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PNS Flashcards

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1
Q

Botulinum Toxin

A

C-terminus of heavy chain binds to ganglioside and complex is endocytosed. N-terminus translocates light chain from endosomal lumen to cell cytoplasm by making a channel in the endosomal membrane. Light chain is metallopeptidase and cleaves target SNARE in cytoplasm

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2
Q

Tetanus Neurotoxin

A

C-terminus if heavy chain binds to ganglioside enabling endocytosis. Toxin moves towards soma of motor neuron by retrograde atonal transport, and gets discharged into intersynaptic space. Binds to presynaptic membrane of inhibitory neurons and is endocytosed. Acidic nature of vesicles causes insertion of N-terminus light chain into cytoplasm where it cleaves synaptobrevin

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3
Q

Alpha-latrotoxin

A

Ca independent endocytosed by binding to neurexins and CL1. Binding leads to formation of a Ca permeable pore within the presynaptic membrane allowing Ca influx and trigger transmitter release

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4
Q

Hemicholinium

A

Inhibits choline transporter (ChT) that co-transports sodium

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5
Q

Trierhylcholine

A

Competes with choline as a substrate of ChAT and gets converted to acetyltriethylcholine which is release in place of ACh. False transmitter

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6
Q

Vesamicol

A

Non-competitive and reversible antagonist of VAChT

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7
Q

Beta-bungarotoxin

A

Bind to and block shaker-type K channels. Subsequent block of ACh release is probably via its PLA2 activity which degrades active zone lipids

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8
Q

Alpha bungarotoxin

A

Irreversible antagonist of the adult Nm and inhibitor of (alpha7)5 Nn in the brain

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9
Q

Decamethonium

A

Depolarising blocker of adult Nm

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10
Q

Trimetaphan

A

Competitive antagonist of ganglionic nAChRs

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11
Q

Hexamethoniun

A

Use-dependent antagonist of ganglionic nAChRs. It is therefore likely to cause an open channel block. This action shortens the duration of current flow because the open channel either becomes occluded or closes

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12
Q

Suxamethonium

A

Depolarising muscle relaxant (hydrolysed by plasma cholinesterase)

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13
Q

d-tubocurarine

A

Non-depolarising blocking agent of No, but poor selectivity between ganglionic and NMJ types of nAChRs. Induces histamine release from mast cells causing transient hypotension

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14
Q

Atracurium

A

Non-depolarising blocking agent at NMJ. Quaternary ammonium compound so poorly absorbed. Induced histamine release so causes transient hypotension. Unstable at physiology pH and so spontaneously breaks down in plasma

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15
Q

Pancuronium

A

Non-depolarising blocking agent at NMJ. Inhibits muscarinic receptors and this induces mild tachycardia

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16
Q

Nicotine

A

nAChR agonist. Stimulates them blocks autonomic ganglia. Stimulates CNS. tertiary amine

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17
Q

Varenicline

A

Partial agonist for Nn nAChR. Stimulate some dopamine release in mesolimbic dopaminergic pathway, helping to alleviate some nicotine withdrawal symptoms. Full agonist on (alpha7)5 receptor

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18
Q

Carbachol (carbamylcholine), Bethanechol

A

Muscarinic agonist - choline ester. Longer duration of action the ACh

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19
Q

Pilocarpine

A

Muscarinic agonist - naturally occurring cholinomimetic alkaloid. Longer duration of action that ACh as stable to hydrolysis by AChE. Treat glaucoma - contracts ciliary muscle to produce traction on the trabecular meshworkbaround the Schlemm canal causing an immediate drop in intraoccular pressure as a result of increased drainage of aqueous humour. Rapid miosis

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20
Q

Cevimeline

A

M3 selective agonist used to increase salivation and lacrimation (Sjögren’s syndrome)

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21
Q

Atropine

A

Antimuscarinic agent. Pupil dilation

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22
Q

Ipratropium

A

Semisynthetic derivative of atropine. Antimuscarinic agent

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23
Q

Pirenzepine

A

Synthetic antimuscarinic agent. M1 selective

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24
Q

Darifenacin

A

Synthetic antimuscarinic agent. Selective inhibition of m3 receptors that mediate contraction of detrusor muscle - treatment of urinary incontinence

