pharmacokinetics

Question 1

what is pharmacokinetics

Answer 1

journey of drug through body- absorption, distribution, metabolism and excretion

Question 2

types and subtypes of administration of drug

Answer 2

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)

Question 3

enteral vs paraenteral

Answer 3

enteral is GI administration via ingestion, paraenteral is outside GI tract (everything else)

Question 4

how drugs move around body and meaning

Answer 4

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

Question 5

how drugs get across membrane and which method is least relevant

Answer 5

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

Question 6

route of an oral drug

Answer 6

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

Question 7

drugs and pH

Answer 7

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

Question 8

aspirin vs morphine

Answer 8

aspirin is acid (proton donor), morphine is base (proton acceptor)

Question 9

pH partition hypothesis

Answer 9

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

Question 10

what affects ionised vs unionised and what is constant

Answer 10

pKA of drug is CONSTANT, but different body compartments different pH, which changes ionised over unionised

Question 11

rules for acids and bases

Answer 11

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

Question 12

why is pH partition hypothesis important

Answer 12

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

Question 13

why sodium bicarbonate increases aspirin excretion (ONLY ACIDIC DRUGS)

Answer 13

increases urine pH, hence aspirin becomes more ionised, so less likely to diffuse back into bloodstream

Question 14

factors affecting drug distribution

Answer 14

regional blood flow, extracellular binding (plasma protein binding), capillary permeability and localisation in tissues

Question 15

explain regional blood flow

Answer 15

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

Question 16

explain plasma protein binding

Answer 16

plasma protein bound drugs can’t leave the blood, particularly acidic drugs, which are 50-80% bound- warfarin is 90% bound

Question 17

explain capillary permeability

Answer 17

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

Question 18

explain localisation in tissues

Answer 18

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

Question 19

describe routes of excretion

Answer 19

most goes through kidney into urine, but some go through liver into bile, then into faeces

Question 20

excretion through kidney

Answer 20

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

Question 21

explain excretion through liver

Answer 21

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

Question 22

problem with excretion through liver

Answer 22

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

Question 23

other routes of excretion

Answer 23

not very important, but through lungs, sweat, saliva and skin

Question 24

significance of pharmacokinetic processes

Answer 24

can predict time course of drug action

Question 25

define bioavailability and link

Answer 25

how much of the administered drug is available in body to have effect- linked to absorption

Question 26

define apparent volume of distribution and link

Answer 26

volume in which drug is distributed- where it goes in body: fat soluble drugs have a greater volume- linked to distribution

Question 27

define biological half life and link

Answer 27

time taken for conc. of drug to be halved- linked to metabolism and excretion

Question 28

define blood clearance and link

Answer 28

volume of blood cleared of a drug per unit time- linked to excretion