Autonomic Nervous System

Nervous system: - Central (CNS) - Peripheral (ANS) Sympathetic NS (Thoracolumbar) Parasympathetic NS (Craneosacral) Cranial nerves III, VII, IX, X (vagus nerve) NA = Noradrenaline = NE = Norepinephrine Ad = Adrenaline = EP = Epinephrine Ach = Acetylcholine

Symp. C Ach NA O Ach Ach Parsymp. R Ach Motor Nerves D

Sympathetic receptors: ** α-receptors (2 types) : - α1- receptors; postsynaptic receptors; NA & AD agonists Mediate a. Vasoconstriction (skin) → ↑ B.P b. Dilatation of pupils - α2- receptors; presynaptic receptors; inhibitory in nature; clonidine agonist

α1- blockers; phentolamine; prazosin ** β- receptors (2 types): - Β1- receptors; postsynaptic; NA, AD, isoprenaline (agonists) Mediate: - ↑ heart rate (tachycardia) - ↑ heart contractility - ↑ cardiac output

- β2-receptors; postsynaptic; AD, isoprenaline, salbutamol (albuterol) agonists Mediate: - broncchodilation - dilatation of muscle & heart blood vessels β- blockers: - Selective; block only β1 receptors (atenelol) - Nonselective; block β1 & β2 receptors (propranolol)

Sympathomimetic drugs Drugs producing effects similar to sympathetic activity 1. Adrenaline=Epinephrine Effects: - ↑ heart rate & contractility - ↑ systolic B.P - bronchodilatation - pupil dilatation

- ↑ blood sugar level - ↓ GIT motility - ↓ salivary secretions Adrenaline is ineffective orally; given S.C or I.M I.V injection is contraindicated → fatal cardiac arrhythmias (ventricular fibrillation)

AD & NA effects are mainly terminated by a high specific uptake mechanism (inhibited by cocaine & TCA’s) Also metabolized by monoaminoxidase (MAO) & catecholamine O-methyl transferase enzymes (COMT) AD clinical uses: - Anaphylactic shock - Cardiac arrest - Combined with L.A’s

2. Noradrenaline=Norepinephrine: Most important effect is widespread vasoconstriction & ↑ in B.P; bradycardia Mainly used in the management of shock and given in an I.V infusion 3. Isoprenaline (Isoproterenol): Stimulates β1 & β2 receptors; a good bronchodilator & ↑ heart rate & contractility

Isoprenaline clinical uses: - Bronchial asthma Given orally or by inhalation - Shock & cardiac arrest Given I.V Isoprenaline side effects: - Palpitation - Cardiac arrhythmias

4. Selective β2 agonists: Salbutamol (albuterol); terbutaline; perbuterol Salbutamol is the most widely used drug in the management of bronchial asthma and chronic bronchitis Given by inhalation, orally and I.V Produces little if any effects on the heart

5. Dopamine (DA): β1 stimulant used in shock and given in an I.V infusion 6. Amphetamine: Has marked CNS stimulant effect It suppresses appetite ↑ B.P Stimulates respiration

Cont. Amphetamine… ↑ mental activity ↑ alertness Given orally Clinical uses: - Narcolepsy (frequent deep sleep) - Hyperkinetic syndrome Major disadvantage: leads to addiction

Adrenergic blockers - α- blockers (α1) * Phentolamine : Given I.V and used in the management of pheochromocytoma (a tumor affecting the adrenal medulla & characterized by high levels of AD & an ↑ in B.P)

* Prazosin: Another α1 blocker given orally in the management of hypertension B.P = CO × Peripheral resistance Ht. rate & Bld. Vol. Diam. B.V contractility

- β-blockers * Selective (block only β1-receptors) Atenolol; bisoprolol; betaxolol… * Nonselective (block both β1 & β2 receptors) Propranolol; oxprenol; pindolol; timolol; sotalol; nadolol… - α & β blockers Labetalol; carvedilol (block α & β receptors)

