1-2 Hiley Flashcards
Tetanus toxin
Retrogradely transported to motor cell body
Transfers to inhibitory inter neuron, blocking it
Motor neuron more excitable
Targets SNARE synaptobrevin
Botulinum toxins
Preferentially effects cholinergic neurons
C terminus of heavy chain binds ganglioside receptor
N terminus translocates light chain into the cell through a channel
Light chain has peptidase activity, and inside, cleaves the snare
Blocks ACh release
Botulinum toxin C1Target
Syntaxin and SNAP25
Botulinum toxins A&ETarget
SNAP25
Botulinum toxins B,D,F,GTarget
Synaptobrevin
Hemicholinium
Blocks transporter that takes up choline into nerve cell
Vesamicol
Blocks transporter that carries ACh into storage vesicles
Non-Competitive and reversible inhibition
B-bungarotoxin
Blocks ACh release
Acts through phospholipase A2
a-latrotoxin
Binds neurexins
Cause massive release if ACh
a-bungarotoxin
Irreversible antagonist at nmj, at nicotinic ACh receptor
Doesn’t affect ganglionic receptors
Nicotine
Nicotinic ACh agonist
Stimulates post synaptic cell
Long-lasting
Phase I block - VGNa channels inactivated
Phase II block - nicotinic receptors become desensitised -can be directly stimulated by electrical means
Hexamethonium
Use dependent blockade of ganglionic transmission nACh receptor
Double positive charge - had to be administered frequently by injection
Causes loss of sympathetic and parasympathetic control
D-tubocurarine
Nicotinic receptor antagonist
Non selective between ganglion and nmj
Quaternary ammonium compounds so not orally active
Atracurium
Competitive antagonist at the nicotinic receptor of the nmj
Quaternary ammonium compound
Not orally active
Tetanic fade (tetanus is not maintained) due to block of nicotinic receptors on nerve endings auto receptors , positive feedback to maintain transmitter release
Ester - spontaneous hydrolysis and plasma esterases
Pancuronium
Competitive antagonist at the nicotinic receptor of the nmj
Quaternary ammonium compound
Not orally active
Tetanic fade (tetanus is not maintained) due to block of nicotinic receptors on nerve endings auto receptors , positive feedback to maintain transmitter release
Long action, not hydrolysed
Suxamethonium
Block nicotinic receptor at nmj by causing prolonged depolarisation
Depolarisation of phase I- anticholinesterases deepen the blockade
Effects can be opposed by non-depolarising blockers
Phase II - repolarisation, anticholinesterases reverse the blockade
Only depolarising blocker in clinical use
Short duration - ester broken down by plasma BuCHE
Muscarine
Muscarinic receptor (agonist)
Acetylcholine
Non selective agonist at muscarinic acetyl choline receptors
Bethanechol
Non selective agonist at muscarinic acetyl choline receptors
Poorly absorbed in GI tract
Systemic use in bladder dysfunction
Pilocarpine
Non selective agonist at muscarinic acetyl choline receptors
Poorly absorbed from GI tract
Treatment of glaucoma, contracts ciliary muscle, traction on trabecular meshwork, facilitates aqueous humour drainage
Atropine
Non selective antagonist of muscarinic acetylcholine receptor Dilate pupils (mydriasis) Long duration
Darifenacin
Antagonist m3 muscarinic acetylcholine receptor
Mediate bladder constriction
Edrophonium
Short acting, reversible ionic interaction with AChE
Used for diagnosis of myasthenia gravis
Neostigmine
Medium acting, reversible weak covalent bond with AChE
Orally treats myasthenia gravis
Bind esteratic site and carbomylate enzyme
Intravenously to reverse neuromuscular blockade
Dyflos
Long acting, irreversible strong covalent bond with AChE
Glaucoma
Malathion
Long acting, irreversible strong covalent bond with AChE
Insecticide to kill lice
Activated by replacement of S with O
More efficient in insect cytochrome P450
Pralidoxime
Reverse inhibition of AchE by organophosphorous agents
Brings oxime (nucleophile) close to phosphorylated serine
