PHARM Y1 S1: Intro to pharm Flashcards
good resources for looking up drugs
- MIMS
- Aus medicines handbook
- Cochrane library
- PBS website
- Monash ePharm (Moodle)
selectivity vs specificity for receptors
- selectivity is better for tissues because they only display specificity within a particular dose range
- specificity is better for a receptor
- not all keys fit all locks
4 types of targets for drug action (usually proteins)
- receptors (agonist/antagonist)
- ion channels (blockers/modulators)
- enzymes (inhibitor, false substrate, pro-drug)
- carriers/transporters (normal transport, inhibitor, false substrate)
pharmacokinetics vs pharmacodynamics
- kinetics: what the body does to a drug (absorption, distribution, metabolism, excretion)
- dynamics: what the drug does to the body (how drug binds and what happens after)
agonist vs antagonist
- agonist: binds to receptor and activates it
- antagonist: binds to receptor and doesn’t activate it but blocks actions of agonists
3 phases of drug action
- pharmaceutical (released from capsule/tablet)
- pharmokinetic (absorption, distribution, metabolism, excretion)
- pharmacodynamic (binding to target site, stimulus, effect)
law of mass action
the more drug (key) you have, the more chance you have of interacting w/ the receptor (lock) and having desired effect
criteria for a neurotransmitter
- synthesised and released from nerve
- post-synaptic receptor specific to NT
- has a competitive antagonist
- must be an active mechanism to terminate activity of NT
types of nerves + their receptors
- adrenergic nerves: release NA (a/B receptors)
- cholinergic nerves: release ACh (nicotinic (ionotropic) /muscarinic (metabotropic) receptors)
sympathetic and parasympathetic nerves
- pre-ganglionic: cholinergic (N receptor)
- post-ganglionic: parasympathetic is cholinergic (M receptor) and sympathetic is adrenergic (a/B receptor)
somatic nerves
- just one cholinergic nerve (N receptor)
3 types of B-receptors
- β1: increased HR and contraction force (we have 1 heart)
- β2: vasodilation to lungs + pupil dilation (we have 2 lungs)
- β3: lipolysis in adipose tissue
2 types of a-receptors
- a1: vasodilation to muscle (constriction to GIT) + pupil dilation
- a2: noradrenaline -ve feedback + vasoconstriction of vascular smooth muscle
how is Ach synthesised
- choline + acetyl-coA > acetylcholine
- uses enzyme choline acetyltransferase
how is noradrenaline synthesised
- precursor tyrosine (AA)
- -ve feedback system of inhibiting tyrosine hydroxylase
how is noradrenaline removed
- reuptake into pre and post synaptic nerves
- then broken down by 2 enzymes: monoamine oxidase (MOA) and catechol-O-methyltransferase (COMT)
how is Ach removed?
- must be removed almost immediately @ NMJ otherwise depolarising block
- mainly done by enzymatic breakdown by acetylcholinesterase
how do amphetamines work?
- increased NA into synaptic cleft
- sympathetic effects
how does cocaine work?
- inhibits pumping of NA back into neuron > more left in synaptic cleft
- excitatory effect on post-synaptic neuron
2 types of drugs which block NMJ
- non-depolarising blockers
- depolarising blockers
non-depolarising blockers
- competitive antagonists @ N receptors
- overcome by increasing [Ach]
- e.g. rocuronium (synthetic derivative of tubocurarine - can’t be used b/c side effects)
depolarising blockers
- agonist @ N receptors
- keep in depolarised state instead of allowing for depol/repol cycle which is needed for contraction
- inactivate Na+ channel > receptors unresponsive to Ach
- action made worse by increasing Ach
- e.g. suxamethonium (succinylcholine)
why does suxamethonium have a short effect?
- hydrolysed rapidly in body by plasma cholinesterase
- this enzyme is absent in some people > causes paralysis
- no clinically suitable drugs to reverse depolarising blockers
when do we use non-depolarising blockers
- e.g. surgery when we want to produce paralysis, stop breathing
- muscle relaxation, facilitate tracheal intubation + mechanical ventilation
- Pt is conscious but can feel pain
myasthenia gravis
- autoantibodies reduce action of nicotinic receptors > Ach can’t bind to transmit AP
- AP only generated in a small proportion of muscle fibres, contraction not sustained > muscle weakness
how do we treat myasthenia gravis
- give ANTIcholinesterase (pyridostigmine) to reduce breakdown of Ach > increased chance of binding to an available nicotinic receptor
- need atropine to act as a competitive antagonist @ M receptors (prevent parasympathetic side effects of excess ACh)
- don’t just give Ach b/c it won’t get into the NMJ
what does pralidoxime do
reactivates acetylcholinesterase to promote breaking down of ACh
how do orthodontic surgeries achieve delayed absorption, promoting local drug impact and stopping systemic entrance?
- co-administration of the drug with epinephrine
absorption vs penetration
- absorption: travel from site of administration to action
- penetration: ability for drug to disperse in the body
