Week 1

Question 1

Efficacy

Answer 1

The maximal amount of effect

Question 2

Ionisation of weak acids/bases -How does pH effect drug uptake -What is “ion trapping”

Answer 2

Henderson Hasselbalch equation describes pH as a measure of acidity - Ionisation of a drug markedly reduces its lipid permeability and thus ability to penetrate membranes Weak acid gives H+ -More soluble at acidic pH Weak base take H+ -More soluble at alkaline pH In the kidney weak acids are excreted faster if urine is alkaline and vice versa -“Ion trapping” alters urine pH to inhibit reabsorbtion of toxins across to renal tubular membranes

Question 3

Potency

Answer 3

Amount of effect for a given concentration -Reflected by EC50

Question 4

Antagonist

Answer 4

A molecule that binds to a receptor and inhibits it in some way

Question 5

Volume of distribution

Answer 5

VD -The apparent space in the body required to contain the drug if the drug is spread evenly at the concentration in blood -High in lipophilic drugs as they have high concentrations extravascularly

Question 6

First-Pass elimination

Answer 6

Drug metabolism in the gut wall, portal blood and (primarily) hepatic clearance from portal circulation

Question 7

Phase 1 and 2 reaction

Answer 7

Phase 1 -Modification so a polar and reactive group is added to the drug -Can be via oxidation, reduction, hydrolysis or cyclization Phase 2 -Conjugation -Drug is combined with charged molecules such as glucuronidation, acetly, sulfate or glycine -Aims to detoxify and produce more polar molecule, thus more water soluble and easier to renally excrete

Question 8

Partial agonist

Answer 8

An agonist that activates but to a sub-maximal level

Question 9

Drug

Answer 9

An agent that brings about change in biological function through its chemical actions

Question 10

Clearance

Answer 10

Body’s ability to eliminate a drug -Rate of elimination divided by plasma concentration -May be from different organs (kidney, lungs, liver), need to add these together

Question 11

TD 50

Answer 11

Median toxic dose -Dose required to produce a particular toxic effect in 50% of animals

Question 12

Pharmacokinetics

Answer 12

Action of the body on the drug -e.g absorption, distribution, elimination

Question 13

First order elimination vs zero order kinetics

Answer 13

First order -Elimination cannot be saturated, elimination directly proportional to concentration Zero Order -Rate of elimination is constant Mixed Order -Once concentration of drug is too high, saturates elimination and becomes zero order (alcohol, phenytoin)

Question 14

Rate of elimination

Answer 14

(Vmax x C)/(Km + C) -Vmax= max elimination capacity -Km= Drug concentration at which rate of elimination is 50% of max -C= Concentration

Question 15

LD 50

Answer 15

Median lethal dose -Dose required to produce death in 50% of animals

Question 16

Flow dependent elimination

Answer 16

Drugs that are cleared so well most is eliminated on first pass through organ -Elimination solely depends of rate of delivery (ie blood flow) -E.g propanolol, verapamil

Question 17

EC50

Answer 17

Concentration required to reach 50% of maximal effect

Question 18

Pharmacodynamics

Answer 18

Actions of the drug on the body

Question 19

Agonst

Answer 19

A molecule that binds to a receptor and activates it in some way to brin about an action, either indirectrly or directly

Question 20

Therapeutic Index

Answer 20

Dose required to produce desired effect vs the dose required to produce undesired effect (ie TD/effective dose)

Question 21

Dose-Response curves -Draw with EC50 and E max -How do competitive and irreversible antagonists effect this

Answer 21

Competitive antagonist -Increases EC50 but Emax is the same Non-competitive (Irreversible) antagonist/Partial agonist -EC 50 is the same but Emax is reduced

Question 22

Receptor

Answer 22

Site where a ligand binds to effect a change or inhibit the usual action

Question 23

Half life

Answer 23

Time requied to halve the amount of drug in the body -T1.2=O.7xVd/Clearance

Question 24

Extraction ratio

Answer 24

Effect of first pass metabolism on bioavailabilty -ER= Liver clearance/hepatic blood flow

Question 25

Bioavailability

Answer 25

Percentage of unchanged drug reaction systemic circulation -Ie pills affected by absorption and first pass metabolism

Question 26

Second Messengers

Answer 26

A way of transducing messages from surface to intracellular level Ligand binds to receptor -Activation of G protein -Activation of enzyme/ion channel etc -Increase intracellular concentration of second messenger(eg Ca2+, cAMP, phosphoinositides) -Causes the biological effect of the ligand -eg B adrenoceptors, thyrotropin receptors, glucagon