Cholinergics And Anticholinergics Drugs-2

AUTONOMIC SYSTEMS AND DRUGS-2

Epinephrine Norepinephrine Acetyl choline

Adrenergic Cholinergic

HR Contractility Transmitter(s)

Sympathetic

Norepinephrine Epinephrine

Parasympathetic

Acetyl Choline

Vascular smooth muscle

Sympathetic only (or nearly so)

Synthesized from:

Tyrosine

Rate limiting reaction:

Tyrosine hydroxylase

COMT - catechol-O-methyltransferase MAO - monoamine oxidase

Reuptake into the nerve ending by an active transport system

Reserpine

Inhibits storage in vesicles

αMethyldopa

False transmitter

Guanethidine Amphetamine Imipramine Fluoxetine

Inhibits NE release Stimulates NE release Inhibits NE reuptake Inhibits serotonin reuptake

Alpha

Beta

Generally excitatory

Generally inhibitory

Exception: intestinal smooth muscle

Exception: beta1 in the heart

Muscarinic

Nicotinic

Acetylcholinesterase

Cholinergic agonists •Bethanechol •Pilocarpine •Carbachol Antimuscarinics •Atropine •Scopolamine Anticholinesterases •Neostigmine •Organophosphates (e.g. DFP) Neuromuscular blockers •Tubocurarine •Pancuronium •Succinyl Choline

Parasympathomimetics: limited uses •Glaucoma •Pupillary constriction (meiosis) Not used for: •Bronchial Asthma •Coronary Insufficiency •Peptic Ulcer •Hyperthyroidism

Atropine; Scopalamine Therapeutic uses: •Motion sickness •Pupillary dilation •Parkinson’s Disease

Side effects: •Dry mouth •Blurred vision •Tachycardia •Urinary retention •Constipation

Reversible

Irreversible

Neostigmine Physostigmine

Organophosphates (e.g. DFP)

Predict effects on: • Eye • GI tract • Urinary tract • Skeletal muscle

• Atropine • Pralodoxime

Reversal of atropine poisoning: • Physostigmine

• Glaucoma • Paralytic ileus • Mysathenia gravis

Pancuronium

Succinylcholine

Mechanism

Competitive

Depolarizing

Onset

1-2 min

20-40 sec

Duration

30-60 min

2-5 min

Side Effects

BP tendency

Cardiac arrhythmia Prolonged apnea Malignant hyperthermia

Autonomic reflexes modulate drug responses BP

SNS

PSNS

BP

SNS

PSNS

What is the treatment of choice for anaphylactic shock? Epinephrine

Why? It is the only drug that addresses the most serious manifestations: •β

1

•β

2

increases cardiac output relaxes constricted bronchioles

• α 1 constricts capillaries

β 2-Selective Adrenergic Agonists • Albuterol • Terbutaline Bronchial dilators Uterine relaxant (ritodrine)

α 1 Adrenergic Agonists •Phenylephrine •Ephedrine

Therapeutic uses: •Nasal decongestants •Used with local anesthetics •Local hemostasis •Mydriatic •Glaucoma •Vasopressor •Appetite suppressant

Alpha blockers • Prazosin (α 1) • Phenoxybenzamine (α 1α 2) • Phentolamine (α 1α 2) Hypertension

Beta blockers: •Propranolol (β •Metoprolol (β •Atenolol (β •Timolol (β

1 1

1 1

β 2)

)

)

β 2)

Therapeutic uses: •Arrhythmia •Angina pectoris •Hypertension

Alpha blockers • Postural hypotension • Tachycardia • First dose (prazosin)

Beta blockers • Cardiac depression • Asthma attack • Nightmares, lassitude, depression • Angina pectoris (abrupt withdrawal)

Tolcapone

Carbidopa

Selegiline

Reduced with carbidopa

GI - nausea and vomiting Hypotension Dyskinesias Psychiatric reactions

Drugs to Know Levodopa

used in combination

Carbidopa Amantidine

DA reuptake inhibitor (?)

Bromocryptine DA receptor agonist Selegiline MAO-B inhibitor Tolcapone COMT inhibitor