03a: Cholinergic Drugs Flashcards by Nuna H

Parasympathetic preganglionic fiber releases (X) messenger to bind (Y) receptor at synapse.

X = ACh
Y = nicotinic

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Sympathetic preganglionic fiber releases (X) messenger to bind (Y) receptor at synapse.

X = ACh
Y = nicotinic

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Parasympathetic post-gang fibers release (X) messenger to bind (Y) receptor on heart muscle.

X = ACh
Y = muscarinic

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Sympathetics oppose parasymp action on heart by releasing (X) messenger to bind (Y) receptor on (Z) cells.

X = NE
Y = beta1
Z = myocardium

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Sympathetics oppose parasymp action on GI tract by releasing (X) messenger to bind (Y) receptor on (Z) cells.

X = NE
Y = alpha2
Z = post-gang parasymp neuron (terminal)

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Parasympathetic post-gang fibers release (X) messenger to bind (Y) receptor to increase GI motility.

X = ACh
Y = muscarinic

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(Symp/parasymp) responsible for pupil dilation, aka (X).

Symp;

X = mydriasis

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Predominant tone tends to be (parasymp/symp). List the key exceptions.

Parasymp;

Blood vessels
Sweat glands

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(Cholinergics/adrenergics) responsible for predominant tone of salivary glands.

Cholinergics (parasymp)

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(Cholinergics/adrenergics) responsible for predominant tone of blood vessels.

Adrenergics (symp)

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(Cholinergics/adrenergics) responsible for predominant tone of sweat glands.

Cholinergics (but sympathetic NS!)

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Iris radial muscle innervated by (symp/parasymp) and has (X) receptor.

Symp;

X = a1

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(Symp/parasymp) relaxes bronchiolar smooth muscle. And (Symp/parasymp) contracts it. Which receptors involved?

Symp (beta2);

Parasymp (muscarinic - M2, M3)

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Nicotinic receptor is a(n) (X)-gated (transporter/channel/ATPase). It transports (Y).

X = ligand;
Ion channel;

Y = Na, K, Ca

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T/F: Nicotinic receptor is an excitatory receptor.

True

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List the agonists of the nicotinic receptor. Star the muscle relaxant(s).

Nicotine
ACh
Carbamoylcholine
Succinylcholine*

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List the antagonists of the nicotinic receptor. Star the muscle relaxant(s).

Hexamethonium
Tubocurarine*
Atracurium*

(only have to know Tubocurarine)

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ACh (does/doesn’t) penetrate cell membranes because of its structure as a(n) (X).

Doesn’t;

X = quaternary amine

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ACh rapidly inactivated by (X) at which location(s)?

X = AChE (at synapse) and esterases (in blood)

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(X), like ACh, is a quaternary amine and activates both N and M receptors. What’s a key difference between ACh and this agonist?

X = carbamylcholine

It’s an esterase-resistant analog of ACh

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(X) is a nicotinic agonist that’s CNS-penetrating due to its structure as a(n) (Y).

X = nicotine
Y = tertiary amine

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Acute nicotine toxicity typically occurs via (X) route in children and (Y) route in adults.

X = ingestion
Y = dermal contact (i.e. tobacco workers)

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Acute nicotine toxicity: rapid onset of which symptoms initially?

Abd pain, nausea, diarrhea
Disturbed vision, confusion
Weakness

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T/F: Acute nicotine toxicity manifests in the respective symptoms due to overstimulated parasymp.

False - stimulates both parasymp and symp

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Acute nicotine toxicity: central stimulation, in severe poisoning, will present with which symptoms?

Convulsions, coma, respiratory arrest

Acute nicotine toxicity: in severe poisoning, (tremors/paralysis) occurs via which mechanism(s)?

Paralysis; 1. Na channel inactivation 2. Desensitization of nicotinic receptors

List the treatment methods for acute nicotine toxicity.

