Cholinergic Receptors and Agents Acting at the Neuromuscular Junction (Jose Paciano Reyes, MD) Flashcards by Charles Herrera

T/F: Choline entering a neuron via carrier-mediated transport is a rate-limiting step.

True

How well did you know this?

Not at all

Perfectly

Acetylcholine is released into the neuromuscular junction through what mechanism?

Ca2+-mediated exocytosis

How well did you know this?

Not at all

Perfectly

What is the rate of degradation of Ach in fast cholinergic synapses?

Less than or equal to 1 ms

How well did you know this?

Not at all

Perfectly

T/F: Transmission mediated by nicotinic receptors is slower compared to muscarinic receptors.

False

It’s the other way around!

How well did you know this?

Not at all

Perfectly

(1) is an antagonist to the nicotinic receptor, while (2) is an antagonist to the muscarinic receptor.

(1) Curare

(2) atropine

How well did you know this?

Not at all

Perfectly

Where are nicotinic Ach receptors located?

Ganglia (blocked by hexamethonium)
CNS
NMJ (blocked by tubocurarine)

How well did you know this?

Not at all

Perfectly

Where are muscarinic Ach receptors located?

M1 - gastric parietal cells
M2 - cardiac & smooth muscle cells
M3 - exocrine glands and smooth muscles

How well did you know this?

Not at all

Perfectly

T/F: Nicotinic cholinergic receptors mediate fast EPSPs.

True

How well did you know this?

Not at all

Perfectly

What are the two types of nicotinic Ach receptor?

Neuromuscular and ganglional (8 subtypes of alpha and 4 subtypes of beta)

How well did you know this?

Not at all

Perfectly

Enumerate the agonists of the neuromuscular nicotinic Ach receptor

Ach
Carbamylcholine (Cch)
Suxamethonium
Decamethonium

How well did you know this?

Not at all

Perfectly

Enumerate the agonists of the ganglional nicotinic Ach receptor

Ach
Carbamylcholine (Cch)
Nicotine
Lobeline
Cystisine
Epibatidine
DMPP

How well did you know this?

Not at all

Perfectly

Enumerate the antagonists of the neuromuscular nicotinic Ach receptor

Tubocurarine
Pancuronium
Atacurium
Vecuronium
alpha-bungarotoxin

How well did you know this?

Not at all

Perfectly

Enumerate the antagonists of the ganglional nicotinic Ach receptor

Trimetaphan
Mecamyline
Hexamethonium

How well did you know this?

Not at all

Perfectly

Describe the action of alpha-bungarotoxin

It blocks postsynaptic nicotinic receptors

How well did you know this?

Not at all

Perfectly

Describe the action of beta-bungarotoxin

It blocks the presynaptic release of neurotransmitters (similar to botox)

How well did you know this?

Not at all

Perfectly

Which cytoplasmic loop in the muscarinic Ach receptor is linked to the G protein?

3rd

How well did you know this?

Not at all

Perfectly

T/F: Organophosphates are medium-acting, carbamates are long-acting and edrophoniums are very short-acting drug

False

Organophosphate - long-acting
Carbamates - medium-acting

How well did you know this?

Not at all

Perfectly

Enumerate the types of indirect-acting cholinomimetic drugs

Edrophonium
Carbamates
Organophosphates

How well did you know this?

Not at all

Perfectly

Enumerate the types of direct-acting muscarinic cholinomimetic drugs

Choline esters

Alkaloids

How well did you know this?

Not at all

Perfectly

T/F: Choline esters are relatively insoluble in lipids and contain a quaternary ammonium group.

True

How well did you know this?

Not at all

Perfectly

What are the only choline esters given orally

Betanechol and methacholine

This is due to the presence of a beta-methyl group (reduces potency at nicotinic receptor).

How well did you know this?

Not at all

Perfectly

What are examples of choline esters?

Acetylcholine
Methacholine
Carbachol
Bethanecol (given to patients w/ incontinence)

How well did you know this?

Not at all

Perfectly

What are examples of alkaloids?

Pilocarpine
Nicotine
Lobeline

These are tertiary amines of plant origin.

How well did you know this?

Not at all

Perfectly

T/F: Muscarine, a quaternary amine, is less completely absorbed from the GI tract.

True

How well did you know this?

Not at all

Perfectly

Alkaloids are chiefly excreted in the (1), enhanced with (2) of the urine.

