Autonomic Nervous System Drugs in Ocular Pharmacology
The autonomic nervous system (ANS) plays a vital role in regulating the physiological functions of the eye. Many ocular functions such as pupil size, accommodation, aqueous humor formation, and intraocular pressure are under autonomic control. Therefore, drugs that act on the ANS are widely used in ophthalmology for both diagnostic and therapeutic purposes. This section explains the mechanisms, effects, and clinical applications of autonomic drugs in eye care.
Introduction to Autonomic Nervous System
The ANS consists of the sympathetic and parasympathetic divisions. These two divisions often have opposing effects on ocular structures:
- Sympathetic system – generally stimulates the dilator pupillae muscle, increases aqueous humor production, and modulates blood vessels.
- Parasympathetic system – contracts the sphincter pupillae muscle, controls accommodation via the ciliary muscle, and influences aqueous outflow.
Drugs that act on these systems either mimic (agonists) or block (antagonists) the neurotransmitters involved, mainly acetylcholine for parasympathetic and noradrenaline/adrenaline for sympathetic systems.
Ocular Effects of Autonomic Drugs
The main ocular functions influenced by autonomic drugs include:
- Pupil size (mydriasis and miosis)
- Light reflex
- Intraocular pressure (IOP)
- Accommodation
1. Drugs Affecting Pupil Size
(a) Mydriatics – Pupil-Dilating Agents
Mydriatics are drugs that cause dilation of the pupil. They are used in diagnostic procedures such as fundus examination and in therapeutic settings like uveitis to prevent synechiae.
- Sympathomimetic drugs
- Phenylephrine – α1 agonist, stimulates dilator pupillae muscle.
- Produces mydriasis without affecting accommodation significantly.
- Parasympatholytic drugs
- Atropine, Homatropine, Tropicamide, Cyclopentolate – block muscarinic receptors of sphincter pupillae, causing dilation.
- Also produce cycloplegia (loss of accommodation).
(b) Miotics – Pupil-Constricting Agents
Miotics contract the pupil by stimulating the sphincter pupillae muscle. They are used mainly in the treatment of glaucoma.
- Parasympathomimetic drugs
- Pilocarpine – muscarinic receptor agonist.
- Causes miosis and facilitates aqueous outflow by widening trabecular meshwork spaces.
- Cholinesterase inhibitors
- Physostigmine, Echothiophate – inhibit breakdown of acetylcholine, prolonging its effect.
2. Drugs Affecting Light Reflex
The light reflex (pupillary constriction in response to light) is mediated by the parasympathetic pathway via the sphincter pupillae muscle.
- Parasympathomimetic drugs (e.g., pilocarpine) – enhance pupillary constriction and mimic light reflex.
- Parasympatholytics (e.g., atropine, tropicamide) – abolish the light reflex by blocking acetylcholine.
- Sympathomimetics (e.g., phenylephrine) – dilate the pupil without affecting the light reflex pathway significantly.
3. Drugs Affecting Intraocular Pressure (IOP)
Intraocular pressure is determined by the balance between aqueous humor formation and outflow. Autonomic drugs can modify IOP by acting on these mechanisms.
(a) Drugs Reducing IOP
- Parasympathomimetics (Pilocarpine)
- Contracts ciliary muscle → pulls trabecular meshwork open → increases aqueous outflow.
- Sympatholytics (Beta-blockers: Timolol, Betaxolol)
- Block β-receptors in ciliary epithelium → reduce aqueous humor secretion.
- Alpha-2 agonists (Brimonidine, Apraclonidine)
- Decrease aqueous production and increase uveoscleral outflow.
- Carbonic anhydrase inhibitors (systemic and topical) – although not classic autonomic drugs, they reduce aqueous formation.
(b) Drugs Increasing IOP
- Parasympatholytics (Atropine, Tropicamide)
- Cause pupil dilation and block aqueous outflow in narrow angles → may precipitate acute angle-closure glaucoma.
- Sympathomimetics (Epinephrine, Phenylephrine)
- May increase IOP in susceptible individuals, although epinephrine also enhances outflow in open-angle glaucoma.
