Unit 1: General Pharmacology | Basic and Ocular Pharmacology | 4th Semester of Bachelor of Optometry

Introduction to Pharmacology

Pharmacology is the branch of medical science that deals with the study of drugs, their sources, chemical nature, biological effects, mechanism of action, therapeutic uses, and adverse effects. For an optometry student, pharmacology holds immense importance because understanding how drugs act on the eye and visual system forms the foundation of clinical practice in ophthalmology and optometry. From dilating the pupil during refraction to reducing intraocular pressure in glaucoma, drugs play a critical role in diagnosis, prevention, and treatment of ocular diseases.

The term drug is defined as any chemical substance that, when introduced into a living body, modifies one or more of its functions. In other words, drugs are agents that can prevent, diagnose, treat, or cure diseases. The science of pharmacology can broadly be divided into:

• Pharmacokinetics – what the body does to the drug (absorption, distribution, metabolism, excretion).
• Pharmacodynamics – what the drug does to the body (mechanism of action, therapeutic effects, adverse effects).

Importance of Pharmacology in Optometry

For optometrists, a sound understanding of pharmacology is essential because:

• It helps in safe and effective use of diagnostic drugs such as mydriatics and cycloplegics.
• It provides knowledge of therapeutic agents used for conditions like conjunctivitis, dry eye, uveitis, and glaucoma.
• It aids in recognizing adverse drug reactions that may manifest in the eye, such as cataract formation with corticosteroids or optic neuropathy with certain antibiotics.
• It is essential in counseling patients about drug usage, compliance, and possible side effects.

Sources of Drugs

Drugs can originate from a wide variety of sources. Historically, natural sources such as plants and animals provided the majority of drugs. With the advancement of science and technology, synthetic and biotechnological methods have emerged as major contributors. Understanding the sources of drugs is important because it helps in appreciating the diversity of pharmacological agents and their mechanisms.

1. Plant Sources

Plants have been the oldest and most common source of drugs. They contain active chemical constituents such as alkaloids, glycosides, tannins, resins, and volatile oils. Examples include:

• Atropine – obtained from Atropa belladonna, used as a mydriatic and cycloplegic in ophthalmology.
• Pilocarpine – derived from Pilocarpus, used in the treatment of glaucoma.
• Quinine – from the bark of Cinchona, used as an antimalarial.
• Digitalis – obtained from Digitalis purpurea, used in heart failure.

In ocular practice, plant-derived alkaloids such as atropine, homatropine, and pilocarpine are still widely used for diagnostic and therapeutic purposes.

2. Animal Sources

Several drugs are derived from animals or animal products. They are usually proteins, hormones, or enzymes. Examples include:

• Insulin – obtained from the pancreas of pigs and cattle (though now largely synthetic).
• Adrenaline and Noradrenaline – originally extracted from adrenal glands.
• Heparin – obtained from the intestinal mucosa of pigs or cattle.
• Cod liver oil – source of vitamin A and D.

In ophthalmology, hyaluronidase, an enzyme derived from animal sources, has been used to facilitate the diffusion of local anesthetics during ocular surgery.

3. Mineral Sources

Certain drugs are derived from mineral sources, either directly or after purification. Examples include:

• Iron – used in the treatment of iron deficiency anemia.
• Magnesium sulfate – used as a laxative and anticonvulsant.
• Zinc oxide – used in dermatological preparations.
• Sodium chloride – essential for fluid and electrolyte balance.

In ophthalmology, sodium chloride hypertonic solutions are used in corneal edema to draw out excess fluid.

4. Synthetic and Semi-Synthetic Sources

Modern pharmacology has greatly advanced due to the synthesis of drugs in laboratories. These drugs may be entirely synthetic or semi-synthetic derivatives of natural substances. Examples:

• Sulfonamides – synthetic antibacterial drugs.
• Paracetamol – synthetic analgesic and antipyretic.
• Amoxicillin – semi-synthetic derivative of penicillin.
• Latanoprost – synthetic prostaglandin analogue used in glaucoma.

