parasympathetic nervous system drugs

8/11/2019 Parasympathetic Nervous System Drugs

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Parasympathetic Nervous SystemDrugs

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Parasympathetic Nervous System

Drugs

1. MUSCARINIC RECEPTOR AGONISTS OR

CHOLINOMIMETICS2. MUSCARINIC RECEPTOR ANTAGONISTS

OR ANTICHOLINERGICS3. GANGLIONIC NICOTINIC RECEPTOR

ANTAGONIST4. ACETYLCHOLINESTERASE INHIBITORS


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1. MUSCARINIC RECEPTOR

AGONISTS OR CHOLINOMIMETICS

MECHANISM OF ACTION

stimulate muscarinic cholinergic receptors Pilocarpine selectively stimulates these

receptors Bethanechol and methacholine more

selective Acetylcholine and carbachol have

activity at nicotinic receptors


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USES

Pilocarpine glaucoma;sometimes forxerostomia Acetylcholine rarely used; rapid degradation

by cholinesterases; ability to produce effects at

nicotinic receptors; ocular surgery-miosis Bethanechol sometimes used in the tx of

urinary retention or to stimulate GI motility Carbachol used in ocular surgery; acute mngt

of glaucoma




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ADVERSE REACTIONS

Bronchoconstriction Excessive secretion in the upper airways (so

not recommended for asthmatic tendencies) Sudden severe decrease in BP (never be

used in CAD pts or pts with other certainheart problems)

n/v, diarrhea, increased sweating (common

when using pilocarpine in the tx ofglaucoma)


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TOXICITY have atropine (muscarinic

receptor antagonist) readilyavailable when cholinomimeticsare given in a clinical setting

INTERACTIONS

cholinesterase inhibitor


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ANTAGONISTS OR ANTICHOLINERGICS

Parasympatholytic or cholinolytic

MECHANISM OF ACTION binds to muscarinic receptors

but produce no effect; result ofblocking the action of neurallyreleased acetylcholine acting at

muscarinic receptors.


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USES Atropine eye examination for mydriasis and

cycloplegia; eye drops Glycopyrolate preanesthetic agent before surgery in

order to inhibit bronchial and salivary secretions Propantheline depression of overactive GIT in pts with

peptic ulcers Tx of sinus bradycardia and certain forms of heart block Ipratropium blocks contraction of bronchial smooth

muscle Tolterodine tx of overactive bladder reflexes Tx of toxicity caused by cholinergic drugs


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Other uses:

Scopolamine prevents motionsickness

Used to relieve extrapyramidal motor

movements caused by Parkinson'sdisease

Antitremor activity


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Parkinsons Disease

(Parkinsonism)

Chronic neurologic D/O that affects

the extrapyramidal motor tract (w/ccontrols posture, balance andlocomotion)

3 motor features:a. Rigidityb. Bradykinesia

c. Tremors
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Parkinsons Disease

(Parkinsonism)Postural changes

a. Chest and head thrust forward and the knees andhips flexed

b. A shuffling gaitc. Absence of arm swingd. Masked faciesOtherse. Involuntary tremors of the head and neckf. Pill rolling motions of the handsg. Tremors more prevalent at rest
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Parkinsons Disease

(Parkinsonism)

Cause: imbalance of NT ACh & Dopamine

Marked by degeneration of neurons that originatein the substantia nigra of midbrain and terminateat the basal ganglia of the extrapyramidal motortract.

Unexplained degeneration of the dopaminergicneurons, decreased dopamine, ACh isunopposed


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Parkinsons Disease

(Parkinsonism)DRUGS

1. Anticholinergics block cholinergic receptorsTrihexyphenidyl(Artane),Benztropine(Cogentin), Akineton

2. Dopaminergics convert to dopamine e.g. Levodopa,Carbidopa and levodopa (Sinemet)

3. Dopamine Agonists stimulate dopamine receptors eg.

Amantadine hcl(Symmetrel), Bromocriptine (Parlodel)4. MAO-B Inhibitor inhibits Monoamine oxidase-B MAO-B,

enzyme that interferes with dopamine eg. Selegiline5. COMT inhibitors inhibit COMT enzyme that inactivates

dopamine eg. Talcapone(Tasmar), Entacapone (Comtan)


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ADVERSE REACTIONS ANDCONTRAINDICATIONS Xerostomia Constipation Urinary hesitancy or retention Tachycardia Dilated pupils and blurred vision Dry and flushed skin Increase body temp Contraindications: glaucoma, cardiac rhythm

disturbances


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TOXICITY Atropine toxicity confusion and delirium, hot

flushed dry skin, dilated pupils and tachycardia Dry as bone, red as beet, blind as bat, mad as

hatter, hot as hell ANTIDOTES

Syrup of ipecac, activated charcoal Physostigmine (acetlycholinesterase inhibitor)


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3. GANGLIONIC NICOTINIC

RECEPTOR ANTAGONIST

Ganglionic blocker

MECHANISM OF ACTION block nicotinic receptors in

autonomic gangliaUSE effective in lowering BP


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3. GANGLIONIC NICOTINIC

RECEPTOR ANTAGONIST

ADVERSE REACTIONS ANDCONTRAINDICATIONS dry mouth constipation cycloplegia mydriasis urinary retention impotence tachycardia orthostatic hypotension CI: impaired renal function