4. Drugs Affecting Accommodation
Accommodation is mediated by the ciliary muscle, primarily under parasympathetic control.
- Parasympathomimetics (Pilocarpine)
- Stimulate ciliary muscle contraction → increases lens curvature → near vision enhanced.
- Excessive stimulation can cause spasm of accommodation (blurred distance vision).
- Parasympatholytics (Atropine, Cyclopentolate, Tropicamide)
- Cause relaxation (paralysis) of ciliary muscle → cycloplegia → loss of accommodation.
- Used in refraction of children (cycloplegic refraction).
Classification of Autonomic Drugs in Ophthalmology
| Category | Examples | Main Ocular Effect | Clinical Use |
|---|---|---|---|
| Parasympathomimetics | Pilocarpine, Carbachol | Miosis, increased outflow, accommodation | Glaucoma, miotic therapy |
| Parasympatholytics | Atropine, Tropicamide, Cyclopentolate | Mydriasis, cycloplegia | Fundus examination, refraction, uveitis |
| Sympathomimetics | Phenylephrine, Epinephrine | Mydriasis (without cycloplegia) | Diagnostic dilation, decongestant |
| Beta-blockers | Timolol, Betaxolol | Decrease aqueous secretion | Glaucoma |
| Alpha-2 agonists | Brimonidine, Apraclonidine | Decrease aqueous production, increase outflow | Glaucoma |
Clinical Applications of ANS Drugs in Ophthalmology
- Diagnostic mydriasis – Tropicamide, Phenylephrine.
- Cycloplegic refraction – Atropine, Cyclopentolate.
- Treatment of glaucoma – Timolol, Pilocarpine, Brimonidine.
- Prevention of synechiae in uveitis – Atropine, Homatropine.
- Emergency treatment of acute angle-closure glaucoma – Pilocarpine (after IOP reduction with systemic agents).
Adverse Effects of ANS Drugs
- Pilocarpine – headache, brow ache, spasm of accommodation, reduced night vision.
- Atropine – photophobia, blurred near vision, risk of angle-closure glaucoma, systemic toxicity in children.
- Timolol – systemic absorption can cause bradycardia, bronchospasm.
- Phenylephrine – hypertension, tachycardia if absorbed systemically.
Cardiovascular Drugs in Ocular Pharmacology
The cardiovascular system is intimately linked with ocular health. Blood pressure, cardiac output, and vascular status directly affect ocular perfusion, intraocular pressure, and the risk of retinal and optic nerve diseases. Many drugs used to treat cardiovascular diseases such as antihypertensives, antianginal agents, and diuretics have direct or indirect ocular implications. Some are even used as part of ophthalmic therapy (e.g., beta-blockers in glaucoma). This article provides a detailed overview of cardiovascular drugs, their mechanisms, systemic uses, and ocular relevance.
1. Antihypertensive Drugs
Hypertension is a major systemic condition with profound ocular consequences. Chronic uncontrolled hypertension leads to hypertensive retinopathy, optic neuropathy, and increased risk of retinal vascular occlusions. Drugs that lower blood pressure are therefore highly relevant for eye care.
Classes of Antihypertensive Drugs
- Diuretics
- Beta-blockers
- Calcium channel blockers
- ACE inhibitors and Angiotensin receptor blockers (ARBs)
- Alpha-blockers and centrally acting agents
- Vasodilators
1.1 Diuretics as Antihypertensives
Diuretics lower blood pressure by increasing sodium and water excretion, thereby reducing plasma volume and cardiac output.
- Thiazide diuretics – hydrochlorothiazide, chlorthalidone.
- Loop diuretics – furosemide, bumetanide.
- Potassium-sparing diuretics – spironolactone, amiloride.
Ocular relevance: Diuretics like acetazolamide (a carbonic anhydrase inhibitor) are widely used in ophthalmology to reduce intraocular pressure in glaucoma.
1.2 Beta-Blockers
Beta-blockers reduce blood pressure by lowering heart rate, cardiac output, and renin secretion.
- Examples – propranolol, atenolol, metoprolol, carvedilol.
