Session 10.3 Pharmacokinetics 1

Question 1

drugs are

Answer 1

exogenous signalling molecules

Question 2

what are the four main processes in pharmacokinetics

Answer 2

absorption
distribution
metabolism
excretion

Question 3

what is pharmacokinetic process

Answer 3

are drugs getting to site of action to perform therapeutic effect

Question 4

what are the four main processes in drug therapy

Answer 4

pharmaceutical process - dosage
pharmacokinetic
pharmacodynamic - pharmacological effects
therapeutic effect

Question 5

absorption and distribution

Answer 5

drug in

Question 6

metabolism and excretion

Answer 6

drug out

Question 7

how can drugs be administered

Answer 7

enteral - into internal environment, into GI tract - via oral, sublingual, rectal
parenteral - other routes - intraveous, subcutaneous, intramuscular

Question 8

how are drugs absorbed via oral route

Answer 8

little absorption in stomach due to thick mucosae and high acidity
drug mixes with chyme and enters small intestine (due to microvilli, larger SA) - more absorbed and pH of 6-7
constantly mixing to present drug to GI epithelia to be absorbed

Question 9

what are the 3 stages of drug absorption at the molecular level

Answer 9

passive diffusion - lipophilic, eg: steroids, weak acids of bases easily pass through, and drugs immediately taken away by blood supply, maintain conc gradient. if pka lower than pH 6 of gut = 10% protonated = lipophilic as uncharged, which crosses GI epithelia
facilitated diffusion - require carrier protein (organic anion or cation transporters - lots in GI, hepatic and renal epithelia) - ionic compound with complete positive or negative charge down an electrochemical/conc gradient
secondary active transport - uses solute carrier (OAT or OCT) transporters driven by pre-existing electrochemical gradient formed by primary active transport

Question 10

what are example drugs that are absorbed by secondary active transport

Answer 10

flouxetine - sodium gradient formed by Na/K ATPase is used to cotransport Na ion in
Penicillins - co transported with H ion, gradient between cytoplasm and gut lumen

Question 11

what are the physiological factors affected drug absoprtion

Answer 11

SA of gut
drug lipophilicity/pKa - passive diffusion
density of SLC expression in GI - facilitated transport

Question 12

what other factors affect drug absorption

Answer 12

blood flow - increased post meal - so drug carried away more rapidly, reduced uptake in exercise and anxiety
GI motility - slow post meal - more time for drug to be absorbed, rapid in diarrhoea - drug flushed out
food - reduce/increase uptake - lipophilic drugs better absorbed with fatty meal as fat enables liphophilic drug to dissolve in fat so more easily absorbed
pH - low destroys some drugs

Question 13

how are drugs metabolised by GI and liver

Answer 13

metabolized by two major enzyme groups (mainly in liver) - cytochrome P450 (phase 1) - adds hydroxy groups to enhance charge characteristics so more easily passed out in kidneys and conjugating (phase 2) - adds charge groups for kidney excretion