Synthetic sources are important in ocular pharmacology because many anti-glaucoma and anti-allergic drugs are synthetic molecules.

5. Microbial Sources

Microorganisms such as bacteria, fungi, and molds are important producers of antibiotics and other bioactive substances. Examples include:

• Penicillin – obtained from the fungus Penicillium.
• Streptomycin – derived from Streptomyces.
• Tetracycline – produced by Streptomyces species.
• Erythromycin – macrolide antibiotic from Streptomyces erythraeus.

These antibiotics are extensively used in ophthalmology to treat bacterial conjunctivitis, keratitis, blepharitis, and endophthalmitis.

6. Biotechnological and Genetic Engineering Sources

With the advancement of biotechnology, many drugs are now produced using recombinant DNA technology and genetic engineering. Examples include:

• Recombinant Insulin – produced by genetically modified bacteria.
• Monoclonal antibodies – used in cancer therapy and inflammatory conditions.
• Interferons – used as antiviral and anticancer agents.
• Ranibizumab and Bevacizumab – anti-VEGF agents used in the treatment of age-related macular degeneration.

Biotechnology has revolutionized ocular pharmacology by providing highly specific agents such as anti-VEGF drugs for retinal disorders.

7. Marine Sources

Marine organisms like sponges, seaweeds, and mollusks have recently become sources of novel pharmacological agents. Examples include:

• Ziconotide – analgesic derived from cone snail toxin.
• Trabectedin – anticancer agent from sea squirt.

Though not yet widely used in ocular pharmacology, marine sources are promising for future drug development.

Classification of Drugs Based on Source

Source	Examples	Ocular Relevance
Plant	Atropine, Pilocarpine	Mydriatic, Glaucoma therapy
Animal	Adrenaline, Hyaluronidase	Ophthalmic surgery adjuncts
Mineral	Sodium chloride, Iron	Corneal edema therapy
Synthetic	Latanoprost, Paracetamol	Glaucoma, Pain management
Microbial	Penicillin, Streptomycin	Ocular infections
Biotechnological	Ranibizumab, Bevacizumab	Retinal disorders (AMD, DME)

Evolution of Drug Sources

Over the centuries, drug sources have shifted significantly:

• Traditional era – predominantly plant and mineral sources.
• 20th century – rise of synthetic and semi-synthetic drugs.
• Modern era – biotechnological and recombinant DNA products dominate.

In ophthalmology, this evolution is clearly visible. For example, earlier plant-derived alkaloids like atropine were the mainstay, but today synthetic prostaglandin analogues and monoclonal antibodies form the cornerstone of treatment for diseases like glaucoma and AMD.

Routes of Drug Administration

The route of drug administration refers to the path by which a drug enters the body to exert its therapeutic effect. The choice of route depends on several factors such as the drug’s properties, the desired site of action, speed of onset required, patient’s condition, and convenience. For optometrists and ophthalmologists, understanding the different routes of administration is particularly important because many ocular drugs require special delivery systems to achieve effective concentrations in the eye without causing systemic side effects.

Factors Influencing the Choice of Route

• Nature of the drug – solid, liquid, volatile, stable, irritant, lipid soluble, etc.
• Site of action – local (eye, skin) or systemic (whole body).
• Desired speed of action – emergency drugs like adrenaline require rapid action.
• Condition of the patient – unconscious, vomiting, pediatric, geriatric, or cooperative.
• First-pass metabolism – some drugs are extensively metabolized in the liver and hence cannot be given orally (e.g., nitroglycerin).

Main Categories of Routes

Broadly, drug administration routes are divided into two categories:

• Enteral routes – where the drug is placed in the gastrointestinal tract (oral, sublingual, rectal).
• Parenteral routes – routes other than the GI tract (injection, inhalation, topical, ocular, etc.).

Enteral Routes

1. Oral Route

The oral route is the most common, convenient, and economical way of drug administration. The drug is swallowed, absorbed through the gastrointestinal tract, and enters the systemic circulation.