- Ocular application – Timolol and betaxolol eye drops are used in glaucoma to reduce aqueous humor production.
Adverse ocular/systemic effects: Systemic absorption of topical timolol may cause bradycardia, bronchospasm, and hypotension.
1.3 Calcium Channel Blockers (CCBs)
CCBs block calcium entry into vascular smooth muscle, leading to vasodilation and reduced blood pressure.
- Examples – amlodipine, nifedipine, verapamil, diltiazem.
- Ocular relevance:
- Used experimentally to improve optic nerve blood flow in normal-tension glaucoma.
- May cause side effects like conjunctival hyperemia and visual disturbances.
1.4 ACE Inhibitors and ARBs
These drugs act on the renin–angiotensin–aldosterone system (RAAS) to reduce blood pressure.
- ACE inhibitors – enalapril, lisinopril, captopril.
- ARBs – losartan, valsartan, candesartan.
- Ocular relevance: Experimental studies suggest ACE inhibitors may protect against diabetic retinopathy progression by reducing vascular damage.
1.5 Alpha-Blockers and Centrally Acting Agents
- Alpha-blockers – prazosin, doxazosin; cause vasodilation.
- Centrally acting drugs – clonidine, methyldopa.
Ocular relevance: Clonidine derivatives (e.g., apraclonidine, brimonidine) are used topically to lower intraocular pressure in glaucoma.
1.6 Vasodilators
Drugs such as hydralazine and minoxidil act directly on vascular smooth muscle to reduce peripheral resistance.
Ocular note: Vasodilators may cause ocular side effects like conjunctival hyperemia.
2. Antianginal Drugs
Angina pectoris is chest pain due to inadequate blood flow to the myocardium. Antianginal drugs aim to reduce myocardial oxygen demand or increase oxygen supply.
Classes of Antianginal Drugs
- Nitrates
- Beta-blockers
- Calcium channel blockers
2.1 Nitrates
Nitrates are converted to nitric oxide in the body, which relaxes vascular smooth muscle and reduces myocardial oxygen demand.
- Examples – nitroglycerin, isosorbide dinitrate, isosorbide mononitrate.
- Ocular relevance: Excess nitrate use can cause transient visual disturbances such as blurred vision or photophobia due to vasodilation.
2.2 Beta-Blockers
Already discussed in antihypertensives, beta-blockers also reduce anginal attacks by lowering heart rate and contractility.
Ocular relevance: As topical agents, beta-blockers lower IOP but systemic absorption must be monitored in cardiac patients to avoid bradycardia.
2.3 Calcium Channel Blockers
CCBs relieve angina by dilating coronary arteries and reducing afterload.
- Examples – nifedipine, diltiazem, verapamil.
- Ocular relevance: Some studies suggest CCBs may improve ocular blood flow in glaucoma patients, though clinical use remains limited.
3. Diuretics
Diuretics are drugs that increase urine output by promoting sodium and water excretion. They are essential in the management of hypertension, congestive heart failure, and edema. In ophthalmology, diuretics also play a special role in lowering intraocular pressure.
Classes of Diuretics
- Thiazides – hydrochlorothiazide, chlorthalidone.
- Loop diuretics – furosemide, bumetanide.
- Potassium-sparing diuretics – spironolactone, amiloride.
- Carbonic anhydrase inhibitors – acetazolamide, dorzolamide, brinzolamide.
- Osmotic diuretics – mannitol, glycerol.
3.1 Carbonic Anhydrase Inhibitors (CAIs)
These drugs inhibit the enzyme carbonic anhydrase, reducing aqueous humor production and lowering intraocular pressure.
- Systemic CAIs – acetazolamide, methazolamide.
- Topical CAIs – dorzolamide, brinzolamide.
Clinical use in ophthalmology: Widely used in glaucoma management, particularly in acute angle-closure crises along with other IOP-lowering agents.
3.2 Osmotic Diuretics
Osmotic agents increase plasma osmolarity, drawing water from tissues into the bloodstream and reducing intraocular and intracranial pressure.
- Mannitol (IV) – emergency treatment of acute angle-closure glaucoma.
