General pharmacology& pharmacology of the Eye By Dr. MOHAMED A.ETARSHAWI Optometry department

1. General pharmacology& pharmacology of the Eye By Dr. MOHAMED A.ETARSHAWI Optometry department Faulty of Health Sciences-IUG 2015-2014

2. DEPARTMENT OF OPTOMETRY General Pharmacology PART I

3. Contents I- Drug definition, sources and preparation. SLIDE6 and excretionII- Drug absorption , distribution , metabolismSLIDE 35 - Slide- 62III- Drug action , activity and dosage IV-Channels of Drug Administration Slide-79 V- How do drugs work?Slide 90 VI- Side effects and drug toxicitySlide 95 VII- General guidelines for handling medications Slide 110 116VIII-PHARMACODYNAMICSPHARMACOKINETICSIX- CLASSES OF ANTIBACTERIAL AGENTSSlide 121

4. II PART Pharmacology Of the Eye X- Entry of drugs into the eye. Slide -129 XI- Diagnostic drugs and products used in optometry Slide 174. XII- Mydriatics.Slide 242 XIII-Miotics. Slide 277 XIIII- Stains . Slide 294 XV-Contact solutions Slide .315

5. Contents XVI-Therapeutic drugs of eye diseases and their uses Slide 353 XVII-Topical Eye Medication in Infants and Children . Slide 393 XVIII-VERNAL KERATOCONJUNCTIVITIS (VKC)Slide 413 XVIIII-Pharmacology of Ocular Beta- Adrenoceptor Antagonists (Antiglaucoma drugs) Slide 446

6. CHAPTER ONE Drug definition, sources action and preparations

7. General Pharmacology Pharmacology: Pharmacology is a Latin word meaning drug knowledge. Pharmaco = drug . Ology = science or knowledge.

8. General Pharmacology Drug : is defined by the United States food and drug administration (FDA) as “ A substance or agent used in diagnosis, cure, prevention, mitigation التخفيف, or treatment of a disease condition.”

9. General Pharmacology The FDA definition of drug also includes any substance listed in USP (the United States pharmacopia) and BP (British pharmacopia) and all substances other than food or devices capable of altering body structure. Pharmacopia : is a book containing formulas الصيغ, which are standard for preparation and dispensation of drug (distribution) .

10. Branches of pharmacology I- Pharmacotherapeutic: ( Clinical pharmacology) داخل جسم الإنساندراسة التأثير العلاجي للأدوية It deals with relative effect of drugs in the human system for various disorders. Or it deals with the effect of a drug that the Dr. orders for treating a human patient . Or “The study of drug action in diseased man”.

11. General Pharmacology علم الدواء التجريبي II- Pharmacodynamic: Which deals with experimental pharmacology. Or it deals with the interactions between components of living system and foreign chemical including drugs that enter living organism in experiment.

12. General Pharmacology III-Pharmacokinetics: is the study of drug’s alteration during its way through the دراسة التغييرات التي تطرأ على الدواء داخل الجسم body. Or it is the study of the fate of drug in the body as it is absorbed, distributed, bound to or localized in tissues, biotransformed and excreted .دراسة مصير الدواء بعد عمله داخل الجسم

13. Parameters of drug action The parameters of drug action are : Drug absorption and distribution. Drug plasma concentration.تركيز الدواء داخل بلازما الدم Therapeutic plasma levels. التركيز العلاجي للدواء داخل البلازما Concentration of the active drug at the target site. تركيز الدواء داخل العضو المريض Rate of metabolism. Rate of excretion.

14. Factors affecting the Parameters of drug action These parameters in turn are affected by: 1. Physiochmeical nature of the drug e.g. lipid or water solubility of the drug. 2. Formulationتركيب of the drug. 3. Route of administration of the drug . 4. Binding of the drug to plasma and/or body tissues (bioavailability). 5. Individual characteristics of the patient. 6. Concomitant diseases.الأمراض المصاحبة لتناول الدواء 7. Concomitant administration of food or other drugs.المصاحبة لتناول الدواء

15. Sources of drugs Drugs and biologic products are derived from 4 main sources: I- Plants: are the major source of drugs examples of which are digitalis. II- Animals : from which drugs such as insulin, epinephrine are obtained. III- Mineralsالمعادن : examples such as iodine and iron. IV- Chemicals: made in laboratories.

16. General Pharmacology Active constituents of plant drugs: The الاوراقleaves, الجذورroots, البذور seeds and other parts of plants may be dried or otherwise processed تصنع for use as medicine and they are known as crude drugs.دواء خام

17. General Pharmacology On separation of these active plant constituents, the resulting pure drug form are: More potent. أكثر قوة Usually produce effects more reliable فعال than those of the crude drugs. More poisonous and the dose must be smaller .

18. General Pharmacology These plant active constitutes are: Alkaloidsالقلويات : examples are atropine, morphine, codeine and heroine. They are toxic, have bitter taste, potent in small doses, insoluble in water (but their salts are soluble in water) and they usually end with “ine” suffix 2.Glycosides سكريات نباتية: such as Digoxin دواء لعضلة القلب. 3.Gumsالأصماغ : Such as Agar.

19. General Pharmacology 4.Resins النباتية الدهون: they are fatty-like substances that are greasy and irritant such as cathartics النباتيةالملينات. (laxatives) 5.Oils: they are 2 types: a - Volatile طيار such as peppermint oil زيت النعنع and clove oil. القرنفل زيت b –Nonvolatile (Fixed ) oils such as olive oil زيت الزيتون and castor oil. الخروعزيت

20. General Pharmacology Common Drug Preparations:التراكيب الدوائية الشائعة I-Solutions and suspensions : معلقات , محاليل Aqueous solutions: have one or more substance dissolved in water e.g. epinephrine nasal solution. Aqueous suspensions: are preparations of finally divided drugs (undissolved) either intended for suspension or already in suspension in some suitable liquid vehicle.

