Lecture 37 - General mechanism of drug action Flashcards
what is the receptor theory
lock and key concept
eg. histamine
histamine binds to receptor
-cells in stomach produce more acid - inflammation of mucus membranes
how do drugs work by blocking receptors?
antagonist blocks ligand from binding - prevents response
adrenergic receptors
speeds up heart rate
constrics arteries - increases bp
Dilates bronchioles
problem - raise blood pressure and increases heart rate
types of adrenergic receptors
b1 (Mainly on heart) ,b2 (mainly on bronchioles) and alpha (mainly on BV)
side effects of beta blockers
Propranolol blocks ß 1 and ß 2 receptors
makes asthma worse
Selectivity is only relative
atenolol blocks ß 1 more than ß 2
best avoided still in asthma
How do NSAID’s work
inhibt formation of prostaglandins responsible for modulating inflammation
inhibit cyclo-oxgenase
what are the side effects of NSAID’S
As they inhibit prostaglandins
-prostaglandins reduce acid production and icnrease mucus in stomach, increase blood to kidneys
side effects - peptic ulceration, salt and water retention
What is COX-2
an anti-inflammatory drug target
eg. NSAIDS
specific inhibition muscles
COX 1 acts where?
stomach
non-specific inhibition
ACE inhibitors
inhibit enzymes
prevent conversion of angiotensin 1 to 2.
what is the proposed action of anti-depressants on neurotransmitters
action in the nerve synapse
ssri’s cause reuptake and release serotonin
Drugs affecting cell transport
Interfering with the movement of ions across cell membranes
eg. calcium anatagonist - nifedipine
Local anaesthetics
Local anaesthetics generally have a lipid-soluble hydrophobic aromatic group and a charged, hydrophilic amine group.
The bond between these two groups determines the class of the drug, and may be amide or ester.
amides - eg. lignocaine, bupivacaine, prilocaine
esters. cocaine and amethocaine
how do local anaesthetics work
block transmission of nerve impulses between peripheral pain receptors and CNS
prevent neurone action potential - disrupt ion channel function within cell membrane
occur via specific binding of local anaesthetics to sodium channels - hold them in inactive state
mode of action of local anaesthetics
diffuse through the lipophilic nerve membrane unionized
Low pH in cell generates ionized form
Ionized LA blocks the channel
Impulses stopped
Slowly returns to normal and impulses return as block ends
factors affecting anaesthetic effects
Small diameter nerve fibres are more sensitive to local anaesthetics than larger fibres so pain sensation is blocked more readily than touch and movement.
The action is dose dependent
The action is pH dependent (inflamed tissues are often acidic and resistant to local anaesthetics)
Adverse effects of local anaesthetics
block sodium channels in heart - Myocardial depression, vasodilation
affect CNS - restlessness and at high doses - convulsions
addition of adrenaline - constriction of peripheral vessels
Effects of local anaesthetics on absorption and distribution
vasodilatory effects at low concentrations
increases systemic absorption
distribution influenced by degree of tissue and plasma protein binding of the drug
more protein bound agent - more duration of action
metabolism and excretion of anaesthetics
Esters (except cocaine) are broken down rapidly by plasma esterases to inactive compounds and consequently have a short half life.
Amides are metabolised hepatically by amidases. This is a slower process, hence their half-life is longer and they can accumulate if given in repeated doses or by infusion.
Prilocaine is also metabolised extra-hepatically.
Drugs with a non-specific action
Antacids e.g. aluminum hydroxide
neutralise acid in stomach
Emollients
moisturise skin
General anaesthetics
reduce CNS function
Mode of action of antimicrobials
Beta Lactam antibiotics e.g. Penicillins
inhibit bacterial cell wall synthesis
Macrolides e.g. erythromycin
inhibit bacterial protein synthesis
Antifungal agents e.g. nystatin
inhibit ergosterole in fungal cell membrane
mammalian cells use cholesterol
Mode of action of antihelminthics
Ascaracides for worm infestatione.g. threadworm
Paralyses worm by acting on nervous system
not absorbed
