Cholinergic Drugs Overview

Cholinergic Drugs

• Cholinergic drugs are agonists or stimulants that promote the action of acetylcholine, the neurotransmitter.
• They're also called parasympathomimetic drugs because they mimic the parasympathetic nervous system's effects.
• Two major classes of cholinergic drugs are:
  • Cholinergic agonists: Directly stimulate cholinergic receptors, mimicking acetylcholine's action. Examples include acetylcholine, bethanecol, carbachol, and pilocarpine.
  • Anticholinesterase: Inhibit acetylcholine's breakdown at cholinergic receptor sites. Examples include ambenonium, donepezil, edrophonium, neostigmine, physostigmine salicylate, pyridostigmine, and tacrine for reversible effects, and echothiophate for irreversible effects.

Cholinergic Agonists: Pharmacokinetics

• Actions and metabolism vary widely.
• Poorly penetrate the central nervous system (CNS), primarily working peripherally.
• Rapidly destroyed in the body making intravenous (IV) or intramuscular (IM) administration risky.
• Commonly administered topically (eye drops), orally, or via subcutaneous (SQ) injections.
• Metabolized by cholinesterases at muscarinic and nicotinic receptor sites, in plasma, and in the liver.
• Excreted by the kidneys.

Cholinergic Agonists: Pharmacodynamics

• Mimic acetylcholine's action on neurons in target organs.
• Stimulate muscle and produce:
  • Salivation
  • Bradycardia
  • Vasodilation
  • Bronchoconstriction
  • Increased activity of the gastrointestinal (GI) tract
  • Increased tone and contraction of the bladder muscles
  • Constriction of the pupils

Cholinergic Agonists: Pharmacotherapeutics

• Treat atonic bladder conditions and postoperative/postpartum urine retention.
• Treat GI disorders like postoperative abdominal distention and GI atony.
• Reduce eye pressure in patients with glaucoma and during eye surgery.
• Treat salivary gland hypofunction caused by radiation therapy and Sjogren’s syndrome.

### Anticholinesterase Drugs: Pharmacokinetics

• Most are easily absorbed via the gastrointestinal tract (GIT), SQ, and mucous membranes.
• Neostigmine requires a higher dose compared to others.
• Only physostigmine can cross the blood-brain barrier (BBB).
• Donepezil is highly protein-bound, while tacrine is about 55% bound to plasma proteins.
• Most are metabolized by plasma enzymes and excreted in the urine.
• Donepezil and tacrine are metabolized in the liver.

Anticholinesterase Drugs: Pharmacodynamics

• Promote acetylcholine's action at receptor sites.
• Reversible anticholinesterases block acetylcholine breakdown for minutes to hours, while irreversible effects last for days or weeks.

Anticholinesterase Drugs: Pharmacotherapeutics

• Reduce eye pressure in glaucoma and during eye surgery.
• Increase bladder tone.
• Improve GI tone and peristalsis in patients with reduced motility and paralytic ileus.
• Promote muscular contraction in myasthenia gravis patients.
• Diagnose myasthenia gravis using neostigmine and edrophonium.
• Act as an antidote to cholinergic blocking drugs (anticholinergics), tricyclic antidepressants (TCAs), belladonna alkaloids, and narcotics.
• Treat mild to moderate Alzheimer's type dementia.

Anticholinesterase Drugs: Nursing Responsibilities

• Emphasize compliance with prescribed doses.
• Report side effects like dizziness or decreased heart rate.
• Rise slowly from a lying position to prevent dizziness.
• Maintain effective oral hygiene.
• Report signs and symptoms of respiratory distress.

Cholinergic Blocking Drugs

• Include major drugs like atropine, belladonna, homatropine, hyoscyamine sulfate, and scopolamine hydrobromide.
• Synthetic derivatives or quaternary ammonium drugs include:
  • Clidinium, glycopyrrolate, and propantheline
• Tertiary amines include:
  • Benztropine, dicyclomine, ethopropazine, oxybutynin, and trihexyphenidyl.