- Oral glycerol – alternative in certain cases.
Adverse effects: Dehydration, electrolyte imbalance, nausea, rebound IOP increase if discontinued suddenly.
Summary Table: Cardiovascular Drugs in Ophthalmology
| Drug Class | Examples | Systemic Use | Ocular Relevance |
|---|---|---|---|
| Beta-blockers | Propranolol, Timolol | Hypertension, angina | Glaucoma (reduce aqueous humor) |
| Calcium channel blockers | Amlodipine, Nifedipine | Hypertension, angina | Experimental use in normal-tension glaucoma |
| ACE inhibitors/ARBs | Enalapril, Losartan | Hypertension, heart failure | Possible protective role in diabetic retinopathy |
| Nitrates | Nitroglycerin | Angina | May cause transient blurred vision, photophobia |
| Carbonic anhydrase inhibitors | Acetazolamide, Dorzolamide | Diuretic, metabolic alkalosis | Glaucoma therapy (reduce aqueous production) |
| Osmotic diuretics | Mannitol, Glycerol | Raised intracranial pressure | Emergency lowering of IOP |
Drugs Used in Ocular Disorders
Ocular disorders such as glaucoma, infections, inflammation, allergic conditions, and dry eye disease are commonly managed with pharmacological agents. The choice of drug depends on the pathology, desired therapeutic outcome, and patient-specific considerations. For optometrists and ophthalmologists, understanding the mechanism of action (MOA), uses, and adverse effects of these drugs is critical for safe and effective practice. This article provides a detailed overview of drugs used in ocular disorders with emphasis on MOA and ocular relevance.
1. Anti-Glaucoma Drugs
Glaucoma is characterized by progressive optic neuropathy and visual field loss, commonly associated with increased intraocular pressure (IOP). The therapeutic goal is to lower IOP by either reducing aqueous humor production or enhancing its outflow.
1.1 Prostaglandin Analogues
Examples: Latanoprost, Travoprost, Bimatoprost, Tafluprost. MOA: These are prostaglandin F2α analogues that bind to FP receptors in the ciliary muscle, remodeling extracellular matrix and increasing uveoscleral outflow of aqueous humor. Uses: First-line therapy in open-angle glaucoma. Adverse effects: Iris pigmentation, eyelash growth, periocular skin darkening, conjunctival hyperemia.
1.2 Beta-Adrenergic Blockers
Examples: Timolol, Betaxolol, Levobunolol. MOA: Block β-adrenergic receptors in the ciliary epithelium, reducing aqueous humor secretion. Uses: Open-angle glaucoma, adjunct in combination therapy. Adverse effects: Systemic absorption may cause bradycardia, bronchospasm, hypotension.
1.3 Alpha-2 Adrenergic Agonists
Examples: Brimonidine, Apraclonidine. MOA: Stimulate α2 receptors → decrease aqueous humor production and increase uveoscleral outflow. Uses: Adjunctive therapy in glaucoma, short-term IOP reduction. Adverse effects: Allergic conjunctivitis, dry mouth, systemic hypotension.
1.4 Carbonic Anhydrase Inhibitors (CAIs)
Examples: Acetazolamide (oral), Dorzolamide, Brinzolamide (topical). MOA: Inhibit carbonic anhydrase in ciliary epithelium → reduce bicarbonate ion formation → decrease aqueous humor secretion. Uses: Acute angle-closure crisis (oral/IV acetazolamide), chronic glaucoma (topical). Adverse effects: Oral forms – metabolic acidosis, paresthesias; topical forms – stinging, bitter taste.
1.5 Miotics (Cholinergic Agonists)
Example: Pilocarpine. MOA: Stimulates muscarinic receptors → contracts ciliary muscle → widens trabecular meshwork spaces → increases aqueous humor outflow. Uses: Narrow-angle glaucoma, post-laser iridotomy. Adverse effects: Brow ache, induced myopia, retinal detachment (rare).
