first pass saturation kinetics, fraction removed decreases as liver ethanol conc increases
- portal vein concentration is high, most escapes into systematic circulation |
|
|
Term
| Where is ethanol metabolised? |
|
Definition
|
|
Term
| What is a cofactor in the oxidation process of ethanol? |
|
Definition
NAD+
also the limiting factor |
|
|
Term
| Describe ethanol metabolism |
|
Definition
alcohol + ADH + NAD+
= acetaldehyde
+ALDH
+NAD+
= acetic acid |
|
|
Term
| What is the common ethanol metabolism misconception |
|
Definition
its acetaldehyde poisoning not acetic acid
because ALDH is not induceable |
|
|
Term
| What are the effects of ALDH dysfunction |
|
Definition
- flushing
- tachycardia
- hyperventilation
- panic
- low alcholism |
|
|
Term
|
Definition
| ALDH inhibitor used in aversive therapy |
|
|
Term
|
Definition
| inhibits noradrenaline and dopaminergic transporter therefore there is no uptake in teh CNS |
|
|
Term
| What are the adverse effects of cocaine? |
|
Definition
| tachycardia and hypertension |
|
|
Term
|
Definition
-small infectious agents that can replicate only inside the living cells of a host
-protein coat that encapsulates a genome (nucleic acid) |
|
|
Term
| What do viruses depend on? |
|
Definition
| a host cell machinery to enter, replicate, assemble new viruses and persist |
|
|
Term
| What does a neurotropic disease affect? |
|
Definition
| neuronal cells (eg rabies) |
|
|
Term
| What does a pneumotropic disease affect? |
|
Definition
| upper and lower respiratory tract epithelial cells (eg flu) |
|
|
Term
| What does a lymphotropic disease affect? |
|
Definition
| lymphatic cells (eg HIV caused by CD4+ T cells) |
|
|
Term
| What does a enterotropic disease affect? |
|
Definition
| gut epithelial cells and liver cells |
|
|
Term
| What is a susceptible cell? |
|
Definition
- one that a virus can enter
- requires a specific receptor that can bind a viral attachment protein
- the cell must also support replication |
|
|
Term
| What receptor does flu require? |
|
Definition
| sialic acid receptor found on epithelial cells |
|
|
Term
| What receptor does HIV require? |
|
Definition
| a CD4 receptor found on CD4+ helper T cells, macrophages and dendritic cells |
|
|
Term
| What 6 things do viruses depend on host cells to achieve? |
|
Definition
- translate viral mRNA
- generate energy
- process proteins
- provide structures for virus factories
- assemble viruses
- replicate and transcribe DNA |
|
|
Term
| Describe an acute infection and give an example |
|
Definition
flu
- rapid onset of symptoms (1-4 days)
- immune system can contain and clear
- virus undetectable, typically 7-10 days later |
|
|
Term
| Describe a latent/persistent infection and give an example |
|
Definition
herpes simplex virus
- rapid onset of initial symptoms
- immune system cannot contain and clear
- virus frequently reactivates |
|
|
Term
| Describe an slow infection and give an example |
|
Definition
hepatitis C or HIV
- rapid onset of initial symptoms
- immune system cannot contain and clear
- virus replication can continue for years |
|
|
Term
|
Definition
AIDS
progressive failure of the immune system |
|
|
Term
| What events follow a HIV infection? |
|
Definition
1. HIV hijacks the CD4+ T cells and turns them into factories that produce 1000s of virus copies
2. causes apoptosis of infected cells and uninfected bystander cells |
|
|
Term
|
Definition
| rapid decline in CD4+ T cells below critical level |
|
|
Term
|
Definition
- unprotected sex with an infected partner
- sharing needles with an infected person
- transmission from infected mother to fetus
- infection from blood products |
|
|
Term
| How are HIV drugs classified? |
|
Definition
By which stage of the virus life cycle they block
1. entry/binding and fusion
2. integration
3. transcription
4. assembly
5. release/budding |
|
|
Term
| Describe HIV binding and fusion |
|
Definition
1. HIV enters a CD4 cell by binding to CD4 receptors
2. must bind to a second co-receptor (CCR5 or CXCR4)
3. after fusion, HIV releases its RNA and enzymes into the cell |
|
|
Term
| What are entry inhibitors? |
|
Definition
| drugs that stop HIV entering a CD4 cell |
|
|
Term
| Name some entry inhibitors |
|
Definition
Fusion inhibitor: fuzeon (enfurirtide)
CCR5 antagonist: selzentry (maraviroc) |
|
|
Term
|
Definition
- newly formed HIV DNA enters the nucleus of the CD4 cell
- HIV enzymes called integrase combines or integrates HIV's DNA with the CD4 cells DNA |
|
|
Term
| What are integrase inhibitors? |
|
Definition
| drugs that interfere with HIV integrase enzyme |
|
|
Term
| Describe HIV transcription |
|
Definition
- once the virus has integrated into the CD4 cell, it commands it to start making new HIV proteins
