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33 Cards in this Set
- Front
- Back
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What is the first pass effect?
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The biotransformation of a drug before it reaches it's site of action. Avoided when drugs are given IV, SL, PR, IA, etc.
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Define bioavailability. What is absolute and relative?
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Bioavailability = % of the drug that enters the circulation unchanged
Absolute: amount of drug absorbed through non IV routes, when compared to the IV concentration of the same drung. Relative: Bavailability of a drug when compared with another formulation of the same drug |
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What is first order elimination?
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constant proportion of drug being eliminated per unit of time. (linear slope for a log graph)
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What does it mean to bioequivalent and therapeutic equivalent drungs?
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Bioequiv = comparable [plasma] vs. time profiles of drugs.
Thx = comparable clinical effectiveness and safety. |
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What is the formula for partition coefficient? What does this mean?
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[drug] in lipid
[drug] in water if this is high, then the compound has a higher lipid solubility and thus more diffusion. The coefficient is increased when Hphobic groups are added to it. |
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What is the H-H equation?
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pKa - pH = log [HA]
[A] Higher pH = more charged forms of a drug and thus less diffusible the drug is. |
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What is an example of drug-drug interaction involving transporters?
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MDR1 transports digoxin out of a cell into lumens. If a pt is given clarithromyocin, this will inhibit the MDR1 and cause the accumulation of digoxin.
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What is a volume of distribution? What is the formula?
What does it mean? |
The volume in which the amount of drug would need to be uniformly distributed to produce the observed blood concentration.
Vd = total amount of drug in the body initial plasma concentration * a low [plasma] = drug is bound to plasma proteins or stored in fat. * a fixed property of the drug - won't change unless pt changes! |
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MDR1 is important for maintaining what? What is a relevant drug-drug interaction?
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The blood - brain barrier.
Quinidine will inhibit MDR1 and this can allow loperamide to enter the brain and cause respiratory depression. |
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What is the main goal of biotransformation? How is it different from elimination?
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To increase the water solubility of drug so that it can be excreted.
Biotransformation + excretion = elimination |
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What is a prodrug? Give an example.
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Compounds with no therapeutic activity until they get biotransformed into an activated, therapeutic form.
E.g. Codein --> morphine |
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Why is it dangerous to give too high a dose of acetamenophen?
How does body usually compensate? |
Because it can overwhelm it's usual pathways and cause the accumulation of NAPQ1 which is hepatotoxic.
Glutathion usually mops this up! |
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What types of reactions are done by Phase I and Phase II enzymes?
What are the effects of phase I and II? |
Phase I: Hydrolysis, Oxidation, Reduction.
- CYP450, alcohol dehydrogenase Phase II: conjugation with glucuronide, glutathione, sulfate, methyl groups, acetyl groups, and amino acides. "GAG SAM" Phase I = small increase in hphilicity Phase II = large increase in water solubility (attach an endogenous substance onto the functional group of a drug!) |
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Where do biotransforming reactions occur?
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Most in the liver but also in a lot of other tissue (GI, lungs, kidneys, skin, etc). Tissue-specific toxicity may be a result of enzyme expression.
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What does enterohepatic circulation mean?
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When a drugs' metabolite can be reactivated into the parent compound; can extend the action of a drug.
Eg metabolism in proximal gut is reversed by metabolism of distal gut, and parent compound is re-absorbed. |
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What does it mean to have a high extraction drug? Low extraction drug?
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High = hepatic clearance is governed by the rate of blood flow (strong first pass effect).
Low = biotransformation is limited by diffusion, hepatic clearance is governed by rate of enzymatic activity. |
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Where are CYP 450's found in the cell? What is the main thing they do? (ie main reaction?)
If a CYP has > 44% identical a acids then they are in the same _____. What about if > 50%? |
They are integral membrane proteins. They insert oxygen.
> 44% = same family > 55% = same sub-family |
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CYP1A2
- found where? - induced by what? - Btransforms what? (4) |
CYP 1A2
- liver - cigarrette smoke - caffeine, acetamenophen, carcinogens, aflatoxin |
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CYP 2C9:
- found where? - Btransforms what? WITP |
Liver!!
Warfarin Ibuprofen Tolbutamide phenytoin |
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CYP 2D6:
-found where? -It is polymorphic, what is the implication of this? - What does it B transform? (3 anti's, an a and a B) |
- mostly in the liver (low levels)
- means that there are different rates of transformation among different morphisms. - Antiarrhythmics, antidepressants, antipsychotics, analgesia, B-blockers |
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CYP 2E1:
- found where? - induced in who? - B transforms what (1) |
- E-verywhere!! (liver, kidney, lung)
- Induced in alcoholics - alcohol |
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What is the most abundant CYP?
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CYP 3A - B transforms about 50% of all therapeutic drugs!!
*** inhibited by grapefruit juice! *** |
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Define potency and Efficacy/
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Potency = the dose required for a specific effect
Efficacy = the maximum effect that a drug can have |
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What is the relationship of CL to GFR when you have
- net secretion - net reabsorption |
- secretion: CL > GFR
- absorption: CL < GFR |
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What is a graded dose response curve? How about a Quantal D-R curve?
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Graded: when the y axis is the amount or % of an effect (ie lowering blood pressure). Used to determine the effects of increasing doses.
Quantal: when the y-axis is the % of population that responded (eg. pain relieved yes or no?) Used to examine a defined response in a group of people/animals. |
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What is the formula for therapeutic index?
What do TD50 and ED50 mean? |
TI = TD 50 / ED 50
TD50 = dose that is toxic in 50% of population ED50 = dose that is therapeutic in 50% of population |
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What is the difference between an anticipated and a bizarre adverse drug reaction?
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Anticipated depends on the dose given, bizarre does not (therefore you d/c the drug!)
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What are the stages of drug development? (1-4)
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I - health volunteers
II - small # of pt's III - big # of pt's IV - post marketing monitoring |
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What happens to the % of a drug that is ionized when the pH is above the pKa for a weak acid?
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when pH > pKa weak acids will be charged and weak bases will be uncharged.
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If a pt is pregnant how might this change her dosing?
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May need to give more b/c she has a bigger Vd and more renal clearance.
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What could happen if you gave a basic drug to a pregnant woman?
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The fetal circulation is slightly more acidic therefore the basic drug would get charged and once charged it won't return to maternal circulation = ion trapping = accumulation.
** Same thing happens to basic drugs in breast milk (which is also more acidic) |
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What is an antagonist?
(there are irreversible and reversible) |
Drugs that bind to their receptor but do not activate the effector system associated with that receptor. The irreversible ones bind so effectively that they stay bound for the duration of that receptors life.
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What is an inverse agonist?
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Drugs that when bound to their receptor they decrease the activity of that receptor to below basal levels.
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