1.6 Osmotic Agents
Examples: Mannitol (IV), Glycerol (oral). MOA: Increase plasma osmolarity → draw water from vitreous body into circulation → reduce IOP rapidly. Uses: Emergency management of acute angle-closure glaucoma. Adverse effects: Dehydration, electrolyte imbalance, nausea, rebound rise in IOP.
2. Anti-Inflammatory Drugs
Inflammation in the eye may result from uveitis, conjunctivitis, keratitis, or postoperative conditions. Control of ocular inflammation is essential to prevent complications like scarring, synechiae, and vision loss.
2.1 Corticosteroids
Examples: Prednisolone acetate, Dexamethasone, Fluorometholone. MOA: Bind to cytoplasmic steroid receptors → translocate to nucleus → suppress phospholipase A2 → reduce prostaglandin and leukotriene synthesis → inhibit inflammation. Uses: Uveitis, keratitis, postoperative inflammation, severe allergic conjunctivitis. Adverse effects: Steroid-induced glaucoma, cataract formation, secondary infections.
2.2 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Examples: Ketorolac, Diclofenac, Nepafenac. MOA: Inhibit cyclooxygenase (COX-1 and COX-2) → block prostaglandin synthesis. Uses: Post-cataract surgery inflammation, cystoid macular edema, allergic conjunctivitis. Adverse effects: Stinging, corneal melting (rare with older drugs).
3. Anti-Infective Drugs
Infective ocular diseases include conjunctivitis, keratitis, blepharitis, and endophthalmitis. Treatment is based on causative organisms: bacteria, viruses, fungi, or parasites.
3.1 Antibiotics
Examples: Ciprofloxacin, Tobramycin, Azithromycin. MOA:
- Fluoroquinolones (ciprofloxacin) – inhibit DNA gyrase and topoisomerase IV.
- Aminoglycosides (tobramycin) – bind 30S ribosome, inhibit protein synthesis.
- Macrolides (azithromycin) – bind 50S ribosome, block protein elongation.
Uses: Bacterial conjunctivitis, keratitis, blepharitis. Adverse effects: Allergy, resistance development, corneal deposits (fluoroquinolones).
3.2 Antivirals
Examples: Acyclovir, Ganciclovir, Trifluridine. MOA: Phosphorylated by viral thymidine kinase → inhibit viral DNA polymerase → prevent DNA synthesis. Uses: Herpes simplex keratitis, herpes zoster ophthalmicus, CMV retinitis. Adverse effects: Superficial punctate keratopathy, ocular irritation.
3.3 Antifungals
Examples: Natamycin, Amphotericin B, Voriconazole. MOA: Bind to ergosterol in fungal cell membranes → create pores → leakage of cellular contents. Uses: Fungal keratitis, endophthalmitis. Adverse effects: Corneal toxicity, nephrotoxicity (IV amphotericin).
3.4 Antiprotozoals
Examples: PHMB (Polyhexamethylene biguanide), Chlorhexidine. MOA: Disrupt protozoal cell membranes, leading to cell death. Uses: Acanthamoeba keratitis (common in contact lens wearers). Adverse effects: Ocular surface irritation.
4. Anti-Allergic Drugs
Allergic conjunctivitis is common in clinical practice and requires pharmacological management.
4.1 Antihistamines
Examples: Olopatadine, Epinastine, Azelastine. MOA: Block H1 histamine receptors → reduce itching, redness, tearing. Uses: Seasonal and perennial allergic conjunctivitis. Adverse effects: Mild irritation, headache.
4.2 Mast Cell Stabilizers
Examples: Cromolyn sodium, Nedocromil. MOA: Stabilize mast cell membranes → prevent release of histamine and other mediators. Uses: Chronic allergic conjunctivitis, vernal keratoconjunctivitis. Adverse effects: Stinging, delayed onset of action.
4.3 Dual-Action Agents
Examples: Ketotifen, Olopatadine. MOA: Both antihistamine and mast cell stabilization. Uses: First-line therapy for allergic eye disease. Adverse effects: Minimal.
5. Lubricants and Tear Substitutes
Dry eye disease results from reduced tear production or increased tear evaporation.
