pharmacology: fundamental principles

Question 1

what are drugs

Answer 1

exogenous molecules that mimic or block the action of endogenous molecules/systems

Question 2

type of drugs

Answer 2

agonist: bind to receptor specific to it, provoking a response
antagonist: binds to receptor specific to it -> prevents receptor from being activated

Question 3

what determines if a drug reaction is reversible or irreversible

Answer 3

reversible: ionic attractions + hydrophobic interactions (lipophilic parts)
irreversible: covalent bonds formed

Question 4

pharmacodynamics vs pharmacokinetics definition

Answer 4

pharmacodynamics: what drug does to an organism
pharmacokinetics: what organism does to the drug (absorption/distribution/metabolism/excretion)

Question 5

what factors affect absorption of a drug

Answer 5

molecular size
lipid solubility/ionisation
chemical/metabolic vulnerability (how easily it is broken down/altered)
route of administration
pt characteristics (size/weight/fed state/health condition)

Question 6

routes of administration (15)

Answer 6

inhalational 
intra-arterial (ia)
intracerebroventricular (icv)
intradermal 
intramuscular (im)
intrathecal (it; into membranes enclosing spinal cord) 
intravaginal 
intravenous (iv)
nasal 
oral (po) 
rectal 
subcutaneous (sc) 
sublingual 
topical 
transcutaneous (blasted through skin under pressure)

Question 7

factors affecting distribution of a drug

Answer 7

solubility
does it stick to proteins/cells (eg wafarin is plasma protein bound-> tends to stay within vascular compartment)
does it concentrate in fats/aqueous compartments (will distribute to adipose or CNS if lipophilic)
does pt have adequate circulation? (blood supply might be cut off to one part of the body)

Question 8

factors affecting metabolism/excretion

Answer 8

state of liver (unhealthy liver-> 1/2 life increases; clearance decreases)
state of kidneys (unhealthy kidneys-> 1/2 life increases; clearance decreases; plasma levels increases)
are the metabolites active
are the metabolites toxic

Question 9

3 names that drugs have

Answer 9

proprietary (tradename)
common name
chemical name

Question 10

how are drugs characterised; eg

Answer 10

3 names, therapeutic use, mechanism
eg disprin/aspirin/acetylsalicylic acid
use: analgesic/anti-pyretic/anti-platelet/anti-inflammatory
mechanism: cyclooxygenase inhibitor

Question 11

preclinical drug discovery

Answer 11

5-10 years;
natural products + compound libraries + combinatorial chemistry = starting chemicals -> assay systems -> active chemicals + optimisation-> animal models-> drug candidate

Question 12

clinical development

Answer 12

phase I: 20-80 healthy volunteers; discover side effects/safety/clearance/bioavailability; tolerability and dose-finding
phase II: 100-300 pt volunteers that have condition; discover side effects/safety/effectiveness
phase III: 1000-3000 pt volunteers; discover LT side effects/safety/effectiveness; compare with other meds -> REGISTRATION
phase IV: ongoing post reg studies/LT safety

Question 13

concentration dose relationship, what happens when you log it

Answer 13

hyperbola-> symmetrical sigmoid

Question 14

whats Emax and EC50

Answer 14

emax : max response that a drug can produce

ec50: concentration of drug that produces 50% of max response

Question 15

receptor properties and function
how are they classified
how do pharmacologist design drugs with fewer side effects

Answer 15

protein macromolecules; recognition/detection and transduction
classification according to which drugs they bind
design drugs that are highly specific -> only binds to certain subtypes of receptor

Question 16

is binding of a drug to receptor reversible?

shape of plot of proportion of receptors occupies vs drug concentration + what happens when you log it

Answer 16

yes

rectangular hyperbola-> sigmoid

Question 17

affinity and kd definition; their relationship

Answer 17

affinity: the molar concentration of drug required to occupy 50% of receptors at equilibrium
kd: measure of chemical attraction
inverse relationship

Question 18

affinity vs efficacy

Answer 18

many drugs have affinity, but only agonists have affinity + efficacy because they bind AND cause conformational change, activating the receptor

Question 19

two types of agonists; response against proportion of receptors occupied graph (and in log form) what does this imply

Answer 19

full agonists have high efficacy; partial agonists have low efficacy
full agnosts have full response even if only some receptors r occupies
partial agonists never react full response, even if all receptors are occupied
log form: symmetrical sigmoid

Question 20

antagonist types

Answer 20

competitive (reversible/irreversible)

non-competitive: binds to different site/closely associated molecule

Question 21

how to overcome effects of reversible competitive antagonist?
how does graph (response vs log agonist) move in the presence of an increasing amount of antagonist?
what does the extent of shift imply?
how to measure extent of shift?

Answer 21

increase [agonist];
parallel shift to right;
implies affinity of antagonist for receptor;
dose ratio: [agonist] producing response in presence and absence of antagonist

Question 22

how does graph (response vs log agonist) move in the presence of an increasing amount of irreversible antagonist?

Answer 22

rightward and downward shift

Question 23

what is pa2? how to calculate pa2? what does an bigger pa2 imply?

Answer 23

affinity for antagonist
negative log of [antagonist]
implies greater affinity