DD, CT, & RoA
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Define biotransformation
process by which lipophilic xenobiotics are transformed to more polar (inactive) metabolites (some products gain activity)
the mode of transport across the cell membrane utilized by MOST drugs and the requirement for a drug to be able to use this mechanism
passive diffusion, lipid soluble
factors that cause a drug to be excreted more rapidly (speed up drug excretion)
enhancing blood flow, increasing glomerular filtration rate, decreasing plasma protein binding
Reasons a drug stays in plasma (3)
too big to cross slit & tight junctions
charged (ionized)
bound to plasma proteins
Stage of clinical trials where researchers find out how the drug works in the human body and how best to administer the drug to reduce side effects & maximize benefits
Phase 1
reactions that occur in (or make up) Phase I Reactions of Biotransformation (3)
Oxidation, reduction, hydrolysis
the effects of the drug (e.g. toxic or effectiveness) -- looking for the term that matches this definition
pharmacodynamics
Define pH trapping found in the proximal and distal tubules
renal tubular fluid is typically acidic, favoring trapping of weak bases
factors affecting distribution of a drug
molecular size, lipid / water solubility, protein binding (drug binds to plasma or tissue proteins)
A suppository does not 100% bypass 1st pass metabolism, *this* vessel (found in the rectal venous drainage system) is the reason a suppository goes through 1st pass metabolism
Superior rectal vein (which drains into the inferior mesenteric vein) goes into portal circulation
peripheral neuropathy and SLE-like syndrome (drug induced lupus (DLE)) may develop from a genetic polymorphism in an individual's ability to metabolize which kind of drug?
slow acetylators
In what pH (the medium) would a weak base be ionized?
acidic
Rate of elimination is DIRECTLY proportional to plasma concentration of drug
First order kinetics
the place a sample must be obtained from in order to determine drug concentration for volume of distribution
plasma
in regard to concentration gradient ( a factor affecting pharmacologic response), what is the relationship between concentration & mass of a drug transferred per unit time
proportional (as one goes up the other does too, vice versa)
Failure of contraception is an adverse reaction of taking phenytoin (anticonvulsant). Why does this occur?
phenytoin is an enzyme inducer --> decreased duration and intensity of oral contraceptive action
In BASIC drug poisoning, what would need to be done to the pH of the urine? How would you accomplish this?
acidification;
ammonium chloride, vitamin C, cranberry juice
when would a loading dose be indicated
drug with long half-life (time to reach steady-state is appreciably high), it would quickly raise concentration of drug in plasma to target concentration
the volume apparently necessary to contain the amount of drug homogeneously at the concentration found in the blood, plasma, or water
Apparent Volume of Distribution
the route of drug administration with the following: no first-pass, occurs rapidly, is absorbed by mucosa which then goes into veins that drain into the heart
sublingual
*this*, in normal metabolism, is converted into a reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI) which is normally conjugated by glutathione (GSH) and inactivated
acetaminophen
How would we treat an overdose of phenobarbitone?
alkalinizing urine via sodium bicarbonate or acetazolamide (cation inhibitor)
phenobarbitone is weakly acidic drug, remains ionized in alkaline pH
Two drugs that - when in higher doses - follow zero order kinetics; however, when at normal doses - follow first order kinetics
Aspirin, phenytoin
drug that is strongly bound to plasma albumin, restricting its distribution to the vascular compartment, leading to an increase in plasma concentration and a smaller volume of distribution
Warfarin because acidic drugs bind to plasma albumin (also sulfonamide because it displaces warfarin leading to excessive bleeding)