Cholinergic Drugs PDF

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Cholinergic Drugs notes...

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HLSC 3P19: Pharmacology Chapter 21: Cholinergic Drugs: Autonomic Nervous System: •

ANS controlled by 2 primary neurotransmitters: o Acetylcholine o Norepinephrine

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There are two divisions of the ANS: o Parasympathetic nervous system (PNS): ▪ Stimulated smooth muscle, cardiac muscle, and glands ▪ Has muscarinic or cholinergic receptors •

To types of cholinergic receptors: o Nicotinic receptor o Muscarinic receptor

▪ Stimulated by acetylcholine and cholinergic agonist drugs ▪ Maintains homeostasis and the body at rest o Sympathetic nervous system (SNS): ▪ Stimulates heart, blood vessels, skeletal muscles ▪ Has adrenergic or noradrenergic receptors ▪ Stimulated by norepinephrine, epinephrine and adrenergic agonist drugs Cholinergic Drugs: •

Cholinergic drugs (AKA cholinergic agonists or parasympathomimetic)

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Cholinergic drugs: stimulate the PNS and mimic the effects of ACh (of the PNS) o Direct acting cholinergic agonists: bind directly to cholinergic receptors and activate them o Indirect acting cholinergic agonists: stimulate the postsynaptic release of ACH and allows ACh to bind and stimulate the receptor

Mechanism of Action & Drug Effect:

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When ACh binds directly to its receptor, stimulation occurs. o Once binding occurs, permeability of cell changes and calcium and sodium are permitted to flow into the cell.

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Direct-acting cholinergic agonists: o Bind to cholinergic receptors, activating them

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Indirect-acting cholinergic agonists: (AKA. Cholinesterase inhibitors) o Inhibit the enzyme acetylcholinesterase -breaks down ACh o Results in more ACh available at the receptors. o Two categories of cholinesterase: ▪ Reversible: bind to cholinesterase for a short period of time ▪ Irreversible: bind to cholinesterase for a long period of time, forms a permanent covalent bond. •

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The body must make new cholinesterase to break these bonds.

Drug effects are seen when parasympathetic system is stimulated o This system is the “rest and digest” system o SNS is the “flight or fight” system

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Cholinergic primarily used for their effects on: GI system, bladder and eyes o Stimulate the intestine and bladder: ▪ Increased gastric secretions ▪ Increased GI motility ▪ Increased urinary frequency o Stimulate pupils: ▪ Pupil constriction (miosis) ▪ Reduced intraocular pressure o Increased salivation and sweating o Cardiovascular effects: ▪ Decreased heart rate

▪ Vasodilation o Respiratory effects: ▪ Bronchial constriction ▪ Narrowed airways •

At recommended doses, cholinergic primarily affect muscarinic receptors o At high doses, cholinergics stimulate nicotinic receptors

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Desired effect are from muscarinic receptor stimulation.

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Many undesirable effects are caused by stimulation of nicotinic receptors

Indications: •

Direct-acting drugs: pilocarpine & carbachol o Used to reduce intraocular pressure o Useful for glaucoma and intraocular surgery o Used primarily as topical application since there is poor oral absorption o Succinylcholine: ▪ Used as a neuromuscular blocker in general anaesthesia ▪ Given intravenously o Bethanechol (Urecholine ®): ▪ Administered orally ▪ Affects detrusor muscle of the urinary bladder and the smooth muscles of the GI tract •

Causes increased bladder and GI tract tone and motility

▪ Used to treat atony of the bladder and GI tract •

Indirect acting drugs: o Increase ACh concentrations at the receptor sites, leading to the stimulation of the effector cells o Causes skeletal muscle contractions o Used for the diagnosis and treatment of myasthenia gravis

o Used to reverse neuromuscular blocking drugs o Used to reverse anticholinergic poisoning (antidote) – (e.g. physostigmine) o Used for treatment of mild to moderate Alzheimer’s disease – (e.g. donepezil [Aricept®], galantamine [Reminyl ®]) ▪ Increases the ACh to help enhance or maintain memory and learning capabilities since Alzheimer’s disease causing decrease in ACh Contraindications: •

Contraindications include: o Known drug allergy o GI or GU tract obstruction o Bradycardia o Defects in cardiac impulse conduction o Hyperthyroidism o Epilepsy o Hypotension o Chronic obstructive pulmonary disease o Parkinson’s disease

Adverse Effects: •

Adverse effects are a result of overstimulation of the PNS.