Advantages:

• Safe, easy, and painless.
• Economical and does not require sterile precautions.
• Convenient for self-administration.

Disadvantages:

• Unsuitable for unconscious or vomiting patients.
• Slow onset of action compared to parenteral routes.
• First-pass metabolism in the liver may inactivate some drugs.
• Not suitable for irritant or unstable drugs in gastric acid.

Examples: Antibiotics (amoxicillin), analgesics (paracetamol), anti-glaucoma drugs (oral acetazolamide).

2. Sublingual and Buccal Routes

Drugs are placed under the tongue (sublingual) or in the buccal cavity where they are absorbed directly into the systemic circulation through the oral mucosa.

Advantages:

• Rapid absorption and quick onset of action.
• Bypasses first-pass metabolism.
• Useful for emergency drugs.

Disadvantages:

• Unpleasant taste or irritation may occur.
• Only suitable for lipid-soluble, non-irritant drugs.

Examples: Nitroglycerin for angina, isosorbide dinitrate.

3. Rectal Route

Drugs administered as suppositories or enemas are absorbed through the rectal mucosa.

Advantages:

• Useful when oral administration is not possible (vomiting, unconscious).
• Bypasses partial first-pass metabolism.

Disadvantages:

• Unpredictable absorption.
• May cause irritation or discomfort.

Examples: Antiemetics, antipyretics, sedatives, rectal diazepam.

Parenteral Routes

1. Intravenous (IV) Route

The drug is injected directly into the bloodstream via a vein.

Advantages:

• Immediate effect – ideal for emergencies.
• Accurate, predictable, and titratable response.
• Suitable for large volumes and irritant drugs.

Disadvantages:

• Requires sterile technique and trained personnel.
• Risk of infection, thrombophlebitis, and embolism.
• Once given, cannot be recalled.

Examples: IV mannitol in raised intraocular pressure, IV antibiotics in orbital cellulitis.

2. Intramuscular (IM) Route

The drug is injected into a muscle (usually deltoid, gluteal, or thigh).

Advantages:

• Rapid absorption compared to oral route.
• Sustained release preparations can be given.

Disadvantages:

• Pain, abscess, or nerve injury possible.
• Requires trained personnel.

Examples: IM atropine, IM corticosteroids in uveitis.

3. Subcutaneous (SC) Route

The drug is injected into the subcutaneous tissue beneath the skin.

Advantages:

• Slower, sustained absorption compared to IM and IV.
• Useful for self-administration.

Disadvantages:

• Only small volumes can be given.
• Local irritation and necrosis possible.

Examples: Insulin, heparin, some vaccines.

4. Intradermal Route

The drug is injected into the dermis, just under the epidermis.

Examples: Tuberculin test, allergy testing in ophthalmology.

5. Inhalation Route

Drugs are inhaled in the form of gases, vapors, or aerosols.

Advantages:

• Rapid absorption due to large surface area of alveoli.
• Useful for both local (bronchodilators) and systemic effects (anesthesia).

Disadvantages:

• Special apparatus required.
• Not suitable for irritant drugs.

Examples: General anesthetics (halothane), bronchodilators (salbutamol).

Topical Routes

1. Cutaneous (Skin)

Drugs are applied on the skin for local or systemic effects.

• Ointments, creams, lotions for dermatological conditions.
• Transdermal patches for systemic absorption (e.g., nicotine patch).

2. Ocular (Eye)

This is one of the most important routes for optometrists. Drugs are applied directly to the eye in the form of drops, ointments, gels, inserts, or intraocular injections.

Advantages:

• Direct local effect on ocular tissues.
• Lower systemic side effects compared to oral or IV routes.
• Convenient and non-invasive.

Disadvantages:

• Rapid drainage due to tear flow and blinking reduces drug contact time.
• Only a small fraction of the dose actually penetrates the cornea.
• Patient compliance issues with frequent dosing.