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25
Tropicamide
Short acting antimuscarinic agent. Pupil dilation
26
Edrophonium
Non covalent short acting inhibitory of AChE. Quaternary ammonium compound. Binds to catalytic anionic site of the enzyme. Used to diagnose myasthenia gravis.
27
Donepezil
Prevent binding of beta-amyloid protein to the PAS of AChE and inhibit it’s catalytic activity. Also has inhibitory effect on protein aggregation.
28
Neostigmine
Covalent reversible inhibitor of AChE and binds to and activates nAChR at the NMJ. intermediate acting. Interact with anionic site of AChE slowing down its hydrolysation. Treat myasthenia gravis
29
Rivastigmine
Carbamic acid ester. Uncharged so can act centrally - useful in mild to moderate dementia associated with AD and Parkinson’s
30
Dyflos
Irreversible inhibitor of AChE - organophosphate. Glaucoma
31
Ecothiophate
Irreversible inhibitor of AChE - organophosphate. Glaucoma
32
Pralidoxime
Reactivate AChE after poisoning by irreversible anticholinesterases - brings oxime group into close proximity with phosphorylated serine, causing phosphate to transfer to oxime freeing the serine hydroxyl group
33
Alpha-methyltyrosine
Competitive inhibitor of tyrosine hydroxylase
34
L-DOPA
Product of TOH that readily reaches the CNS and so is used to boost DA synthesis in the Parkinsonian brain
35
Carbidopa
Cannot cross the bbb but inhibits the peripheral decarboxylase of of L-DOPA to ensure DA synthesis occurs predominantly in CNS where it is needed
36
Disulfiram
Treat alcohol abuse by inhibiting aldehyde dehydrogenase which causes actetaldehyde to buildup when alcohol is imbibed. Used experimentally to inhibit DBH. chelates copper ion, an essential cofactor to the enzyme, or attacks sulphurhandling system for the methyl donor, s-adenosyl methionine
37
Methyldopa
Converted into alpha-methyl NA, a false transmitter less active at a1 receptors and more active at a2 receptors - less constriction following sympathetic nerve stimulation
38
Clonidine
Selective alpha2 adrenoceptor agonist. Antihypertensive drug. Binds to imidazoline receptors. Helps to ameliorate some adverse sympathetic actions during drug withdrawal in addicts
39
Reserpine
Naturally occurring alkaloid. Binds to amine binding site of VMAT2 blocking uptake and causing long lasting depletion of stored NA since the vesicles allow leakage of stored amine into cytoplasm where it is metabolised by presynaptic MAO
40
Guanethidine
Direct blocking of adrenergic neurons by preventing NA release. Selectively accumulate in adrenergic neurons by NET and compete with NA. It’s vesicular release upon sympathetic stimulation does not elicit a post synaptic response
41
Ephedrine
Indirectly acting sympatheticomimetic capable of releasing stored transmitter from noradrenergic nerves by ca independent process. Poor agonist at adrenoceptors but excellent substrate for NET. avidly taken up into noradrenergic nerve ending and into vesicles by VMAT in exchange for NA, which is subsequently expelled into synaptic space. Nasal decongestant
42
Cocaine
Blocks NET (Na+ dependent)
43
Imipramine
Blocks NET. Tricyclic antidepressant
44
Phenoxybenzamine
Irreversible alpha-adrenoceptor blocking agent. Inhibits ENT
45
Moclobemide
Selective MAO-A inhibitor used in depression
46
Trancylopromine
Non-selective MAO inhibitor
47
Entacapone
COMT inhibitor. Used in Parkinson’s disease in combination with L-DOPA and carbidopa - reduces metabolism of L-DOPA in the periphery
48
Xylometazoline
Alpha adrenoceptor selective agent but with poor selectivity between the subtypes. Typically used to relieve nasal congestion by causing vasoconstriction in nasal mucosa
49
Phenylephrine
Selective a1 agonist. Nasal decongestant. Treat acute hypotension
50
Xylazine
Selective a2 agonist. Veterinary use as sedative.
51
Dobutamine
B1 adrenoceptor agonist. Increase cardiac output in cases of cardiogenic shock
52
Salbutamol
Short acting selecting b1 agonist. Bronchodilator action in asthma
53
Salmeterol
Long lasting b2 agonist used prophylactically in chronic asthma. COPD treatment
54
Indacaterol
Ultra long lasting b2 agonist. COPD treatment
55
Mirabegron
B3 agonist. Relaxes detrusor muscle and increases bladder capacity. Treat overactive bladder. Promotes lipolysis - obesity treatment?
56
Labetalol
Mixed a1/b adrenoceptor agonist. A1 receptor blockade results in vasodilation. B1 blockades prevents reflex sympathetic tachycardia. Decreased blood pressure. Treat hypertension associated with pregnancy.
57
Carvedilol
Mixed a1/b adrenoceptor agonist. A1 receptor blockade results in vasodilation. B1 blockades prevents reflex sympathetic tachycardia. Decrease in blood pressure.
58
Prazosin
Selective and competitive a1 adrenoceptor antagonist. Decrease vascular resistance and lower blood pressure via relaxation of both arterial and venous smooth muscle. No reflex tachycardia
59
Tamsulosin
Selective a1a adrenoceptor agonist. Allows better bladder emptying this reduce urinary retention associated with benign prostatic hypertrophy
60
Yohimbine
Selective a2 adrenoceptor antagonist
61
Propranolol
Non selective b blocker. Treat hypertension through decreased cardiac output and inhibition of renin secretion
62
Atenolol
Selective b1 adrenoceptor antagonist
63
Nevivolol
Selective b1 adrenoceptor antagonist. One of its metabolites is a b3 adrenoceptor agonist which mediates increased NO production and vasodilation - treat hypertension. Treat angina and cardiac dysrythmias
64
Suramin
ATP antagonist
65
Dipyridamole
Nucleoside transporter antagonist which indirectly increases the concentration of extracellular adenosine
66
Caffeine
Competitive antagonist of A1 receptors
67
Methotrexate
Increase extracellular adenosine

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