Cholinergic Blocking Drugs: Pharmacokinetics

• Belladonna alkaloids are absorbed from the eyes, GIT, mucous membranes, and skin.
• Quaternary and tertiary amines are primarily absorbed through the GIT.
• Belladonna alkaloids have broader distribution compared to quaternary amines.
• Belladonna alkaloids have low to moderate protein binding, are metabolized in the liver, and excreted by the kidneys as unchanged drugs and metabolites.

Cholinergic Blocking Drugs: Pharmacodynamics

• Can have paradoxical effects, stimulating or depressing, depending on the dosage and condition.
• Effects vary depending on the targeted organ.

Cholinergic Blocking Drugs: Pharmacotherapeutics

• Treat spastic or hyperactive conditions of the GI and urinary tracts.
• Belladonna alkaloids are used with morphine for biliary colic.
• Injectables are used pre-endoscopy and pre-sigmoidoscopy to relax GI smooth muscle.
• Atropine is used pre-surgery to reduce oral and gastric secretions, and in the respiratory system, to prevent vagal nerve stimulation-induced heart rate drops during anesthesia.

Cholinergic Blocking Drugs: Pharmacotherapeutics (Continued)

• Belladonna alkaloids impact the brain:
  • Scopolamine combined with pain medications like morphine or meperidine causes drowsiness and amnesia during surgery and is also used to treat motion sickness.
  • Cholinergic blockers treat extrapyramidal (Parkinson-like) symptoms caused by drugs and in Parkinson's disease.
• Atropine is the drug of choice (DOC) to treat symptomatic sinus bradycardia and arrhythmias caused by anesthetics.
• Atropine is a cycloplegic, acting as a mydriatic.

Cholinergic Blocking Drugs: Nursing Responsibilities

• Inform patients about common side effects like dry mouth, decreased urination, and constipation due to long-term use.
• Increase fluid intake to counter constipation.
• Offer hard candies, ice chips, or chewing gum to relieve dry mouth.
• Encourage patients to urinate before taking anticholinergics.

Adrenergic Drugs

• Also known as sympathomimetic drugs.
• Classified based on chemical structure:
  • Catecholamines (both naturally occurring and synthetic)
  • Non-catecholamines
• Classified based on action:
  • Direct-acting: Act directly on organs or tissues innervated by the sympathetic nervous system (SNS).
  • Indirect-acting: Trigger the release of a neurotransmitter, usually norepinephrine.
  • Dual-acting: Have both direct and indirect actions.

Adrenergic Drugs (Continued)

• Affect alpha-beta adrenergic receptors, beta-adrenergic receptors, and dopamine receptors.
• Most stimulate alpha and beta receptors, mimicking the action of norepinephrine or epinephrine.
• Dopamine drugs primarily act on dopamine-stimulated sympathetic nervous system receptors.

Catecholamines

• Stimulate the nervous system, constrict peripheral blood vessels, increase heart rate, and dilate bronchi.
• Common examples include dobutamine, dopamine, epinephrine (bitartrate and hydrochloride), norepinephrine, isoproterenol hydrochloride, and sulfate.

Catecholamines: Pharmacokinetics

• Cannot be taken orally.
• SQ absorption is slowed due to vasoconstriction.
• IM absorption is faster due to less constriction.
• Widely distributed, metabolized primarily in the liver, but also inactivated in the GIT, lungs, kidneys, plasma, and other tissues.
• Primarily excreted in the urine.

Catecholamines: Pharmacodynamics

• Primarily direct-acting.
• When combined with alpha or beta receptors, they can cause excitatory or inhibitory effects.
• Alpha receptor activation is excitatory except for intestinal relaxation.
• Beta receptor activation is mostly inhibitory, except for heart cells.
• They are potent inotropes.