(1) kidney | (2) acidification

What is the duration of action of Ach?

5 - 30 seconds

What are the spectra of action of the different cholinomimetic drugs?

``` Ach - both Bethanecol - M Carbachol - B Pilocarpine - N Nicotine - N Varenicline - N ```

What drug is used for glaucoma as eye drops and has a duration of action of 30 mins to 2 hours?

Pilocarpine

What is the duration of action of nicotine?

1 - 6 hours

T/F: Varenicline is a partila agonist with a duration of 12 - 24 hours

True

What is given to patients to reduce longing for nicotine?

Varenicline

What mediates the dilation of arteries and veins?

EDRF

What drug blocks the overdose of cholinomimetic drugs that normally leads to diarrhoea?

Loperamide

Brain has more (1) receptors, while the spinal cord has more (2) receptors.

(1) muscarinic | (2) nicotinic

Describe the effect of nicotine on the CVS, GI and GU.

CVS - sympathetic | GI and GU - parasympathetic

Which has a broader substrate specificity - acetylcholinesterase or buterylcholinesterase?

Buterylcholinesterase

What drug is used to diagnose myasthenia gravis?

Edrophonium (quaternary alcohol)

What is the duration of action of edrophonium?

10 minutes (very short-acting)

Enumerate the medium-duration anticholinesterases

Neostigmine Pyridostigmine Physostigmine These are carbamic acid esters of alcohol

T/F: Medium-duration anticholinesterases are maintenance drugs for myasthenia gravis and IV forms reverse neuromuscular block.

True

For which class of compounds does this phrase apply? "The longer the bonds stay, the stronger they get."

Organophosphates

What class of compounds permanently binds to and deactivates acetylcholinesterase?

Organophosphates

What are the signs of organophosphate toxicity?

Salivation and seizures

Organophosphates can cause a severe type of (1)

(1) peripheral nerve demyelination

Give an example of a cholinesterase regenerator

Pralidoxime

What is the mechanism of action of pralidoxime?

Splits phosphorus-enzyme bond and is most effective before ageing has occurred

What is a drug of choice for suicide?

Malathion

What are examples of long-acting cholinesterase inhibitors?

Dyfios Ecothiopate Parathion

For the GI tract, anticholinesterases are used if there is (1)

(1) postoperative ileus

Cholinesterase inhibitors may be used for the treatment of (1) and overdose of (2)

(1) atropine toxicity | (2) tricyclic antidepressants

What drugs are used for postoperative ileus?

Bethanechol | Neostigmine

What drugs are used to treat glaucoma?

Carbachol Pilocarpine Physostigmine Echothiaphate

What drugs are used to treat symptoms of myasthenia gravis?

Neostigmine Pyridostigmine Edrophonium

What are the symptoms of toxicity of indirect acting agents?

``` Diarrhea Urination Myosis Bronchoconstriction Excitation Lacrimation Salivation ```

What drugs are used in the treatment of Alzheimer's disease and dementia?

Rivastigmine, galantamine and donepezil These are centrally-acting cholinesterase inhibitors.

T/F: Ganglion stimulants are used as experimental tools and not as clinical treatments.

True

Enumerate the effects of ganglion stimulants

Tachycardia Increased BP Bronchial, salivary and sweat secretions

Give examples of ganglion stimulants

Nicotine Lobeline Dimethylphenylpiperazinium

Give an example of a cholinesterase regenerator

Oximes (pralidoxime)

Give examples of anti nicotinic classes of drugs

Ganglion blockers | Neuromuscular blockers

Give examples of anti muscarinic classes of drugs

M1-selective (pirenzepine) | Non-selective (atropine)

Where is atropine derived from?

``` Atropa belladona (deadly nightshade) Datura stramonium (jimsonweed) ```

Where is scopolamine derived from?

Hyoscyanius niger (henbane)

Atropine and scopolamine are classified as what?

Natural alkaloids

Give examples of tertiary ammonium cholinergic receptor blockers.

Pirenzipine | Tropicamide

Give examples of quaternary ammonium cholinergic receptor blockers.

Ipratropium | Benztropine

T/F: Many antihistamine and antidepressant drugs have similar structures to tertiary ammonium analogs.

True

Enumerate the different tissues that are sensitive to atropine and their level of sensitivity to it.

Most sensitive - salivary, bronchial and sweat glands Intermediate sensitivity - smooth muscles and cardiac tissue Least sensitive - gastric parietal cells

T/F: Atropine is highly selective for muscarinic receptors.

True

What anticholinergic compounds are less specific and may have ganglion-blocking actions?

Synthetic anti-muscarinic drugs (e.g. quaternary ammonium's)

What anticholinergic compounds are well absorbed by the gut?

Natural alkaloids and tertiary ammonium's

What is the antidote for organophosphate poisoning?

Atropine

What are the symptoms of atropine toxicity?

