Term
|
Definition
| What the body does to the drug, including absorption, distribution, biotransformation, excretion and the time course of action. |
|
|
Term
| What is Pharmacodynamics? |
|
Definition
| What the drug does to the body, including its effects, mechanism of action and location of action. |
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|
Term
| Pharmacogenomics deals with what? |
|
Definition
| The role genetic factors play in Pharmacokinetics and Pharmacodynamics |
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Term
| T/F: Every drug is toxic at high enough concentrations. |
|
Definition
|
|
Term
|
Definition
| Any chemical substance used in the diagnosis and treatment of disease |
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Term
| What is a drug, but does not meet the definition of a drug? |
|
Definition
| Anesthetics. It does not diagnose or treat a disease. It is used for pain |
|
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Term
|
Definition
Poison squad
(Eat foods that were treated with chemical preservatives to measure safety) |
|
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Term
|
Definition
Federal Pure Food and Drug Act
(aka Wiley Act) |
|
|
Term
| What does the Wiley act prohibit? |
|
Definition
The misbranding/adulterating of foods, drinks or drugs. Prohibits false claims on labels.
Also need to register addicting substances |
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Term
|
Definition
| Shirely Amendment that prohibited fradulent therapeutic claims |
|
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Term
| When was the FDC act and what lead to it? |
|
Definition
Elixir of Sulfanilamide in 1937. Lead to 107 deaths.
FDC act of 1938 |
|
|
Term
| What is the Federal Food,Drug Cosmetic Act of 1938? |
|
Definition
Requires safety
Complete and accurate labels
Allowed factory inspections
Removed requirements of Shirely Amendment |
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Term
| When was the Durham Humphrey Amendment enacted? And What did it require? |
|
Definition
In 1951
"Caution"-Federal Law prohibits dispensing w/out prescription on all labels.
Also gave OTC status |
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Term
| Which amendment required for both safety and effectiveness for new drugs? |
|
Definition
| 1962- Kefauver Harris Amendment |
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Term
| T/F: The FDA requires safety and effectiveness testing for Dietary Supplements. |
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Definition
| False; The Dietary Supplement Health and Education Act does not require it. Only regulate the labeling and therapeutic claims of them. |
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Term
| What required manufacturers of new and existent biological products to assess safety and efficacy in children? |
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Definition
|
|
Term
| Where do drugs come from? |
|
Definition
Natural substances
Semi-synthetics
Synthetic |
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|
Term
| Drug design is ____________ and ____________-. |
|
Definition
|
|
Term
| T/F: Therapeutic effects and side effects may have different mechanisms. |
|
Definition
True
They bind to several different receptor types |
|
|
Term
| Give an example of a drug that was discovered accidentally. |
|
Definition
B-blockers for HT
Minoxidil for hair loss
Latisee for eyelahses |
|
|
Term
| What is the most important concept in Pharmacology? |
|
Definition
The mechanism of Action
(How drugs work to produce their therapeutic actions and side effects) |
|
|
Term
| ________________ has biochemical changes measured in hrs, but therapetuic effects may take up to 4 weeks to develop |
|
Definition
Antidepressants
(Time course vs. Therapeutic actions) |
|
|
Term
|
Definition
1. Cure disease = antibiocs
2. Replacement therapy = hormones
3. Treat symptoms |
|
|
Term
| New Drugs approved every ____________. |
|
Definition
|
|
Term
| In 2008 the FDA approved 33 drugs. How many were me 2 drugs? How many were new? |
|
Definition
|
|
Term
| ______________ of all physician visits result in prescription. |
|
Definition
|
|
Term
|
Definition
| Hospitilzaed > nursing home > self |
|
|
Term
| How long does it take to get a drug approved? How long does the patent last? |
|
Definition
|
|
Term
| Describe the steps to get a drug approved? |
|
Definition
1. Approval process = Synthesis + screening
2. IND submitted to FDA
Phase1 = very few, healthy peeps
Phase2 = Few , have the disease
Phase3 = Thousands and compare drug 2 placebo and a known standard |
|
|
Term
| Once the NDA is submitted to fDA, how long till its approved? |
|
Definition
|
|
Term
|
Definition
| FDA may ask for lcinical testing |
|
|
Term
| whats the deal with Avandia? |
|
Definition
improves target cell response to insulin but also increased CV evnts.