β- blockers differ in potency, duration of action & route of administration General effects to β-blockers: - ↓ Ht. rate, ↓ Ht. contractility, ↓ cardiac output - ↓ B.P - ↓ sweating, ↓ tremors, ↓ nervousness (antianxiety or anxiolytic effect) - Bronchospasm

Clinical uses to β-blockers: - Hypertension - Angina pectoris - Cardiac arrhythmias - Thyrotoxicosis - Essential tremors, Parkinson’s disease - Anxiety (stage phobia)

Preparations to β-blockers: Oral and parenteral dosage forms Side effects to β-blockers: - Bronchospasm - Severe drop in CO Contraindications to β-blockers: - Bronchial asthma - Severe heart failure

Parasympathomimetic drugs Cholinergic system Acetylcholine (Ach) - Parasympathetic nerve terminal & sweat glands Muscarinic receptors - Ganglia & voluntary muscles Nicotinic receptors Not used clinically; quickly broken down by cholinesterase enzyme

Ach effects: - ↓ heart rate - ↑ salivation - ↑ GIT motility - ↑ urinary bladder muscle contraction - Dilates blood vessels - Contracts bronchi - Constricts pupils and accommodates for near vision

Carbachol & bethanechol: Synthetic Ach-like drugs. Have similar effects to Ach but not affected by cholinesterase so have more prolonged effect. Given orally & S.C Clinical uses: - urine retention following surgery or child birth - Clear bowel gases before x-rays Side effects: Abdominal pain; diarrhea, ↓ B.P

Anticholinesterases - Physostigmine ↑ Ach effects at all sites. Most important effects: a. Constriction of pupils b. ↑ intestinal movement Clinical uses: a. Glaucoma b. Myasthenia gravis Given orally; S.C; locally to eye

- Neostigmine Has similar effects to physostigmine but has more effect at neuromuscular junction Given orally; S.C; I.M Clinical uses: a. Myasthenia gravis b. Paralytic ileus c. Urine retention

Many anticholinesterases are not used clinically but used as insecticides or weapons in war (chemical weapons) known as nerve gases, therefore side effects produced by such drugs are important to know Side effects include: Abdominal pain, diarrhea, sweating, constriction of pupils, salivation, ↓ B.P → death Rx: - Atropine S.C - Pralidoxime (cholinesterase reactivator) given I.V

Parasympatholytics (inhibitorrs of Ach action) Anticholinergics Antimuscarinics Atropine: An anticholinergic drug blocks muscarinic receptors at all sites Origin: plant source Atropa belladona

Atropine actions: (anticholinergic effects) - ↓ intestinal movement (↓ spasm) - ↑ heart rate - Dilatation of the pupils; cycloplegia; loss of accommodation to near vision - ↓ salivary and respiratory secretions - Dilatation of bronchi Atropine could be given orally; S.C; I.M & I.V

Atropine clinical uses: - Preoperative medication ( to ↓ salivary and bronchial secretions) - To dilate pupils for eye examinations Homatropine is used because it has shorter duration of action - Abdominal pain or spasm Hyoscine (scopolamine is better) - Bradycardia; atropine I.V

Cont. atropine clinical uses… - Bronchial asthma Ipratropium bromide…atropine-like drug given by inhalation to patients with bronchial asthma - Parkinson’s disease Benzhexol…atropine-like drug reduces over activity of Ach in patients with Parkinsonism

Cont. atropine clinical uses… - Peptic ulcer disease Atropine ↓ acid secretion, but replaced recently by newer drugs due to it’s side effects - Congenital pyloric stenosis Atropine methonitrate is used. It relaxes the pylorus and given orally ½ hr before feeds - Poisoning with anticholinesterases

Atropine side effects (anticholinergic effects): - Dry mouth - Blurred vision - Constipation - Difficulty in micturition - Loss of accommodation to near vision - Hallucination - Delirium

Hyoscine (scopolamine) - Atropine-like drug - Synthetic - Has more CNS effects e.g. drowsiness and sedation - Used as an antiemetic and antispasmodic - Given orally, parenterally and rectally