Pharmacokinetics Flashcards
when do drugs reach their peak effect?
not instantaneously, takes time (lag period)
what are 3 important considerations for routes of administration?
- convenience (oral vs injection)
- bioavailability (efficiency of absorption in gut)
- processing (hepatic portal circ.)
what are 3 aspects of pharmacokinetics that alter a drugs effect?
Absorption, distribution, excretion
first pass metabolism
loss of drug ingested orally during its first pass through hepatic circ. into liver, before entering systemic circ. (affects bioavailability)
what is the extraction ratio?
clearance (liver) / blood flow (inverse of bioavailability)
clearance
V of blood that can be rid of a certain drug over a period of time (better processing in liver = higher clearance = higher extraction ratio)
5 factors of oral route of administration
most common and convenient, absorption is slow, affected by food intake, influenced by “first pass metabolism”
4 factors of intravenous route of administration
direct into circ., most rapid onset, requires expertise, high control over circulating level
3 factors of intramuscular/subcutaneous
painful, rate of absorption depends on blood flow, depot preparations (slow dissolving) for sustained release
2 factors of inhalation route of administration
absorption through epithelium in lungs, rapid onset
2 factors of sublingual (dissolve under tongue) route of administration
rapid, bypasses “first pass metabolism” effects despite taken orally
4 factors of transdermal (ointment/patch) route of administration
convenient, slow absorption, sustained exposure, no “first pass metabolism”
what is bioavailability?
fraction of unprocessed drug that reaches systemic circ. after administration
what 4 routes of administration has the highest % of bioavailability?
intravenous (100), intramuscular and subcutaneous (75-100), transdermal (80-100)
what are 2 key factors for drug distribution?
- binding to plasma proteins
2. drug accumulation in tissues
how is drug distribution affected by binding to plasma proteins?
drugs circulate in an equil. btwn free and bound, only the free fraction is pharmacologically active
what 2 factors affect drug accumulation in tissues?
lipophilic drugs easily accumulate in tissues, highly perfused tissues accumulate more easily
what is the volume of distribution?
relative comparison of how well different drugs are distributed in body (not specific V)
what is the volume of distribution equation?
V of dist. = total amount in body / [drug] (in blood, plasma, serum, or unbound)
what drugs have a VOD close to blood V? ex?
drugs restricted to circ./plasma (highly bound to plasma proteins); heparin
what drugs can be distributed into ECF?
poorly lipid-soluble drugs
what drugs can distribute throughout entire body water?
drugs that can be transported into cells
what drugs have the highest VOD?
lipophilic drugs (accumulated in fat)
rank the types of drugs from smallest to largest VOD, what are the general VOD / 70 kg?
restricted to circ./plasma (~3.5 L), poorly lipid soluble (~14 L), distribute throughout entire body water (>35 L), lipophilic (?)
how does distribution affect elimination of a drug?
[drug] decr w/ exponential decay kinetics (elimination rate/slope depends on [drug])
What is the difference between multiple compartment distribution systems without an elimination pathway vs with?
Without an elimination pathway, the concentration briefly peaks then decr and levels off once distributed evenly throughout body. With an elimination pathway, the graph does not level off as the drug is eliminated but decr slower than single-compartment bcse distribution decr effective conc. in blood/drug has to return from extra vascular V to blood (incr lifetime)
How are drugs eliminated?
Metabolism in the liver (biotransformation) and excretion (kidney/gut)
What is phase 1 and phase 2 of liver metabolism of drugs?
- don’t necessarily occur sequentially
1: mixed function oxidase system (CYP family enzymes) ie. hydroxylation, dehydrogenation, etc
2: addition of large polar adducts to parent compound or phase 1 product to make it easier to excrete
What is the most abundant/important CYP enzyme?
CYP3A4
Can >1 CYP enzyme modify a drug?
Yes
What is hepatotoxicity?
Toxic/reactive intermediates formed by biotransformation
How are drugs excreted through feces?
Biotransformed drugs incorporated into bile & phase 2 modifications make drug more polar and less prone to reabsorption in digestive tract
How are drugs excreted through urine?
Drug passes through glomerular filtration in kidneys, hard to be reabsorbed so excreted
How is drug elimination usually described?
Half-life (exponential decay - rate vs conc.)
What does “capacity-limited elimination” mean?
[drug] has saturated enzymes so rate of elimination is constant (does not depend on [drug])
