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