Only occur a few hours after inhibition - before ageing occurs
Carbidopa
Inhibit peripheral dopadecarboxylase
Reduce peripheral side effects of increased NA and DA
Methyldopa (a-methyldopa)
Converted by DDC to alphamethyldopamine Then by DBH to alphamethylnoradrenaline Stored and released with NA False transmitter Anti hypertensive agent in CNS
Reserpine
Binds amine binding site
Irreversibly blocks VMAT (vesicular monoamine transporter)
Prevents transport of NA and DA from cytoplasm into vesicles
Blocks uptake
Long lasting depletion of stored NA
Anti hypertensive
Side effects of psychological depression from serotonin depletion
Tyramine
In cheese, red wine and marmite
Transported into nerve endings and storage vesicles
Displaces NA from vesicle, NA reaches extra cellular space and activates local adrenoceptors= indirectly acting sympathomimetic amine
Uptake 1 substrate
Dexamfetamine (D-amphetamine)
Alpha methyl group so not metabolised by MAO
Weak inhibitor of MAO
Taken up into vesicles, reduces pH gradient and packing of amines
Displaced NA leaves nerve and stimulates receptors
Uptake 1 substrate
Guanethidine
Taken up into nerve by uptake 1 (substrate)
Low doses - block release of NA
High doses - act as indirectly acting sympathomimetic amines
Cocaine
Blocks NET (norepinephrine transport protein), blocks uptake 1
Imipramine
Tricyclic antidepressant
Blocks NET (norepinephrine transporter protein), blocks uptake 1
Block NA and 5HT transport
Amitryptyline
Tricyclic antidepressant
Blocks NET (norepinephrine transporter protein), blocks uptake 1
Block NA and 5HT transport
Clorgiline
Selectively inhibits MAO-A
Used in depression
Selegiline
Selectively inhibits MAO-B
Treats Parkinson’s (MAO-B metabolises DA)
Tranylcypromine
Non selective irreversible inhibitor MAO
Treatment of refractory depression
Entacapone
Inhibitor of COMT (catechol-I-methyltransferase)
Treat parkinsons
Noradrenaline
Adrenoreceptor agonist
a1a2 B1B2
Adrenaline
Adrenoreceptor agonist
a2a1B
Isoprenaline
Adrenoreceptor agonist B Asthma - relax bronchi But increase in heart rate Replaced by salbutamol
Phenylephrine
Adrenoreceptor agonist
a1B1
Raise blood pressure in acute hypotension
Methyl INA
Adrenoreceptor agonist
a2a1
Clonidine
Adrenoceptor agonist
a2a1
Anti hypertensive agent
Xylazine
Adrenoreceptor agonist
a2a1
Veterinary sedative
Salbutamol
Adrenoreceptor agonist
B2B1
Dobutamine
Adrenoreceptor agonist
B1B2
Acute cardiogenic shock
Phentolamine
Adrenoreceptor antagonist
a1 a2
Anti hypertensive - but bring about large heart rate increase
Prazosin
Adrenoreceptor antagonist
a1a2
Used in hypertension
Idazoxan
Adrenoreceptor antagonist
a2a1
Propranolol
Adrenoreceptor antagonist
B1 B2
Used to treat hypertension - but risk of bronch constriction
Replaced by atenolol
Atenolol
Adrenoreceptor antagonist
B1B2
Hypertension, cardiac dysrhythmia, angina
With phenoxybenzamine, prevent effects of large releases of catecholamines after tumour displacement
Butaxamine
Adrenoreceptor antagonist
B2B1
Labetalol
Adrenoreceptor antagonist a1 B1 B2 3rd generation B blocker Treat hypertension in pregnancy 4 isomers -RR B blocker, weak a blocker -RS a blocker, weak B blocker -SR no activity -SS a1 blocker
Caffeine
A1 receptor antagonist
Non-selective, also inhibits phosphodiesterase (breaks down cyclic nucleotides) increase rate and force of cardiac contraction
Potentiation of cAMP mediated signalling
Dipyridamole
Blocks transport of adenosine back into cells
Potentiation responses mediated by adenosine
Glyceryl trinitrate(Nitroglycerin)
Nitric oxide donor
Nitrovasodilator(Produce NO2)
Treat angina
L-NMMA
NOS inhibitor
Analogue of L-arginine
Not very selective
D-isomers are inactive
ATP
Released from sympathetic neurons
Rapid responses
***Mecamylamine(Inversine)
Non selective,non competitive antagonist of nicotinic acetylcholine receptors
Orally active
Anti hypertensive drug
