Unit 3: General Pharmacology ll | Basic and Ocular Pharmacology | 4th Semester of Bachelor of Optometry

General and Local Anaesthetics in Ocular Pharmacology

Anaesthetics are drugs that cause reversible loss of sensation. They are essential in ophthalmic practice for surgical procedures, diagnostic interventions, and pain control. Depending on their site and method of action, anaesthetics are classified into general anaesthetics (which cause loss of consciousness and total body anesthesia) and local anaesthetics (which block sensation in a specific area without loss of consciousness). Both play an important role in ocular pharmacology.

1. General Anaesthetics

General anaesthetics are drugs that produce a controlled, reversible state of unconsciousness with analgesia, muscle relaxation, and loss of reflexes. They are commonly used in ophthalmic surgeries such as pediatric strabismus surgery, retinal detachment repair, and complex intraocular procedures.

1.1 Mechanism of Action

Although the exact mechanism is complex and multifactorial, general anaesthetics primarily act on CNS ion channels:

• Potentiate inhibitory neurotransmission – enhance GABA-A receptor activity, leading to increased chloride influx and neuronal hyperpolarization.
• Reduce excitatory neurotransmission – inhibit NMDA (glutamate) receptors and decrease sodium and calcium channel activity.
• Result: loss of consciousness, analgesia, muscle relaxation, and amnesia.

1.2 Types of General Anaesthetics

(a) Inhalational Agents

Examples: Nitrous oxide, Halothane, Isoflurane, Sevoflurane, Desflurane. MOA: Enhance GABA-A activity, inhibit excitatory synapses. Uses in ophthalmology: Pediatric ocular surgery, long-duration intraocular procedures. Adverse effects: Nausea, vomiting, malignant hyperthermia (rare).

(b) Intravenous Agents

Examples: Propofol, Thiopental sodium, Ketamine, Etomidate. MOA: Potentiate GABA-A activity (propofol, thiopental, etomidate); antagonize NMDA receptors (ketamine). Uses: Induction of anesthesia, short ocular procedures. Adverse effects: Respiratory depression (propofol, thiopental), emergence hallucinations (ketamine).

1.3 Ocular Effects of General Anaesthetics

• Reduce intraocular pressure (beneficial in many ocular surgeries).
• Alter ocular motility (important for strabismus surgery assessments).
• Cause nystagmus or diplopia in recovery phase (rare, transient).

1.4 Clinical Applications in Ophthalmology

• Strabismus surgery in children (to prevent awareness and movement).
• Complex intraocular surgeries (e.g., vitreoretinal operations).
• Uncooperative patients or those with special needs.

2. Local Anaesthetics

Local anaesthetics block sensation in a localized area without affecting consciousness. They are more commonly used than general anaesthetics in ophthalmology due to safety and rapid recovery.

2.1 Mechanism of Action

Local anaesthetics act by blocking voltage-gated sodium channels in neuronal membranes, preventing depolarization and conduction of nerve impulses.

• They exist in ionized and unionized forms. The unionized form crosses neuronal membranes, while the ionized form binds sodium channels.
• Result: reversible loss of pain, touch, and temperature sensation.

2.2 Classification

(a) Esters

Examples: Procaine, Tetracaine, Benzocaine. Features: Short-acting, metabolized by plasma esterases. Ocular use: Surface anesthesia for tonometry, minor procedures. Limitation: Higher risk of allergy.

(b) Amides

Examples: Lidocaine, Bupivacaine, Mepivacaine. Features: Longer-acting, metabolized in liver. Ocular use: Infiltration for peribulbar or retrobulbar anesthesia. Advantage: Safer, less allergic potential.

2.3 Local Anaesthetic Agents in Ophthalmology

(a) Topical Anaesthetics

Examples: Proparacaine, Tetracaine, Oxybuprocaine. Uses: Tonometry, foreign body removal, gonioscopy, minor corneal procedures. Adverse effects: Corneal epithelial toxicity if overused.

(b) Injectable Anaesthetics

Techniques:

• Retrobulbar injection – injection into muscle cone behind the globe; provides complete anesthesia and akinesia.
• Peribulbar injection – injection outside the muscle cone; safer but slower onset.
• Sub-Tenon’s injection – blunt cannula delivers drug into sub-Tenon’s space; less risk of perforation.

Examples: Lidocaine (rapid onset), Bupivacaine (longer duration). Adverse effects: Hemorrhage, globe perforation, optic nerve damage (rare).

