Pharm: Autonomic Drugs Flashcards
Botulinum toxin inhibits which particular SNARE protein?
T SNARE, synaptobrevin
What is the neurotransmitter at the sympathetic postganglionic neurons to the thermoregulatory sweat glands?
Acetylcholine
What 2 organs have Ach at their post ganglionic sympathetic synapse?
Thermoregulatory eccrine sweat glands AND vasodilatory sympathetic nerve fibers in the skeletal muscle.
Which transporter transports norepinephrine and dopamine into vesicles where they are stored? Which inhibits these transporters?
Vesicular monoamine transporter
Reserpine
This drug blocks release of norepinephrine from vesicles
Guanethidine
These drugs promote catecholamine release
Amphetamines
Release of renin is stimulated by action of catecholamines on which receptors.
Beta 1
Which 2 direct acting cholinomimetics are useful for BOTH muscarinic and nicotinic receptors?
Acetylcholine and carbachol
Which is a muscarinic cholinomimetic that has GOOD lipid solubility?
ONLY Pilocarpine.
Acetylcholine carbs hop and bethenachol all fulfill the the criteria EXCEPT for lipid solubility.
What is an example of an M1 selective anti muscarinic?
Pirenzipine ad tirenzipine
Which adrenergic receptor is found in the liver?
Beta 2. Increase with glycogenolysis
Where is the dopamine 1 receptor located and what is its function?
Smooth muscle.
Relax renal vascular smooth muscle
Is the myenteric plexus activated or inhibited by the parasympathetic system? On which receptors does acetylcholine act on?
Activates.
M1
What is the action of the SNS on:
- Pilomotor smooth muscles
- Thermoregulatory sweat glands
- Apocrine (sweat) glands
- Contracts (alpha)
- Activates (M; acetylcholine)
- Activates (alpha)
Acts on nerve terminal Ca channels and prevent transmitter release
Conotoxin
Inhibit uptake of adrenergic neurotransmitter a prolonging effect on postsynaptic receptors
Cocaine
TCA
What is the predominant autonomic tone in the:
- Heart
- Blood vessels
- Parasympathetic
2. Sympathetic
Which inhibits breakdown of adrenergic neurotransmitters at the nerve terminal?
Monoamine oxidase
Tranylcypromine
Nicotinic agonist with partial agonist properties; reduces craving in persons addicted to nicotine
Varenicline
This cholinesterase inhibitor is exclusively used in Alzheimer’s disease
Rivastigmine
Name two organophosphates used in medicine and their indications
Malathion - scabicide
Metrifonate - antihelminthic
How does edrophonium differentiate between myasthenic crisis and cholinergic crisis?
Improves strength in myasthenic crisis; weakens it in cholinergic crisis
T/F. Atropine, the antidote in organophosphate poisoning, effectively decreases nicotinic signs of toxicity.
False. Atropine acts on muscarinic receptors. Nicotinic toxicity is treated by regenerating active cholinesterase.
Direct acting muscarinic agonist used in bladder and bowel atony
Bethanechol
Nicotinic receptor agonist used for muscle relaxation. With prolonged action in px with abnormal butylcholinesterase
Succinylcholine
What inhibits the rate limiting step in adrenergic transmission using NE?
Metyrosine. The conversion of TYR to Dopa accomplished by tyrosine hydroxylase is the rate limiting step.
Give the noradrenergic system equivalent of: Hemicholinium, vesamicol and botulinum
Metyrosine, reserpine and guanethedine
Rate limiting step in the synthesis of acetylcholine.
Which experimental drug inhibits this step?
Transport of choline into the nerve terminal.
Hemicholinium
This drug inhibits transport of acetylcholine into vesicles by vesicle-associated transporter.
Vesamicol
Most dangerous effect of atropine toxicity in children
“Atropine fever”
Blockade of thermoregulatory sweating
Nicotinic ganglion blocker that enters the CNS and has shown benefit in smoking cessation and amelioration of Tourette’s syndrome
Mecamylamine
Nonselectice anti muscarinic drug used in incontinence and urinary urgency
Oxybutynin
Anti-muscarinic used in motion sickness
Scopolamine
Anti muscarinic drug used in COPD
Tiotropium
Platelets have which type of adrenergic receptor. Activation of this receptor would lead to which action.
Alpha-2
Platelet aggregation
This drug of abuse promotes release of adrenergic neurotransmitters while another drug of abuse prevents its reuptake
Amphetamine promotes release
Cocaine prevents reuptake
Name 2 alpha-2 selective antagonists
Yohimbine
Rauwolscine
Name 2 non selective alpha blockers
Phenoxybenzamine
Phentolamine
These beta blockers are in fact partial agonists and in theory may be beneficial in patients with asthma.
Pindolol
Acebutolol
Pwede sa Asthma (Pindolol, Acebutolol)
What is the longest acting beta blocker?
Nadolol
Besides its use in pheochromocytoma what conditions may also be remedied by phenoxybenzamine?
