Roots of the theory and practice of ocular pharmacology may be traced to the ancient Mesopotamian code of Hammurabi and then to several papyri reflecting the clinical interests of the Egyptians. The evolution of its art and science was irregularly paced until the nineteenth century when Kohler, in 1884, proved the anesthetic effect of cocaine on the cornea, and when Fraser, Laquer, Schmiedeberg, Meyer, and others studied the pharmacology of the autonomic nervous system by way of observations of the pupil. Advances in the past few decades have been nothing short of explosive. How can the student, physician, or basic research scientist stay in touch with these electrifying studies? To help with the answer to this question, the authors set as their goal the development of increased understanding so that the student, research scientist, and ophthalmologist can cope with the latest discoveries. The authors want to narrow what appears to be an ever-increasing gap between basic science and ophthalmology. The basic aspects of pharmacology have been presented in light of the natural physiology. In this regard, while distinctions among endogenous mechanisms, drug effects, and the pathogenesis of disease are to be separately recognized, appreciation must be given to the concept that both the desirable and unwanted manifestations or functions caused by either disease or drugs must very often represent a quantitative change in normal metabolic pathways.

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1 The History of Ophthalmic Therapeutics With 7 Figures.- References.- 2 Ocular Pharmacokinetics With 20 Figures.- Abbreviations.- A. Introduction.- I. Objectives.- II. Compartments and Barriers.- III. Routes of Administration and Penetration.- 1. Topical Administration.- 2. Local Injection.- 3. Systemic Administration.- IV. Animal Models and Human Experimentation.- 1. Animal Models.- 2. Human Experiments.- B. Topical Administration.- I. Factors Involved in Intraocular Penetration.- 1. The Tears and Contact with Ocular Surface.- 2. Corneal Penetration.- 3. Conjunctiva and Sclera.- 4. Intraocular Structures.- 5. Metabolism of Drugs During Intraocular Penetration.- II. Compartmental Analysis.- 1. Compartmentation.- 2. Two-Compartment Model.- 3. Tear Patterns.- 4. Other Compartments.- 5. Kinetics of Ocular Responses to Drugs.- 6. Parameter Determination.- III. Conclusions and Recommendations.- C. Local Injections.- I. Subconjunctival.- 1. Regurgitation.- 2. Depot Dynamics.- 3. Aqueous Humor Concentration.- 4. Entry Pathways.- 5. Vitreous Penetration.- 6. Retrobulbar Injection.- II. Intravitreal Injection.- 1. Diffusion in Vitreous.- 2. Loss from the Vitreous Chamber.- 3. Drug Kinetics.- 4. Application to Humans.- D. Systemic Administration.- I. Intraocular Drug Penetration.- 1. Structures Related to Entry from Blood.- 2. The Blood-Vitreous Barrier.- 3. Chemical Factors in Drug Penetration.- 4. Drug Distribution in the Eye.- II. Compartmental Analysis.- 1. Formulation of Aqueous Humor Dynamics.- 2. One-Compartment Approximation.- 3. Changes in Aqueous Concentration.- 4. Kinetics of Intracameral Penetration.- 5. Penetration into the Vitreous.- 6. Penetration into the Cornea and Lens.- III. Conclusions and Recommendations.- E. Kinetics in Ocular Disease.- I. Inflammation and its Models.- II. Effects on Ocular Parameters.- 1. Permeability.- 2. Active Transport.- 3. Vasomotor Effects.- III. Effects on Drug Kinetics.- 1. Topical Application.- 2. Systemic Penetration.- 3. Periocular Injection.- 4. Intravitreal Injection.- F. Conclusion.- References.- 3 Biotransformation and Drug Metabolism With 25 Figures.- A. Introduction.- B. Hepatic Drug-Metabolizing Systems.- I. Microsomal Electron Transport Systems (Phase I Enzymes).- 1. Cytochrome P-450.- 2. NADPH · Cytochrome P-450 Reductase.- 3. Cytochrome b5 and NADH · Cytochrome b5 Reductase.- II. Reactions Catalyzed by the Cytochrome P-450 System.- 1. Oxidative Reactions.- 2. Reductive Reactions.