Ocular Pharmacology & Autonomic Review

👁️ Glaucoma Overview

Open‑angle glaucoma – chronic, progressive optic neuropathy
Elevated IOP due to reduced aqueous humor outflow (trabecular meshwork dysfunction)
Painless visual field loss → eventual blindness if untreated
IOP = (aqueous production) – (outflow via trabecular + uveoscleral routes)

                    Drug strategies target either ↓ production (β‑blockers) or ↑ outflow (PGF₂α analogs)

                

β-blockers (timolol) → ↓ ciliary epithelium secretion ↕ PGF₂α (latanoprost) → ↑ uveoscleral outflow

Direct muscarinic agonists
- Bethanechol (M₃ selective) – bladder, GI
- Pilocarpine – glaucoma (miosis, ↑ outflow)
- Cevimeline – xerostomia (M₁/M₃)
AChE inhibitors – increase synaptic ACh
- Reversible: edrophonium (short), physostigmine (crosses BBB), neostigmine, donepezil
- Irreversible: malathion, parathion (organophosphates)
Muscarinic antagonists
- Atropine – mydriasis, cycloplegia, antispasmodic
- Ipratropium – inhaled for COPD/asthma
- Scopolamine – motion sickness, anticholinergic
Ganglionic blockers (nicotinic)
- Hexamethonium, mecamylamine – block both SNS & PNS ganglionic transmission
- Used in research / refractory hypertension (rare)

Drug	Receptor	Key Use
Bethanechol	M₃	Urinary retention
Pilocarpine	M	Glaucoma, xerostomia
Neostigmine	AChE inhibitor	Myasthenia gravis
Atropine	M antagonist	Bradycardia, anticholinesterase overdose

α₁ agonists – phenylephrine (vasoconstriction, mydriasis)
α₂ agonists – clonidine, methyldopa (↓ sympathetic outflow)
β agonists
- Isoproterenol (β₁=β₂) – non‑selective, cardiac + bronchodilation
- Dobutamine (β₁>β₂) – inotrope in cardiogenic shock
- Albuterol, terbutaline, salmeterol – β₂ selective (bronchodilation, tocolytic)
Mixed / indirect
- Epinephrine (α₁, α₂, β₁, β₂) – anaphylaxis, cardiac arrest
- Norepinephrine (α₁, α₂, β₁) – septic shock
- Dopamine (D₁, β₁, α₁) – dose‑dependent
- Indirect: amphetamine, cocaine, ephedrine, tyramine (↑ NE release)

α₁ antagonists – prazosin, doxazosin, terazosin (BPH, hypertension)
α₂ antagonists – mirtazapine (antidepressant)
Mixed α antagonists – phenoxybenzamine (irreversible), phentolamine (reversible)
β₁‑selective – atenolol, metoprolol, acebutolol (hypertension, angina)
Nonselective β – propranolol, timolol, pindolol (glaucoma, migraine, tremor)
α + β blockers – carvedilol, labetalol (heart failure, hypertension)

Drug X decreases BP + reflex tachycardia → blocked by mecamylamine → X is a vasodilator (e.g., hydralazine) or β₂ agonist (terbutaline)
α‑agonist (phenylephrine) – ↑ BP, reflex bradycardia (vagal)
Norepinephrine – α + β₁ effects; α‑block reduces pressor, β‑block reduces tachycardia
Epinephrine “reversal” – after α‑block, BP drops due to unopposed β₂ vasodilation
Isoproterenol – β₁ (tachycardia) + β₂ (vasodilation) → ↓ TPR, ↑ HR; blocked by propranolol
Acetylcholine (i.v.) – ↓ BP + ↓ HR; reflex tachycardia is blocked by ganglionic blocker (hexamethonium)

Phenylephrine→α₁→vasoconstriction + reflex brady Isoproterenol→β₁+β₂→tachy + vasodilation

Denervation supersensitivity – denervated tissue ↑ response to direct agonists (e.g., phenylephrine), but no response to indirect (amphetamine)
Pupil size – atropine → mydriasis; physostigmine → miosis; prazosin → minimal effect
Glaucoma medications
- β‑blockers (timolol) – reduce aqueous production
- PGF₂α (latanoprost) – ↑ uveoscleral outflow; first‑line
- Pilocarpine – ↑ trabecular outflow (miosis)
Drug X / Y problems – identify by receptor profile and reflex patterns

                    Mecamylamine blocks ganglionic transmission → abolishes reflex tachycardia, but not direct drug actions.

                

Drug	Receptor	Key effect
Phenylephrine	α₁	Pressor + reflex bradycardia
Terbutaline	β₂	Vasodilation + reflex tachycardia
Epinephrine	α+β	Pressor reversed by α‑block
Norepinephrine	α+β₁	Pressor, tachycardia blocked by β₁