AUTONMOIC NEURVOUS SYSTEM

DENTAL PHARMACOLOGY

ADRENERGIC AGONISTS (SYMPATHOMIMETIC AGENTS)

• Adrenergic agonists mimic the actions of sympathetic.

• Adrenergic neurons release norepinephrine as the primary neurotransmitter.

• NA from the synaptic cleft diffuses into circulation and gets inactivated by catechol-O-methyltransferase (COMT) and monoamine oxidase ( MAO)

Types, Distribution and Functions of Adrenergic Receptors

1. Direct-acting SympathomimeticsAdrenergic Agonists Receptor Action Therapeutic Uses1. Directly acting

Adrenaline a1-, a2-, B1-, B2- and Anaphylactic shock, Bronchial asthma(acute), Cardiac arrest, to prolong theDuration of local anaesthesia, to controlEpistaxis (ABCDE)

• Noradrenaline a1-, a2- and B1-agonist Hypotensive statesIsoprenaline B1- and B2-agonist Heart block, cardiac arrest

• Dobutamine Relatively selective Cardiogenic shock due to acuteB1-agonist myocardial infarction (MI), congestive

cardiac failure (CCF) or cardiac surgerySalbutamol (Albuterol) Selective B2-agonists Bronchial asthma

Phenylephrine Selective a1-agonists Vasopressor agents, nasal decongestants,as mydriatic (phenylephrine), allergicrhinitis

• Naphazoline a1 + a2-agonists Nasal decongestants(a1-stimulation),

• Clonidine, a-Methyldopa a2-agonists Hypertension

Adverse effects and contraindications direct-acting

Adverse effects– They are tachycardia, palpitation, headache,

restlessness, tremor and rise in BP. – The serious side effects are cerebral haemorrhage

and cardiac arrhythmias.contraindicated in most of the cardiovascular

diseases such as hypertension, angina, cardiac arrhythmias, CCF, etc

2 .Indirect-acting SympathomimeticsAdrenergic Agonists Receptor Action Therapeutic Uses2. Indirectly acting

Amphetamine They act by releasing NA Narcolepsy, attention-deficit hyperkinetic

Methamphetamine disorder (ADHD)

Methylphenidate

3. Mixed actingEphedrine a1, a2, B1 and B2 (direct

action)Intravenous ephedrine is used

for the+ releases NA (indirect

action)treatment of hypotension due

to spinalanaesthesia

Dopamine a1, a2, B1 and D1 + releases NA

Cardiogenic shock, CCF with oliguria

Adverse effects and contraindicationsIndirect-acting

• The side effects are restlessness, insomnia, confusion, fatigue, tremor, hallucinations and suicidal tendencies.

• The cardiac side effects are tachycardia, palpitation, hypertension, angina and cardiac arrhythmias

ADRENERGIC RECEPTOR BLOCKERS(SYMPATHOLYTIC AGENTS)

• Adrenergic-receptor antagonists block the effects of sympathetic pathway.

ALPHA-ADRENERGIC BLOCKERS

Irreversible Nonselective a-Blocker

Phenoxybenzamine• Peripheral vascular resistance is reduced due

to the blockade of vascular α1-receptors.• Used in the treatment of pheochromocytoma.• The side effects are hypotension, tachycardia,

palpitation, diarrhea, and impotence.

Reversible Nonselective a-Blocker

Phentolamine• Has rapid onset but short duration of action. It

is used intra-operatively during surgery of pheochromocytoma, in hypertensive emergencies

• Adverse effects– They include tachycardia, palpitation, arrhythmias;

angina and Myocardial Infraction may be precipitated.

Selective α1-Blockers Prazosin, Doxazosin, Tamsulosin, Terazosin

• Prazosin is a potent and selective a1-adrenergic receptor blocker.

• Doxazosin is the longest-acting, selective a1-blocker.

• Tamsulosin – an uroselective a1-blocker (a1A). At low doses, it

reduces the resistance to flow of urine with little effect on BP.

– It is the preferred a1-blocker for the treatment of benign prostatic hyperplasia (BPH)

Selective α1-Blockers• Therapeutic Uses– Essential hypertension– Benign prostatic hyperplasia– Pheochromocytoma

• Adverse effects– First-dose phenomenon: Within 30–90 min of oral administration

of prazosin, severe hypotension and syncopal attacks may be seen with first dose.• Therefore, the initial dose should be small . It is usually given at bed time

so that the patient remains in bed for several hours and the risk of syncopal attack is reduced

BETA-ADRENERGIC BLOCKERS

BETA-ADRENERGIC BLOCKERSMechanism of action– competitively block β-receptors.

Pharmacological actions– Cardiovascular system:• Decrease heart rate (negative chronotropic effect).• Decrease the force of myocardial contractility (negative inotropic effect).

– Respiratory system: • Blockade of B2-receptors in bronchial smooth muscle can produce severe

bronchospasm in patients with COPD and asthma.• Selective B1-blockers such as atenolol, metoprolol, etc. are less likely to cause

bronchospasm.– Skeletal muscle:

• On chronic use, B-blockers may cause skeletal muscle weakness and tiredness due to blockade of B2-receptors of the skeletal muscle and blood vessels supplying it. They also reduce stress-induced tremors.