Blackbox |
|
|
Term
| Cox2 inhibitors were used as analgesic and anti-inflammatory caused what? |
|
Definition
|
|
Term
| What is the main otucome of biotransformation? |
|
Definition
| To increase water solubility thereby increase rate of excretion. |
|
|
Term
| What is the most common scenario for biotransformation? |
|
Definition
| Active drug to inactive metabolite |
|
|
Term
| The ________and ___________ of biotransformation will affect the ________________ of the drug. |
|
Definition
|
|
Term
| T/F: Biotransformation can alters a drugs toxicity. |
|
Definition
|
|
Term
| Where is the major site of biotransformation? |
|
Definition
|
|
Term
| What are some internal factors that influence the types of metabolites that are made from any one drug? |
|
Definition
Genetic make up
age
gender |
|
|
Term
| The Gi tract, especially the upper intestine is improtant for wat? |
|
Definition
|
|
Term
| What does the lvier and the upper intestine participate in? |
|
Definition
| Entero-hepatic cycling of glucoronides |
|
|
Term
| What are external factors that influce drug metabolism? |
|
Definition
1. Nutritional status
2. Diet
3. other drugs, including herbals
4. disease state |
|
|
Term
| Where are drug glucornides transported to if MW of the conjugate > 400? What about if <400? |
|
Definition
Into bile
Into blood for urinary elimination |
|
|
Term
| Describe the entero-hepatic cycle? |
|
Definition
| Drugs and metabolites formed in the liver and excreted in bile will reach the intestine. Some of these glucornides may be converted to the unconjated drug and is reabsored. |
|
|
Term
| What drugs are likely to metabolized in the lungs? |
|
Definition
Basic N2- contianing drugs
And drugs for inahlation |
|
|
Term
| What is the kidney improtant for? |
|
Definition
| A.A conjugation of COOH and for further metabolism of glutathione conjugates. |
|
|
Term
| What are the msot important considerations of biotransformation? |
|
Definition
1. Molecular structure of drug
2. Affinity of drug for the enzyme
3. Amount of drug-metabolizing enzyme present
4. The availabilty of co-factors and co-subtrates
5. Presence of other xenobiotics which compete for the same pathway of biotransformation or which otherswise affect the enzyme |
|
|
Term
| What determines the drugs affinity for an enzyme? |
|
Definition
| The structure of the enzyme protein at its active site and the enzymes micro environment. |
|
|
Term
If a drug can undergo more than 1 pathway, what will determine the pathway it will take?
(ex: Acetaminophen can glucuronidate or sulfated) |
|
Definition
The Km of the enzyme for that drug
and the [M+] of the drug present |
|
|
Term
| If you have a higher affinity, the Km would be _____________. |
|
Definition
Lower
(inverse relationship) |
|
|
Term
| Does Acetaminophen have a higher affinity for Sulfotransferase or Glucronosyltransferase? |
|
Definition
Higher affinity for Sulfotransferase.
