Cholinergic Drugs

ANS function

Responsible for our response to daily activities. Includes the PNS and the SNS

PNS = 

“Rest and digest” system

SNS =

“Fight or flight” system

Cholinergic drugs stimulate

• Stimulates PNS

• AKA cholinergic agonists and parasympathomimetics

• Mimic effects of the PSNS neurotransmitter ACh

MOA of direct-acting cholinergic (bethanechol)

Binds to and activates cholinergic receptors

Direct-acting cholinergics indications (bethanechol)

• Glaucoma & Intraocular surgery

• Urinary retention, dry mouth

• Neuromuscular blocker in general anesthesia

Indirect acting cholinergic drugs MOA

• AKA cholinesterase inhibitors. Inhibits enzyme acetylcholinesterase (enzyme that breaks down ACh)

• Results in more ACh available at receptors

Indirect acting cholinergic drugs indications (pyridostigmine; donepezil)

Diagnosis and treatment of myasthenia gravis, and treatment of AD

2 types of cholinergic receptors

• Nicotinic receptors

• Muscarinic

Cholinergic drug effects

Make things wet

• Stimulates intestine and bladder

  • Increased gastric secretions (more acidic)

  • Increased GI motility

  • Increased urinary frequency

• Stimulate pupils

  • Constriction (miosis)

  • Reduced IOP

• Respiratory effects

  • Bronchoconstriction, narrowed airways

Make things WET

• Stimulates intestine and bladder

  • Increased gastric secretions (more acidic)

  • Increased GI motility

  • Increased urinary frequency

• Increased salivation & sweat

• Stimulate pupils

  • Constriction (miosis)

  • Reduced IOP

• Respiratory effects

  • Bronchoconstriction, narrowed airways

Cholinergic SEs

How do cholinergic drugs stimulate intestine and bladder?

• Increased gastric secretions (more acidic)

• Increased GI motility

• Increased urinary frequency

How do cholinergic drugs stimulate pupils?

• Pupil constriction (miosis)

• Reduced IOP

CV effects of cholinergics

• Decreased HR

• Vasodilation → ↓ BP

Respiratory effects of cholinergics

Bronchial constriction, narrowed airways

DUMBELLS (cholinergic SE)

D – Diarrhea

U – Urination

M – Miosis

B – Bradycardia

B – Bronchospasm

E – Emesis

L – Lacrimation

L – Lethargy

S – Salivation

Cholinergic SE

• Diarrhea

• Urination

• Miosis

• Bradycardia

• Bronchospasm

• Emesis

• Lacrimation

• Lethargy

• Salivation

Early signs of cholinergic crisis

• OH

• Dyspnea

• NVD

• Flushing of skin

• Abd cramps

• Salivation; bronchorrhea; rhinorrhea

• Miosis; lacrimation

• Transient syncope

• Transient complete heart block, bradycardia

• NV

ODFASTTNV (early S&S cholinergic crisis)

• OH

• Dyspnea

• Flushing of the skin

• Abd cramps

• Salivation

• Transient complete heart block

• Transient syncope

• NV

Late S&S of cholinergic crisis

• Circulatory collapse

• Cardiac arrest

• Hypotension

• Bloody diarrhea

• Shock

CCHBS (Late S&S of cholinergic crisis)

• Circulatory collapse

• Cardiac arrest

• Hypotension

• Bloody diarrhea

• Shock

Treatment for cholinergic crisis

Atropine and epinephrine (adrenergic agonist) → treat severe cardiovascular reactions or bronchoconstriction

Prodrug of direct-acting cholinergic agonists

Bethanechol (Urecholine)

Direct-acting cholinergic agonists (bethanechol)

• Selectively muscarinic receptors of the PNS

• Primarily affects the detrusor muscle of the urinary bladder and the smooth muscle of the GI tract

  • Increased bladder tone, leading to contraction and initiation of urination

  • Increased GI motility and tone, which may restore peristalsis

Direct-acting cholinergic agonists indication

Non-obstructive urinary retention: postoperative, postpartum, or neurogenic urinary retention.