2.4 Adjuvants Used with Local Anaesthetics

• Vasoconstrictors (e.g., epinephrine) – reduce systemic absorption, prolong effect, decrease bleeding.
• Hyaluronidase – facilitates drug diffusion in ocular tissues.

3. Comparison: General vs Local Anaesthetics in Ophthalmology

Feature	General Anaesthesia	Local Anaesthesia
Consciousness	Loss of consciousness	Consciousness preserved
Indication	Major ocular surgeries, pediatrics	Routine cataract, corneal procedures
Onset	Rapid (IV), variable (inhalation)	Fast with topical/injectable
Recovery	Slower, requires monitoring	Rapid, outpatient friendly
Risks	Respiratory depression, systemic complications	Local toxicity, rare perforation

4. Adverse Effects of Anaesthetics

General Anaesthetics

• Nausea, vomiting, hypotension.
• Respiratory depression (IV agents).
• Malignant hyperthermia (rare, with halothane or succinylcholine).

Local Anaesthetics

• Local irritation, corneal toxicity (topical overuse).
• Systemic toxicity – seizures, cardiac arrhythmias (with accidental intravascular injection).
• Allergic reactions (esters more than amides).

5. Clinical Importance for Optometry and Ophthalmology

1. Patient safety – careful selection of anaesthetic method based on age, systemic health, and ocular procedure.
2. Drug interactions – awareness of interactions with systemic drugs (e.g., beta-blockers, anticoagulants).
3. Ocular side effects – recognizing corneal toxicity and systemic complications early.
4. Emerging methods – newer agents like ropivacaine and advanced delivery techniques (sub-Tenon’s block) improve safety profiles.

Opioids and Non-Opioids in Pharmacology with Ocular Relevance

Pain is a universal symptom in medicine and can arise from trauma, inflammation, surgery, or chronic disease. In ophthalmology, pain management is particularly important after ocular surgery, in corneal ulcers, trauma, or severe inflammatory eye conditions. Drugs used for pain relief are broadly classified into opioids (narcotic analgesics) and non-opioids (non-narcotic analgesics). Understanding their mechanism of action (MOA), uses, and ocular relevance is essential for optometrists and ophthalmologists.

1. Opioid Analgesics

Opioids are natural or synthetic compounds that act on opioid receptors in the central nervous system to produce analgesia, sedation, and euphoria. They are among the most effective analgesics available but are associated with risks of tolerance, dependence, and addiction.

1.1 Mechanism of Action

Opioids exert their effects by binding to specific G-protein coupled receptors (GPCRs) located in the brain, spinal cord, and peripheral tissues. The major receptor types are:

• Mu (μ) receptors – analgesia, euphoria, respiratory depression, miosis, dependence.
• Kappa (κ) receptors – spinal analgesia, sedation, dysphoria, miosis.
• Delta (δ) receptors – analgesia, mood regulation.

MOA at cellular level:

• Opioid receptor activation → inhibition of adenylate cyclase → decreased cAMP.
• Opening of potassium channels → hyperpolarization of neurons.
• Closure of voltage-gated calcium channels → reduced neurotransmitter release.
• Result: reduced pain signal transmission and enhanced pain tolerance.

1.2 Classification of Opioids

• Natural alkaloids – Morphine, Codeine.
• Semi-synthetic – Heroin, Oxycodone, Hydromorphone.
• Synthetic – Fentanyl, Methadone, Tramadol.
• Partial agonists/antagonists – Buprenorphine, Nalbuphine.
• Antagonists – Naloxone, Naltrexone (used to reverse opioid toxicity).

1.3 Clinical Uses

• Relief of moderate to severe pain (postoperative, trauma, cancer pain).
• Cough suppression (codeine).
• Pre-anesthetic medication (morphine, fentanyl).
• Treatment of acute pulmonary edema (morphine reduces preload and anxiety).

1.4 Adverse Effects

• Respiratory depression (major cause of death in overdose).
• Miosis (pinpoint pupils – a diagnostic feature of opioid overdose).
• Nausea, vomiting, constipation.
• Dependence, tolerance, and withdrawal symptoms.

1.5 Ocular Relevance

• Miosis – all opioids cause constriction of pupils by stimulating Edinger–Westphal nucleus of oculomotor nerve.
• Useful as a diagnostic sign in suspected opioid overdose (pinpoint pupils + respiratory depression).
• Postoperative ocular pain management – opioids may be prescribed after enucleation or complex surgery.
• Ocular side effects – blurred vision, diplopia, reduced accommodation due to CNS depression.