If PAP-SO4 present will bind more readily. |
|
|
Term
|
Definition
| Genes that code for a drug metabolizing enzyme vary between people |
|
|
Term
| What can genetic variation lead to? |
|
Definition
| Changes in the protein structure, which can alter the affinity of the drug for the enzyme or change the stability of the enzyme protein. |
|
|
Term
| Which enzyme hydroxylates a number of drugs that have N and an aliphatic ring/chain? |
|
Definition
|
|
Term
| Name some drugs that have an N and a liphatic ring/chain that can be metabolized by CYP2D6. |
|
Definition
1. Bufuralol
2. Propranolol
3. Dextromethorphan
4. Desmethyl-imipramine |
|
|
Term
| How was the polymorphism of CYP2D6 discovered? |
|
Definition
| During a study of the mtabolism of Debrisoquine (an Anti-hypertensive drug) |
|
|
Term
| If you have a lower activity of CYP2D6 because of polymorphism then you may need a ______________ dose than the normal metabolizers to have the same therapeutic effect. |
|
Definition
|
|
Term
| What does the enzyme CYP2C19 catalyze? |
|
Definition
S-mephenytoin 4-Hydroxylation
(and other drugs such as omeprazole and diazepam) |
|
|
Term
| There are many polymorphisms of CYP2C19 that lead to ______________. |
|
Definition
| Non expression of the protein |
|
|
Term
| What race are poor metabolizers of mephenytoin? |
|
Definition
| Japanese and Chinese (20-30% are poor metabolizers) |
|
|
Term
| Variants in what can affect the ability of a person to form glucuronide conjuages of bilirubin and drugs such as thinylestradiol? |
|
Definition
| UDP-glucuronosyltransferase UGT 1A1 |
|
|
Term
| What syndrome has low rates of conjugation of bilirubin? |
|
Definition
|
|
Term
| The level of expression of a drug metabolizing enzyme can vary btwn peeps. Which enzyme is low in newborns? |
|
Definition
| UDP Glucuronosyltransferase (UGT) |
|
|
Term
| Why should infants be given very low doses of drugs like Tylenol? |
|
Definition
| Because they have very low levels of UGT |
|
|
Term
| Several drug metabolizing enzymes show a ______________ in activity in older people, so they need require a ______________ dose for optimization. |
|
Definition
|
|
Term
| What was the first drug metabolizing enzyme polymorphism to be id? |
|
Definition
| N-acetyltransferase (NAT2) |
|
|
Term
| What is the one major pathway of metabolism for the drug Isoniazid that is used to treat TB? |
|
Definition
|
|
Term
| If you have little NAT-2 protein then you are a ______________ |
|
Definition
|
|
Term
| Native North Americans have a low incidence of being slow acetylators (0%). Which ethnic group has 70% of the population being slow acetylators? |
|
Definition
|
|
Term
| If you are a slow acetylator and are given a single dose of isoniazid, what can you experience? |
|
Definition
|
|
Term
| If you are a fast acetylator and are given Isoniazid what can happen? |
|
Definition
| Since you metabolize fast then you dont have enough active drug to cure the TB. |
|
|
Term
| Some people have alterations in the gene for CYP2D6 such that they do not express active protein. _______% of white and ______% of black are poor metabolizers. |
|
Definition
|
|
Term
| People who are ultra rapid metabolizers of CYP2D6 substrates produced ___________ CYP2D6 in their ___________. |
|
Definition
|
|
Term
| To achieve the desired therapeutic benefit, what must ultra rapid metabolizers of CYP2D6 do? |
|
Definition
| Obtain higher doses of drugs that are substrates for CYP2D6. |
|
|
Term
|
Definition
| Drugs or food constituents that induce the synthesis of one or more members of the CYP450 faimly so that more of the enzymes are expressed in the liver and other organs. This leads to increaesd metabolism of drugs that are substrates for these enzymes. May require an adjustment of the dose. |
|
|
Term
| What does Phenobarbital and other barbituates induce? |
|
Definition
| CYP2 dependent monooxygenation as well as glucuronidation and glutathione conjugation. |
|
|
Term
| Which form of P450 is the most abundant in the human liver? |
|
Definition
|
|
Term
| What enzyme do Phenytoin and carbamazepine induce, to a less extent than phenobarbital? |
|
Definition
|
|
Term
| What do the antibiotics Rifampin and Erythromycin induce? |
|
Definition
|
|
Term
| Why do women who are taking Rifampin and Oral contraceptive become pregnant? |
|
Definition
| Because there is an increased metabolism of there oral contraceptives. Lowered efficacy of their contraceptives. |
|
|
Term
| What enzyme does chronic EtOH induce? |
|
Definition
|
|
Term
| What does tobacco and char broiled food induce? |
|
Definition
|
|
Term
| Certain vegetable components including bio-flavonoids and garlic oil are weak inducers of _______________, _______________ and _______________. |
|
Definition
CYP450
Epoxide Hydrolase
Glutathione S transferase |
|
|
Term
| What do the food preservatives BHT and BHA induce? |
|
Definition
Glutathione S transferase and
Glucuronyosyltransferase |
|
|
Term
| What does chronic intake of green/black tea slightly induce? |
|
Definition
CYP1A2 and
Glucuronyosyltransferase |
|
|
Term
| What do viral infections do to your drug metabolizing capacity? |
|
Definition
|
|
Term
| Why do viral infections lower the drug metabolizing capacity? |
|
Definition
| Because infectious agents cause the synthesis of interferon and cytokine release which supresses the liver's CYP synthesis. |
|
|
Term
| What types of diseases lead to lowered drug metabolizing enzymes? |
|
Definition
| Liver disease like cirrhosis |
|
|
Term
Normally Acetaminophen gets sulfated at low [M+], but gets glucuronidated at high [M+]. Why? |
|
Definition
Because there is a lck of PAP sulfate in the cell.