Examples:

• Mydriatics and Cycloplegics (atropine, tropicamide) – diagnostic purposes.
• Anti-glaucoma drugs (timolol, latanoprost, brimonidine).
• Antibiotic drops (ciprofloxacin, tobramycin) – bacterial conjunctivitis, keratitis.
• Lubricating drops (artificial tears) – dry eye management.

3. Intravitreal and Periocular Injections

Drugs can be injected directly into the vitreous cavity or around the eyeball for posterior segment diseases.

• Intravitreal anti-VEGF agents – ranibizumab, bevacizumab in age-related macular degeneration.
• Intravitreal antibiotics – vancomycin, ceftazidime in endophthalmitis.
• Peribulbar and retrobulbar injections – local anesthesia in ocular surgery.

Novel Drug Delivery Systems

To overcome the limitations of conventional routes, newer methods have been developed:

• Ocular inserts – sustained release drug delivery (pilocarpine ocusert).
• Nanoparticles and liposomes – targeted delivery with enhanced penetration.
• Implants – intraocular implants releasing drugs slowly over months.

Comparison of Different Routes

Route	Onset of Action	Examples in Ocular Practice
Oral	Slow (30–60 min)	Acetazolamide for glaucoma
IV	Immediate	Mannitol for acute angle closure glaucoma
Topical ocular	Fast (minutes)	Timolol, Latanoprost, Tropicamide
Intravitreal	Local sustained effect	Anti-VEGF agents in AMD
Sublingual	Very fast (2–5 min)	Nitroglycerin (systemic, relevant in ocular emergencies with angina)

Pharmacokinetics (with Special Reference to Ocular Pharmacokinetics)

Pharmacokinetics is the branch of pharmacology that deals with the study of how the body handles a drug after its administration. In simpler words, it answers the question: “What does the body do to the drug?” It involves the processes of Absorption, Distribution, Metabolism, and Excretion (commonly abbreviated as ADME). For optometrists and ophthalmologists, understanding pharmacokinetics is crucial because the eye is a unique and relatively isolated organ, where drug penetration is influenced by special anatomical and physiological barriers.

Basic Principles of Pharmacokinetics

Once a drug is introduced into the body, it undergoes a series of processes before exerting its action and eventually being eliminated. These stages include:

1. Absorption – the process by which a drug moves from its site of administration into the bloodstream.
2. Distribution – transport of the drug from blood to tissues and organs.
3. Metabolism (Biotransformation) – chemical alteration of the drug, mainly in the liver, into active or inactive forms.
4. Excretion – removal of the drug and its metabolites from the body, mainly via kidneys.

1. Absorption

Drug absorption refers to the passage of drug molecules from the site of administration into the systemic circulation. Factors affecting absorption include:

• Route of administration – oral, IV, IM, topical, ocular, etc.
• Physicochemical properties – lipid solubility, molecular size, ionization.
• Formulation – tablets, capsules, drops, ointments, suspensions.
• Physiological factors – blood flow, pH, presence of food in the stomach.

In ocular pharmacology: Absorption from topical eye drops depends on corneal penetration, tear film stability, blinking, and nasolacrimal drainage.

2. Distribution

After absorption, drugs are distributed via the blood to various tissues. Factors influencing distribution include:

• Plasma protein binding – drugs bound to plasma proteins are inactive.
• Tissue binding – some drugs accumulate in specific tissues.
• Blood flow – highly perfused organs (liver, kidney, brain) receive more drug.

In ocular pharmacology: Distribution is affected by barriers such as the blood–aqueous barrier and blood–retinal barrier, which restrict drug entry into the eye.

3. Metabolism (Biotransformation)

Metabolism refers to the enzymatic conversion of drugs into more water-soluble compounds that can be easily excreted. The liver is the principal site of metabolism.

• Phase I reactions – oxidation, reduction, hydrolysis (cytochrome P450 enzymes).
• Phase II reactions – conjugation with glucuronic acid, sulfate, or acetyl groups.