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Cardiovascular effects: o Bradycardia o Hypotension o Syncope o Conduction abnormalities (atrioventricular block and cardiac arrest)

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CNS effect: o Headache o Dizziness

o Convulsions o Ataxia •

GI effects: o Abdominal cramps o Increased secretions o Nausea o Vomiting o Diarrhea o Weight loss

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Respiratory effects: o Increased bronchial secretions o Bronchospasms

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Other: o Lacrimation o Sweating o Salivation o Miosis

Toxicity & Overdose: •

Cholinergic crisis: o Symptoms include: ▪ Circulatory collapse ▪ Hypotension ▪ Bloody diarrhea ▪ Shock ▪ Cardiac arrest o SLUDGE: Use this to remember the effects of cholinergic poisoning ▪ S – salivation

▪ L – lacrimation ▪ U – urinary incontinence ▪ D- diarrhea ▪ G – GI cramps ▪ E – emesis o Early signs include: ▪ Abdominal cramps ▪ Salivation ▪ Flushing of the skin ▪ Nausea & vomiting ▪ Transient syncope ▪ Transient complete heart block ▪ Dyspnea ▪ Orthostatic hypotension o Treatment in early phase: ▪ The symptoms can be reversed promptly by the administration of atropine sulphate (cholinergic antagonist). o Treatment of severe cardiovascular reactions or bronchoconstriction: ▪ Epinephrine (an adrenergic agonist) Interactions: •

Anticholinergics, antihistamine, sympathomimetics: o Antagonize cholinergic drugs – resulting in decreased responses

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Other cholinergic drug – cause additive effect

Donepezil (Aricept ®): •

Cholinesterase inhibitor that works centrally in the brain to increase levels of ACh by inhibiting acetylcholinesterase.

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Used in the treatment of mild to moderate Alzheimer’s disease

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Similar cholinesterase inhibitors include: o Galantamine o Rivastigmine

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Contraindication: o Known drug allergy

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Adverse effects: o GI upset (including ulcer risk caused by increased gastric secretions) o Drowsiness o Dizziness o Insomnia o Muscle cramps o Effects on cardiovascular system are complex and may include: ▪ Bradycardia ▪ Syncope hypotension with reflex tachycardia ▪ Hypertension

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Interacting drugs: o Anticholinergics (counteract donepezil effects) o NSAIDs

Neostigmine & Physostigmine: •

Uses: o Reversing the effects of nondepolarizing neuromuscular blocking drugs o Treating severe overdoses of tricyclic antidepressants o Antidote after toxic exposure to nondrug anticholinergic agents including those used in chemical warfare

Nursing Management: Nursing assessment: •

Perform a thorough assessment and obtain a health history and medication history.

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Document allergies and past/present medical conditions

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Assess and document vital signs (attention to BP)

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Assess the patient for allergies, cautions, contraindications, and drug actions

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Assess urinary patterns

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Identify the presence or absence of a family support system

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Assess the patient’s response to the medications

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Note any changes within the first 6 weeks of therapy

Nursing Implications: •

Encourage ambulation and increased intake of fluids and fibre, unless contraindicated.

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Drugs used to treat myasthenia gravis – give oral medication ~30 minutes before meals to allow for onset of action and therapeutic effects

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Medications should be taken as ordered and not abruptly stopped.

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Doses should be spread evenly apart to optimize the effects of the medication

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Overdosing can cause life threatening problems – patient should not adjust dosage unless directed by HCP.

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When cholinergic drugs are prescribed for Alzheimer’s disease, be honest with caregivers and patients and tell them that the drugs are for the management of symptoms, not a cure.

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Teach therapeutic effects of anti-Alzheimer’s drugs may not occur for up to 6 weeks....