- III. Conjugation Reactions (Phase II Reactions).- 1. Glucuronidation.- 2. Sulfation.- 3. Acetylation.- 4. Conjugation with Amino Acids.- 5. Methylation.- 6. Conjugation with Glutathione.- IV. Induction of Drug-Metabolizing Enzymes.- C. Ocular Drug Metabolism.- I. Aryl Hydrocarbon Hydroxylase Induction in the Eye.- II. Tissue Distribution of Drug-Metabolizing Enzymes in the Eye.- III. Drug Toxicity - An Experimental Approach.- D. Concluding Remarks.- References.- 4 Cholinergics With 11 Figures.- A. Chemistry Related to Biological Activity.- I. Cholinergic Neurotransmission.- II. Direct-Acting Agonists.- 1. Muscarinic Agents.- 2. Nicotinic Agents.- III. Indirect-Acting Agonists: Anticholinesterases.- 1. Carbamates.- 2. Organophosphorous Compounds.- B. Ocular Anatomy/Physiology Relevant to Cholinergic Mechanisms: Acute Effects of Cholinergic Drugs.- I. Lacrimation.- II. Cornea.- III. Lens.- IV. Pupillary Movement and Accommodation.- V. Aqueous Humor Formation, Removal, and Composition; Blood-Aqueous Barrier.- 1. Basic Anatomy and Physiology.- 2. Acute Effects of Cholinergic Drugs.- VI. Retina.- VII. Oculorotary and Respiratory Skeletal Muscles.- C. Longer-Term Effects of Cholinergic Drugs or Altered Cholinergic Neurotransmission.- I. Cholinergic Sensitivity in Ocular Smooth Muscles.- 1. Physiologically and Pharmacologically Induced Alterations.- 2. Disease-Induced Alterations.- 3. Surgically Induced Alterations.- II. Cholinergic Toxicity.- 1. Lens (Cataractogenesis).- 2. Iris/Ciliary Muscle/Trabecular Meshwork.- References.- 5 a Autonomic Nervous System: Adrenergic Agonists With 21 Figures.- A. Introduction.- B. Cellular Sites and Mechanism of Adrenergic Action.- C. Modulation and Interaction of Receptor Types.- D. Sensitivity.- E. Stereoisomerism.- F. Storage, Release, and Degradation.- I. Monoamine Oxidase.- II. Catechol-O-methyltransferase.- G. Pharmacokinetics.- I. Penetration.- II. Distribution and Accumulation.- III. Duration.- IV. Action of Drugs on Intraocular Pressure.- H. Tissue Functions.- I. Lacrimal Gland.- II. Cornea and Lens.- III. Iris.- J. Blood Flow.- K. Intraocular Pressure.- L. Other Interactions.- I. Guanyl Cyclase.- II. Steroids and Adrenergics.- III. Adrenergics and Prostaglandins.- IV. Adrenergics and Ocular Pigment.- M. Retina.- References.- 5b Autonomic Nervous System: Adrenergic Antagonists.- A. Introduction.- B. Beta-Adrenergic Antagonists.- I. Animal Pharmacology.- 1. Intraocular Pressure.- 2. Aqueous Humor Dynamics.- 3. Interactions with Beta-Adrenergic Receptors in the Eye.- 4. Mechanisms of Action on Intraocular Pressure.- 5. Ocular Penetration and Distribution.- 6. Other Ocular Pharmacology.- II. Clinical Pharmacology.- 1. Intraocular Pressure.- 2. Aqueous Humor Dynamics.- 3. Beta-Adrenergic Receptor Blockade in the Eye.- 4. Mechanisms of Action.- 5. Ocular Penetration.- C. Alpha-Adrenergic Antagonists.- I. Animal Pharmacology.- 1. Selective Alpha-Adrenergic Antagonists.- 2. Alpha- and Beta-Adrenergic Antagonists (Labetalol).- II. Clinical Pharmacology.- References.- 6 Carbonic Anhydrase: Pharmacology of Inhibitors and Treatment of Glaucoma With 10 Figures.- A. History.- B. Pharmacology of the Clinically Used Carbonic Anhydrase Inhibitors..- C. Physiology of Ocular Carbonic Anhydrase Inhibition.- I. Aqueous Humor Dynamics.- II. Aqueous Flow.- III. Relation to Pressure.- IV. Chemical Mechanisms of Flow.- V. Relation to Systemic Effects.- VI. Pharmacology of the Inhibitors Related to Ocular Effect and Enzyme Inhibition.- D. Clinical Uses of Carbonic Anhydrase Inhibitors.- I. Glaucoma.- II. Miscellaneous Uses and Effects.- E. Urolithiasis with Carbonic Anhydrase Inhibitors.- F. Other Toxic Effects.- G. Summary.- References.- 7 Autacoids and Neuropeptides With 5 Figures.- A. Introduction.- B. Prostaglandins, Prostacyclin, Thromboxane, and Lipoxygenase Products.- I. General Background.- II. Occurrence and Biosynthesis in the Eye.- III. Elimination.- IV. Effects in the Eye.- 1. Blood Flow.- 2. Blood-Aqueous Barrier and Formation of Aqueou…