Autonomic Pharmacology Flashcards
Symptoms of excess parasympathetic activity?
Diarrhea Urinary retention Miosis / ciliary muscle contraction Bradycardia BronchoSPASM Excitation (muscles and CNS) Lacrimation Salivation Sweating
Parasympathetic inhibition is aka ______ or ______ inhibition. Symptoms of parasympathetic inhibition?
Parasympathetic = muscarinic inhib, or anti-cholinergic. Sx =
Hot as a hare
Dry as a bone
Red as a beet
Blind as a bat (cycloplegia, mydriasis)
Mad as a hatter
Bloated as a toad (urinary retention & constipation)
Effect of anti-muscarinics on heart rate?
Inhibition of vagal tone = tachycardia
Three anti-muscarinic drugs used topically for pupillary dilation:
Homatropine
Tropicamide
Cyclopent.
Atropine is used mainly for (2):
Treatment of bradycardia
As an antidote to organophosphate poisoning (organophosphates inhibit AChE, too much ACh, need to switch parasympathetics off).
This drug is helpful in Parkinson’s and in tx of EPS from antipsychotic use:
Benztropine
Antimuscarinic used in tx of motion sickness:
Scopolamine
Antimuscarinic for COPD and asthma (2):
Ipratropium
Tiotropium
Antimuscarinics used to help increase urinary retention in urge incontinence (5):
Oxybutynin Tolterodine Darifenacin Solifenacin Trospium
This antimuscarinic drug helps decrease oral secretions in intubated patients. What is its other main use?
Scopolamine
Also used for motion sickness
This drug helps decrease oral secretions when given parenterally:
Glycopyrrolate
Physostigmine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-cholinesterase
Pilocarpine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Direct cholinergic agonist
Oxybutynin: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Atropine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Direct cholinergic agonist
Donepezil: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-cholinesterase
Pralidoxime: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Trick question!
Cholinesterase RE-GENERATOR.
Bethanecol: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Direct cholinergic agonist
Neostigmine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-cholinesterase
Darifenacin: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Ipratropium: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Tropicamide: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Benztropine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Scopolamine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Edrophonium: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-cholinesterase
Tolterodine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Trospium: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Rivastigmine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-cholinesterase
Homatropine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-muscarinic
Pyridostigmine: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Anti-cholinesterase
Carbachol: Direct cholinergic agonist, anticholinesterase, or anti-muscarinic?
Direct cholinergic agonist
Where does botulinum toxin act?
Botulinum toxin inhibits release of ACh from presynaptic nerve terminals causing paralysis.
The neurotransmitter of choice for all pre-ganglionic synapses:
ACh
Receptor type found in all autonomic ganglia:
Nicotinic
The adrenal medulla is innervated by what arm of the autonomic nervous system?
Sympathetic, but the fibers are cholinergic
Where are nicotinic receptors found? What kind of receptor are they?
All autonomic ganglia are nicotinic.
These are ligand-gated Na+ channels
What kind of receptor are muscarinic receptors?
G-protein coupled.
Where are muscarinic receptors found?
Parasympathetic post-ganglionic target organs
Sympathetic sweat glands
Direct cholinergic agonist used to treat post-operative ileus and urinary retention:
Bethanechol
Direct cholinergic agonist used in treatment of acute closure glaucoma:
Carbachol
This drug is a direct cholinergic agonist and is used to stimulate sweat / tears / saliva secretion.
Pilocarpine
Which direct cholinergic agent is resistant to AChE?
Pilocarpine
This anti-cholinesterase penetrates the BBB.
These do not:
Physostigmine Passes the BBB.
NeOstigmine (NO), Pyridostigmine = pyridNOstigmine do NOT cross the BBB
Drug used in treatment of atropine OD:
Physostigmine (“phyxes” it)
Drug used in diagnosis of myasthenia gravis (generic and brand names):
Echothiophate = Tensilon
Drug used in treatment of myasthenia gravis, has a long half life. T/F: This drug crosses the BBB.
Pyridostigmine, does not cross the BBB.
What kind of drug is echothiophate? What is it used for?
AChE inhibitor, used in glaucoma.
Mechanism of action of organophosphate poisoning? Antidote?
Organophosphates = irreversible AChE inhibitors. Give atropine to antagonize parasympathetics, give pralidoxime to regenerate AChE.