2. Non-Opioid Analgesics

Non-opioid analgesics are a diverse group of drugs that provide pain relief without acting on opioid receptors and without causing dependence. They are also called non-narcotic analgesics. These drugs often have antipyretic and anti-inflammatory properties.

2.1 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Examples: Aspirin, Ibuprofen, Diclofenac, Indomethacin, Ketorolac. MOA: Inhibit cyclooxygenase enzymes (COX-1 and COX-2) → block prostaglandin synthesis → reduce pain, inflammation, and fever. Uses: Mild to moderate pain, ocular inflammation, postoperative pain, fever. Ocular uses: Topical NSAIDs (ketorolac, nepafenac) are used in cataract surgery to reduce inflammation and cystoid macular edema. Adverse effects: Gastric irritation, peptic ulcer, renal toxicity; corneal melting (rare with topical NSAIDs).

2.2 Acetaminophen (Paracetamol)

MOA: Weak inhibitor of COX in peripheral tissues; stronger inhibition in CNS → produces analgesic and antipyretic effects but minimal anti-inflammatory activity. Uses: Mild to moderate pain, fever, safe in children. Ocular relevance: Occasionally used systemically for ocular pain or fever in post-surgical patients. Adverse effects: Hepatotoxicity in overdose.

2.3 Selective COX-2 Inhibitors

Examples: Celecoxib, Etoricoxib. MOA: Selectively inhibit COX-2 → reduce inflammation and pain with fewer gastric side effects. Uses: Arthritis, postoperative pain. Ocular effects: Limited direct role, but safer for systemic pain in ocular patients with gastric sensitivity. Adverse effects: Cardiovascular risks (MI, stroke).

2.4 Other Non-Opioid Analgesics

• Metamizole (Dipyrone) – strong analgesic and antipyretic, banned in some countries due to agranulocytosis.
• Tramadol – weak opioid agonist + serotonin/norepinephrine reuptake inhibitor; intermediate between opioids and non-opioids.

3. Comparative Features of Opioids and Non-Opioids

Feature	Opioids	Non-Opioids
Site of action	Opioid receptors (CNS & periphery)	COX enzymes, CNS (for paracetamol)
Potency	Very high (morphine, fentanyl)	Mild to moderate (NSAIDs, paracetamol)
Dependence	Yes, high risk	No dependence
Use in ophthalmology	Postoperative severe ocular pain	Ocular inflammation, mild pain
Ocular side effects	Miosis, blurred vision, diplopia	Topical NSAIDs: corneal irritation, rare melting

4. Clinical Implications in Ophthalmology

1. Postoperative pain – Non-opioids (NSAIDs, paracetamol) are preferred for mild to moderate pain, while opioids may be required for severe pain after major ocular surgery.
2. Inflammation control – NSAIDs are crucial in preventing cystoid macular edema after cataract surgery.
3. Diagnostic importance – Miosis is a classic sign of opioid overdose, useful in emergency diagnosis.
4. Patient safety – Topical NSAIDs should be used cautiously to avoid corneal complications; systemic opioids require monitoring for respiratory depression.

Chemotherapy in Ocular Pharmacology

Chemotherapy in pharmacology refers to the use of chemical substances to destroy or inhibit the growth of microorganisms or abnormal cells. In ophthalmology, chemotherapy primarily involves the use of antimicrobial drugs such as antibiotics, antivirals, and antifungals for ocular infections, as well as antiparasitic drugs in special cases. The goal is to eradicate the causative pathogen while minimizing harm to host tissues. Understanding the mechanism of action (MOA), spectrum, and ocular relevance of these drugs is essential for rational therapy.

1. General Principles of Chemotherapy

• Selective toxicity: The drug should target the pathogen without harming host cells (e.g., antibiotics act on bacterial cell walls, which human cells lack).
• Spectrum of activity: Narrow-spectrum drugs target specific organisms, while broad-spectrum drugs act against multiple pathogens.
• Resistance: Microorganisms may develop resistance through mutation or gene transfer, necessitating rational drug use.
• Combination therapy: Sometimes drugs are combined to broaden coverage, prevent resistance, or achieve synergy.

