pharmacokinetics Flashcards
what is pharmacokinetics
journey of drug through body- absorption, distribution, metabolism and excretion
types and subtypes of administration of drug
systemically (affecting whole organism, needed for affecting brain, so goes into bloodstream) or locally ingestion (GI), inhalation (lungs), intravenouly, intraperitoneal. subcutaneous or intramuscular (blood) or dermally (skin)
enteral vs paraenteral
enteral is GI administration via ingestion, paraenteral is outside GI tract (everything else)
how drugs move around body and meaning
via bulk flow over a large distance (bloodstream) and diffusion over a short distance, meaning drugs need to be in an aqueous and lipid environment
how drugs get across membrane and which method is least relevant
by simple diffusion (lipid soluble drug), diffusion across aqueous pores or carrier mediated transport a water soluble drug needs to be very small to use aqueous pores, otherwise it needs carrier mediated transport
route of an oral drug
goes into stomach and intestine via bulk flow, then crosses villi into ECF, then crosses capillary wall then bulk flow via bloodstream, then crosses capillary membrane again and binds to target cell, usually on outside
drugs and pH
drugs are weak acids or bases, hence they can either be ionised/polar or unionised/non-polar ie move through lipid barrier- this depends on pH
aspirin vs morphine
aspirin is acid (proton donor), morphine is base (proton acceptor)
pH partition hypothesis
henderson hasselbach can be rearranged to 10^(pka-pH)= (AH)/(A-) or (BH+)/(B), telling you how much of your drug is ionised or not- acid is UNIONISED OVER IONISED, BASE IS OPPOSITE
what affects ionised vs unionised and what is constant
pKA of drug is CONSTANT, but different body compartments different pH, which changes ionised over unionised
rules for acids and bases
if pH is below drugs pKA for acids, you have more unionised, so more lipid soluble if pH below pKA for bases, you have more ionised if pH and pKA are equal, its 50/50
why is pH partition hypothesis important
leads to ion trapping- if aspirin in stomach, it easily diffuses out, but if in blood, it is difficult to move out, so is trapped, hence dosage needed to affect a tissue needs to be calculated, and pKA of drug is needed too
why sodium bicarbonate increases aspirin excretion (ONLY ACIDIC DRUGS)
increases urine pH, hence aspirin becomes more ionised, so less likely to diffuse back into bloodstream
factors affecting drug distribution
regional blood flow, extracellular binding (plasma protein binding), capillary permeability and localisation in tissues
explain regional blood flow
the more blood going to a tissue, the more drug goes there organs that receive more blood (liver ,kidney and brain) receive more drug- but metabolically active tissues have denser capillary networks, hence muscles get more drug during exercise, and gut gets more after a meal
explain plasma protein binding
plasma protein bound drugs can’t leave the blood, particularly acidic drugs, which are 50-80% bound- warfarin is 90% bound
explain capillary permeability
lipid soluble drugs don’t need to worry, but water soluble drugs need to leave the blood- it can leave continuous capillaries, fenestrated and discontinuous, but blood brain barrier has tight junctions
explain localisation in tissues
fat gets very little blood so usually not much drug goes there, but very lipid soluble drugs can sit in adipose tissue and not get to other tissue
describe routes of excretion
most goes through kidney into urine, but some go through liver into bile, then into faeces
excretion through kidney
20% of blood goes to kidney, and only the smaller drug molecules are filtered through the glomerulus, so most are actively secreted via transporters, although lipid soluble drugs can be passively reabsorbed back into the blood
explain excretion through liver
capillaries in liver are discontinuous, hence drugs can easily get to hepatocytes for metabolism- they are then made water soluble, so to get into bile duct, active transport is needed
problem with excretion through liver
enterohepatic cylcing- water soluble conjugate broken down by gut bacteria, so free drug is now lipid soluble and goes back to liver, and goes into circulation= persistence
other routes of excretion
not very important, but through lungs, sweat, saliva and skin
significance of pharmacokinetic processes
can predict time course of drug action
define bioavailability and link
how much of the administered drug is available in body to have effect- linked to absorption
define apparent volume of distribution and link
volume in which drug is distributed- where it goes in body: fat soluble drugs have a greater volume- linked to distribution
define biological half life and link
time taken for conc. of drug to be halved- linked to metabolism and excretion
define blood clearance and link
volume of blood cleared of a drug per unit time- linked to excretion
