AUTONOMIC SYSTEMS AND DRUGS-2

Epinephrine

NorepinephrineAdrenergic

CholinergicAcetyl choline

Sympathetic

Parasympathetic

HR Transmitter(s)Contractility

Norepinephrine

Epinephrine

Acetyl Choline

Vascular smooth muscle

Sympathetic only (or nearly so)

Synthesized from: Tyrosine

Tyrosine hydroxylaseRate limiting reaction:

COMT - catechol-O-methyltransferase

MAO - monoamine oxidase

Reuptake into the nerve ending by an active transport system

Reserpine

-Methyldopa

Guanethidine

Amphetamine

Imipramine

Fluoxetine

Inhibits storage in vesicles

False transmitter

Inhibits NE release

Stimulates NE release

Inhibits NE reuptake

Inhibits serotonin reuptake

Alpha Beta

Generally excitatory

Exception: intestinal smooth muscle

Generally inhibitory

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

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

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

Atropine; Scopalamine

Reversible Irreversible

Predict effects on:

• Eye

• GI tract

• Urinary tract

• Skeletal muscle

Neostigmine

Physostigmine

Organophosphates(e.g. DFP)

• Atropine

• Pralodoxime

Reversal of atropine poisoning:

• Physostigmine

• Glaucoma

• Paralytic ileus

• Mysathenia gravis

Pancuronium Succinylcholine

Mechanism

Onset

Side Effects

Competitive Depolarizing

1-2 min

Duration

20-40 sec

30-60 min 2-5 min

BP tendency Cardiac arrhythmia

Prolonged apnea

Malignant hyperthermia

Autonomic reflexes modulate drug responses

BP SNS PSNS

SNS PSNSBP

What is the treatment of choice for anaphylactic shock?

Epinephrine

Why?

It is the only drug that addresses the most serious manifestations:

• increases cardiac output

• relaxes constricted bronchioles

• 1 constricts capillaries

• Albuterol

• Terbutaline

2-Selective Adrenergic Agonists

Bronchial dilators

Uterine relaxant (ritodrine)

1 Adrenergic Agonists

•Phenylephrine•Ephedrine

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

Therapeutic uses:

Alpha blockers

• Prazosin (1)

• Phenoxybenzamine (12)

• Phentolamine (12)

Hypertension

Beta blockers:

•Propranolol (1 2)

•Metoprolol (1 )

•Atenolol (1 )

•Timolol (1 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)

Carbidopa

Tolcapone

Selegiline

GI - nausea and vomiting

Hypotension

Dyskinesias

Psychiatric reactions

Reduced with

carbidopa

Drugs to Know

Levodopa

Carbidopa

Amantidine

Bromocryptine

Selegiline

Tolcapone

DA reuptake inhibitor (?)

DA receptor agonist

MAO-B inhibitor

COMT inhibitor

used in combination