Term
| What is the difference between absorption and distribution? |
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Definition
Absorption - from outside into the systemic circulation
Distribution - from systemic circulation to tissue |
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Term
| If pharmacokinetics is the drug getting to the site of action and pharmacodynamics is how the drugs intracellularly produces the pharacologic effects, what is the pharmaceutical process? |
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Definition
| is the drug even getting into the patient - issue of compliance |
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Term
| which gets drugs into system quicker: Subcutaneous or intramuscular? |
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Definition
| Intramuscular....oral is slowest |
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Term
| What is drug bioavailability? |
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Definition
| Fraction of UNCHANGED! drug that reaches the systemic circulation AKA target organ (he used those interchangably) |
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Term
| Name some things that effect bioavailability. |
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Definition
1. first pass hepatic metabolism (oral)
2. Drug solubility - the more lipophilic the drug is, the quicker it is absorbed to the target organ
3. Molecular weight/ size: smaller the easier it is to get to target organ
4. Chemical Instability: low gastric pH destroys penicillin |
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Term
| What is the bioavailability of IM and subcutaneous drugs? |
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Definition
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Term
| What is the bioavailability of oral drugs |
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Definition
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Term
| What is the bioavailability of rectal drugs? |
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Definition
| 30 - 100 cuz half rectal circulation bypasses the "first pass" system |
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Term
| What is the bioavailability of inhalant drugs? |
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Definition
| 5-100 cuz they're often used incorrectly |
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Term
| What is the bioavailability of transdermal drugs? |
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Definition
| 80-100 but VERY SLOW absorption |
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Term
| When does half life remain constant? |
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Definition
1. when the drug elimination follow first-order kinetics
2. if the dose doesn't exceed the capacity for elimination |
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Term
| How many half lives does it take any drug to reach steady state? |
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Definition
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Term
| How many half lives does it take any drug to get to 90% of its steady state? |
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Definition
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Term
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Definition
| Concentration at Steady State |
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Term
| Therapeutic window is between the minimum _____ concentration and minimum _______ concentration. |
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Definition
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Term
| Therapeutic index (TI) below ____ is considered a "toxic drug". |
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Definition
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Term
| What is the difference between lag and onset of activity in a drug disposition graph? |
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Definition
Lag: time between ADMINISTRATION and 1ST SEEN IN BLOOD
Onset of activity: time between ADMINISTRATION and MEC (minimum effective concentration) |
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Term
| Duration of action occurs any time the plasma drug concentration is above ____ ____ ____. |
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Definition
| Minimum effective concentration |
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Term
| lipid soluble drugs have an (easier/harder) time moving across membranes? |
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Definition
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Term
| What is facilitated diffusion and what is one example? |
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Definition
| CARRIER-Mediated (like active transport) but REQUIRES NO ENERGY (like passive transport)....L-DOPA |
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Term
| What are 2 examples of things that are absorbed by pinocytosis? |
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Definition
1. iron-transferrin
2. vitaminB12:intrinsic factor |
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Term
When the pH of a solution is BELOW the pKa of a chemical:
Acids will be ______ed and
Bases will be ______ed. |
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Definition
Acids unionized
Bases ionized |
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Term
When the pH of a solution is ABOVE the pKa of a chemical:
Acids will be ______ed and
Bases will be ______ed. |
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Definition
Acids - ionized
Bases - unionized |
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Term
In a basic solution, bases are ______ed.
In an acidic solution, acids are _____ed. |
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Definition
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Term
| Where are weak acids mostly absorbed. Why? |
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Definition
| Proximal (more acidic) parts of the intestine because weak acids are unionized in the acidic part of the intestines (unionized = great absorption = more lipid soluble) |
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Term
| Where are weak bases mostly absorbed? Why? |
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Definition
| Distal (more basic) parts of the intestine because weak bases are unionized in the basic parts of the intestine (unionized = better absorption = lipid soluble) |
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Term
| What is drug distribuation? |
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Definition
| drug REVERSIBLY leaving the blood stream and entering the interstitium. |
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Term
| What proteins to drugs bind? Is this reversible or not? Are these drugs available for action? |
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Definition
Albumin (the mop of the circulation)....yes reversible.