2. Antibiotics in Ocular Therapy

Antibiotics are chemical agents that kill bacteria (bactericidal) or inhibit their growth (bacteriostatic). They are the cornerstone of treatment for bacterial conjunctivitis, keratitis, endophthalmitis, and blepharitis.

2.1 Classification of Antibiotics

• Cell wall synthesis inhibitors – Penicillins, Cephalosporins, Vancomycin.
• Protein synthesis inhibitors – Aminoglycosides, Tetracyclines, Macrolides, Chloramphenicol.
• Nucleic acid synthesis inhibitors – Fluoroquinolones, Rifamycins.
• Metabolic inhibitors – Sulfonamides, Trimethoprim.

2.2 Mechanism of Action and Ocular Uses

(a) Cell Wall Synthesis Inhibitors

Examples: Penicillins, Cephalosporins, Vancomycin. MOA: Inhibit bacterial transpeptidase enzymes → prevent peptidoglycan cross-linking → weak bacterial cell wall → lysis. Ocular uses: Severe bacterial keratitis, orbital cellulitis, endophthalmitis. Adverse effects: Allergy, hypersensitivity reactions.

(b) Protein Synthesis Inhibitors

Aminoglycosides: Tobramycin, Gentamicin. MOA: Bind 30S ribosomal subunit → misreading of mRNA → defective proteins. Uses: Bacterial keratitis, conjunctivitis. Adverse effects: Corneal epithelial toxicity with prolonged use.

Tetracyclines: Doxycycline. MOA: Bind 30S ribosome → block tRNA binding → inhibit protein synthesis. Uses: Meibomian gland dysfunction, ocular rosacea. Adverse effects: GI upset, photosensitivity.

Macrolides: Erythromycin, Azithromycin. MOA: Bind 50S ribosomal subunit → inhibit translocation. Uses: Bacterial conjunctivitis, neonatal prophylaxis. Adverse effects: Minimal ocular irritation.

Chloramphenicol: MOA: Binds 50S ribosome → inhibits peptidyl transferase. Uses: Bacterial conjunctivitis. Adverse effects: Rare aplastic anemia (systemic use).

(c) Nucleic Acid Synthesis Inhibitors

Fluoroquinolones: Ciprofloxacin, Ofloxacin, Moxifloxacin. MOA: Inhibit DNA gyrase and topoisomerase IV → block bacterial DNA replication. Uses: Bacterial keratitis, corneal ulcers, post-surgical prophylaxis. Adverse effects: White corneal precipitates (ciprofloxacin).

(d) Metabolic Inhibitors

Sulfonamides and Trimethoprim: MOA: Block folic acid synthesis (sulfonamides inhibit dihydropteroate synthase, trimethoprim inhibits dihydrofolate reductase). Uses: Bacterial conjunctivitis, prophylaxis in ocular infections. Adverse effects: Hypersensitivity, Stevens-Johnson syndrome (rare).

3. Antivirals in Ocular Therapy

Viral infections of the eye include herpes simplex keratitis, herpes zoster ophthalmicus, adenoviral conjunctivitis, and cytomegalovirus retinitis. Antiviral drugs target viral DNA or RNA replication.

3.1 Classification

• DNA polymerase inhibitors – Acyclovir, Ganciclovir, Trifluridine.
• RNA polymerase inhibitors – Ribavirin.
• Reverse transcriptase inhibitors – Zidovudine (for HIV-related ocular disease).
• Neuraminidase inhibitors – Oseltamivir (for influenza-related ocular complications).

3.2 Mechanism of Action and Ocular Uses

Acyclovir: Activated by viral thymidine kinase → inhibits viral DNA polymerase → prevents DNA synthesis. Uses: Herpes simplex keratitis, herpes zoster ophthalmicus. Adverse effects: Ocular irritation (topical), nephrotoxicity (systemic).

Ganciclovir: Inhibits viral DNA polymerase. Uses: Cytomegalovirus (CMV) retinitis in AIDS patients. Adverse effects: Myelosuppression (systemic), ocular irritation (topical gel).

Trifluridine: Thymidine analog → incorporates into viral DNA → faulty replication. Uses: Herpes simplex keratitis. Adverse effects: Corneal epithelial toxicity.

Ribavirin: Inhibits viral RNA polymerase. Uses: Viral hemorrhagic conjunctivitis (rarely used now). Adverse effects: Retinal toxicity in systemic use.

