Pharmacology of ANS - Part I (Drugs Acting on Sympathetic System) PDF

DRUGS ACTING ON SYMPATHETIC NERVOUS SYSTEM ADRENERGIC & ADRENORECEPTOR BLOCKING AGENTS Lecture - 26/08/2024 By MS. RINI DINESH SANGARRAN 1  LEARNING OUTCOMES At the end of the lecture, students must be able to, 1. state the commo...

DRUGS ACTING ON SYMPATHETIC NERVOUS SYSTEM ADRENERGIC & ADRENORECEPTOR BLOCKING AGENTS Lecture - 26/08/2024 By MS. RINI DINESH SANGARRAN 1  LEARNING OUTCOMES At the end of the lecture, students must be able to, 1. state the commonly used adrenergic agonists in optometry. 2. list the commonly used adrenergic antagonists in optometry. 3. briefly describe the actions, uses and untoward effects of commonly used adrenergic agonists and antagonists. 2  LECTURE OUTLINES 1. Component of nervous system 2. Component of CNS and ANS 3. Neurotransmitters of nervous systems 4. Sympathetic nervous system and its receptors 5. Drugs acting on sympathetic nervous system 6. Pharmacological action, uses and untoward effects of commonly used adrenergic agonists and antagonists in optometry 3 NERVOUS SYSTEM Central nervous system Peripheral nervous system The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves. 4  5 KTO OPTOMETRY 6 7  8 9 12 13 TYPES OF DRUGS ACTING ON ANS Sympathomimetic drugs Sympatholytic drugs Parasympathomimetic drugs Parasympatholytic drugs 14 15  SYMPATHOMIMETICS (ADRENERGIC AGONISTS) Effects resemble the effect of stimulation of sympathetic nervous system. Depending on the type of receptor concerned. Acts on: ✓ Alpha (α) - α1 & α2 ✓ Beta (β) - β1, β2 & β3 ✓ Dopamine (D) - D1, D2, D3, D4 & D5 13 ADRENERGIC RECEPRTORS 17 ADRENERGIC RECEPRTORS 18 ADRENERGIC RECEPRTORS 19 17 21 ADRENERGIC DRUGS - CLASSIFICATION 19 COMMON SYMPATHOMIMETIC DRUGS USED IN OPTHOMOLOGY 1. Epinephrine /Adrenaline 2. Dipivalyl epinephrine 3. Phenylepherine 4. Hydroxy amphetamine 5. Clonidine 6. Apraclonidine 7. Brimonidine 8. Ibopamine 25  EPINEPHRINE /ADRENALINE Stimulates both α and β receptors. Pharmacological Actions: Decreases aqueous humor formation. Increases trabecular outflow by stimulating β2 adrenergic receptors in the trabecular meshwork. Mydriasis due to radial muscle of iris contraction (1). Constricts conjunctival blood vessels (1). 26 27 ADRENALINE IN GLAUCOMA 28 USES OF EPINEPHRINE As initial or adjunctive agent in glaucoma therapy. As mydriatic agent. In ocular surgery (to control bleeding). As conjunctival decongestant. 30 31  USES OF EPINEPHRINE (Contd.,) Ocular surgery (to control bleeding): just prior to operation, to avoid capillary oozing during surgery. can be mixed with Local anaesthetic for injection to lessen bleeding at the site of incision and to retard the rate of absorption of LA at the operation site. As conjunctival decongestant: A drop of topical epinephrine causing quick disappearance of congestion of a red eye indicates superficial congestion. 32  OCCULAR SIDE EFFECTS SYSTEMIC SIDE EFFECTS Slight burning sensation Extrasystoles Eye ache Tachycardia Corneal edema Patients with Drug allergy ✓ Heart disease Retinal haemorrhage ✓ Thyrotoxicosis Epinephrine maculopathy ✓ Hypertension (Usually seen in aphakic eye) ✓ Diabetes Aphakia = Absence of the lens of an eye 33  2. DIPIVALYL EPINEPHRINE Prodrug which undergoes biotransformation to epinephrine within the cornea MOA – Reduces IOP by decreasing aqueous production enhancing the outflow facility. increased lipophilicity- its penetration across the cornea is 17 times more than epinephrine. Lesser doses are needed to be administered as compared to epinephrine. It is better tolerated than epinephrine. Use - initial therapy or as an adjunct with other ocular hypotensive agents 36 37  3. PHENYLEPHERINE Selective α1 agonist Uses: ▪ As a mydriatic (2.5% to 10%). Pharmacological Actions: ▪ Used along with miotic to prevent miotic ◦ Mydriasis cyst formation. ◦ Vasoconstriction ▪ Used as conjunctival vasoconstrictor (0.125%). Contraindications: Hyperthyroidism Infants Diabetes mellitus Coronary heart disease Hypertensive individuals 39 31  4. HYDROXY AMPHENATMINE Indirectly acting sympathomimetic agent. Depletes norepinephrine from adrenergic nerve terminals : causes mydriasis. Used as a mydriatic. 