- proteins are the building blocks for new HIV viruses |
|
|
Term
| What drugs block HIV transcription? |
|
Definition
NRTIs/nukes
and NNRTIs/non-nukes
which interfere with HIVs reverse transcriptase enzyme |
|
|
Term
|
Definition
- a HIV enzyme protease cuts the long chains of HIV proteins into smaller pieces
- as the smaller protein pieces came together with copies of HIVs RNA a new virus is put together (assembled) |
|
|
Term
| Describe HIV release/budding |
|
Definition
- the newly assembled virus pushes 'bud's out of the original CD4 cell
- this new virus is now able to target and infect other CD4 cells |
|
|
Term
|
Definition
HAART
combine multiple drugs that act on different viral targets. Attacks HIV at various steps of its life cycle. |
|
|
Term
| Why does taking a combination of drugs work better than monotherapy? |
|
Definition
- HIV mutates when it reproduces and can become resistant to a particular drug
- combinations of drugs from different classes make it harder for HIV to change enough to develop resistance |
|
|
Term
| What is the lung surface area? |
|
Definition
|
|
Term
| how much air do the lungs come into contact with per minute? |
|
Definition
|
|
Term
| How many microorganisms contact lung surface each day? |
|
Definition
|
|
Term
| How are influenza viruses classified? |
|
Definition
by their genetic material:
- rna virus
- negative sense strand
- segmented genome
-orthomyxamidae:
-- influenza A
-- influenza B
-- influenza C |
|
|
Term
| How many proteins do influenza A-C encode? |
|
Definition
|
|
Term
| Who does influenza A infect? |
|
Definition
| humans, pigs, birds, horses, aquatic mammals |
|
|
Term
| Who does influenza B infect? |
|
Definition
|
|
Term
| Who does influenza C infect? |
|
Definition
|
|
Term
| How many segments does influenza A have what else does it encode? |
|
Definition
8 segments
M2 protein (AM2) |
|
|
Term
| How many segments does influenza B have what else does it encode? |
|
Definition
8 segments
variant M2 proteins (BM2) |
|
|
Term
| How many segments does influenza C have what else does it encode? |
|
Definition
7 segments
variant M2 proteins (CM2) |
|
|
Term
| What does influenza A cause? |
|
Definition
| severe disease and global pandemics |
|
|
Term
| What does influenza B cause? |
|
Definition
| severe disease (no pandemics as yet) |
|
|
Term
| What does influenza C cause? |
|
Definition
| severe disease (no pandemics as yet) |
|
|
Term
| How is influenza transmitted? |
|
Definition
1. droplet inhalation
2. exhaled breath |
|
|
Term
| How does droplet inhalation cause flu? |
|
Definition
| large and small droplets directly enter the respiratory tract and their intended cell targets |
|
|
Term
| How does exhaled breath cause flu? |
|
Definition
| transmission can occur through close proximity to an infected individual |
|
|
Term
| What does the influenza virus target? |
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Definition
| the epithelial cells lining the entire respiratory tract |
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Term
| What is disease severity dependent on? flu |
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Definition
| increases the lower the respiratory tract is infected |
|
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Term
| What does flu infection cause? |
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Definition
| general cell destruction via virus mediated death and immune mediated death |
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Term
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Definition
| when two different influenza viruses share the same cell. This process can result in the emergence of radically different viruses that have not been encountered before. |
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Term
| How does antigenic shift lead to a pandemic? |
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Definition
- gross differences between influenzas likely means no humans have immunity to it
- little immunity
- serious disease and many infected (pandemic) |
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Term
| Describe the influenza virus external morphology |
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Definition
- pleomorphic virus particles (80-120nm in diameter)
- occasional rod shaped elongated particles
- outer membrane derived from host cell |
|
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Term
| List influenza's 3 membrane proteins |
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Definition
M2 (tetramer)
NA (tetramer)
HA (trimer) |
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Term
| Describe the influenza virus internal morphology |
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Definition