Examples: Carboxymethylcellulose, Hydroxypropyl methylcellulose, Polyvinyl alcohol. MOA: Act as tear substitutes, improving tear film stability and lubricating the ocular surface. Uses: Dry eye syndrome, ocular surface disease. Adverse effects: Minimal, preservative-related irritation in some cases.
6. Immunomodulatory Agents
In chronic ocular surface inflammation, immunomodulators are used.
Example: Cyclosporine A (topical). MOA: Inhibits calcineurin in T-lymphocytes → reduces cytokine release → suppresses immune-mediated inflammation. Uses: Dry eye disease (keratoconjunctivitis sicca), vernal keratoconjunctivitis. Adverse effects: Burning sensation, ocular irritation.
Summary Table
| Drug Group | Example | Mechanism of Action | Ocular Use |
|---|---|---|---|
| Prostaglandin analogues | Latanoprost | Increase uveoscleral outflow | Glaucoma |
| Beta-blockers | Timolol | Reduce aqueous humor production | Glaucoma |
| Alpha-2 agonists | Brimonidine | ↓ Production, ↑ Outflow | Glaucoma |
| CAIs | Dorzolamide | Inhibit carbonic anhydrase | Glaucoma |
| Miotics | Pilocarpine | Muscarinic agonist → trabecular outflow | Glaucoma |
| Corticosteroids | Prednisolone | Inhibit PLA2 → ↓ PG, LT | Uveitis, inflammation |
| NSAIDs | Ketorolac | COX inhibition | Post-op inflammation |
| Antibiotics | Ciprofloxacin | Inhibit DNA gyrase | Bacterial infections |
| Antivirals | Acyclovir | Inhibit viral DNA polymerase | Herpes keratitis |
| Antifungals | Natamycin | Bind ergosterol → disrupt membrane | Fungal keratitis |
| Immunomodulators | Cyclosporine | Calcineurin inhibitor | Dry eye, VKC |
Central Nervous System Drugs: Alcohol, Sedatives, and Hypnotics
The central nervous system (CNS) is highly sensitive to pharmacological agents. Drugs acting on the CNS include alcohol, sedatives, and hypnotics, which are widely used in medicine and also have significant ocular effects. These drugs either depress or modulate neuronal activity, primarily through neurotransmitter systems such as GABA, glutamate, and dopamine. For optometry students, it is important to understand their mechanism of action (MOA), systemic uses, and ocular implications, since visual disturbances are common side effects of CNS-active drugs.
1. Alcohol (Ethanol)
Ethanol is one of the most commonly consumed psychoactive substances. Although not prescribed as a therapeutic drug, its widespread social use and potential toxicity make it relevant in pharmacology.
Mechanism of Action
- Enhances the inhibitory effect of GABA-A receptors → increased chloride ion influx → neuronal hyperpolarization → CNS depression.
- Inhibits NMDA-type glutamate receptors → reduced excitatory neurotransmission.
- Stimulates mesolimbic dopamine pathways → feeling of euphoria.
Systemic Effects
- Low doses – relaxation, decreased anxiety, impaired judgment.
- Moderate doses – slurred speech, incoordination, prolonged reaction times.
- High doses – respiratory depression, coma, death.
Ocular Effects
- Acute intoxication: blurred vision, diplopia, nystagmus.
- Chronic alcoholism: nutritional optic neuropathy due to vitamin B1 (thiamine) deficiency.
- Methanol poisoning (toxic alcohol): metabolism produces formic acid → damages optic nerve → leads to irreversible blindness.
2. Sedatives
Sedatives are drugs that reduce anxiety and exert a calming effect without inducing sleep at therapeutic doses. At higher doses, they can act as hypnotics.
2.1 Benzodiazepines
Examples: Diazepam, Lorazepam, Alprazolam, Clonazepam. MOA: Bind to benzodiazepine sites on GABA-A receptors → increase frequency of chloride channel opening → enhance inhibitory GABAergic neurotransmission. Effects: Anxiolysis, muscle relaxation, anticonvulsant activity, sedation. Uses: Anxiety disorders, insomnia, seizures, muscle spasms, preoperative medication. Ocular effects: Diplopia, blurred vision, nystagmus, occasionally dry eyes. Adverse effects: Dependence, tolerance, withdrawal symptoms on abrupt cessation.
