Peripheral Neuropharmacology and Acetycholine Agonists Flashcards by David Sisa Gangai

Muscarinic receptors - MoA

Stimulation leads to activation of G proteins which increase or decrease formation of second messengers

How well did you know this?

Not at all

Perfectly

Which muscarinic receptors are coupled with Gq proteins, and what happens when they are activated?

M1, M3 and M5. Stimulates Phospholipase C –> Formation of IP3 and diacylglycerol (DAG)

How well did you know this?

Not at all

Perfectly

Which muscarinic receptors are coupled with Galpha,i proteins, and what happens when they are activated?

M2 and M4. Decreases cAMP levels by inhibiting adenylate cyclase and increases potassium efflux.

How well did you know this?

Not at all

Perfectly

Effects of M2 and M3

Mioisis, accomodation, lacrimation, mucus secretion, salivation, bronchoconstriction, increased hydrochloric acid secretion, increased motility

How well did you know this?

Not at all

Perfectly

Effects of M2

Decreased AV conduction and decreased HR

How well did you know this?

Not at all

Perfectly

Effects of M3

Micturation, erection,

Contracion of smooth muscles and stimulation of glandular secretions. Vasodilation

How well did you know this?

Not at all

Perfectly

M1 - Location and MoA

Neural (autonomic ganglia, presynaptic nerve terminals and CNS).
Stimulates Phospholipase C –> Increases formation of IP3 and diacylglycerol (DAG)

How well did you know this?

Not at all

Perfectly

Effects of M1

Modulation of neurotransmission

How well did you know this?

Not at all

Perfectly

M2 - Location and MoA

Cardiac tissue (SA and AV node)
Decreases cAMP levels by inhibiting adenylate cyclase and increases potassium efflux.

How well did you know this?

Not at all

Perfectly

M3 - Location and MoA

Glandular, found in smooth muscle and glands + vascular smooth muscle
Increases IP3 and cGMP as a result of NO stimulation

How well did you know this?

Not at all

Perfectly

Nicotinic receptors - Location (type) + MoA

Muscle type (somatic neuromuscular junctions)
Ganglionic type (autonomic ganglia)
CNS type
Activation leads to sodium influx and membrane depolarization --> release of Ca from sarcoplasmic reticulum --> muscle contraction

How well did you know this?

Not at all

Perfectly

Muscle type nicotonic receptor - Effects

Muscle contracion

How well did you know this?

Not at all

Perfectly

Ganglionic and CNS type nicotinc receptor - Effects

Excitation of neurons

How well did you know this?

Not at all

Perfectly

Direct-Acting Acetylcholine receptor agonists - Groups + synthetic drugs

Choline esters
Plant alkaloids
Cevimeline
Varenicline

How well did you know this?

Not at all

Perfectly

Choline esters

Acethylcholine
Carbachol
Bethanecol

How well did you know this?

Not at all

Perfectly

Choline esters - Effects

Ocular: Increased lacrimal gland secretion. Stimulates contraction of iris sphincter muscle (miosis) and ciliary muscles (accommodations of lens to focus close objects).

Respiratory: Increased bronchial muscle contraction and mucus secretion.

Cardiac: Decreased impulse formation in SA node by decreasing rate of diastolic depolarization –> slow the heart rate. Slow conduction of cardiac action potential through AV node –> increased PR interval

Vascular: vasodilation(M3 receptor), formation of NO

GI and UT: stimulate salivary, gastric secretion. Increased contraction of GI smooth muscle(Except sphincters) by stim ENS in gut wall –> Increased GI motility.
Stimulate bladder detrusor muscle, promotes emptying of the bladder.

How well did you know this?

Not at all

Perfectly

What can high doses of choline esters lead to?

Excessive salvation, diarrhea, intestinal cramps and urinary incontinence.

How well did you know this?

Not at all

Perfectly

Which choline esters activate both muscarinic and nicotinic receptors?

Acetylcholine and Carbachol

How well did you know this?

Not at all

Perfectly

What is the name of the choline ester that selectively activates muscarinic receptors?

Bethanecol

How well did you know this?

Not at all

Perfectly

Acetylcholine - Indication

Miosis during ophthalmic surgery
Diagnostic coronary angiography
Diagnose vasospastic angina pectoris

How well did you know this?

Not at all

Perfectly

Carbachol - Indication

Miosis during ophthalmic surgery

How well did you know this?

Not at all

Perfectly

Bethanecol - Indication

GI and urinary stimulation. Postop or postpartum to increase bladder muscle tone in pt with nonobstructive neurogenic urinary retention after anesthetics.
Postop adynamic ileus
Atonic stomach (gastroparesis)
Congenital megacolon

How well did you know this?

Not at all

Perfectly

Bethanecol - Contraindication

IV adm –>leads to hypotension and bradycardia

Obstruction, BPH, PUD, COPD, Ischemic heart disease, Hyperthyroidsm, Parkinson

How well did you know this?

Not at all

Perfectly

Plant alkaloids

Muscarine
Nicotine
Pilocarpine

How well did you know this?

Not at all

Perfectly

Where is muscarine found and what is its adverse effects?