- beneath the membrane is a sheath of matrix protein
- the virus interior includes 8 DNA 'segments' which comprise viral genes |
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Term
| Describe the influenza life cycle |
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Definition
1. virus binds sialic acid receptor via HA and internalised via endocytosis
2. low pH of endosome causes the virus to fuse with membrane
3. segments released into cytoplasm
4. segments are imported into nucleus
5. RNA synthesis
6. RNA/RNP export
7. viral assembly at plasma membrane
8. release |
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Term
| What are the current targets for anti-influenza drugs? |
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Definition
1. release (as the cell eventually dies you can trap the bad stuff in it)
2. endosome escape (release of segments) |
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Term
| What drugs target neuraminidase (NA)? |
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Definition
zanamir and oseltaminir
administered orally |
|
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Term
| What are the two functions of NA? |
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Definition
1. NA cleaves sialic acid from HA on neighbouring viruses
2. NA cleaves sialic acid from the previously infected cell |
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Term
| How were TAMIFLU and RELENZA developed? |
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Definition
using structure based drug design
they should not encounter resistance problems |
|
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Term
| Name the 4 bones that makes up the pelvis |
|
Definition
Left innominate
Right innominate
Sacrum: 5 fused vertebrae
Coccyx: 4 fused vertebrae |
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|
Term
| What is each innominate made up of? |
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Definition
|
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Term
| What are the pelvic divisions and what separates them? |
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Definition
| Greater pelvis and lesser pelvis, seperated by the pelvic brim/inlet |
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Term
| Name and describe the 3 parts of the unterine/fallopian tubes |
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Definition
Laterally (infundibulum)
Ampulla (usual fertilisation site)
Isthmus (narrow part) |
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Term
| What are the 3 layers of the uterus? |
|
Definition
Perimetrium
Myometrium
Endometrium
(out to in) |
|
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Term
| What are uterine fibroids? |
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Definition
| non cancerous uterine growths (variable size and location) |
|
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Term
| When is the uterus usually damaged? and why |
|
Definition
When pregnant.
Uterus enlarges and rises out of pelvis
can obstruct the inferior vena cava |
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Term
| How does a mother adapt to prevent injury? |
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Definition
increased blood volume to protect from hypovolemic shock
uterus is thick and muscular and distributes force of trauma uniformally to fetus |
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Term
| What are the male glands and what do they produce? |
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Definition
seminal vescile -> seminal fluid
prostate -> produces prostatic fluid
bulbaretural -> produces pre-ejaculate |
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Term
| What is the spermatic cord and what does it include? |
|
Definition
Attaches scrotum to the body
-ductus deferens
- blood vessels
-nerves
(enclosed in a muscular sheath) |
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Term
| Describe the ejaculatory pathway |
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Definition
testes -> ductus deferens (and seminal vesicles) -> ejaculatory ducts -> prostatic/membranous urethra -> penis
TRAV picks up DANA AND SAM and EATS DOMINOS, they PULL UP at the MEET UP and PARTY |
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Term
| Describe the composition of semen |
|
Definition
Sperm (2-5%)
Semen (65-75%)
Prostatic fluid (25-30%) |
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|
Term
|
Definition
Used to cut off bad prostate
Resectoscope enters urethra and electrical currents heats the hoop to cut parts off.
Water is flushed through to remove pieces. |
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