Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
101 Cards in this Set
- Front
- Back
Uninnervated receptors
|
muscarinic on vascular endothelium
|
|
Adrenoceptor
|
A receptor that binds one of the catecholamine neurotransmitters (norepi, epi, dopamine)
|
|
Homeostatic reflex
|
A compensatory mechanism for maintaining a body function at a predetermined level. eg. baroreceptor reflex
|
|
Primary PBT nerve receptor for dopamine
|
Located in the kidney, sympathetic D1 receptor
|
|
Rate-limiting step in ACH synthesis
|
Transport of choline into the nerve terminal
|
|
Choline transport inhibitor
|
Hemicholinum
|
|
Name of transporter responsible for packing ACH into small dense vesicles? Inhibition?
|
The VAT H+ antiporter, inhibited by the research drug vesamicol.
|
|
Cholinergic VAT inhibitor
|
Vesamicol
|
|
Vesicle-associated proteins that respond to influx of Ca at nerve terminal?
|
Synaptobrevin, synaptotagmin
|
|
Nerve-ending membrane associated proteins that release vesicular contents?
|
SNAP25, syntaxin, etc.
|
|
Effect of botulinum toxin
|
Prevent neurotransmitter release via altering synaptobrevin and other docking/fusion proteins in cholinergic neurons
|
|
Effect of dopamine on renal smooth muscle
|
Vasodilation. Important treatment in shock that results in oliguria.
|
|
Rate limiting step in catecholamine synthesis
|
Conversion of Tyrosine to L-DOPA via tyrosine hydroxylase
|
|
Inhibitor of tyrosine hydroxylase
|
Metyrosine
|
|
Role of MAO in adrenergic nerve endings
|
Inactivates a small portion of newly synthesized catecholamine neurotransmitters, resulting in less stored.
|
|
Inhibition of adrenergic vesicular transport?
|
Reserpine
|
|
Inhibition of adrenergic docking/fusion proteins?
|
Guanethidine
|
|
Inhibition of catecholamine reuptake?
|
Cocaine and tricyclic antidepressants
|
|
Does metabolism stop the effect of adrenergic neurotransmitters?
|
No, only reuptake does.
|
|
Metabolism of catecholamines outside the synaptic cleft?
|
MAO and COMT
|
|
How many subtypes of muscarinic receptors are there?
|
5, only 3 are truly important in peripheral autonomic transmission
|
|
How many subtypes of nicotinic receptors are there?
|
2, M and N referring to muscular and neuronic, respectively.
|
|
M1 receptors: location/mechanism/function
|
Nerve endings/Gq/IP3 and DAG cascade
|
|
M2 receptors: location/mechanism/function
|
Heart/Gi/decrease cAMP and open potassium channels
|
|
M3 receptors: location/mechanism/function
|
Smooth, glands, endo/Gq/IP3 and DAG cascade
|
|
Major function of nicotinic receptors
|
depolarization and activation of the action potential
|
|
Which system dominates the pupil and the SA node? Therefore, what will happen if you remove all autonomic input?
|
Parasympathetic.
Mydriasis and tachycardia |
|
alpha-1 receptors: location/mechanism/function
|
Smooth, glands/Gq/contraction and secretion
|
|
alpha-2 receptors: location/mechanism/function
|
Nerve endings, smooth/Gi/contraction, decrease of neurotransmitter release
|
|
Beta-1 receptors: location/mechanism/function
|
Cardiac muscle, juxtaglomerular/Gs/increase heart rate, increase contractile force, increase renin release
|
|
Beta-2 receptors: location/mechanism/function
|
Smooth, liver, heart/Gs/relax smooth muscle, increase glycogenolysis, increase heart rate, force
|
|
Beta-3 receptors: location/mechanism/function
|
Adipose tissue/Gs/increase lipolysis
|
|
Effect of dopamine on renal smooth muscle?
|
Relaxation via Gs receptor
|
|
Feedback of norepi on itself? How?
|
Negative, prohibitory. Alpha-2 receptors on the pre-synaptic nerve membrane (I said pre-synaptic, not pre-ganglionic)
|
|
Sym effects on eye
|
Contraction of radial muscle: distance accomodation/mydriasis, alpha-1 receptor. Relaxation via non-select B receptor.