``` Blind as a bat (cyclopegia) Dry as a bone (decreased sweating) Red as a beet (thermoregulation) Mad as a hatter (hallucinations) Hot as hell (fever) ```

Enumerate the different presynaptic cholinergic inhibitors

``` Hemicholinium Triethylcholine Vesamicol Botulinum toxin Beta-bungarotoxin Aminoglycoside antibiotics ```

Enumerate the sites of action of the different presynaptic cholinergic inhibitors

``` Hemicholinium - reuptake Triethylcholine - synthesis Vesamicol - storage Botulinum - release (ganglion blocker) Beta-bungarotoxin - release Aminoglycoside antibiotics - release ```

What is the active ingredient of beta-bungarotoxin?

Phospholipase

Enumerate the ganglion-blocking drugs that interfere with acetylcholine release

Botulinum toxin Hemicholinum Mg2+

What is given to patients with preeclampsia to prevent seizures and hypertension?

Magnesium ion

What ganglion-blocking drug causes prolonged depolarisation?

Nicotine

Enumerate the ganglion-blocking drugs that interfere with postsynaptic action of acetylcholine

Hexamethonium Trimetaphan Tubocurarine

What are the manifestations of ganglionic blockage?

``` Loss of CV reflexes Inhibition of secretions GI paralysis Impaired micturition Hypotension ```

What secondary ammonium compound can enter the CNS and cause sedation, tremor, etc.?

Mecamylamine

T/F: Hexamethonium has no clinical use.

True

What is trimetaphan used for?

Blood pressure lowering

Differentiate hexamethonium from decamethonium.

Hexamethonium is a ganglionic blocker | Decamethonium is a neuromuscular blocker

When are neuromuscular blockers used?

1. Surgery to decrease dose of anaesthetic 2. Paralysis for intubation 3. Muscle spasm control

What is the mechanism of action of strychnine?

Blocks glycine and GABA in spinal cord

What are the two classifications under neuromuscular-blocking drugs?

Non-depolarizing | Depolarizing

What prototype non-depolarising drug prevents access of Ach to its receptors by competitive inhibition?

Tubocurarine

What is the mechanism of action of the non-depolarising drugs?

1. Act mainly at nicotinic receptor sites | 2. May block pre-junctional Na+ channels

Non-depolarizing drugs may induce (1) while (2)

Motor paralysis | Conscious and aware of pain

What is the sequence of motor paralysis by non-depolarising drugs?

Extrinsic eye muscles Small facial muscles Limbs and pharynx Respiratory muscles

Enumerate the unwanted effects of non-depolarising drugs

Tubocurarine - fall in arterial BP and histamine release Vecuronium - less ganglion block and release of histamine Gallamine/pancuronium - Tachycardia (M receptor block in heart)

Describe depolarizing drugs

They are agonists at acetylcholine receptor.

What are the two phases in the mechanism of action of depolarising drugs?

Phase 1: Depolarizing block (fasciculations) | Phase 2: Desensitizing

T/F: Phase 1 block is augmented by cholinesterase inhibitors

True

What are the effects of tetanic stimulation, cholinesterase inhibitors and increased Ach on the block?

Tetanic stimulation - relieve Cholinesterase inhibitors - reverse Increased Ach - reverse

What are the unwanted effects of depolarising drugs?

``` Bradycardia (prevented by atropine) Potassium release Increased intraocular pressure Prolong paralysis Malignant hyperthermia Postoperative muscle pain ```

What do you use to treat patients with malignant hyperthermia?

Dantrolene

Are Down Syndrome patients at greater risk if they are given succinylcholine?

Yes

Cholinergic Receptors and Agents Acting at the Neuromuscular Junction (Jose Paciano Reyes, MD) Flashcards

(100 cards)