(Intrinsic factor) |
|
|
Term
| What can affect the [M+] of cofactors and cosubstrates? |
|
Definition
| The composition of the diet |
|
|
Term
| Why does EtOH limit the extent of oxidation by CYP and other oxidative enzymes? |
|
Definition
| Becuase EtOH lowers the available concentration of NADPH (a cofactor) |
|
|
Term
| Co-substrate, GSH, is usually high in the cells, what lowers its [M+] in the liver? How is it reversed? |
|
Definition
Starvation
Take antioxidants (found in foods) |
|
|
Term
| Glycine conjugation is reduced in ____________________. |
|
Definition
| Protein Calorie Malnutrition |
|
|
Term
| T/F: Some drugs and foods can affect biotransformation by inhibiting or stimulating a drug biotransformation pathway. |
|
Definition
|
|
Term
| Erythromycin metabolite _____________ CYP3A4 by binding tightly and preventing metabolism of other drugs. |
|
Definition
|
|
Term
| Why is Ritonavir used in AIDs peeps? |
|
Definition
| When Ritonavir is co-admin w/ another PI, it can increase the bioavailability and prolong the elimination half life of the PI. |
|
|
Term
| How do the imidazole containing drugs inhibit CYP? |
|
Definition
| By preventing oxygen from binding to P450 |
|
|
Term
| What does grapefruit inhibit? |
|
Definition
CYP3 family members
An efflux transporter, the p-glycoprotein (MDR-1) |
|
|
Term
| Drug metabolizing enzymes convert _____________ drugs to _____________ metabolites which are then readily excreted. |
|
Definition
|
|
Term
| What are the Receptors for Glutamate? |
|
Definition
Kainate
NMDA
AMPA
G-protein = decrease cAMP, increase IP3
(All increase Na and decrease K) |
|
|
Term
| What are the receptors for GABA? |
|
Definition
GABAa = decrease cAMP and Ca2+ and K+
GABAb = Increases Cl- |
|
|
Term
| What are the receptors for NE? |
|
Definition
QIS
Alpha1 = Increase IP3/DAG = Gq
Alpha2 = Decrease cAMP & K & Ca2+ = Gi
Beta = Increase cAMP and Ca2+ = Gs |
|
|
Term
| What are the receptors for Serotonin? |
|
Definition
IQ(Iono)SI
5HT1 = decreaes cAMP and K = Gi
5HT2 = Increase IP3/DAG = Gq
5HT3= Increase Na and Ca = Iono
5HT4,6,7 = Increase cAMP = Gs
5HT5= decrease cAMP = Gi |
|
|
Term
| What are the receptors for DA? |
|
Definition
SI?IS
D1 = increase cAMP = Gs
D2 = decrease cAMP and K = Gi
D3 = ?