NOT available for action at target tissue |
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Term
| What are some drugs that are highly bound to albumin? What is this result? Give an example for neonates. |
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Definition
>80% bound think 4 drugs:
Digoxin, Warfarin (98%!), sulfonamides, and NSAIDs
These drugs can kick other things off of albumin that will now become active (cuz they free) and possibly toxic.
EX: Sulfonamines are 100% contraindicated in neonates cuz they will out-compete bilirubin for binding on albumin. This free bilirubin is toxic and causes KERNICTERUS - irreverbile CNS damage |
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Term
| Volume of drug distribution equation |
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Definition
Vd: Dose administered/ Co
Co - concentration of drug in plasma at time 0 |
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Term
| Very briefly, what happens during phase 1 and 2 of hepatic drug metabolism? |
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Definition
1 - alters structure
2 - encompases drug and makes it inactive??? |
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Term
| Where is the major site of drug metabolism? |
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Definition
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Term
| Name some things that can result from drug metabolism. |
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Definition
Inactive metabolites (ionized metabolites easily excreted)
Metabolites that do totally differing things
metabolites that do the same thing but just weaker or stronger
toxic metabolites
active metabolites (from a prodrug) |
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Term
| What are some Phase 1 biotransformations? |
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Definition
Non-microsomal - Redox reactions, hyrolysis, alcohol metabolism (enzyme catalyzed reactions)
Microsomal - cytochrome p450 enzymes (17 groups of 39 subgroups) |
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Term
| How can drugs change the p450 cytochrome system? |
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Definition
They can inhibit it - resutling in decreased metabolism of other drugs causing them to build up in body (toxicity) OR
They can INDUCE the p450 system - increasing the drug metabolism (treatment failure) |
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Term
| What CYP metabolizes acetaminophen? |
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Definition
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Term
| What does 2A6 metabolize? |
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Definition
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Term
| Diazepam is metabolized by what CYP? |
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Definition
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Term
| What CYP does MOST (70-80%) of the metabolism of drugs? |
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Definition
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Term
| Name 6 INHIBITORS of CYP 450 system? |
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Definition
| Grapefruit juice, azole antifungals, macrolite antibiotics, omeprazole, cimetidine and ACUTE alcohol |
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Term
| What would you not want to prescribe if a patient were on diazepam (a muscle relaxant)? |
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Definition
| cimetidine cuz it inhibits 2C19 (or 9)??, which is what degrades diazepam. Diazepam will reach toxic levels and respiratory distress and severe CNS depression will occur |
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Term
| When a patient is on statin drugs, what MUST they avoid and why? |
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Definition
| Grapefruit juice....this is a p450 inhibitor and will cause statin buildup (tissue damage --> myglobin release --> renal failure) |
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Term
| Name 4 INDUCERS of CYP 450 System. |
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Definition
| CHRONIC alcohol, barbiturates, all anticonvuslants (except valproate), and rifampin |
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Term
| What drug causes oral contraceptive failure and why? |
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Definition
| Rifampin (anti-TB) cuz it induces the 3A4 CYP system which increases the metabolism of oral contraceptive (rendering it useless) |
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Term
| What common drug must chronic alcoholics avoid? Why? |
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Definition
| Acetaminophen. Its metabolites will buildup too fast cuz chronic alcohol will INDUCE the CYP system to metabolize acetaminophen quicker....allowing its toxic metabolites to buildup quicker |
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Term
| What are phase 2 biotransformation? |
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Definition
| Conjugations reactions - reactions that turn the drug inactive and ionized (hydrophilic) |
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Term
| Name 4 enzymes usually involved in phase 2 biotransformations. |
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Definition
Glucuronyl Transferase (glucoronidation)
Sulfotransferase (sulfate conjugation)
Transacylases (aa conjugation)
Glutathione conjugation |
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Term
| Why is chloramphenicol contraindicated in neonates? |