Direct-acting cholinergic agonist (bethanechol (Urecholine)) C/I

• Mechanical obstruction of the GI/GU

• Active bronchial asthma

• Peptic ulcer

• Parkinsonism

• Cardiac disease

MAPPC (direct-acting cholinergics; bethanechol C/I)

M – Mechanical obstruction of the GI/GU

A – Active bronchial asthma

P – Peptic ulcer

P – Parkinsonism

C – Cardiac disease

Nursing considerations for direct-acting cholinergic agonists (bethanechol)

• Administer on an empty stomach to avoid GI upset

• Monitor I&Os; assess post-void residual as ordered

• Patient education on safety (OH → change positions/get up slowly)

• Antidote: atropine

Antidote for direct-acting cholinergic agonists

Atropine

Neuromuscular autoimmune disease; immune system creates antibodies that

• Block ACh from binding to the receptors

• Actively destroys the receptors

• Main problem is that body cannot use ACh

Patient has various degrees of painless muscle weakness

Myasthenia Gravis

S&S of myasthenia Gravis

• Drooped eyelids (ptosis), double vision (diplopia), impaired speech (dysarthria)

• Commonly the eyelids affect first; but depending on severity the patient may range from mild symptoms to respiratory insufficiency/failure (when ICS muscles become affected) → difficulty breathing/dysphagia

Direct-acting cholinergic agonist SE/AE (bethanechol)

• DUMBELLS

• Syncope, hypotension, reflex tachycardia

• HA, seizures

• GI upset

• Asthma attacks/bronchoconstriction

Myasthenia Gravis S&S

• Drooped eyelids (ptosis)

• Double vision (Diplopia)

• Blurred vision

• Impaired speech (dysarthria) 

• Respiratory insufficiency/failure → difficulty breathing/SOB

• Changes in facial expression

• Difficulty chewing/swallowing (dysphagia)
  Slurred speech

• Muscle fatigue; arm and leg weakness

Prodrug of acetylcholinesterase inhibitors (for MG)

Pyridostigmine (Mestinon) 

Name the acetylcholinesterase inhibitors (cholinergics)

• Pyridostigmine (Mestinon)

• Edrophonium (Tensilon)

MOA of acetylcholinesterase inhibitors 

• Reverse inhibitor of the enzyme acetylcholinesterase (AChE) at the neuromuscular junction

• Inhibits breakdown of ACh to increase the concentration

• Enhances signal transmission overcomes the block caused by antibodies in myasthenia gravis

• Does not cross BBB; limits CNS SEs

AChE inhibitors cross BBB and affect the CNS. True or false?

False

AChE inhibitors (pyridostigmine; edrophonium) indication

• Myasthenia gravis

• Antidote for nondepolarizing NMBDs (eg rocuronium)

• Edrophonium → used to dx MG or differentiate between MG or cholinergic crisis

Edrophonium indication

AChE inhibitor used to diagnose MG or differentiate between MG and cholinergic crisis.

Drugs are the antidote for nondepolarizing NMBDs (eg rocuronium)

AChE inhibitors (pyridostigmine)

SE/AE of AChE inhibitors (pyridostigmine)

• DUMBELLS

• Muscle fasciculations (twitching)

• Muscle cramps

• Muscle weakness (a key sign of OD/cholinergic crisis)

How can muscle weakness caused by AChE inhibitor/myasthenia gravis be distinguished from muscle weakness caused by cholinergic crisis?

Use Edrophonium:

• Strength IMPROVES (ptosis lifts, voice stronger, VC up): Myasthenic crisis / under-medicated → increase AChE inhibitor or other MG therapy.

• Strength WORSENS or no improvement, with muscarinic signs (sweating, salivation, abdominal cramping, miosis, bradycardia, bronchospasm): Cholinergic crisis / over-medicated → hold AChE inhibitor and treat symptoms (give atropine if needed, airway support).

Nursing considerations for AChE inhibitors

• Administration: timing is important → give 30-45 min before meal time. Helps improve patient’s ability to chew and swallow

• Monitor for signs of a worsening condition

  • Myasthenic crisis (under-dosing)

  • Cholinergic crisis (over-dosing)

• Antidote is atropine

S&S of this condition are severe weakness, especially of respiratory muscles, leading to respiratory distress; caused by under-dosing of AChE (pyridostigmine)

Myasthenic crisis

S&S of this condition are worsening muscle weakness accompanied by excessive cholinergic symptoms (severe diarrhea, sweating, salivation, bradycardia); caused by OD of AChE (donepezil)

Cholinergic crisis

Give these medications 30-45 min before meal time for optimal therapeutic effect (improve patient’s ability to chew and swallow).