Anti-cholinesterases FDA approved for Alzheimer disease (3):
Donepezil
Rivastigmine
Galantamine
Three topical drugs used to induce mydriasis:
Homotropine
Tropicamide
Cyclopent
This drug is used to treat EPS and is helpful in Parkinson disease:
Benztropine
Name 3 huge medication classes with anti-cholinergic effects:
H1 blockers (diphenhydramine, doxylamine, chlorpheniramine)
Neuroleptics
TCAs
Amantadine
5 anti-muscarinics used to treat urge incontinence:
Oxybutynin
Tolteridine
Darifenacin / Solifenacin
Trospium
The synthesis of catecholamines starts with this molecule:
Phenylalanine
The enzyme that converts phenylalanine to tyrosine is:
Deficiency of this enzyme causes what disease?
Phenylalanine hydroxylase.
PKU = defective phenylalanine hydroxylase
Tyrosine is converted to dopa with this enzyme. Where did the tyrosine come from?
Tyrosine hydroxylase. Tyrosine was made from phenylalanine.
Dopa is converted to dopamine by this enzyme. What drug inhibits this conversion?
Dopa decarboxylase is the enzyme,
Carbidopa inhibits the conversion
In the synthesis of catecholamines, where is vitamin B6 required? What about vitamin C?
Vitamin B6 is needed for dopa -> dopamine.
Vitamin C is needed for dopamine -> NE.
The conversion of NE to Epi requires this co-factor:
SAM
The enzyme that converts NE to Epi? This hormone encourages this conversion. Co-factor required?
Phenylalanine N-methyltransferase. Cortisol helps NE -> Epi. SAM is needed.
Where does melanin come from?
Dopa
Which vitamin is needed to make dopamine?
B6
Which vitamin is needed to make NE?
Vitamin C
Sympathetic receptor for vascular smooth muscle contraction:
a1
Sympathetic receptor responsible for decreased sympathetic outflow. This is coupled to which G protein?
a2, Gi coupled
Sympathetic receptor that modulates heart rate and contractility:
b1
Sympathetic receptor that bronchodilates and vasodilates:
b2
Gq coupled receptors include:
q-C HAV 1M&M:
H1, a1, V1
M1, M3
Gi coupled receptors include:
MAD 2’s
M2, a2, D2
The second messenger for Gq coupled receptor:
Which protein kinase is associated with the Gq cascade?
Phospholipase C -> PIP2 -> DAG / IP3
Protein kinase C
Gs and Gi are coupled to this molecule:
Adenylyl cyclase
Protein kinase for Gs and Gi?
Protein kinase for Gq?
Gs and Gi are protein kinase A,
Gq is protein kinase C
M1 parasympathetic receptors are found mostly in this organ system:
Gut
M2 parasympathetic receptors are found mainly in the:
Heart
Parasympathetic receptor whose activation causes everything to leak:
M3
Receptor activation relaxes renal vascular smooth muscle:
D1
Three autoreceptors on noradrenergic terminals:
a2, m2, AT2
Two drugs that block the release of NE from nerve terminals:
Guanethidine
Bretylium
Three drugs that encourage NE release:
Amphetamines
Tyramine
Ephedrine
Two drugs that block NE reuptake
Cocaine
TCAs
Drug that blocks the uptake of choline into a nerve terminal:
Hemicholinium
Drug that keeps ACh from being packaged into vesicles:
Vesamicol
What is the mechanism of action of black widow toxin? What kind of paralysis does this cause?
Black widow toxin encourages release of all ACh from nerve terminals, causes spastic paralysis.
Botox causes what kind of paralysis, what mechanism?
Flaccid, it prevents ACh from being released.
Main effect of a1 adrenergic receptor stimulation:
Vascular smooth muscle contraction.
Main effect of a2 receptor stimulation is:
Modulatory. Most a2 receptors are autoreceptors, main outcome of stimulation is to turn down sympathetic tone.
b1 receptors are found mainly in this organ. What is the overall effect of activating them?
b1 are in the heart mostly, get an increase in myocardial contractility, heart rate, and conduction through the AV node.
b2 receptors have two huge effects when activated:
Bronchodilation, vasodilation.
