lecture 2

Question 1

4 types of drug antagonism

Answer 1

receptor blockade, physiological antagonism, chemical antagonism, pharmacokinetic antagonism

Question 2

receptor blockade

Answer 2

competitive or irreversible; “use-dependency” of ion channel blockers e.g. local anaesthetics by binding to inside of Na+ channels when open, so increased tissue activity means work more quickly or effectively

Question 3

physiological antagonism

Answer 3

where drugs interact with different receptors so have opposite effects in same tissue e.g. noradrenaline or histamine to vasculature on blood pressure acting on different receptors and producing opposite effects to produce antagonism

Question 4

chemical antagonism

Answer 4

interaction of drugs in solution e.g. dimercaprol (chelating agent forms complexes with heavy metals which are more easily excreted by kidney)

Question 5

pharmacokinetic antagonism

Answer 5

antagonist so decreases [active drug] at action site, decreases absorption, increases metabolism or excretion; e.g. barbiturates (anti-epillepsy; causes enzyme induction - more enzymes produced which break it down are produced - if constantly given; give higher warfarin dose to thin blood as more induced enzymes so less duration of action)

Question 6

define drug tolerance and example

Answer 6

gradual decrease in responsiveness to drug with repeated administration, e.g. benzodiazepines (anti-epileptic)

Question 7

pharmacokinetic factors causing drug tolerance

Answer 7

increased rate of metabolism, e.g. barbiturates and alcohol causes increased induced enzymes

Question 8

loss of receptors causing drug tolerance

Answer 8

prevent stimulation so downregulate by membrane endocytosis, receptor “down-regulation”, e.g. B-adrenoreceptors susceptible

Question 9

receptor up-regulation

Answer 9

if input taken away, receptor is up-regulated; important in denervation supersensitivity (following soft tissue injury attempt to regulate neurotransmission - bigger response to nicotinic receptor agonists)

Question 10

change in receptors causing drug tolerance

Answer 10

receptor desensitisation by conformational change, e.g. nicotinic acetylcholine receptor at neuromuscular junction

Question 11

exhaustion of mediator stores causing drug tolerance

Answer 11

e.g. amphetamine (binds to uptake transporter on noradrenaline neurones; causes release of noradrenaline into synaptic cleft in brain -> euphoric effects)

Question 12

physiological adaption causing drug tolerance

Answer 12

due to homeostatic responses (e.g. osmoregulation), does contribute to tolerance to drug side effects as well as therapeutic effects

Question 13

what are receptor families types based on

Answer 13

molecular structure, signal transduction systems

Question 14

type 1 receptor family

Answer 14

ion channel-linked (ligand-gated) receptors; membrane; channel; direct; fast responses (m secs) e.g. nicotinic acetylcholine receptor, GABA a (action potential inhibitor in brain; linked to Cl- channels; hyperpolarises membrane); 4 or 5 different transmembrane subunits

Question 15

type 2 receptor family

Answer 15

G protein-coupled receptors; membrane; enzyme or channel; direct; slower responses (secs) e.g. B1-adrenoceptors in heart, muscarinic acetycholine receptors; 7 transmembrane a-helix segments

Question 16

type 3 receptor family

Answer 16

kinase-linked type; membrane; enzyme; e.g. insulin receptor or growth factor and cytokine receptors (mins); 1 transmembrane a-helix segment; IC catalytic domain

Question 17

type 4 receptor family

Answer 17

IC steroid type receptors e.g. steroids/thyroid hormones to regulate DNA transcription (hrs); DNA binding domain contains zinc