03a: Cholinergic Drugs Flashcards
Parasympathetic preganglionic fiber releases (X) messenger to bind (Y) receptor at synapse.
X = ACh Y = nicotinic
Sympathetic preganglionic fiber releases (X) messenger to bind (Y) receptor at synapse.
X = ACh Y = nicotinic
Parasympathetic post-gang fibers release (X) messenger to bind (Y) receptor on heart muscle.
X = ACh Y = muscarinic
Sympathetics oppose parasymp action on heart by releasing (X) messenger to bind (Y) receptor on (Z) cells.
X = NE Y = beta1 Z = myocardium
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)
Parasympathetic post-gang fibers release (X) messenger to bind (Y) receptor to increase GI motility.
X = ACh Y = muscarinic
(Symp/parasymp) responsible for pupil dilation, aka (X).
Symp;
X = mydriasis
Predominant tone tends to be (parasymp/symp). List the key exceptions.
Parasymp;
- Blood vessels
- Sweat glands
(Cholinergics/adrenergics) responsible for predominant tone of salivary glands.
Cholinergics (parasymp)
(Cholinergics/adrenergics) responsible for predominant tone of blood vessels.
Adrenergics (symp)
(Cholinergics/adrenergics) responsible for predominant tone of sweat glands.
Cholinergics (but sympathetic NS!)
Iris radial muscle innervated by (symp/parasymp) and has (X) receptor.
Symp;
X = a1
(Symp/parasymp) relaxes bronchiolar smooth muscle. And (Symp/parasymp) contracts it. Which receptors involved?
Symp (beta2);
Parasymp (muscarinic - M2, M3)
Nicotinic receptor is a(n) (X)-gated (transporter/channel/ATPase). It transports (Y).
X = ligand;
Ion channel;
Y = Na, K, Ca
T/F: Nicotinic receptor is an excitatory receptor.
True
List the agonists of the nicotinic receptor. Star the muscle relaxant(s).
- Nicotine
- ACh
- Carbamoylcholine
- Succinylcholine*
List the antagonists of the nicotinic receptor. Star the muscle relaxant(s).
- Hexamethonium
- Tubocurarine*
- Atracurium*
(only have to know Tubocurarine)
ACh (does/doesn’t) penetrate cell membranes because of its structure as a(n) (X).
Doesn’t;
X = quaternary amine
ACh rapidly inactivated by (X) at which location(s)?
X = AChE (at synapse) and esterases (in blood)
(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
(X) is a nicotinic agonist that’s CNS-penetrating due to its structure as a(n) (Y).
X = nicotine Y = tertiary amine
Acute nicotine toxicity typically occurs via (X) route in children and (Y) route in adults.
X = ingestion Y = dermal contact (i.e. tobacco workers)
Acute nicotine toxicity: rapid onset of which symptoms initially?
- Abd pain, nausea, diarrhea
- Disturbed vision, confusion
- Weakness
T/F: Acute nicotine toxicity manifests in the respective symptoms due to overstimulated parasymp.
False - stimulates both parasymp and symp
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;
- Na channel inactivation
- Desensitization of nicotinic receptors
List the treatment methods for acute nicotine toxicity.
- Activated charcoal (reduce GI absorption)
- Benzos (control seizures)
- IV fluids (increase/maintain BP)
- 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
- Tracheal intubation
- Set fractures
- Surgical muscle relaxant
Neuromuscular (NMJ) blocking agents can fall into which categories? State which type of inhibition is found in each.
- 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
- Fasciculation
- Phase I (depolarizing)
- 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
- Malignant hyperthermia
- Hyperkalemia
- Cardiac dysrhythmias
- 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.
- 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.
- 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).
- ACh*
- Carbamoylcholine*
- Muscarine
- Pilocarpine
- 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
- Orally (treat xerostomia)
- Topically (treat glaucoma)
List clinical presentation of muscarinic agonist toxicity.
- Salivation
- Lacrimation
- Urination
- Diarrhea
- GI distress
- Emesis (vomiting)
(Plus bronchoconstriction, hypothension, bradycardia)
Belladonna alkaloids are (X) agents/drugs. List some examples.
X = anti-muscarinic
- Atropine
- 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.
- Dry as a bone
- Hot as a pistol
- Red as a beet
- Blind as a bat
- 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.
- AD
- Myasthenia Gravis
- Post-surg paralytic ileus
- Urinary bladder atony
List some conditions for which AChE inhibitors can serve as treatment.
- AD
- Myasthenia Gravis
- Post-surg paralytic ileus
- Urinary bladder atony
List the major classes of AChE inhibitors. What’s the primary difference between them? Star the one used clinically.
- Alcohols
- Carbamate esters*
- Organophosphates
Duration of action
List the major classes of AChE inhibitors. What’s the primary difference between them?
- Alcohols
- Carbamate esters
- 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)
- SLUDGE (muscarinic toxicity)
- Neuromuscular block
- Resp failure
- Confusion, coma, convulsions
Sarin (nerve gas) poisoning likely due to (X) class of compounds. How might the individual present, clinically?
X = organophosphates (AChE inhibitors)
- SLUDGE (muscarinic toxicity)
- Neuromuscular block
- Resp failure
- 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)