– Metabolic effects:• B-Blockers inhibit glycogenolysis and delay recovery from hypoglycaemia.• They also mask the warning signs and symptoms of hypoglycaemia

– Eye: B-Blockers on topical administration decrease IOP

BETA-ADRENERGIC BLOCKERS• Therapeutic uses

– Hypertension– Angina pectoris and MI: B-Blockers reduce myocardial O2

demand – Congestive cardiac failure , carvedilol, metoprolol and

bisoprolol – Pheochromocytoma– Glaucoma ,Timolol– Prophylaxis of migraine: Propranolol, atenolol and metoprolol – Hyperthyroidism: The signs and symptoms of hyperthyroidism

such as tachycardia, palpitation, tremor, anxiety, etc– Acute anxiety states

BETA-ADRENERGIC BLOCKERS

• Adverse effects – CNS: Sleep disturbances, fatigue and mental

depression.– CVS: Bradycardia, heart block – Muscular weakness and tiredness– Withdrawal symptoms– Mask the warning signs and symptoms of

hypoglycaemia

CHOLINERGIC AGENTS (CHOLINOMIMETICS, PARASYMPATHOMIMETICS)

• Acetylcholine is rapidly hydrolyzed by cholin-esterases it has no therapeutic application.

Cholinergic receptors • Muscarinic: M1, M2, M3

Activated by muscarine, Ach.• Nicotinic: NM (Skeletal muscle), NN

(neuronal ) Activated by nicotine, Ach.

Muscarinic Receptor Stimulation

• Eye (M3) - miosis• Heart (M2) - bradycardia and a decrease in

blood pressure • Lungs (M3) – bronchospasm, increase secretion• Gastrointestinal - increase in motility (M3) , and

secretion (M1) .• Glands (M3) - increase Secretion-sweat,

salivation, and lacrimation• Blood vessels (M3) – vasodilatation

Cholinergic agonists

Directly acting (on the receptors)

Pilocarpine

Acetylcholine

Carbachol

Bethanechol

Indirectly acting(anti-cholinesterase)

Reversible

Physostigmine

Edrophonium

Neostigmine

Irreversible

Organophosphorus compounds

Parathion

Malathion

Sarin (nerve gases)

Clinical Uses Directly acting

• Postoperative urinary retention, paralytic ileus and dry mouth Bethanechol

• Glaucoma Carbachol, Pilocarpine• Xerostomia Pilocarpine

Clinical Uses Indirectly acting

Reversible Anticholinesterases• Glaucoma Physostigmine• Atropine poisoning Physostigmine• Myasthenia gravis Neostigmine , Edrophonium

• Curare poisoning and reversal of non-depolarising neuromuscular blockade Neostigmine

• Postoperative urinary retention and paralytic ileus Neostigmine

Clinical Uses Indirectly acting

• Irreversible Anti-cholinesterasesOrganophosphorus compounds insecticidesAcute toxicity• Excessive muscarinic and nicotinic stimulationsMuscarinic effects:- Diarrhea- Urination- Miosis- Bradycardia- Bronchoconstriction- Lacrimation- Salivation- Sweating

Nicotinic effects:- Skeletal muscle excitation followed by paralysis- CNS stimulation :confusion, convulsions, coma, and death occurs usually due to respiratory failure.

Irreversible Anti-cholinesterases

Management of Organophosphorus compounds toxicity :

• Muscarinic effects: atropine ( antimuscarinic)• Regeneration of AChE: pralidoxime

ANTICHOLINERGIC AGENTS (CHOLINERGIC RECEPTOR BLOCKERS)

SKELETAL MUSCLE RELAXENT

ANTIMUSCARINIC AGENTS

• These drugs block muscarinic-receptor-mediated actions of acetylcholine on heart, CNS, smooth muscles and exocrine glands.

• Leading to opposite action of parasympathommetics.

Pharmacological Actions• Central Nervous System

– Inhibit vomiting centre – excitation , hallucinations, Sedation, coma (high dose)

• Exocrine Glands– Decreased secretions (salivary, bronchiolar, sweat)

• Smooth Muscle– Relax smooth muscles in gastrointestinal tracts and Delay gastric emptying

constipation– Relax smooth muscles in the respiratory Bronchial dilation.– Urinary retention

• Eye– Mydriasis , decrease Lacrimation

• Cardiovascular– Tachycardia

Clinical Uses

• Preoperative Medication : (Atropine )– They inhibit salivary and bronchial secretions.– To prevent bradycardia during anaesthesia.

• Sialorrhoea (hypersalivation):(glycopyrrolate, propantheline)– Used to decrease salivary secretion, e.g. during dental

procedures.• COPD and bronchial asthma:

(Ipratropium ,Tiotropium)– They produce bronchodilatation

Clinical Uses

• Antispasmodics in intestinal, renal colic and dysmenorrhoea. (hyoscine N- butyl bromide)

• Ophthalmologic Examinations (Tropicamide)

• Parkinsonism —Benzhexol

• Motion Sickness —Scopolamine (hyoscine).

ANTIMUSCARINIC Adverse Effects

• Decreased secretions (salivary, bronchiolar, sweat) ……. Dryness of the mouth

• Mydriasis• Hyperthermia• Tachycardia• Sedation• Urinary retention and constipation• Behavioral: excitation and hallucinations

GANGLIONIC BLOCKERS

• Blockade of sympathetic ganglia results in marked hypotension.

• Blockade of parasympathetic ganglia results in ‘atropine-like’ actions.

• Nicotine is obtained from tobacco leaves. It has a prolonged blocking effect on the autonomic ganglia.

THE END