In ocular pharmacology: The cornea, conjunctiva, and retina possess some metabolic enzymes that may inactivate or activate drugs before they reach their site of action.

4. Excretion

Excretion is the final elimination of drugs and their metabolites from the body.

• Kidneys – most important (urine).
• Bile and feces.
• Lungs – for volatile agents (anesthetics).
• Skin and sweat.

In ocular pharmacology: Topically administered ocular drugs are mainly lost through nasolacrimal drainage into the systemic circulation and excreted by the kidneys.

Pharmacokinetic Parameters

• Bioavailability – fraction of unchanged drug reaching systemic circulation.
• Half-life (t½) – time required for plasma concentration of drug to reduce by half.
• Volume of distribution (Vd) – theoretical volume in which a drug is distributed.
• Clearance – volume of plasma cleared of drug per unit time.

Ocular Pharmacokinetics

The eye is a complex organ with unique protective mechanisms that make drug delivery challenging. Understanding ocular pharmacokinetics is essential for optometrists to appreciate why certain drugs are chosen, how they are administered, and why frequent dosing is sometimes required.

Barriers to Ocular Drug Absorption

1. Tear film – dilutes and drains drug solution rapidly.
2. Corneal epithelium – lipophilic barrier limiting entry of hydrophilic drugs.
3. Blood–aqueous barrier – limits entry of drugs into the aqueous humor.
4. Blood–retinal barrier – restricts drug penetration into the posterior segment.

Routes of Ocular Drug Entry

• Corneal route – main pathway for topical drugs to reach the anterior chamber.
• Conjunctival–scleral route – for hydrophilic drugs.
• Systemic route – drugs may reach ocular tissues via systemic circulation.
• Intravitreal injections – direct delivery to the posterior segment.

Fate of Topically Applied Eye Drops

When an eye drop is instilled:

• A major fraction (about 70–80%) drains into the nasolacrimal duct.
• A small fraction penetrates the cornea into the aqueous humor.
• Some may be absorbed through conjunctiva and sclera.
• Systemic absorption can occur via nasal mucosa, leading to side effects.

Factors Affecting Ocular Pharmacokinetics

• Formulation – solutions, suspensions, ointments, gels, inserts.
• Drug properties – lipid solubility, molecular weight, ionization.
• Tear turnover and blinking – reduce drug contact time.
• Pathological conditions – inflammation can increase drug permeability.
• Use of punctal occlusion – reduces systemic absorption and increases ocular bioavailability.

Clinical Relevance of Ocular Pharmacokinetics

1. Topical therapy limitations – Frequent instillation is required due to rapid drug loss from tear drainage.
2. Systemic side effects – Beta-blocker eye drops (timolol) can cause bradycardia due to systemic absorption.
3. Drug delivery systems – inserts, gels, liposomes, and implants improve ocular drug bioavailability.
4. Posterior segment diseases – intravitreal injections are required since topical drugs poorly reach the retina.

Comparison: Systemic vs Ocular Pharmacokinetics

Aspect	Systemic Pharmacokinetics	Ocular Pharmacokinetics
Absorption	Gastrointestinal tract, skin, lungs	Cornea, conjunctiva, sclera
Distribution	Throughout body via blood	Limited by blood–aqueous and blood–retinal barriers
Metabolism	Mainly in liver	Cornea, conjunctiva, retina have local enzymes
Excretion	Mainly kidney, bile, lungs	Tear drainage, systemic absorption, renal excretion

Pharmacokinetics of Common Ocular Drugs

• Atropine – topically absorbed, penetrates cornea, metabolized in liver, systemic effects if absorbed nasally.
• Timolol – rapid absorption from conjunctiva/nasal mucosa, may cause systemic beta-blocker effects.
• Latanoprost – absorbed through cornea, hydrolyzed to active form in aqueous humor.
• Ranibizumab (intravitreal) – remains in vitreous for weeks, eliminated by diffusion and proteolysis.