1. Activated charcoal (reduce GI absorption) 2. Benzos (control seizures) 3. IV fluids (increase/maintain BP) 4. Atropine (if needed for bradycardia)

NMJ (neuromuscular junction) blocking agents have which general goal of action? What might these be used for?

Block ACh action at NMJ 1. Tracheal intubation 2. Set fractures 3. Surgical muscle relaxant

Neuromuscular (NMJ) blocking agents can fall into which categories? State which type of inhibition is found in each.

1. Depolarizing (non-competitive) | 2. Non-depolarizing (competitive)

Tubocurarine is an example of (X) drug. What's its mechanism?

X = muscle relaxant (non-depolarizing neuromuscular blocker) Competitive inhibition of ACh binding to nicotinic receptors at skeletal muscle endplate

When approximately (X)% of tubocurarine is bound, it is effective in (stimulating/preventing) (Y). What would this look like clinically?

X = 70 Preventing; Y = ACh evoking muscle contraction Flaccid paralysis of all skeletal muscle

AChE inhibitors (assist/oppose) action of tubocurarine. How?When might these be used?

Opposes; increase endogenous ACh Post-surgically to speed recovery

Succinylcholine is an example of (X) drug. What's its mechanism?

X = muscle relaxant (depolarizing neuromuscular blocker) Bind nicotinic receptor (AGONIST) and evokes desensitization

T/F: Effect of Succinylcholine cannot be reversed without synapse regeneration.

False - desensitized receptor can gradually reset (quick recovery) once agonist dissociates

T/F: Succinylcholine is esterase-resistant.

False - rapidly hydrolyzed by plasma cholinesterase

AChE inhibitors (assist/oppose) action of Succinylcholine. How?

Assist; | Increase endogenous ACh and further desensitize nicotinic receptors

List the stages of block by neuromuscular depolarizing agents, such as (X).

X = Succinylcholine 1. Fasciculation 2. Phase I (depolarizing) 3. Phase II (desensitizing)

T/F: Block by neuromuscular depolarizing agents prevents muscle from repolarizing at all.

False - in Phase II, muscle repolarizes (channels are closed), but continues to exhibit flaccid paralysis

Toxicity of nondepolarizing neuromuscular blocking agents, such as (X) involves:

X = tubocurarine Histamine release (allergic rxn)

Toxicity of depolarizing neuromuscular blocking agents, such as (X) involves:

X = succinylcholine 1. Malignant hyperthermia 2. Hyperkalemia 3. Cardiac dysrhythmias 4. Post-op muscle pain

Malignant hyperthermia can be the result of a toxic dose of (X). This is prolonged in patients with (low/high) levels of which enzyme?

X = succinylcholine Low; plasma cholinesterase

(Low/high) levels of which ion are responsible for malignant hyperthermia?

High; Ca

Toxicity via (X) neuromuscular blocking agent can result in (hyper/hypo)-kalemia via which mechanism?

X = succinylcholine Hyperkalemia; Excess K release through nicotinic receptor channels

(X) falls into the class of denervating neurotoxins. It binds specifically to (Y) terminals.

``` X = botulinum toxin Y = cholinergic nerve ```

T/F: Botulinum toxin has prolonged action (months).

True

T/F: Nerve terminals can recover within minutes to hours of removal of botulinum toxin.

False - only via axonal sprouting

List some adverse effects of botulinum toxin.

1. Muscle weakness (potentially long-lasting) | 2. Paralysis of respiratory muscles (can result in death)

T/F: Although botulinum toxin has been FDA approved for certain uses, a 2008 FDA warning was issued for some cases of resp failure/death.

True

T/F: there is no treatment for toxicity by botulism.

False - antitoxin exists (but doesn't reverse toxicity in nerve terminal)

Muscarinic receptor is a(n) (X) (transporter/channel/ATPase).

X = GPCR

List the subtypes of muscarinic receptors and the respective 2nd messenger pathways associated with each.

1. M1, 3, 5: Increase PLC activity (and thus DAG, IP3) | 2. M2, 4: Decrease cAMP (thus increase K and decrease Ca channel activation)

List the muscarinic receptor agonists and star those that also bind nicotinic receptors (non-selective).

1. ACh* 2. Carbamoylcholine* 3. Muscarine 4. Pilocarpine 5. Bethanchol (don't need to know)

List the clinical uses of ACh.

NONE! No clinical use

Pilocarpine is a(n) (X) class drug with some selectivity for (Y) tissues/organs. How is it used clinically?