|
|
Parasym effects on eye
|
Contraction of circular muscle: miosis, near accomodation, M3 receptor. Contraction of ciliary muscle, M3 receptor.
|
|
Sym effects on heart
|
SA: Increase, B1B2
Ectopic pacemaker: Increase, B1B2 Contractility: Increase. B1B2 |
|
Parasym effects on heart
|
SA: Decrease, M2
Contractility: Atrial decrease, M2 |
|
Is there parasympathetic innervation to the blood vessels?
|
No.
|
|
Sym effects on vasculature
|
Skin: contract, A
Skeletal: ?? relax, B2 contract, A |
|
Sym effects on bronchiolar smooth?
|
Relax via B2
|
|
Parasym effects on bronchiolar smooth?
|
Contract via M3
|
|
Sym effects on GI?
|
Inhibition of secretion via A2. Sphincter contraction via A1. Relaxation of walls via parasym override on A2 and B2
|
|
Parasym effects on GI? (digest)
|
Wall contraction, sphincter relaxation, increased secretion via M3. M1 receptors in Meissner's plexuses are activated.
|
|
Sym effects on GU?
|
Bladder relax via B2. Sphincter contraction via A1. Pregnant uterus relaxes via B2 or contracts via A. Ejaculation via A.
|
|
Parasym effects on GU?
|
Bladder contracts, Sphincter opens, uterine contractions all via M3. Erection via M.
|
|
Is there parasympathetic innervation to the skin?
|
Nope
|
|
Sym effects on skin
|
Pilomotor contraction via A. Thermoregulatory sweat via M. Stress sweat via A.
|
|
Sym effects on metabolism
|
Gluconeogenesis/glycolysis via B2, A. Lipolysis via B3. Renin release via B1.
|
|
Local anaesthetic effects on nerves
|
Bind to axons, block Na and conduction
|
|
Effect of amphetamine family on adrenergic nerve terminals?
|
Promote transmitter release
|
|
Effect of black widow spider bite on transmitter release? (YIKES)
|
Explosive release
|
|
Effect of 6-hydroxydopamine on transmitter uptake?
|
Destroys synaptic terminals
|
|
Norepi
|
Alpha receptor agonist
|
|
Phentolamine
|
Alpha receptor antagonist
|
|
Isoproterenol
|
Beta receptor agonist
|
|
Propranolol
|
Beta receptor antagonist
|
|
Nicotine
|
Nicotinic receptor agonist
|
|
Tubocurarine
|
Nm receptor antagonist
|
|
Bethanechol
|
Muscarinic receptor agonist
|
|
Atropine
|
Muscarinic receptor antagonist
|
|
Effect of neostigmine on acetylcholinesterase
|
Inhibition, prolongs ACH action and intensity.
|
|
Effect of tranylcypromine on MAO
|
Inhibition, increases stored catecholamine neurotransmitters
|
|
What is metanephrine?
|
A metabolite of epinephrine created by COMT. A high presence in plasma indicates a pheochromocytoma, or adrenal tumor.
|
|
Do sympathetic neurotransmitters block the release of parasym neurotransmitters? Vice versa?
|
Yes. Yes. This is heteroreceptor mediated feedback.
|
|
Hydralazine
|
Vasodilator. Used in the treatment of hypertension.
|
|
Homeostatic effect of baroreceptors
|
Modulation of heart rate (brady/tachycardia)
|
|
Homeostatic effect of renin-angiotensin system?
|
Regulation of salt-water retention/release. And that's probably the worst oversimplification I've ever been guilty of.
|
|
Outline of cholinomimetic drugs (drugs that either mimic cholinergic ligands or stop the destruction of cholinergic ligands)
|
1. Direct
a. Muscarinic i. Choline esters ii. Alkaloids b. Nicotinic 2. Indirect a. Edrophonium (short) b. Carbamates (medium) c. Organophosphates (long) |
|
Prototype for a direct-acting cholinomimetic? Indirect?
|
ACH. Neostigmine.
|
|
Characteristic choline esters
|
ACh, Methacholine, Carbachol, Bethanechol.