43 44 45 46  5. CLONIDINE α2 agonist. Mechanism of anti-glaucoma action: Stimulation of α2 → Norepinephrine release → less stimulation of β r/c → AH formation. Improvement in uveoscleral or trabecular flow. Use – Glaucoma Adverse reactions: ✓ Fall of blood pressure ✓ Slight conjunctival irritation, blanching. 49  6. APRACLONIDINE Selective α2 agonist. Use - Mainly as short time medication. E.g.: Management of IOP after laser surgery, prior to cataract as an adjuvant with mydriatics (with anatomical narrow angle) Side effects: Similar to those of clonidine except no effect on BP. Slight conjunctival irritation, blanching Drawback – On prolonged use, may give rise to allergic manifestation (local) in 50% of cases. 37  7. BRIMONIDINE Specific α2 agonist ↓IOP USES: ✓ Acute IOP rise after surgery ✓ Glaucoma Side effects: ✓ Systemic (dry mouth, sedation, fatigue) ✓ Local (blanching, allergy) 54  8. IBOPAMINE Prodrug of N-methyl dopamine that has dual mechanism of action. Acts on both adrenergic and dopaminergic receptors. Its alpha-adrenergic action is responsible for a marked mydriasis without accommodative paralysis, while the dopaminergic action promotes the production of aqueous humor. Uses: As mydriatic agent. 1% is used for provocative test for glaucoma (for diagnostic purposes). 56 ADRENERGIC ANTAGONISTS/ ANTI- ADRENERGICS 40  MOA OF ADRENERGIC ANTAGONISTS Inhibits the effects of catecholamine by competing for adrenergic receptor sites. Preventing endogenous catecholamine from exerting their effects. - Inhibit specifically alpha or beta receptors. 58  COMMONLY USED ADRENERGIC ANTAGONISTS IN OPTHAMOLOGY Alpha 1 antagonists : Thymoxamine, Dapiprazole. Beta antagonists: ✓ Non-selective – Carteolol, Levobunolol, Metipranolol, Timolol. ✓ Selective – Betaxolol, Levobetaxolol. 59  1. ALPHA-1 ANTAGONISTS THYMOXAMINE / DAPIPRAZOLE: Blockade of α1 receptor causes miosis, no action on IOP and accommodation. Uses: ✓ Reversal of mydriasis produced by phenylepherine, tropicamide etc. (complete recovery within 30 min) AE: ✓ Little conjunctival hyperaemia (loss of vascular tone) 60  2. BETA-BLOCKERS OF OPTHALMIC IMPORTANCE Inhibition of β2 receptors of eye. Inhibition of cAMP in the ciliary epithelial cells. AH production is minimized. Pharmacological Action: Ocular hypotensive action (↓ IOP) Therapeutic use: Glaucoma - chronic open angle glaucoma - ocular hypertension and open-angle glaucoma 61  DIFFERENT PREPARATIONS OF BETA-BLOCKERS Betaxolol: Beta 1 specific antagonist. ✓ Relatively safer to use in patients with ischaemia, bradycardia and depressed pulmonary function. ✓ Should be avoided in patients having bronchospasm. Levobunolol: ✓ As eye drop once or twice daily. Metipranolol: ✓ Eye drop once or twice daily. 63  DIFFERENT PREPARATIONS OF BETA-BLOCKERS Cartelol ✓ Nonselective beta blocker. ✓ Twice daily. Adaprolol ✓ One of the newer agents. ✓ Very short plasma half life (about 7 min). ✓ Locally beta blocker , by acting on local ocular tissues and quickly metabolized. ✓ Systemic toxicity is practically nil. 64  ADVERSE EFFECTS OF BETA-BLOCKERS Systemic: ✓ CVS - bradycardia, hypotension, heart block. Local: ✓ Respi - bronchospasm (esp in bronchial asthma) ** ✓ Dry eye syndrome ✓ CNS - mental depression, loss of memory, lack of libido. ✓ Ocular and orbital ✓ GI - anorexia, nausea, vomiting, diarrhoea. pain. ✓ Dermal – allergic rash. ✓ Endocrine – masking signs and symptoms of hypoglycaemia. ✓ General – headache, fatigue, muscle asthenia. 47 48 CONTRAINDICATIONS OF BETA-BLOCKERS Patients with - Respiratory obstructive disease Bronchial asthma Heart block 67  IMPORTANT DRUG INTERATIONS OF BETA-BLOCKERS Potentiation of drug – if the patient is already on any other (oral) beta blocker. Topical beta blocker + oral CVS drugs – Caution Heart block, Hypotension, Cardiac failure. Diabetes - Mask signs and symptoms of hypoglycaemia Thyrotoxicosis - Withdrawal of beta blockers may worsen the disease. 68 51