Lec 16_Cholinergic ANTagonists

What makes cholinergic antagonists different from cholinergic agonists?

Cholinergic antagonists block the action of acetylcholine at the receptor sites, inhibiting the effects of the parasympathetic nervous system, whereas cholinergic agonists enhance acetylcholine activity, facilitating parasympathetic responses.

Cholinergic antagonists are mainly used to block muscarinic receptors in the parasympathetic system, leading to sympathetic-like effects

What is the target of cholinergic antagonist drug actions?

Block the release of acetylcholine

Competitively block sympathetic receptors: muscarinic, nicotinic

• most of the clinically relavant action is competitive antagonism of the muscarinic receptor

Muscarinic antagonists can be selective or non-selective. What is the difference?

Selective - blocking the receptor and it will not allow ACh to bind

Non-selective - prevent ACh from leaving the vesicle, being made, or being broken down. There is no interaction with the receptor

What are the therapeutic indications for the use of drugs that act as cholinergic antagonists?

• aspiration prophylaxis

• bradycardia

• COPD

• cycloplegia or mydriasis (dilation) induction

• IBS

• motion sickness

• overactive bladder, urinary incontinece

• Parkinson’s

• Agonist overdose

What are signs of anticholinergic toxidrome?

BLIND as a bat = trouble with vision

Mad as a hatter = confusion, dizzy

RED as a beet = flushed skin

HOT as a desert = unable to sweat

DRY as a bone = drying all secretions

What are some contraindications and precautions for use of cholirnergic antagonist medications?

Don’t give meds to:

• Glaucoma patients, esp narrow angle

• BPH

• Cardiac disease

• Arrythmias

• Use in infants - the infants can’t already regulate body temp with their own system and it could cause a hyperthermia risk

Describe Atropine

M non-selective

highly selective muscarinic receptors that do not distinguish between subtypes

Inhibits PNS causing unopposed SNS responses in target tissues

What is atropine used for?

• acute symptomatic bradycardia

• cholinesterase inhibitor intoxication (poisons)

• Aspiration prophylaxis (reduction of secretions)

What is a derivative of the belladonna plant used today?

Scopolamine (Transderm Scop)

• a transdermal patch theraputically used for motion sickness

• able to pass BBB

What are the ADE of Scopolamine (Transderm Scop)?

CNS effects: drowsy, amnesia, fatigue

dry mouth

What is the mechanism of cholinergic antagonists drugs on an overactive bladder (M3 receptor)?

• decrease intravesicular pressure

• increase capacity

• reduce the frequency of contractions

Which drugs can be used for an overactive bladder?

• Oxybutyin (Ditropan)

• Tolerodine (Detrol)

• Trospium chloride (Sanctura)

• Darifenacin (Enablex)

• Solifenacin (Vesicare)

• Fesoterodine (Toviaz)

What is the mechanism of Glycopyrrolate and its uses?

Mechanism: blocks the action of ACh at parasympathetic sites in the smooth muscle, secretory glands, and the CNS

Uses

• duodenal ulcer

• sialorrhea (drooling)

• primary axillary hyperhidosis

• COPD

What is the mechanism of Dicyclomine and its uses?

Mechanism: weak muscarinic receptor antagonist

• more specific to M1 subtype (CNS + gastric parietal cells)

Uses

• diarrhea predominant irritable bowel syndrome

What is the mechanism of Trihexyphenidyl and Benztropine and its uses?

mechanism: exerts a direct inhibitory effect on the PNS

Uses

• treatment for parkinson’s

  • for tremors

• treatment for drug induced extrapyramidal sx

What mechanisms do cholinergic antagonists drugs have on the resp system (M - nonselective)?

What are drug options?

any ADEs?

Mechanism

• bronchodilation + reduction of secretion

Agents

• Ipratropium

• tiotropium

• glycopyrrolate

• Aclidinium

• Umeclidinium

ADE

• minimal absorption as quaternary amine

which of these is not considered an anticholinergic side effect

a. decreased sweating

b. salivation

c. blurry vision

d. urinary retention

b. salivation

Describe the M1 selective drugs

Dicyclomine and Hyoscyamaine

Therapeutic use: diarrhea and IBS

MOA: weak M antagonist, reduce GI spasm

Describe the M3 selective drugs

Oxybutynin, tolterodine, trospium chloride, darifenacin, solifenacin, and festerodine

therapeutic use: overactive bladder

MOA: antagonize PNS control of the bladder, decrease pressure, increase capacity, reduce conractions

Describe Homatropine, what drug class is it in?

Class: M non-selective

therapeutic use: used in optho exams to dilate pupils and reduce pain.

MOA: block PNS

What is class is glycopyrrolate?

M non-selective

What are atroprine’s ADE?

Xerostomia

constipation

blurred vision

dyspepsia

cognitive impairement

A patient begins to experience constipation, blurred vision, dyspepsia, xerostomia, and cog impairment. Which drugs can cause these ADE?

• Atropine

• Dicyclomine + Hyoscyamine (M1 selective)

• Oxybutynin, tolterodine, trospium chloride, darifenacin, solifenacin, and festerodine (M3 selective)

• Trihexyphenidyl and benztropine (M1 non-selective)