Found in toxic mushrooms. | Diarrhea, sweating, salivation and lacrimation

Nicotine - Indication

Smoking cessation programs

Pilocarpine - MoA

Greater affinity for muscarinic receptor

Pilocarpine - Indication

2nd line drug for chronic open angle glaucoma and acute angle closure glaucoma (by lowering intraocular pressure) Xerostomia (by stimulating salivary gland secretion)

Pilocarpine - Adverse effects

Decreased night vision (caused by miosis) Difficulty focusing on distal objects (lens accommodates for close vision) Seizures CNS damage

Cevimeline - MoA

Selectively activates M3 receptors

Cevimeline - Indication

Xerostomia in pt who have had radiation therapy for head/neck cancer Pt with sjögren syndrome

Cevimeline - Adverse effects and Contraindication

Increased sweating, Nausea, Visual disturbances Used cautiously in pt with asthma or cardiac arrhythmias

Varenicline - MoA

Partial agonist at the nicotinic receptor subtype found in the brain that mediates reinforcing effects of nicotine in smokers

Varenicline - Indication

Smoking cessation

Indirect-acting acetylcholine receptor agonist - MoA

Affect neurotransmitter synthesis, storage, release or metabolism

Edrophonium - MoA

Inhibits cholinesterase, preventing the breakdown of acetylcholine at all cholinergic synapses --> rapidly increases acetylcholine concentration

Edrophonium - Indication

Diagnosis of Myasthenia Gravis Distinguish between myasthenia crisis and cholinergic crisis in pt treated with cholinesterase inhibitors Anesthesia (reverse effect of neuromuscular blockade)

Physostigmine, Neostigmine and Pyridostigmine - MoA

Inh acetylcholinesterase which is responsible for the degradation of acetylcholine

Physostigmine - Indication

Myasthenia gravis Reverse seizures and other CNS effects antimuscarinic drugs Stimulate bladder and bowel Overdose of atropine, phenothiazine, tricyclic antidepressants

Neostigmine - Indication

``` Myasthenia gravis Lambert-Eaton syndrome Diplopia Blurred vision Postop urinary retention and abdominal distention Tubocurarine toxicity Stimulate bowel and bladder ```

Neostigmine and Pyridostigmine - Adverse effects

In case of too high dose: increased muscle weakness due to neuromuscular blockade resulting from excessive ACh

Which drugs are used during surgery to reverse the effect of curariform when muscle relaxation is no longer required?

Edrophonium Neostigmine Pyridostigmine

Pyridostigmine - Indication

Myasthenia gravis (chronic) Diplopia Blurred vision

Which drugs are used for Alzheimer disease?

Donepezil Galantamine Rivastigmine

Donepezil, Galantamine, Rivastigmine - MoA

Crosses the blood brain barrier and act to increase the concentration of Ach at central cholinergic synapses

Echothiophate, Isoflurophate, Malathion - MoA

Irreversible acetylcholinesterase inh.

Echothiophate - Indication

Pesticide Chronic glaucoma Stabismus

Echothiophate - Adverse effects

Organophosphate toxicity Systemic exposure: effects of muscarinic receptor activation; salivation, lacrimation, miosis, accommodative spasm, bronchoconstriction, intestinal cramps, urinary incontinence

Isoflurophate - Indication

Chronic glaucoma

Malathion - Indication

Pesticide, head lice

Type 5 phosphodiesterase inhibitors - MoA

ACh activates M3 receptors which leads to increased NO --> NO binds to guanylate cyclase and increase synthesis of cGMP. Type 5 phosphodiesterase inhibit breakdown of cGMP leading to increased smooth muscle relaxation --> increased blood flow into penis and erection.

Type 5 phosphodiesterase inhibitors - Adverse effects

Headache, Nasal congestion, dyspepsia, myalgia, backpain, visual disturbances. Reduces supine blood pressure(blood pressure when lying on back) Augments hypotensive effect of vasodilators (alpha-adrenoceptor antagonist) ---> used to treat symptoms of urinary obstruction in men with BPH

Type 5 phosphodiesterase inhibitors - Contraindication

Men who use nitroglycerin or other organic nitrate. Leads to hypotension, reflex tachycardia, worsening of angina pectoris

Quasireversible cholinesterase inhibitors

Echothiophate Isoflurophate Malathion

Type 5 phosphodiesterase inhibitors

Sildenafil Tadalafil Vardenafil Avanafil

Sildenafil - Indication

Erectile dysfunction | Pulmonary arterial hypertension

Which type 5 phosphodiesterase inhibitor should not be taken with high-fat meal and why?

Sildenafil, absorption is reduced

Tadalafil - Indication

Symptoms of BPH | Pulmonary arterial hypertension

Riociguat - MoA

Increases cGMP by directly stimulating guanylate cyclase

Riociguat - Indication

Pulmonary arterial hypertension

Riociguat - Contraindication

Not use with phosphodiesterase inhibitors due to resulting systemic hypotension

Indirect-Acting Acetylcholine Receptor Agonists groups

``` Reversible cholinesterase inhibitors Quasireversible cholinesterase inhibitors Hemicholinium Vesamicol Botulinum toxin Latrotoxin (Black Widow Spider) ```

Reversible cholinesterase inhibitors

``` Edrophonium Physostigmine Neostigmine Pyridostigmine Donepezil Galantamine Rivastigmine ```

Hemicholinium - MoA

Inhibit choline trasporters which will inhibit Acetylcholine synthesis

Vesamicol - MoA

Inhibit choline proton transporters on the vesicular membrane, so storage is inhibited

Botulinum toxin - MoA

Inhibits release of Acetylcholine from vesicles, causes muscle paralysis

Latrotoxin (Black Widow Spider) - MoA

Release massive amount of Acetylcholine which causes cholinergic crisis