Principle of pharmacology

Question 1

Types of receptors

Answer 1

Physiologoical (e.g. for compounds like hormones, neurostransmitters), other proteins (enzymes, ion channels), nucleic acids (drugs may bind to influence gene expression or protein synthesis)

Question 2

Which type of drug interactions are reversible and which are irreversible

Answer 2

reversible-hydrophobic interactions, ionic interactions

irrreversible-covalent bonding e.g aspirin

Question 3

Pharmacodynamics define

Answer 3

what drug does to organsim-the sum of all actions of drug

Question 4

Pharmacokinetic define

Answer 4

what organism does to drug (absorption, distribution, metabolism and exccretion of drug). Determines how quickly drug acts in patient

Question 5

What are the speed of absorption and how much drug enters the system influenced by

Answer 5

molecular size, lipid solubility, chemical and metabolic vulnerability

Question 6

Meanings of: icv, it, topical, transcutaneous

Answer 6

icv=injected to cerebral ventricles
im=injected into membranes enclosing spinal cord
topical=applied directly to affected areas
transcutaneous=powder blasted through skin under pressure using deviceor by diffusion from adherent patch

Question 7

What does pharmaacokinetics determine

Answer 7

how quickly drug acts on patient, whether drug effect systemic or local, how long the effects last

Question 8

3 name categories of drugs

Answer 8

proprietary name, common name, chemical name

Question 9

What are drugs grouped according to

Answer 9

therapeutic use (analgesis, anti inflammatory, anti pyretic, anti platelet) or by mechanism of action

Question 10

Drug discovery flow chart

Answer 10

ref. notes

Question 11

Drug development phases

Answer 11

Phase 0: fifrst in human trial, sub therapeutic dose. Pharmacokinetic info
Phase 1: 20-80 healthy side effect safety, tolerability and dose finding
Phase 2: 100-300 wide effect safety works out effectiveness
Phase 3: 1000-3000 side effect, safety, effectiveness comparison with current available drug.

Question 12

What happens after phase 3 drug trials

Answer 12

registration with UK’s MHRA or EU’s EMA or USA’s FDA and ongoing phase IV post registration studies, different populations and long term safetu

Question 13

Sketch [drug] x response curve and log[drug] x response curve

Answer 13

[drug] x response curve=rectangular hyperbola

and log[drug] x response curve=symmetrical sigmoidal, 20-80%=linear

Question 14

Emax and EC50 define

Answer 14

Emax=max response that drug can produce

EC50=conc of drug that can produce 50% of max response Both used to quantify potency of drug

Question 15

Receptor what and functions

Answer 15

protein macromolecules usually inserted in lipid bilayer.

Functions: recognition/detection and transdducction. Selectively bind to certain chemicals

Question 16

Sketch curve of [D] and proportion of receptors occupied as well as log[D] and proportion of receptors occupied

Answer 16

[D] and proportion of receptors occupied=rectangular hyperbola
log[D] and proportion of receptors occupied=symmetrical sigmoid

Question 17

How is the affinity for a drug to its receptor quantified

Answer 17

molar conc of drug required to occupy 50% of receptors at equilibrium aka high affinity=slow dissociation rate. This conc given in KD

Question 18

Do drugs with high affinity have high or low KD

Answer 18

low

Question 19

What is KD

Answer 19

measure of chemical attraction

Question 20

Many drugs have ____ but only agonists have ____

Answer 20

affinity, efficacy. Agonists bind and activate receptor as opposed to just occupy it. After bindiing, agonists profuce conformational change

Question 21

Efficacy define

Answer 21

ability of drug to activate receptor and cause conformational change in receptor structure

Question 22

what are all agonists

Answer 22

neurotransmitters and hormones

Question 23

Full and partial agonist difference

Answer 23

full=high efficacy, very efffective result at producing biological response
parial=low efficacy, less effective

Question 24

Compare p x response line for partial and full agonist. Sketch this and log{agonist}xresponse curve for both

Answer 24

Full agonist produce max response whilst activating only a fraction of available recceptors.
Partial agonists fail to produce full response sdespite occupying all available receptors. ref. notes

Question 25

why would symmetrical sigmoid from log {agonist} x response not accurately reflect affinity

Answer 25

response to agonist is dependent on both affinity and eefficacy

Question 26

comment on affinity and efficacy of competitive antagonist

Answer 26

have affinity but no efficacy

Question 27

what happens to effect of antagonist when agonist concentration increases

Answer 27

the blockade effect of antagonist is surmountable

Question 28

What happens to log [agonist] x response curve in the presence of antagonist

Answer 28

shifts to right. shifts further to right with more antagonist

Question 29

How to measure antagonist affinity to receptor

Answer 29

extent of shift in position of agonist curve measured using the dose ratio. aka how many times increase [agonist] to overcome antagonist

Question 30

pA2 what

Answer 30

affinity of antagonist quantified using this. Negative logartihm of molar conc of antagonist that necessiates that you double the agonist concentration to produce the same response (i.e. dose ratio=2.0)

Question 31

What do irreversible competitive agonists do to log[agonist] x response curve

Answer 31

This shifts the curve to right but shift i not parallel because block is not surmountable ref. notes