AChE inhibitors (pyridostigmine, edrophonium)

Disease is most common cause of dementia in older adults

AD

Progressive brain disorder that affects memory, thinking, and behavior. Causes 4 main changes in the brain

• Beta-amyloid plaques → abnormal protein deposits that build up between nerve cells

• Neurofibrillary tangles → twisted protein fibers (tau) inside nerve cells

• Loss of connections between neurons

• Neuron death → leads to brain shrinkage (atrophy)

• These changes greatly affect ACh and cholinergic neurons

AD

Pharmacotherapy goal for AD

• Increase ACh to decrease cognitive decline

  • Does NOT reverse memory loss

AChE inhibitor used to treat AD

Donepezil (Aricept)

MOA of AChE (donepezil) used to treat AD

• Selective and reversible inhibitor of the enzyme AChE in the brain

• Inhibits breakdown of ACh to increase concentration

Donepezil (AChE inhibitor) indication

Mild to moderate AD

Donepezil (AChE inhibitor) SE/AE

• DUMBELLS

• GI: risk for ulcers caused by increased gastric secretions

• CNS: drowsiness, dizziness, insomnia

• CV: effects are complex; may include bradycardia, syncope, hypotension with reflex tachycardia, and HTN

• Muscle cramps

SLUDGE (cholinergic SE)

S – Salivation

L – Lacrimation

U – Urination/freqent

D – Diarrhea

G – GI cramps/GI secretions increased

E – Emesis

Caution using this drug w/

• Heart conditions

• PUD; risk for GI bleeding; NSAIDs

• Asthma or COPD

Donepezil

Caution using this drug with NSAIDs (r/o GI bleeds/ulcers) or asthma/COPD patients.

Donepezil 

HAP (caution use w/ donepezil) 

H – Heart conditions

A – Asthma/COPD

P – PUD; GI bleeding; NSAIDs

Nursing considerations for donepezil

• Compliance may be a problem due to poor memory; risk for OD due to inability to remember if they took the med already

  • Need reminders and family members to assist

• Monitor BP, HR, S&S of GI bleed

• Therapeutic effects may not occur for up to 6 weeks

• Antidote: atropine

What to monitor for patient taking donepezil?

• R/o OD due to memory issues

• BP, HR, S&S of GI bleed

Drugs used for AD that takes up to 6 weeks for therapeutic effects to kick in.

Donepezil; memantine

Prodrug of NMDA receptor antagonists

Memantine (Namenda)

NMDA antagonists (memantine) MOA

• Not a cholinergic drug; N-methyl-D-aspartate (NMDA) receptor antagonist

• Glutamate (excitatory neurotransmitter) over-activates receptors in AD and can damage neurons

• NMDA receptor antagonists block overstimulation while still allowing normal glutamate activity needed for learning and memory

NMDA receptor antagonists (memantine)

• Treatment of AD

  • Improves cognition and QOL

NMDA receptor antagonists SE/AE (memantine)

• Dizziness, HA, drowsiness

• CV: HTN

• GI: GI upset

• Muscle pain, fatigue, ataxia

Drugs used to treat AD that is not a cholinergic drug (does not have cholinergic SE/AE)

NMDA receptor antagonists (memantine)

Drug has these SEs:

• Dizziness, HA, drowsiness

• CV: HTN

• GI: GI upset

• Muscle pain, fatigue, ataxia

What is this drug?

NMDA receptor antagonists (memantine)

Nursing considerations for NMDA receptor antagonists (memantine)

• Titrate doses slowly to minimize SE

• Therapeutic effects may not occur for up to 6 weeks

• Educate patients on safety (fall prevention due to dizziness/drowsiness)

Titrate doses for these drugs slowly to minimize SEs.

NMDA receptor antagonists (memantine)

Gingko biloba (herbal product) MOA

• Improves blood flow to the brain by dilating blood vessels

• Antioxidant properties that may protect nerve cells from damage

• Anti-inflammatory effects may inhibit platelet-activating factor (affects blood clotting)

Gingko biloba indication

• Memory loss

• Vertigo

• Tinnitus

Gingko biloba SE

• GI upset

• HA

• Bleeding

Nursing considerations for herbal products (gingko biloba)

• Potential drug interactions

  • ASA, NSAIDs, anticoagulants

  • Anticonvulsants

• Monitor for S&S of bleeding

Gingko biloba has potential drug interactions with

• ASA, NSAIDs, anticoagulants

• Anticonvulsants

Indirect-acting cholinergic drugs

• AChE inhibitors

• NMDA receptor antagonist

Name the direct-acting cholinergic drug; is used for non-obstructive urinary retention, postoperative, postpartum, or neurogenic urinary retention

Bethanechol (Urecholine)