D4 = decrease cAMP= Gi
D5 = Increase cAMP = Gs |
|
|
Term
| What are the receptors for AcH? |
|
Definition
QIQ (iono)
M1 = Increase IP3/DAG = Gq
M2,4 = Decrease cAMP and K = Gi
M3 = Increase IP3/DAG = Gq
N = Increase Na, Ca and K = Iono |
|
|
Term
| EC50 gives you the _________ |
|
Definition
|
|
Term
| Drugs with similar mechanisms of action will have parallel log dose response curves. So they have the same ____________ and ___________. |
|
Definition
|
|
Term
|
Definition
Median effective dose
(50% of peopel will show your effect) |
|
|
Term
|
Definition
Median Toxic dose (Toxic in 50% of peeps)
Median lethal dose (death in 50% of peeps) |
|
|
Term
| How do you find the therapeutic index? |
|
Definition
|
|
Term
| How do you calculate the Certain Safety Factor (CSF)? |
|
Definition
|
|
Term
|
Definition
| The drug concentration that causes 50% receptor occupation |
|
|
Term
|
Definition
| Maximal receptor occupation = the number of receptors |
|
|
Term
|
Definition
| The competing drug concentration that displaces 50% specific binding of radiolabeled drug to receptors |
|
|
Term
|
Definition
| Affinity of competing drug for receptor |
|
|
Term
| What are some reasons for variability? |
|
Definition
1. Imprecision
2. Pharmacokinetics
3. Pharmacodynamics |
|
|
Term
| Factors contributing to variability include |
|
Definition
1. Age
2. Weight
3. Body composition
4. Gender
5. Disease state
6. Genetics |
|
|
Term
| Which has a greater influence. Pharmacodynamic or pharmacokinetics? |
|
Definition
|
|
Term
| what is the Langmuir equation? |
|
Definition
|
|
Term
|
Definition
Binds to receptor and fully activates effector.
Elicits Emax at Bmax
alpha = 1 |
|
|
Term
| Describe a partial agonist. |
|
Definition
Binds to receptor and partially activates effector.
Never elcits Emax
0<a<1 |
|
|
Term
|
Definition
| No effct unless an agonist is present. Will compete for receptor |
|
|
Term
| Describe noncompetitive graph |
|
Definition
Shifts agonist curve and Emax downward
No effect on EC50 or slope |
|
|
Term
| What happens with a competivie agonsit |
|
Definition
Shifts agonist curve and EC50 to the right
No effect on Emax/slope |
|
|
Term
| Inverse agonist bind to receptor and _______________- effector. |
|
Definition
|
|
Term
| If there is an full agonist and a partial agonist, then the partial will look like a noncompetitive agonist. |
|
Definition
|
|
Term
| List the drugs that do not act via receptors |
|
Definition
1. Anesthetics
2. Seme sedatives
3. Osmotically driven drugs
4. Acidifying and alkalinizing drugs
5. Antispetics |
|
|
Term
| If the log dose slope is > 1 then there is ___________________ if it is <1 there is____________________. |
|
Definition
Positive cooperativity
Negative cooperativity (mulitple receptors) |
|
|
Term
| Intracellular signals can induce or inhibit protein synthesis. Give an example. |
|
Definition
Thryoid hormone
(Steroids, progesterone, testosterone, coritsol,e tc) |
|
|
Term
| What does Gq activate? And Which Receptors have this? |
|
Definition
PLC to make IP3 and DAG
ACH M1
NE alpha 1
5HT2 |
|
|
Term
|
Definition
| AC to increase cAMP production |
|
|
Term
|
Definition
| PLA2 to liberate arachidonate from membranes |
|
|
Term
|
Definition
| A receptor for the same NT within the nueron |
|
|
Term
| What do impulse modulating autoreceptors do? |
|
Definition
| They are located on the dendrites or cell bodies and decrease the chance of an AP |
|
|
Term
| What do synthesis modulating autoreceptors do? |
|
Definition
| Are on the presynatic terminal and inhibit NT synthesis |
|
|
Term
| What are the 3 different types of autoreceptors |
|
Definition
1. Impusle modulating
2. Synthesis modulating
3. Release modulating |
|
|
Term
| If you have an overstimulation of a nuerone due to an agonist what things do you expect to decrease? |
|
Definition
| 1. NT synthesis, release, postsynptic recpts and 2nd messnerg generation/interaction |
|
|
Term
| If you see an understimulation of a nueron due to an antagonist what things do you expect to increase? |
|
Definition
| NT synthesis, rlease, postsynt. recpt, 2nd messenger generation/interaction |
|
|
Term
| What are spare receptors and what do they protect agsint? |
|
Definition
Occupation of 25% of the receptor gives Emax.
EC50 <Kd
Protecct against recepotr loss from disease/irreversible antagonist |
|
|
Term
| What do spare receptors make nonceomptetive antagonist look like? |
|
Definition
|
|
