Cholinergic Drugs

Describe the Synthesis, release, & degradation of acetylcholine

List out the classes of Cholinergic Drugs

Describe Bethanechol 

• AKA?

• Clinical Uses?

• MOA?

Bethanechol 

• AKA: (Duvoid)

• Clinical Uses:

  • Disorders associated w/ decreased parasympathetic tone

  • Postoperative & postpartum:

    • urinary retention 

    • Bladder inadequate emptying 

    • abdominal distension 

    • GI tract atony or paresis

• MOA:

  • Acts on muscarinic receptors

    • contract detrusor muscle

    • increase GI motility

Describe PILOCARPINE

• AKA?

• Clinical Use

• MOA?

• AKA:

  • OCUSERT

  • PILOCAR

• Clinical Uses: 

  • reduce intraocular pressure (IOP) in open angle glaucoma

  • treat dry mouth (xerostomia)

• MOA

  • IOP Reduction:

    • M3 -> Contracts Sphincter -> Reduces Angle Block -> Improves drainage of aqueous humor.

  • Xerostomia

    • M3 Receptors on Salivary Gland

NOTE: Topical 

List the Muscarinic agonists: Side effects

• Diarrhea

• Diaphoresis

• Miosis

• Nausea

• Salivation

• Urinary urgency

• CNS Disturbances

  • w/ drugs that crosses BBB (Pilocarpine)

Describe ACh Esterases

• What is it?

• What is Pseudo cholinesterase (plasma cholinesterase, Butyryl cholinesterase)

ACh Esterases

• What is it?

  • Resides in synapse  -> degrades AcH from Nerve Terminals

• What is Pseudo cholinesterase (plasma cholinesterase, Butyryl cholinesterase)

  • Circulating, non-specific esterase

  • Removes circulating Ach

Describe AChE inhibitors

• MOA

• Potential sites of action

AChE inhibitors

• MOA:

  • Inhibit AcHesterase -> prolongs activity of AcH

• Potential sites of action:

  • @ all sites innervated by para

    • Eye, GI, urinary bladder

  • NMJ

  • All autonomic ganglia

List the Types of AChE inhibitors

List the CLINICAL USES OF AChE inhibitors

Describe NEOSTIGMINE

• Clinical Use

• Adverse Effects

NEOSTIGMINE

• Clinical Use:

  • myasthenia gravis

• Adverse effects: 

  • Generalized cholinergic stimulation

  • BP Drop

  • Overdose: cholinergic crisis & muscle paralysis

NOTE: cannot enter the brain

Describe Physostigmine

• MOA

• Clinical Usage

• Adverse Effects

• MOA:

  • Potentiates Ach effects by preventing degradation.

• Clinical Usage:

  • Antidote for overdoses of atropin + other anticholinergic drugs

  • Reduces IOP in Glaucoma

    • Similar mechanism as pilocarpine

• Adverse effects

  • Diarrhea, nausea, sweating, miosis, urinary urgency

  • @ high Doses: 

    • Convulsions

    • bradycardia 

    • hypotension

NOTE: Tertiary amine that can cross the BBB

Describe Organophosphate poisoning

• What causes it

• Symptoms

• MOA

• Aging Effect

• Treatment

• What causes it?

  •  insecticides and pesticides

    • Contains compounds that are Long acting acetylcholinesterase inhibitors

      • Act. Muscarinic/Nicotinic

• Symptoms:

  • DUMBBELLS

  • Increased GI motility, emesis/vomiting,

• MOA:

  • phosphorylate AchE -> Inactivation

    • @ serine hydroxyl groups

• Aging Effect:

  • These can permanently inactivate AchE

• Treatments:

  • AChE Regen:

    • Pyridostigmine: Regen of AChE

  • Reversing Poisoning

    • Post-exposure-High doses of muscarinic antagonist atropine 

    • Injection of Pralidoxime (2-PAM)

      • Breaks Phosphate Bonds

List the MUSCARINIC RECEPTOR ANTAGONISTS

Describe Atropine

• Clinical Uses

• Side Effects

ATROPINE

Class: Muscarinic Antagonist

Clinical Uses:

• Reversal of severe bradycardia

• produce mydriasis and cycloplegia (loss of accommodation) -> eye exam

• Antispasmodic

• suppress respiratory secretions prior to surgery

• treat organophosphate (AChE inhibitors) insecticide poisoning

• treat mushroom poisoning

---

Side effects 

• Dry mouth

• Constipation

• Dilated pupils (Mydriasis)

• Blurred vision due to cycloplegia

• Hot, dry flushed skin

• Tachycardia

• Fever

• CNS disturbances

Describe SCOPOLAMINE

• Clinical Use

• Contrast to Atropine?

• Side Effects

SCOPOLAMINE

• Clinical uses:

  • Prophylactic for motion sickness (~ 4 hrs before travel)

  • Adjunct drug in anesthesia

    • sedation & amnesia

  • Opthalmic use

• Contrast to atropine

  • crosses BBB much more 

• Side effects

  • Similar to Atropine

    • CNS effects more prominent

Describe IPRATROPIUM BROMIDE

• AKA?

• Clinical Uses

• MOA

• Compared to Atropine?

• AKA: ATROVENT

• Clinical uses:

  • Adjunct to albuterol

    • Treat Asthma and COPD

  • Can also be an alt. to albuterol 

    • For pts. Who can’t take adrenergic agonists

• MOA

  • Blocks M receptors -> reduces Para. induced bronchoconstriction

• Compared to Atropine:

  • Minimal inhibitory effect on mucociliary clearance

  • Less CNS effects

Describe Tiotropium Bromide

• AKA?

• Clinical Uses?

• AKA: SPIRIVA

• Clinical Uses:

  • COPD and Asthma

    • Much more selective action at the bronchioles

    • Greater affinity for M3 vs M2

Describe TOLTERODINE

• AKA?

• Clinical Uses?

• MOA?

• Other drugs in the same category as Tolterodine

TOLTERODINE 

• AKA: DETROL

• Clinical Uses: Treatment of overactive bladder

  • Reduces # of incontinent episodes

  • Increase # urine bladder can hold

  • Reduce # of urination

  • Decrease urgency

• MOA

  • Blocks M3 on Detrusor Muscles 

  • Blocks  parasympathetic tone to the sphincter

    • Prevents leaks

• Other drugs in the same category as Tolterodine

  • Solifenacin (Vesicare)

  • Darifenacin (Enablex)

  • Oxybutynin (Ditropan)

  • ***Indicated for overactive bladder.***

List the contraindication for M3 Antagonists

M3 Antagonists: Contraindication

• Slows Voiding

  • Not for PTs w/ BPH (Benign prostatic Hyperplasia)

• Kidneys problem w/ urination

• Glaucoma

• Myasthenia Gravis

• Excessive constipation

Describe GANGLIONIC BLOCKERS

• MOA

• Drugs in this Category

• MOA:

  • Block the ganglionic (Nn) receptor

• Drugs in this category

  • Very Few

  • Hexamethonium bromide, Trimethopham