``` X = muscarinic agonist (parasympathomimetic) Y = salivary glands ``` 1. Orally (treat xerostomia) 2. Topically (treat glaucoma)

List clinical presentation of muscarinic agonist toxicity.

1. Salivation 2. Lacrimation 3. Urination 4. Diarrhea 5. GI distress 6. Emesis (vomiting) (Plus bronchoconstriction, hypothension, bradycardia)

Belladonna alkaloids are (X) agents/drugs. List some examples.

X = anti-muscarinic 1. Atropine 2. Scopolamine

Anti-muscarinic agent would be used to treat (diarrhea/constipation) and (under/over)-active bladder.

Diarrhea; over-active

Muscarinic (agonist/antagonist) used to reduce HR, by preventing vagal stimulation, during MI.

Antagonist

Muscarinic (agonist/antagonist) used to treat AChE inhibitor poisoning.

Antagonist

Clinical presentation of muscarinic antagonist toxicity.

1. Dry as a bone 2. Hot as a pistol 3. Red as a beet 4. Blind as a bat 5. Mad as a hatter

Treatment for patient presenting with muscarinic antagonist toxicity.

AChE inhibitor (physostigmine)

List some conditions for which AChE inhibitors can serve as treatment.

1. AD 2. Myasthenia Gravis 3. Post-surg paralytic ileus 4. Urinary bladder atony

List some conditions for which AChE inhibitors can serve as treatment.

1. AD 2. Myasthenia Gravis 3. Post-surg paralytic ileus 4. Urinary bladder atony

List the major classes of AChE inhibitors. What's the primary difference between them? Star the one used clinically.

1. Alcohols 2. Carbamate esters* 3. Organophosphates Duration of action

List the major classes of AChE inhibitors. What's the primary difference between them?

1. Alcohols 2. Carbamate esters 3. Organophosphates Duration of action

T/F: Alcohols are rapidly reversible competitive inhibitors of AChE.

True

MOA of carbamate esters: form (reversible/irreversible) (X) bond that lasts on the order of (sec/min/hours/days).

Reversible; X = covalent Hours (about 1-6)

MOA of organophosphates: form (reversible/irreversible) (X) bond that lasts on the order of (sec/min/hours/days).

Irreversible X = phosphate Forever...

MOA of organophosphates: form (reversible/irreversible) (X) bond that lasts on the order of (sec/min/hours/days).

Irreversible X = phosphate Forever...

Sarin (nerve gas) poisoning likely due to (X) class of compounds. How might the individual present, clinically?

X = organophosphates (AChE inhibitors) 1. SLUDGE (muscarinic toxicity) 2. Neuromuscular block 3. Resp failure 4. Confusion, coma, convulsions

Sarin (nerve gas) poisoning likely due to (X) class of compounds. How might the individual present, clinically?

X = organophosphates (AChE inhibitors) 1. SLUDGE (muscarinic toxicity) 2. Neuromuscular block 3. Resp failure 4. Confusion, coma, convulsions

AChE inhibitor overdose/toxicity typically treated with (X). What's the MOA?

X = Atropine Blocks action at muscarinic (NOT NICOTINIC) receptors

(X) is known as "cholinesterase regenerator" and is, in a way, better than atropine for treating (Y) toxicity. Why?

``` X = Pralidoxime Y = AChE inhibitor (organophosphates) ``` Affects N and M receptor responses by binding organophosphates and causing them to release AChE (restores its function)