Carcinoid and mastocytosis
Nonselective beta blockers lacking anesthetic action; useful in glaucoma
Timolol
Betaxolol
What is the effect of sympathetic stimulation on insulin function
Alpha 2 activation leads to inhibition of insulin release
Beta 2 activations leads to insulin release
Beta 3 receptors are found on which cells? Activation leads to __
Fat cells
Lipolysis
Clonidine is sometimes given in hypertension. What is its mechanism of action?
It is an alpha 2 agonist, accumulates in the CNS and reduce sympathetic outflow and BP.
What drug do you use for pheochromocytoma patients preoperatively? During surgery?
Phenoxybenzamine used pre-op; with long duration of action (24-48h).
Phentolamine used during surgery.
Indications for use of phenoxybenzamine
Pheochromocytoma
Carcinoid
Mastocytosis
Raynaud’s Phenomenon
Name b1-selective beta blockers.
Atenolol
Esmolol
Metoprolol
Beta blocker used for perioperative and thyroid storm arrhythmia and hypertensive emergencies
Esmolol
Name 2 drugs that block both alpha and beta receptors
Labetalol
Carvedilol
Both with mortality benefit in heart failure.
Name one b2-selective blocker.
Butoxamine
This drug is used in Cushing’s disease and reduces catecholamine levels by inhibiting tyrosine hydroxylase.
Metyrosine
Peripheral dopamine hydroxylase inhibitor given along with L-DOPA in the treatment of Parkinson’s disease
Carbidopa
This local anesthetic impairs reuptake of catecholamine transmitters.
Cocaine
Differentiate hemicholinium from hexamethonium.
Hemicholinium - inhibit transport of choline into cholinergic nerve endings
Hexamethonium - research drug that blocks all ANS ganglia
T/F. Vagal stimulation and administration of cholinomimetic agents cause bradycardia.
False!
Vagal stimulation causes bradycardia. Cholinomimetic agents, on the other hand, cause vasodilation (by releasing EDRF) and subsequent reflex tachycardia.
3/M eats a mushroom and experiences nausea, vomiting and diarrhea. What is responsible for this reaction?
Muscarine and alkaloids in certain mushrooms cause muscarinic toxicity
Only a few organosphosphates are used in medicine:
- Antihelminthic agent
- Scabicide
- Metrifonate
2. Malathion
Atropine is used for muscarinic toxicity. What is the antidote for nictonitic toxicity?
Pralidoxime inhibits anticholinesterase inhibitors; and are effective in both muscarinic and nicotinic toxicity.
Indirect acting cholinomimetics
- Reversal of severe atropine poisoning
- Alzheimer’s disease
- Treatment of MG
- Physostigmine
PHysostigmine PHixes atropine toxicity. - Rivastigmine, galantamine, donepezil
- Pyridostigmine
Many muscarine antagonists are nonselective except ____ which is selective for M1. What is a current indication for its use?
Pirenzepine.
Peptic ulcer
Two smoking cessation agents act on cholinergic transmission.
- Partial muscarinic agonist
- Nicotinic ganglion blocker
- Varenicline
2. Mecamylamine
This ganglion-blocking drug may ameliorate symptoms of Tourette’s syndrome.
Mecamylamine
Which antimuscarinic is indicated in the following conditions:
- COPD
- Motion sickness
- Ophthalmic use to produce mydriasis
- Incontinence
- Tiotropium, ipratropium
- Scopolamine
- Atropine, homatropine, cyclotropine, tropicamide
(EYE’M At Home when the Cyclone hit the Tropics) - Oxybutinin
Explain how the different autonomic drug classes can help reduce IOP in glaucoma.
- Beta blocker
- A2-agonist
- Muscarinic agonist
- Anticholinesterase inhibitor
- Alpha nonselective
1 and 2 decrease aqueous humor production (“turn the tap off”). Examples include timolol and carteolol (beta blockers); and brimonidine and apraclonidine (a2-agonist).
3 and 4 increase outflow of aqueous humor (“unclog the drain”) by contracting the ciliary muscle and pulling on the trabecular meshwork. Examples include pilocarpine and carbachol (cholinomimetic) and physostigmine (AChe inhibitor.)
5 increases aqueous outflow via uveoscleral veins
Clonidine decreases the blood pressure. T/F.
Not always!
IV/intranasal clonidine increases BP.
Activation of the following beta hormones increase release of which hormones.
- Beta 1
- Beta 2
- Renin
2. Insulin
Autonomic drug used in the treatment of attention deficit disorder
Methylphenidate
Amphetamine analog
The effects of all alpha-antagonists except this drug can be surmounted by increased concentration of agonist.
Phenoxybenzamine
Produces an irreversible block
What is epinephrine reversal? This effect is not seen with phenylephrine or norepinephrine. Why?
Epinephrine reversal describes the reversal of BP effect of large doses of epinephrine from a pressor response (alpha) to a depressor response (beta 2); after administration of an alpha blocker. This is NOT seen with phenylephrine or norepinephrine because these drugs lack sufficient B2 effects.
This alpha-2 selective blocker is used in the treatment of depression.
Mirtazapine
This beta two agonist is used to reduce premature uterine contractions. It acts on which receptor subtype.
Ritodrine
B2-selective blocker
Guanethedine becomes inactive because this drug inhibits its transport into nerve terminals.
TCA / cocaine
