Drugs Flashcards
What are agonists?
Agonists are drugs that bind to a receptor to produce a response. They have affinity and efficacy.
What is the efficacy of a full agonist?
1
What is an antagonist?
A drug that binds to a receptor but does not produce a response. They have affinity but not efficacy.
What is the equation for occupancy?
p = [AR]/[Rt] = [A]/Kd + [A]
Where are benzodiasepine receptors found and what are they?
They are allosteric modulatory sites on GABAA receptors increasing the affinity for GABA and increasing channel opening
What are the different types of antagonism
competitive antagonists irreversible antagonists allosteric antagonist channel blockers physiological antagonists
What is an example of a physiological antagonist?
acetylcholine and adrenaline in the heart, they produce opposite effects on the tissue and produce a non-selective suppression of the response
What are local anaesthetics?
reversibly block nerve conduction when applied to a restricted area of the body without loss of consciousness.
All local anaesthetics contain a benzene ring
How do local anaesthetics work?
Sodium channels blocked so AP can’t be generated to send information from nociceptors to brain
What is an example of a local anaesthetic?
lidocaine (medium length)
bupivacaine (long length)
What factors can affect the effectiveness of local anaesthetics?
tissue pH
- infection can lead to increased acidity which can lead to an increased in ionised form making it less effective
sensitivity of nerve fibres
- smaller diameters (eg nociceptor neurones) are more sensitive so are more affected by LAs
What does drug absorption depend on?
- route of administration
- chemical nature eg lipohilic, charge, size
- packaging
- blood flow rate to site of delivery
What is the volume of distribution?
How much drug needs to be in the body to get a certain concentration in the plasma
Vd = total amount of drug in body/amount of drug in plasma
What are cytochrome P450s?
Used in phase 1 metabolism of drugs, can metabolise a wide range of different molecules, creates highly reactive compounds as substrates for phase 2
What molecules could be used for conjugation in phase 2 metabolism?
glutathione
sulfate
glycine
glucaronic acid
Paracetamol metabolism
phase 1 - N-hydroxylation by CYP2E1 or CYP1A2 to form NAP2D6
phase 2 - conjugation to glutathione
What are the routes for excretion?
Renal - filtration and secretion
Hepatic/biliary - faecal
sweat, breath
What are the receptors at the neuromuscular junction?
nicotinic acetylcholine receptors
What transports acetylcholine into vesicles and what blocks it?
An ACh carrier
Vesamicol
What the choline transporter (to the plasma membrane)?
hemicholinium
What blocks exocytosis of the vesicle of ACh?
toxins
What are types of neuromuscular blockers?
non-depolarising blockers - antagonists - tubocurarine
depolarising blockers - agonists - suxamethonium
How do non-polarising blockers work?
They are competitive antagonists at nACHRs
They decrease the endplate potential so not enough receptors are occupied by ACh
How do polarising blockers work?
Suxamethonium is an agonist at nAChRs and cause endplate depolarisation. Action potentials cause fasciculations. It isn’t broken down by acetylcholinesterase so it causes prolonged depolarisation