2.2 Barbiturates
Examples: Phenobarbital, Pentobarbital, Thiopental. MOA: Bind to GABA-A receptors → prolong duration of chloride channel opening → stronger CNS depression compared to benzodiazepines. Effects: Sedation, hypnosis, anticonvulsant action, anesthesia. Uses: Seizures (phenobarbital), induction of anesthesia (thiopental). Ocular effects: Nystagmus, diplopia, ocular ataxia. Adverse effects: High risk of respiratory depression, drug interactions, dependence.
2.3 Non-Benzodiazepine Sedatives (Z-drugs)
Examples: Zolpidem, Zaleplon, Eszopiclone. MOA: Selectively bind to GABA-A receptor subtypes (α1 subunit) → induce sleep with minimal anxiolytic or muscle relaxant effects. Uses: Insomnia (short-term). Ocular effects: Rare visual hallucinations, blurred vision, complex sleep behaviors. Adverse effects: Dizziness, dependence with prolonged use.
3. Hypnotics
Hypnotics are drugs that induce sleep. In practice, sedatives and hypnotics overlap, as many sedatives cause hypnosis at higher doses.
3.1 Benzodiazepine Hypnotics
At higher doses, benzodiazepines such as Temazepam and Triazolam act as hypnotics. MOA: Same as benzodiazepines – enhance GABA-A receptor-mediated inhibition. Ocular effects: Diplopia, blurred vision, reduced contrast sensitivity.
3.2 Barbiturate Hypnotics
Barbiturates like Pentobarbital may be used as hypnotics but are now rarely prescribed due to risk of overdose. MOA: Prolong chloride channel opening via GABA-A receptors → CNS depression. Ocular effects: Severe nystagmus, ocular muscle incoordination in overdose.
3.3 Other Hypnotics
Z-drugs like Zolpidem are now preferred due to safety. Melatonin and its analogues (e.g., Ramelteon) act on melatonin receptors and regulate circadian rhythm. Ocular relevance: Melatonin analogues may have a role in regulating circadian rhythm of IOP, currently under study.
Adverse Ocular Effects of CNS Drugs
- Alcohol – blurred vision, diplopia, nystagmus, optic neuropathy (chronic), blindness (methanol).
- Benzodiazepines – diplopia, blurred vision, abnormal eye movements.
- Barbiturates – nystagmus, ocular ataxia, sedation-related blurred vision.
- Z-drugs – hallucinations with visual disturbances in rare cases.
Clinical Implications for Optometrists
- Visual side effects are often the first signs of CNS drug toxicity (e.g., nystagmus from barbiturates).
- Alcoholism-related optic neuropathy must be recognized early to prevent irreversible vision loss.
- Drug interactions – sedatives/hypnotics may interact with other medications used in ocular patients, requiring careful history-taking.
- Patient education – patients on benzodiazepines or barbiturates should be warned about potential visual disturbances.
Summary Table: CNS Drugs and Ocular Effects
| Drug Group | Examples | MOA | Ocular Effects |
|---|---|---|---|
| Alcohol (Ethanol) | — | ↑ GABA-A, ↓ NMDA, ↑ dopamine | Blurred vision, diplopia, optic neuropathy |
| Toxic alcohol | Methanol | Metabolized to formic acid → optic nerve damage | Severe visual loss, blindness |
| Benzodiazepines | Diazepam, Lorazepam | ↑ Frequency of Cl⁻ channel opening via GABA-A | Diplopia, nystagmus, blurred vision |
| Barbiturates | Phenobarbital, Thiopental | ↑ Duration of Cl⁻ channel opening via GABA-A | Nystagmus, ocular incoordination |
| Z-drugs | Zolpidem, Zaleplon | Selective GABA-A α1 agonists | Rare visual hallucinations, blurred vision |
| Melatonin analogues | Ramelteon | Agonist at MT1/MT2 receptors | Possible role in circadian IOP regulation |