|
|
Characteristic alkaloids
|
Muscarine, pilocarpine, nicotine, lobeline
|
|
Why is an indirect-cholinomimetic called that?
|
Because it inhibits acetylcholinesterase, thus potentiating ACh effects indirectly.
|
|
Organophosphate aging
|
After organophosphate binding to (and inhibition of) cholinesterase, the compond will age, becoming more covalent and harder to displace
|
|
Where are botulinum receptors for endocytosis located?
|
On the membrane of cholinergic neurons, but not adrenergic
|
|
Which muscarinic receptors use Gq?
|
M1 and M3
|
|
Which muscarinic receptor uses Gi?
|
M2, downregulating cAMP via the alpha subunit, while opening K channels via the beta-gamma subunit
|
|
Pharmacokinetics of bethanechol and carbachol
|
Muscarinic agonist, acts for 30min-2hr. Carbachol is identical but it also works on nicotinic receptors.
|
|
Can edrophonium or neostigmine cross the BBB?
|
No, they have quaternary ammonium groups, rendering them totally lipid insoluble
|
|
What is the problem with using physostigmine as a treatment for myasthenia gravis (block ACHesterase)
|
It is lipid soluble, able to cross the BBB, and causes unpleasant, frequent CNS side effects.
|
|
The most dangerous organophosphate
|
Parathion
|
|
What happens when you inject someone with muscarinic cholinomimetics?
|
Relaxation of blood vessels, BUT, resultant drop in blood pressure activates sympathetic discharge to heart via baroreceptors, results in tachycardia (not expected response) If there was a true parasym discharge to the heart, the result would be bradycardia. Additionally, the thermoregulatory sweat glands (muscarinic receptors!) will activate.
|
|
Effect of nicotinic drugs on vasculature (Blood vessels are dominated by sympathetic control)
|
Vasoconstriction due to stimulation of nicotinic receptors at ganglionic synapse (remember both parasym and sym have nicotinic receptors at ganglion)
|
|
Effect of nicotinic drugs on gut (GI is dominated by parasym control)
|
Motility and secretion increase due to parasym nerve endings firing. (remember both parasym and sym have nicotinic receptors at ganglion)
|
|
Effects of cholinomimetics on the bronchi?
|
Bronchocontriction
|
|
Do we use nicotinic agonists clinically?
|
No, they are way too non-specific
|
|
Use of bethanechol
|
Postop/neurogen intestinal or urinary retention to activate bowel movement and voiding
|
|
Use of pilocarpine
|
Topical treatment of glaucoma and stimulation of salivation
|
|
Use of neostigmine (indirect-acting cholinomimetics in general)
|
Treatment of myasthenia gravis, antidote to neuromuscular blocks
|
|
Use of topical physostigmine
|
Treatment of glaucoma
|
|
Use of malathion (organophosphate)
|
Kill scabies, lice, etc.
|
|
Use of metrifonate (organophosphate)
|
Kill helminths
|
|
Use of edrophonium
|
Rapid treatment of depolarizing neuromuscular blockade, differential of myasthenia verses cholinergic crisis--it will strengthen myasthenia patients and weaken those suffering from cholinergic crisis
|
|
Use of succinylcholine
|
Paralysis via nondepolarizing neuromuscular block, because it cannot be degraded by acetylcholinesterase
|
|
Outline of Anticholinergic Drugs
|
1. Antimuscarinic
a. M1-selective b. non-selective 2. Antinicotinic a. ganglion blockers b. Neuromuscular blockers |
|
Requirement for eye/CNS muscarinic blockers
|
Lipid solubility
|
|
Prototype of nonselective muscarinic blocker. Characteristics?
|
Atropine. Alkaloid, tertiary amine, good lipid solubility, 2hr half life
|
|
Atropine fever/flush
|
Sweating caused by muscarinic inhibition, cutaneous vasodilation
|
|
Cycloplegia
|
Paralysis of accomodation
|
|
Depolarizing blockage vs. nondepolarizing blockade
|
Skeletal paralysis caused by persistent depolarization of end plate vs. blockade of the nicotinic endplate receptor
|
|
Are muscarinic blocking agents competitive or irreversible antagonists?
|
Competitive
|