4. Antifungals in Ocular Therapy

Fungal keratitis and endophthalmitis are serious conditions often associated with trauma, agricultural exposure, or immunosuppression. Antifungals are critical for management.

4.1 Classification

• Polyene antifungals – Natamycin, Amphotericin B.
• Azoles – Fluconazole, Voriconazole.
• Echinocandins – Caspofungin (rare in ocular use).

4.2 Mechanism of Action and Ocular Uses

Natamycin: Binds to ergosterol in fungal membranes → creates pores → leakage of cell contents. Uses: First-line for filamentous fungal keratitis. Adverse effects: Ocular irritation, delayed healing.

Amphotericin B: Binds ergosterol, forms pores. Uses: Severe fungal keratitis, endophthalmitis. Adverse effects: Corneal toxicity, systemic nephrotoxicity.

Azoles (Voriconazole, Fluconazole): Inhibit ergosterol synthesis by blocking cytochrome P450-dependent 14α-demethylase. Uses: Fusarium and Aspergillus keratitis, systemic fungal infections with ocular involvement. Adverse effects: Hepatotoxicity (systemic), ocular irritation.

5. Antiprotozoals

Example: PHMB (Polyhexamethylene biguanide), Chlorhexidine. MOA: Disrupt protozoal cell membranes. Uses: Acanthamoeba keratitis (common in contact lens wearers). Adverse effects: Ocular surface irritation, delayed epithelial healing.

Summary Table: Chemotherapeutic Agents in Ocular Pharmacology

Drug Group	Examples	MOA	Ocular Uses
Cell wall inhibitors	Penicillin, Vancomycin	Inhibit peptidoglycan cross-linking	Keratitis, endophthalmitis
Protein synthesis inhibitors	Tobramycin, Azithromycin	Bind ribosomes (30S or 50S)	Conjunctivitis, blepharitis
DNA synthesis inhibitors	Ciprofloxacin	Inhibit DNA gyrase/topoisomerase	Corneal ulcers, prophylaxis
Antivirals	Acyclovir, Ganciclovir	Inhibit viral DNA polymerase	Herpes keratitis, CMV retinitis
Antifungals	Natamycin, Amphotericin B	Bind ergosterol → pores	Fungal keratitis
Antiprotozoals	PHMB, Chlorhexidine	Disrupt membranes	Acanthamoeba keratitis

Hormones and Corticosteroids in Ocular Pharmacology

Hormones are natural chemical messengers produced by endocrine glands to regulate physiological functions. In pharmacology, synthetic or natural hormones and their analogues are used therapeutically in various systemic and ocular conditions. Among these, corticosteroids are of special importance in ophthalmology due to their powerful anti-inflammatory and immunosuppressive properties. This article discusses the major categories of hormones relevant to pharmacology, with emphasis on corticosteroids and their role in ocular practice.

1. General Introduction to Hormones

Hormones can be classified based on their origin and function:

• Peptide and protein hormones – insulin, growth hormone, ACTH.
• Steroid hormones – corticosteroids, sex hormones (estrogen, progesterone, androgens).
• Amino acid derivatives – thyroxine, adrenaline.

Each hormone acts on specific receptors in target tissues to regulate metabolism, growth, reproduction, or stress responses. Some systemic hormones also influence ocular health directly or indirectly.

2. Corticosteroids

Corticosteroids are steroid hormones produced by the adrenal cortex. They are divided into:

• Glucocorticoids – regulate carbohydrate, protein, and fat metabolism; possess strong anti-inflammatory and immunosuppressive effects (e.g., cortisol, prednisolone, dexamethasone).
• Mineralocorticoids – regulate electrolyte and water balance (e.g., aldosterone).

2.1 Mechanism of Action

Corticosteroids act through intracellular receptors:

• They diffuse across cell membranes due to lipophilic nature.
• Bind to glucocorticoid receptors in the cytoplasm → receptor–drug complex enters nucleus.
• Complex binds to glucocorticoid response elements on DNA → modulates gene transcription.
• Suppresses pro-inflammatory proteins (cytokines, prostaglandins, leukotrienes).
• Enhances anti-inflammatory proteins (lipocortin, which inhibits phospholipase A2).

Result: powerful suppression of inflammation, immune response, and tissue damage.

2.2 Corticosteroids Used in Ophthalmology

• Topical steroids – Prednisolone acetate, Dexamethasone, Fluorometholone, Loteprednol.
• Periocular or intravitreal steroids – Triamcinolone acetonide, Dexamethasone implant.
• Systemic steroids – Oral prednisolone, intravenous methylprednisolone for severe ocular diseases.