Pharmacodynamics

Pharmacodynamics is the study of the biochemical and physiological effects of drugs and the mechanisms by which they exert their action on the body. In simple terms, it answers the question: “What does the drug do to the body?” For optometrists and ophthalmologists, pharmacodynamics provides the basis for understanding how ocular drugs such as mydriatics, cycloplegics, anti-glaucoma medications, and anti-inflammatory agents act at the molecular and cellular levels to produce clinical effects.

Basic Concepts of Pharmacodynamics

The pharmacodynamic phase begins once the drug reaches its site of action. The major aspects include:

• Drug–receptor interactions – how drugs bind to cellular receptors.
• Dose–response relationship – the relationship between the drug dose and its pharmacological effect.
• Mechanism of action – how the drug produces its therapeutic effects.
• Therapeutic index and safety – the margin between effective and toxic doses.

1. Drug–Receptor Interaction

Most drugs exert their effects by interacting with specific receptors located on the surface or inside cells. A receptor is a macromolecule (usually a protein) that specifically binds to a drug (ligand) and initiates a biological response.

Types of drug–receptor interactions:

• Agonists – drugs that bind to receptors and activate them to produce a response (e.g., pilocarpine acts as a muscarinic agonist to constrict the pupil).
• Antagonists – drugs that bind to receptors but block the action of agonists (e.g., atropine blocks muscarinic receptors to dilate the pupil).
• Partial agonists – drugs that activate receptors but produce a weaker response than full agonists.
• Inverse agonists – drugs that bind to receptors and produce the opposite effect of an agonist.

2. Receptor Types

Receptors are classified based on their structure and signaling mechanism:

1. Ion channel receptors – ligand binding opens or closes ion channels (e.g., GABA receptors).
2. G-protein coupled receptors (GPCRs) – mediate effects of many ocular drugs (e.g., adrenergic and muscarinic receptors in the eye).
3. Enzyme-linked receptors – receptor activation triggers enzymatic activity (e.g., insulin receptor).
4. Intracellular receptors – located in cytoplasm or nucleus, usually for steroid hormones (e.g., corticosteroids in ocular inflammation).

3. Dose–Response Relationship

The intensity of a drug’s effect is directly related to its concentration at the site of action. This is described by the dose–response curve.

• Graded dose–response – continuous increase in response with increasing dose.
• Quantal dose–response – all-or-none response (e.g., whether a patient’s IOP is controlled or not).

Important pharmacodynamic parameters include:

• Potency – the dose required to produce a specific effect. A more potent drug requires a lower dose (e.g., latanoprost is more potent than timolol in lowering IOP).
• Efficacy – the maximum effect a drug can produce, regardless of dose.

4. Mechanisms of Drug Action

Drugs can act through different mechanisms:

• Receptor-mediated action – agonists and antagonists at receptors.
• Enzyme inhibition – e.g., acetazolamide inhibits carbonic anhydrase to reduce aqueous humor production.
• Ion channel blockade – e.g., local anesthetics block sodium channels to prevent nerve conduction.
• Physicochemical action – e.g., osmotic diuretics (mannitol) increase osmotic pressure to reduce intraocular pressure.

Therapeutic Index and Safety

The therapeutic index (TI) is the ratio of the toxic dose to the effective dose. A high TI indicates a wide margin of safety, whereas a low TI indicates a narrow margin, requiring careful monitoring.

Example in ophthalmology:

• Topical artificial tears – very safe, wide therapeutic index.
• Systemic acetazolamide – narrow therapeutic index, requires caution in patients with kidney disease.

Ocular Pharmacodynamics

In the eye, drugs act on specific receptors to alter pupil size, intraocular pressure (IOP), accommodation, tear production, or inflammatory responses.

1. Drugs Affecting Pupil Size

• Mydriatics (pupil-dilating drugs)
  • Atropine, tropicamide (muscarinic antagonists) – block parasympathetic tone.
  • Phenylephrine (α1 agonist) – stimulates dilator pupillae muscle.
• Miotics (pupil-constricting drugs)
  • Pilocarpine (muscarinic agonist) – stimulates sphincter pupillae.