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4. ACETYLCHOLINESTERASE

INHIBITORS

Reversible ambenonium (Mytelase) donepezil (Aricept) edrophonium (Tensilon) galantamine (Reminyl) neostigmine (Prostigmin) physostigmine (Antilirium, Eserine, Isopto Eserine) pyridostigmine (Mestinon, Regonol) rivastigmine (Exelon) tacrine (Cognex)

Irreversible demecarium (Humorsol) echothiophate (Phospholine)


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INHIBITORS

MECHANISM OF ACTION prevention of the rapid degradation of synaptically released

ACh by acetylcholinesterase allows the ACh released to remain intact longer because its

degradation is inhibited ACh has more opportunity to act at cholinergic receptors Some drugs bind to the enzyme reversibly Most drugs act as substrates for the enzyme, that is the

enzyme interacts with the drug molecule in the same way itinteracts with acetylcholine

Irreversible cholinesterase inhibitors form a permanent

covalent bond with Acetylcholinesterase


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INHIBITORS

USES

Pyridostigmine, neostigmine andambenonium tx of Myasthenia Gravis

Demecarium, echothiophate

glaucoma Treatment of Alzheimers Dse (improve

cognitive function in early stage, tx ofmild to moderate dementia)


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Myasthenia Gravis- characterized by rapid

development of fatigue andmuscular weakness; caused byan autoimmune reaction by thebody to nicotinic receptors onskeletal muscles; neuromusculartransmission becomes impaired,and muscle contraction cannot besustained and therefore weakens.


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Myasthenia GravisSymptoms

PtosisDysphagiaWeakness of skeletal muscles

Neostigmine: symptomatic relief- Inhibits acetlycholinesterase, the released ACh has

more opportunity to interact with the greatly reducednumber of receptors, thus improving muscle strength


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INHIBITORS

ADVERSE REACTIONS

Salivation Sweating Nausea Diarrhea Bradycardia Muscle Fasciculation and weakness


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TOXICITY

ANTIDOTES

Atropine blocks the muscarinic effecst onthe periphery and CNSPralidoxime reverses neuromuscularparalysis


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Sympathetic Nervous SystemDrugs


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Sympathetic Nervous System Drugs

1. ALPHA-ADRENERGIC RECEPTOR AGONISTS

2. ALPHA-ADRENERGIC RECEPTOR ANTAGONISTS

3. BETA-ADRENERGIC RECEPTOR

AGONISTS4. BETA-ADRENERGIC RECEPTOR ANTAGONISTS


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1. ALPHA-ADRENERGIC RECEPTOR

AGONISTS

MECHANISM OF ACTION Direct activation of the receptors Stimulates the release of NE from nerve endingsUSES Phenylephrine: Tx of shock or hypotensive states,

nasal decongestant, dilation of pupil Epinephrine: tx of anaphylaxis; injected with local

anesthesia to produce vasoconstriction Dopamine: for shock Mephentermine, methoxamine, metaraminol used

to maintain blood pressure


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AGONISTS

Nonselective Alpha 1 Selective AE & CI

Increase in BPVasoconstriction in extremitiesRestlessness and CNS stimulation

Cardiac rhythym disturbances


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ANTAGONISTS

MECHANISM OF ACTION

acts as competetive antagonistsUSES Tolazoline- pulmonary HTN in NB

Phentolamine sometimes used in mngtof HTN asso. With Pheochromocytoma Selective drugs used in HTN and tx of

BPH


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ANTAGONISTS

AE & CI Orthostatic hypotension Sedation

Nasal congestion Tachycardia First dose phenomenon


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AGONISTS

NonselectiveBeta1, SelectiveBeta2, Selective


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AGONISTS

MECHANISM OF ACTION Reversible binding to and stimulating beta

adrenergic receptors

USES Tx of pts with asthma or COPD

Ritodrine and terbutaline: used to stop prematurelabor

Dobutamine is sometimes useful in mngt ofsevere heart failure


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AGONISTS

AE & CI Tachycardia and cardia

stimulation Chest pain Arrhythmias Muscle tremor

Hyperglycemia


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ANTAGONISTS

MECHANISM OF ACTION Competitive antagonists at beta adrenergic

receptors Propranolol has a membrane-stabilizing effect (in

high doses) Pindolol and Acebutolol are partial agonists Labetalol and Carvedilol also block alpa-receptor

antagonist and so lower peripheral resistance


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ANTAGONISTS

USES

Tx of cardiovascular disease statesincluding angina, hypertension andarrhythmias

Tx of hypertension as monotherapy Timolol tx of glaucoma Tx hyperthyroidism, migraine,

headache, performance anxiety andeven alcohol withdrawal


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ANTAGONISTS

AE & CI Bradycardia Bronchospasm or asthmatic

attacks Fatigue, depression, and

nightmares

parasympathetic nervous system drugs

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