2.3 Ocular Uses of Corticosteroids

• Uveitis – reduce intraocular inflammation and prevent synechiae.
• Postoperative inflammation – after cataract or refractive surgery.
• Allergic eye diseases – vernal keratoconjunctivitis, severe allergic conjunctivitis.
• Keratitis – immune-mediated keratitis (not in active infectious keratitis unless under antimicrobial cover).
• Macular edema – intravitreal steroids used in diabetic macular edema and retinal vein occlusion.

2.4 Adverse Effects of Corticosteroids

• Steroid-induced glaucoma – due to reduced aqueous humor outflow from trabecular meshwork obstruction.
• Posterior subcapsular cataract – common in long-term steroid users.
• Delayed wound healing – risk of corneal thinning and perforation.
• Secondary infections – fungal or viral keratitis may worsen.
• Systemic effects – Cushingoid features, osteoporosis, diabetes (if used long-term systemically).

3. Other Hormones Relevant to Ocular Pharmacology

3.1 Adrenaline and Noradrenaline (Catecholamines)

MOA: Act on adrenergic receptors (α and β) → increase sympathetic activity. Ocular relevance: Adrenaline was historically used in glaucoma to reduce IOP; adrenergic agonists (brimonidine) are derived from this concept.

3.2 Thyroid Hormones

MOA: Increase basal metabolic rate by regulating nuclear transcription. Ocular relevance: Thyroid eye disease (Graves’ orbitopathy) causes proptosis, lid retraction, and diplopia; corticosteroids are often used for management of inflammation.

3.3 Sex Hormones (Estrogens, Progesterone, Androgens)

Ocular relevance:

• Estrogen deficiency in post-menopausal women is associated with dry eye syndrome.
• Androgens stimulate meibomian gland function → androgen deficiency contributes to evaporative dry eye.

3.4 Insulin

MOA: Binds to insulin receptors → stimulates glucose uptake and storage. Ocular relevance: Poorly controlled diabetes leads to diabetic retinopathy, cataract, and keratopathy. Insulin therapy is essential for prevention of ocular complications.

3.5 Growth Hormone

MOA: Acts via IGF-1 (insulin-like growth factor-1) to promote growth and metabolism. Ocular relevance: Acromegaly patients may develop visual field defects due to pituitary tumors compressing the optic chiasm.

4. Summary Table

Hormone / Drug	Mechanism of Action	Ocular Relevance	Adverse Effects
Corticosteroids (Prednisolone, Dexamethasone)	Inhibit phospholipase A2 → ↓ prostaglandins & cytokines	Uveitis, post-op inflammation, macular edema	Glaucoma, cataract, delayed healing, infections
Adrenaline (historical use)	α, β agonist → ↓ aqueous production, ↑ outflow	Glaucoma (older drug)	Tachycardia, irritation
Thyroid hormones	Regulate transcription → ↑ metabolism	Thyroid eye disease	Exophthalmos, lid retraction
Sex hormones	Bind to nuclear receptors → regulate reproductive functions	Androgen deficiency → dry eye	Systemic risks (thrombosis, cancer)
Insulin	Stimulates glucose uptake	Prevents diabetic retinopathy progression	Hypoglycemia (systemic)

5. Clinical Importance

1. Corticosteroids remain the mainstay of ocular pharmacology for inflammatory and immune-mediated diseases but require careful monitoring due to side effects.
2. Systemic hormones like insulin and thyroid hormones indirectly influence ocular health, making endocrine–ocular correlations important.
3. Sex hormones and meibomian gland function highlight the link between systemic endocrinology and ocular surface health.

Antidiabetics and Blood Coagulants in Ocular Pharmacology

Diabetes mellitus and blood coagulation disorders are major systemic diseases with strong ocular implications. Antidiabetic drugs are used to control hyperglycemia and prevent complications such as diabetic retinopathy, while anticoagulants and antiplatelet agents influence ocular health by modifying hemostasis. Understanding the mechanism of action (MOA), therapeutic uses, and ocular significance of these drugs is essential for optometry and ophthalmology students.

1. Antidiabetic Drugs

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia due to inadequate insulin secretion, impaired insulin action, or both. Long-term uncontrolled diabetes leads to complications such as diabetic retinopathy, cataract, keratopathy, and increased risk of infections. Antidiabetic drugs aim to normalize blood glucose and reduce complications.