2. Drugs Affecting Intraocular Pressure

• Decrease aqueous humor production
  • Beta-blockers (timolol).
  • Carbonic anhydrase inhibitors (acetazolamide, dorzolamide).
• Increase aqueous humor outflow
  • Prostaglandin analogues (latanoprost, travoprost).
  • Cholinergic agonists (pilocarpine).

3. Drugs Affecting Accommodation

• Parasympathomimetics (pilocarpine) – stimulate accommodation (used in presbyopia therapy trials).
• Anticholinergics (atropine, cyclopentolate) – cause cycloplegia (paralysis of accommodation).

4. Anti-Inflammatory Drugs

Corticosteroids act on intracellular receptors to inhibit inflammatory gene expression. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase enzymes to reduce prostaglandin synthesis.

Examples of Pharmacodynamics in Ophthalmology

Drug	Receptor/Target	Pharmacodynamic Effect
Pilocarpine	Muscarinic receptor agonist	Miosis, increased aqueous outflow, reduced IOP
Atropine	Muscarinic receptor antagonist	Mydriasis, cycloplegia
Timolol	Beta-adrenergic antagonist	Reduced aqueous humor production, lower IOP
Latanoprost	Prostaglandin analogue	Increased uveoscleral outflow, lower IOP
Mannitol	Osmotic effect	Reduces vitreous volume, decreases IOP

Drug Synergism and Antagonism

• Synergism – combined effect of two drugs is greater than the sum of individual effects (e.g., timolol + latanoprost in glaucoma).
• Antagonism – one drug reduces or inhibits the effect of another (e.g., pilocarpine and atropine have opposing effects on the pupil).

Clinical Relevance of Pharmacodynamics

1. Helps in drug selection – e.g., prostaglandin analogues preferred in glaucoma due to high efficacy.
2. Explains side effects – e.g., atropine causes photophobia due to mydriasis.
3. Assists in dose adjustment – balancing efficacy and toxicity.
4. Predicts drug interactions – additive or antagonistic effects when drugs are combined.

Factors Modifying Drug Actions

Drugs do not act in the same way in all individuals. The intensity, duration, and type of drug response can vary widely among patients due to a variety of factors. These differences may be related to the patient, the drug itself, or the environment. Understanding these modifying factors is crucial for safe and effective therapy, especially in ocular pharmacology where precision in drug action is necessary for conditions like glaucoma, uveitis, and refractive procedures.

Introduction

The study of factors that alter drug action is important for:

• Explaining why the same dose of a drug produces different effects in different individuals.
• Guiding clinicians in adjusting doses according to patient characteristics.
• Predicting adverse effects and avoiding toxicity.
• Optimizing therapeutic outcomes in ocular and systemic diseases.

Main Factors Modifying Drug Action

Factors can be broadly classified into:

1. Patient-related factors – age, sex, body weight, genetic makeup, disease state, etc.
2. Drug-related factors – dose, route of administration, formulation, drug interactions.
3. Environmental and lifestyle factors – diet, climate, stress, compliance.

1. Age

Age is one of the most important determinants of drug response.

• Newborns and infants – immature liver and kidney function result in reduced drug metabolism and excretion. This increases the risk of drug toxicity. For example, chloramphenicol eye drops can cause gray baby syndrome in neonates.
• Children – higher metabolic rates may require higher doses per kilogram body weight for some drugs.
• Elderly – reduced liver function, decreased renal clearance, and multiple comorbidities alter drug response. For example, elderly patients are more sensitive to the cardiovascular side effects of topical beta-blockers like timolol.

2. Sex

Gender differences can modify drug action due to hormonal variations, body composition, and enzyme activity.

• Women generally have more body fat and less body water, which affects distribution of lipophilic drugs.
• Hormonal fluctuations during pregnancy or menstrual cycle may alter drug response.
• Some drugs may be contraindicated in pregnancy due to teratogenic effects, e.g., systemic acetazolamide for glaucoma is avoided in pregnant women.