Catecholamines: Pharmacotherapeutics

• Effects depend on the activated receptor activity.
  • Norepinephrine has mostly pure alpha activity.
  • Dobutamine and isoproterenol have only beta-related therapeutic uses.
  • Epinephrine stimulates alpha and beta receptors.
  • Dopamine primarily exhibits dopaminergic activity.
• Drugs stimulating alpha receptors treat low blood pressure caused by relaxed blood vessel muscle tone and blood loss.

Catecholamines: Pharmacotherapeutics (Continued)

• Drugs stimulating beta 1 receptors treat:
  • Bradycardia, heart block, low cardiac output.
• Drugs with beta 2 activity treat:
  • Acute and chronic bronchial asthma, pulmonary emphysema, bronchitis, acute hypersensitivity reactions to drugs.
• Dopamine in low doses improves renal blood flow by dilating renal blood vessels.

Non-catecholamines: Effects

• Locally or systemically constrict blood vessels (mephentermine, metaraminol, methoxamine, and phenylephrine).
• Cause nasal and eye decongestion and bronchiole dilation (albuterol, ephedrine, isoetharine hydrochloride, isoetharine mesylate, metaproterenol, and terbutaline).
• Relax smooth muscle (ritodrine hydrochloride and terbutaline).

Non-catecholamines: Pharmacokinetics

• Absorption depends on administration route.
  • Inhaled drugs (albuterol) are absorbed from the bronchi.
  • Oral drugs are well absorbed from the GIT and distributed widely in body fluids and tissues.
  • Some (ephedrine) cross the BBB and are found in high concentrations in the brain and cerebrospinal fluid (CSF).
• Primarily metabolized in the liver but also in the lungs, GIT, and other tissues.
• Excreted mainly in the urine.

Non-catecholamines: Pharmacodynamics

• Direct-acting non-catecholamines:
  • Stimulate alpha activity: methoxamine and phenylephrine
  • Stimulate Beta 2 activity: albuterol, isoetharine, metaproterenol, ritodrine, and terbutaline.
• Indirect-acting non-catecholamines:
  • Phenylpropanolamine
• Dual-acting non-catecholamines:
  • Ephedrine, mephentermine, and metaraminol.

Non-catecholamines: Pharmacotherapeutics

• Stimulate the SNS, producing various effects.
• Metaraminol causes vasoconstriction and is used to treat hypotension in severe shock.
• Ritodrine prevents preterm labor.

Adrenergic Blocking Drugs

• Also known as sympatholytic drugs.
• Disrupt the SNS function by blocking impulse transmission at adrenergic neurons or receptor sites.
• Interrupt sympathomimetic drug actions or reduce available norepinephrine.
• Classified as alpha-adrenergic blockers or beta-adrenergic blockers.

Alpha-Adrenergic Blockers

• Interrupt catecholamines epinephrine and norepinephrine actions at alpha receptors, causing:
  • Relaxation of blood vessel smooth muscle
  • Increased vasodilation
  • Decreased blood pressure
• Examples include ergoloid mesylates, ergotamine, phenoxybenzamine, phentolamine, and prazosin.

Alpha-Adrenergic Blockers: Pharmacokinetics

• Action is not well understood.
• Erratic oral absorption, more rapid and complete sublingual absorption.
• Varying onset, peak, and duration.

Alpha-Adrenergic Blockers: Pharmacodynamics

• Interfere or block norepinephrine synthesis, storage, release, and reuptake by neurons.
• Antagonize epinephrine, norepinephrine, or adrenergic drugs at alpha receptor sites.
• Occupy alpha receptor sites on blood vessel smooth muscle, preventing catecholamines from stimulating them.

Alpha-Adrenergic Blockers: Pharmacotherapeutics

• Increase local blood flow to the skin and other organs, reducing blood pressure.
• Indications include:
  • Hypertension
  • Peripheral vascular disorders like Raynaud’s disease, acrocyanosis, and frostbite
  • Pheochromocytoma

Beta-Adrenergic Blockers

• Most widely used adrenergic blockers.
• Prevent SNS stimulation by inhibiting catecholamine action at beta-adrenergic receptor sites.
• Commonly called beta-blockers.