1.1 Classification of Antidiabetic Drugs

• Insulin and analogues – short-acting, intermediate, long-acting.
• Oral hypoglycemic agents:
  • Sulfonylureas
  • Biguanides
  • Thiazolidinediones (TZDs)
  • Alpha-glucosidase inhibitors
  • DPP-4 inhibitors
  • GLP-1 receptor agonists
  • SGLT2 inhibitors

1.2 Insulin

MOA: Insulin binds to insulin receptors (tyrosine kinase) on target cells → activates signaling cascade → increases glucose uptake via GLUT-4 transporters in muscle and fat → promotes glycogen synthesis, inhibits gluconeogenesis. Types: Rapid-acting (lispro, aspart), short-acting (regular insulin), intermediate (NPH), long-acting (glargine, detemir). Ocular relevance: Tight glycemic control reduces risk and progression of diabetic retinopathy, macular edema, and ocular infections. Adverse effects: Hypoglycemia, weight gain, local lipodystrophy.

1.3 Sulfonylureas

Examples: Glibenclamide, Glipizide, Glimepiride. MOA: Block ATP-sensitive K⁺ channels in pancreatic β-cells → depolarization → calcium influx → insulin release. Uses: Type 2 diabetes (when β-cell function is preserved). Adverse effects: Hypoglycemia, weight gain. Ocular relevance: Good control prevents microvascular complications including diabetic retinopathy.

1.4 Biguanides

Example: Metformin (first-line drug for type 2 diabetes). MOA: Activates AMP-activated protein kinase (AMPK) → decreases hepatic glucose production, increases insulin sensitivity, enhances peripheral glucose uptake. Uses: Type 2 diabetes, metabolic syndrome. Adverse effects: Lactic acidosis (rare), GI upset. Ocular relevance: Some studies suggest metformin may reduce risk of age-related macular degeneration and diabetic retinopathy progression.

1.5 Thiazolidinediones (TZDs)

Examples: Pioglitazone, Rosiglitazone. MOA: Activate PPAR-γ nuclear receptors → increase insulin sensitivity in adipose tissue, muscle, and liver. Uses: Type 2 diabetes with insulin resistance. Adverse effects: Weight gain, edema, heart failure risk. Ocular relevance: May worsen macular edema in susceptible patients.

1.6 Alpha-Glucosidase Inhibitors

Examples: Acarbose, Miglitol. MOA: Inhibit intestinal brush-border alpha-glucosidase → delay carbohydrate digestion and absorption → reduce postprandial hyperglycemia. Uses: Type 2 diabetes (post-meal glucose control). Adverse effects: Flatulence, diarrhea. Ocular relevance: By controlling postprandial spikes, they indirectly help in preventing diabetic retinopathy progression.

1.7 DPP-4 Inhibitors (Gliptins)

Examples: Sitagliptin, Vildagliptin, Saxagliptin. MOA: Inhibit DPP-4 enzyme → prolong action of incretins (GLP-1, GIP) → increase insulin secretion, reduce glucagon. Uses: Type 2 diabetes, often in combination with metformin. Adverse effects: Nasopharyngitis, headache, joint pain. Ocular relevance: Emerging research suggests possible neuroprotective effects in diabetic retinopathy.

1.8 GLP-1 Receptor Agonists

Examples: Exenatide, Liraglutide, Semaglutide. MOA: Mimic GLP-1 incretin hormone → increase insulin release, inhibit glucagon, slow gastric emptying, promote satiety. Uses: Type 2 diabetes, obesity. Adverse effects: GI upset, risk of pancreatitis. Ocular relevance: Indirect benefit by improving glycemic control and reducing microvascular complications.

1.9 SGLT2 Inhibitors

Examples: Dapagliflozin, Empagliflozin, Canagliflozin. MOA: Block sodium-glucose cotransporter-2 (SGLT2) in proximal renal tubules → increase urinary glucose excretion → lower blood glucose. Uses: Type 2 diabetes, heart failure. Adverse effects: Genital infections, dehydration, ketoacidosis (rare). Ocular relevance: Improved vascular health may reduce long-term diabetic retinopathy risk.

2. Blood Coagulants and Anticoagulants

Hemostasis is a balance between coagulation and anticoagulation mechanisms. Drugs acting on blood coagulation include coagulants (promote clotting), anticoagulants (prevent clot formation), and antiplatelet agents (inhibit platelet aggregation). These drugs are important in systemic medicine and have ocular implications, especially in retinal vascular diseases and ocular surgeries.