3. Body Weight and Surface Area

The dosage of many drugs is calculated based on body weight or body surface area. A standard dose may not be suitable for very obese or underweight patients.

Example in ophthalmology: Systemic acetazolamide (used in glaucoma) requires dose adjustment in patients with very low or high body weight.

4. Genetic Factors

Genetic makeup plays a major role in determining individual variations in drug response. This branch of study is called pharmacogenetics.

• Some patients are slow acetylators or fast acetylators, which affects metabolism of drugs like isoniazid.
• Deficiency of enzymes like glucose-6-phosphate dehydrogenase (G6PD) can cause hemolysis with certain drugs.
• Polymorphisms in cytochrome P450 enzymes influence drug metabolism and efficacy.

Ocular relevance: Genetic differences influence response to anti-glaucoma medications; for example, variations in β-adrenergic receptor genes may alter timolol response.

5. Pathological State

Disease conditions can significantly alter drug action.

• Liver disease – reduces metabolism, leading to drug accumulation and toxicity.
• Kidney disease – impairs drug excretion, requiring dose adjustments for drugs like acetazolamide.
• Cardiovascular disease – alters drug distribution and clearance.
• Ocular diseases – inflammation of the eye can disrupt blood–aqueous and blood–retinal barriers, increasing drug penetration.

6. Tolerance and Tachyphylaxis

Tolerance is a gradual decrease in drug response after repeated use, requiring higher doses to achieve the same effect. Tachyphylaxis is a rapid decrease in response after initial doses.

Ocular example: Prolonged use of decongestant eye drops (naphazoline) can lead to tachyphylaxis and rebound hyperemia.

7. Drug Interactions

When two or more drugs are given together, they may interact to produce:

• Synergism – enhanced effect (e.g., timolol + latanoprost in glaucoma).
• Antagonism – reduced effect (e.g., pilocarpine vs atropine on pupil size).
• Pharmacokinetic interactions – one drug affects the absorption, metabolism, or excretion of another.

8. Route and Form of Administration

The route of drug delivery can significantly modify its action. For instance:

• Topical timolol acts locally on the eye but may also be absorbed systemically through nasolacrimal drainage.
• Intravitreal injection of anti-VEGF drugs provides high local concentration in the retina compared to topical administration.

9. Psychological Factors (Placebo Effect)

A patient’s mental state and expectations can modify drug action. The placebo effect refers to therapeutic improvement due to belief in treatment, even when receiving an inactive substance.

Ocular relevance: Patient compliance and satisfaction with eye drops can be improved if they believe strongly in the therapy.

10. Environmental Factors

Climate, altitude, and external stressors may alter drug response.

• High temperature and dehydration may enhance toxicity of diuretics.
• Altitude can influence oxygen delivery and drug pharmacokinetics.

11. Compliance and Adherence

The success of therapy depends greatly on whether the patient takes the prescribed drug in the correct dose and frequency. Non-compliance is a major reason for treatment failure, especially in chronic ocular diseases like glaucoma where patients may forget or avoid using eye drops.

Examples of Factors Modifying Ocular Drug Action

Factor	Example in Ophthalmology	Effect on Drug Action
Age	Atropine in children vs elderly	Children tolerate higher doses; elderly more prone to systemic side effects
Genetics	Timolol response varies with β-receptor polymorphism	Alters effectiveness in lowering IOP
Disease state	Inflamed cornea	Increased drug penetration, risk of toxicity
Tolerance	Chronic use of decongestant drops	Reduced effect, rebound redness
Drug interaction	Pilocarpine + atropine	Opposing effects on pupil size

Clinical Importance

• Helps in dose individualization based on patient characteristics.
• Prevents drug toxicity in vulnerable groups like neonates and elderly.
• Improves compliance and patient education in chronic ocular therapy.
• Explains variability in treatment response among patients with the same condition.

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