Stimulation of this receptor relaxes renal vascular smooth muscle:
D1
Activation of this sympathetic receptor decreases insulin release. A different one increases insulin release, what is it?
a2 decreases insulin, b2 increases insulin release.
Sympathetic receptor that mediates mydriasis:
a1
Sympathetic receptor that blocks NE release:
a2
Sympathetic receptor that mediates bronchodilation:
b2
Sympathetic receptor that causes increase in cardiac contractility:
b1
Sympathetic receptor that mediates bladder muscle contraction:
a1
Sympathetic receptor that increases renin:
b1
Sympathetic receptor that decreases uterine tone:
b2
Sympathetic receptors (2) that increase lipolysis:
b1, b2
Sympathetic receptor that vasodilates:
b2
Activation of this sympathetic receptor causes an increase in peripheral resistance. Another causes a decrease in PR.
a1, b2.
Drug that has a1, a2, b1, and b2 activity.
Epi
Drug of choice for anaphylactic shock:
Epi
Drug of choice for cardiogenic shock:
Why?
Dobutamine
Has b1 activity mostly, is an inotrope and chronotrope.
Drug of choice in septic shock:
Receptors:
What is the big risk of using this drug in someone with shock?
NE
a1 and a2 activity w/o much b2.
Decreases renal perfusion.
Drug with a1 and a2 specificity:
NE
Drug with b1 and b2 specificity:
Isoproterenol
Drug that acts at a1 > a2 receptors:
Phenylephrine
Drugs with mainly b2 > b1 activity:
Albuterol, salmetrol, terbutaline
Drug that works almost purely at b2 receptors:
Ritodrine
Receptors stimulated by phenylephrine:
a1, a2
Receptors stimulated by NE
a1, a2, some b1
Receptors stimulated by isoproterenol:
b1, b2
Dobutamine stimulates:
b1 mostly
This drug causes short QT and can make bradyarrhythmias worse:
Isoproterenol
This drug is used in cardiac stress testing:
Dobutamine
This drug reduces premature uterine contractions:
Ritodrine
Name 3 indirect sympathomimetics:
Which is also a reuptake inhibitor?
Amphetamines
Ephedrine
Cocaine *
What is a sympathoplegic? Can you name 2? What are these drugs used for?
An a2 adrenergic agonist. Clonidine, a-methyldopa. Used in malignant HTN.
Name 2 non-selective a-blockers:
Which is irreversible?
Phenoxybenzamine *
Phentolamine
You give this drug to people with a pheo before you try to remove their tumor:
Phenoxybenzamine
Sympathetic blockers ending in -osin tend to block this receptor:
a1
Prazosin, terazosin, doxazosin, and tamulosin are used to treat…
HTN and urinary retention
Prazosin, terazosin, doxazosin, and tamulosin act to block this receptor:
a1
Mirtazapine blocks what sympathetic receptor?
a2
Name 3 non-selective b-blockers:
Propranolol, timolol, nadolol
Two drugs that block both a1 and b1:
These drugs overall have what effect on the heart?
Carvedilol, labetalol.
Decrease work of the heart – a1 stimulation tends to drop PR, b1 stimulation drops HR and contractility.
4 b1-selective blockers:
Metoprolol
Atenolol
Esmolol
Nebivolol
Two drugs that are weak b1 / b2 agonists and therefore act as b-blockers:
These drugs are particularly useful in what scenario?
Acebutolol, pindolol
Useful in people w/ HTN and bradycardia: b1 stimulation helps maintain HR at the same time as b2 stimulation drops the BP
Receptor stimulated by this sympathomimetic:
Clonidine
a2
Receptor stimulated by this sympathomimetic:
Dopamine
d1&2, b2, b1, a2, a1 as dose increases progressively
Receptor stimulated by this sympathomimetic:
Phenylephrine
a1 > a2
Receptor stimulated by this sympathomimetic:
Albuterol
b2 (some b1)
Receptor stimulated by this sympathomimetic:
NE
a1, a2, b1
Receptor stimulated by this sympathomimetic:
Isoproterenol
b1, b2
Receptor stimulated by this sympathomimetic:
Epi
a1, a2, b1, b2
Receptor stimulated by this sympathomimetic:
Dobutamine
b1
Receptor stimulated by this sympathomimetic:
Terbutaline
b2 (some b1)
This drug is used to halt premature labor:
Terbutaline