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Definition
| Chloramphenicol is metabolized (phase II) via glucoronidation by glucuronyl transferase. This enzyme is not present in the body until about age 3 |
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Term
| What is the only drug activated by glucoronidation? |
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Definition
| Morphine get glucoronidationed by glucuronyl transferase to 6-beta-glucoronide (active form) |
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Term
| What drug gets conjugated by glutathione? |
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Definition
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Term
| Name 2 drugs that get sulfonated |
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Definition
| acetaminophen and methydopa |
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Term
| What are the HIP drugs and why are they noteworthy/ |
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Definition
Hydralazine, Isoniazid, Procainamide
In slow acetylators (genetcially dependent), these drugs cause SLE syndrome |
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Term
| 3 ethnicities that are poor metabolizers for the CYP2D6 |
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Definition
Caucasians 5-10%
Blacks 2-5%
Asians <1% |
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Term
| 3 ethnicities that are ultrarapid metabolizers of CYP2D6 |
|
Definition
Ethiopians 20%
Spanish 7%
Scandinavians 1.5% |
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Term
At high doses, drug metabolism follow ____ order kinetics. Which means what?
At low doses, drug metabolism follows ____ order kinetics. Which means what? |
|
Definition
High doses - 0th order kinetics. system is saturated so only so much of a drug can be metabolized independent of the dose (extra just has to wait around)
Low dose - 1st order kinetics - the more drug you give the patient, the more of the drug will metabolize (the amount of drug what will metabolize is proportional to the amount given) |
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Term
| For drugs, secretion is always _____ and reabsorptin is always ____. |
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Definition
Active secretion
Passive reabsorption |
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Term
| What will always be passively reabsorpted in the kidney? |
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Definition
| Non-ionized (lipophilic drugs) |
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Term
| What is clearance (Cl)? When does it equal GFR? |
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Definition
Clearance is the volume of blood that is filtered from the drug per unit of time.
Cl= GFR when no reabsorption or secretion occurs (inulin) |
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Term
| How do protein-carriers effect Clearance? |
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Definition
| Drugs bound to protein carrier are NEVER cleared from the kidney |
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Term
|
Definition
| 125 mL/min (about a fourth of total renal plasma flow) |
|
|
Term
| what order elimination rates deals with half lives? |
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Definition
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Term
| WHat are 3 examples of drugs that follow 0th order elimination rates? |
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Definition
Alcohol
Phenytoin
Salicylates
***all in high doses |
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Term
| WHere (along the tubule) does secretion and reabsorption occur? |
|
Definition
secretion - proximal tubule
Reabsorption - distal tubule/collecting duct |
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Term
| What is the difference between elimination and excretion? |
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Definition
| Metabolism can eliminate a drug, but the kidneys must excrete it....an eliminated drug can still do damage but NOT an excreted one |
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Term
| How do we counteract (generally and specifically) a Quinidine overdose? |
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Definition
Quinidine is a weak base....so we want to acidify the urine to ionize weak bases....to acidify the urine we use:
cranberry juice, vitamin C, NH4Cl (but this one can cause tissue damage) |
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Term
| How do we counteract (generally and specifically) a Aspirin overdose? |
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Definition
Aspirin is a weak acid, so we want to make urine more alkaline (which will ionize the weak acid for better excretion). We use:
NaHCO3 and acetazolamide |
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Term
| What is the equation for Loading dose? |
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Definition
LD = Cp x Vd / f
Cp - plasma concentration
Vd - volume of distribution
f - bioavailability (1.00 if IV) |
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Term
| What is the equation for Maintenance dose? |
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Definition
MD = Cp x Cl / f
Cp - plasma concentration
Cl - clearance
f - bioavailability (1.00 if IV) |
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Term
| What is biggest difference between loading and maintenance doeses? |
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Definition
Loading dose considers Vd, whereas MD's dont.
MD's consider clearance, whereas LD's dont. |
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