2.1 Coagulants

Examples: Vitamin K, Fibrinogen, Desmopressin. MOA:

• Vitamin K – required for synthesis of clotting factors II, VII, IX, X.
• Fibrinogen – administered in hypofibrinogenemia to restore clotting.
• Desmopressin – increases factor VIII and von Willebrand factor release.

Ocular relevance: Used in bleeding disorders that may complicate ocular trauma or surgery.

2.2 Anticoagulants

(a) Heparin

MOA: Activates antithrombin III → inactivates thrombin and factor Xa → prevents clot formation. Uses: Deep vein thrombosis, pulmonary embolism, prevention during ocular surgery in high-risk patients. Adverse effects: Bleeding, thrombocytopenia. Ocular relevance: Increases risk of subconjunctival or retinal hemorrhage during surgery.

(b) Low Molecular Weight Heparins (LMWH)

Examples: Enoxaparin, Dalteparin. MOA: More selective inhibition of factor Xa than thrombin. Uses: Safer anticoagulation, postoperative prophylaxis. Adverse effects: Lower bleeding risk than unfractionated heparin. Ocular relevance: Safer choice in patients undergoing ocular procedures.

(c) Vitamin K Antagonists

Example: Warfarin. MOA: Inhibits vitamin K epoxide reductase → prevents activation of vitamin K → decreases synthesis of clotting factors II, VII, IX, X. Uses: Chronic anticoagulation for atrial fibrillation, prosthetic valves. Adverse effects: Bleeding, drug interactions. Ocular relevance: Retinal hemorrhages more likely in anticoagulated patients.

(d) Direct Oral Anticoagulants (DOACs)

Examples: Rivaroxaban, Apixaban (factor Xa inhibitors), Dabigatran (direct thrombin inhibitor). MOA: Directly inhibit clotting enzymes (Xa or IIa). Uses: Safer alternatives to warfarin in atrial fibrillation, venous thrombosis. Adverse effects: Bleeding. Ocular relevance: Need to be withheld prior to intraocular surgery to reduce bleeding risk.

2.3 Antiplatelet Agents

Examples: Aspirin, Clopidogrel, Ticagrelor. MOA:

• Aspirin – irreversibly inhibits COX-1 in platelets → prevents thromboxane A2 formation → inhibits aggregation.
• Clopidogrel – blocks ADP receptor (P2Y12) on platelets → inhibits activation.
• Glycoprotein IIb/IIIa inhibitors – prevent fibrinogen binding to platelets.

Uses: Prevention of MI, stroke, retinal vascular occlusions. Adverse effects: Bleeding, gastric irritation (aspirin). Ocular relevance: Reduce risk of central retinal artery occlusion (CRAO) or vein occlusion but increase risk of subconjunctival hemorrhage.

3. Clinical Importance for Ophthalmology

1. Diabetic retinopathy – best prevented by tight glycemic control with insulin, metformin, or other antidiabetics.
2. Macular edema – some drugs like TZDs can worsen macular edema, requiring careful patient monitoring.
3. Ocular surgeries – anticoagulants and antiplatelets may increase risk of intraoperative or postoperative bleeding; sometimes they must be adjusted before surgery.
4. Thromboembolic events – antiplatelets and anticoagulants reduce systemic and ocular ischemic events such as retinal vascular occlusions.

Summary Table

Drug Group	Example	MOA	Ocular Relevance
Insulin	Glargine, Lispro	Stimulates glucose uptake via GLUT-4	Prevents diabetic retinopathy
Biguanides	Metformin	Activates AMPK → ↓ glucose production	Delays diabetic retinopathy progression
TZDs	Pioglitazone	PPAR-γ agonist → ↑ insulin sensitivity	May worsen macular edema
Heparin	Unfractionated heparin	Activates antithrombin III → inhibits thrombin, Xa	Risk of ocular hemorrhage
Warfarin	—	Vitamin K antagonist → ↓ clotting factor synthesis	Retinal hemorrhage risk
Aspirin	—	Irreversible COX-1 inhibition → ↓ TXA2	Prevents retinal vascular occlusion

For more units of "Basic and Ocular Pharmacology" click below 👇 

✅ Unit 1

✅ Unit 2

✅ Unit 4

✅ Unit 5