21. Common Drug Preparations: Sterile suspensions are intended for intramuscular or subcutaneous injections but they can’t be given intravenously . Oral suspensions are NOT sterile and must NOT be injected. N.B : Suspensions tend to settle slowly and should be SHAKED WELL before use to provide uniform distribution of the drug.

22. Common Drug Preparations: II-Elixir :إكسير clear fluid containing the drug ,water and alcohol designed for oral use, usually has a sweetener added ,e.g most cough drugs.شراب الكحة III-Syrupشراب: drug dissolved in a concentrated sugar solution.

23. Common Drug Preparations: IV-Capsules: are a convenient way of giving drugs that have unpleasant taste. Capsules are solid dosage form for oral use medication in a powder, liquid or oil form are incased in gelatin shell, capsule colored to avoid mistakes in product identification. Capsules may be controlled- release or sustained- release capsules.

24. Common Drug Preparations: V-Coated tabletsالاقراص المغلفة “Enteric coating” drugs are used for the following reasons:- To prevent decomposition of chemically sensitive drugs by gastric secretions. To prevent dilution of the drug before it reaches the intestine.(giving weak action) To prevent nausea and vomiting due to gastric irritation. To provide delayed action of the drug .

25. Capsules N.B. : Capsule forms are absorbed more rapidly than tablets because the powder inside capsules affords تغطي a larger surface area of stomach mucosa than the compressed tablets.

26. General Pharmacology VI-Tablets أقراص: are powdered dosage form compressed into hard disks or cylinders. In addition to primary drug , they contain binders (adhesive to allow powder to stick together). VII-Pills برشامة دواء: are solid round dosage form containing one or more drug. Pillsare used to provide a drug or mixture of drugs into definite doses and avoid the inconvenience الإزعاجof preparing the dose from dry powder.

27. General Pharmacology NOTES:- 1-Some gelatin capsules and coated tablets may be coated with substances that resist the action of gastric juice so that will not disintegrate until they reach the alkaline secretions of mall intestine. 2-Sustained – release dosage capsules and tablets forms contain small particles of the drug coated with materials that require a varying amount of time to dissolve. This provides for a long continuous period of absorption and effect.

28. General Pharmacology VIII-Ampoules and vials:- Ampoules and vials contain powder or liquid drug usually intended for injection. VIIII-Disposable syringes:- Disposable syringes containing single dose of drug preparations are widely used today.

29. Disposable syringes

30. General Pharmacology X-Large volume intravenous solutions:- In glass, flexible plastic or semi-rigid plastic bag usually of 250, 500, 1000 ml e.g. 0.9% sodium chloride for I.V. injection. XI-Intermittent I.V Solution:- These solutions are similar to the I.V. solutions except they come in smaller volumes .

32. General Pharmacology X11- Additional Formulations:- A- Drops:- are aqueous solutions that anesthetize, soothe or medicate (treat) eyes, ears, or nose. Drops are aqueous solution instilled into the body cavities like eyes , nose or ears allowed to stay there in contact with tissue to treat certain disorders.

33. General Pharmacology B- Foamsأبخرة and aerosols رذاذ:- are powders or solutions for spraying skin as topical anesthesia to soothe or protect skin or inhalation for bronchodilation in cases of bronchial asthma.

34. General Pharmacology XIII-Other Formulations :- A-Lotions:- Liquid suspensions used for external applications e.g. calamine lotion as antipruiritic. B-Creams:- aqueous and oily emulsions to soothe skin. C- Skin ointments:مَراهَمsemisolid preparations of medical substances in some type of base such as petrolatum lanolin used for skin soothing or have a bacteriostatic effect. D- Ophthalmic ointments: are sterile (e.g. antibiotics ) ophthalmic ointment. E-Pasts:- Ointment- like preparations suited for only external skin application. e.g. Zinc oxide past.

35. General Pharmacology XIIII- Suppositories:- are mixtures of drugs with a firm base that can be molded in shapes suitable for insertion manually or with an applicator into certain body cavity or orifice rectal or vaginal e.g. aminophylline suppositories in bronchospasm (bronchial asthma). N.B. :- They should be kept cool.

36. Suppositories

37. CHAPTER TWO Drug absorption , distribution, metabolism and excretion

38. Drug Absorption, Distribution metabolism and Excretion Absorption Is the process that involves the movement of drug molecules from the site of entry into the body to the circulating body fluids (blood or lymph). The process of absorption begins at the site of administration and is essential to the subsequent processes (distribution, metabolism and excretion).

39. Absorption Absorption as a process varies according to: The route of administration. Drug form (preparation ). The dose of the drug.

40. Factors Affecting Drug Absorption 1-Nature of the absorbing surface: Cell membrane through which the drug must traverse. The drug molecule may pass through a single layer of cells (intestinal epithelium of villi) faster than several layers of cells (skin). Inverse proportion 2-Surface area of the absorbing surface: N.B. : The more extensive the absorbing surface, the greater the absorption rate and more rapid effect of the used drug. Direct proportion

42. Blood flow to the site of administration 3-Blood supply of the absorbing area: Rich blood supply (sublingual) enhances absorption where as, poorly vascular site (subcutaneous) delays it. (Direct proportion). For example, patient in shock may not respond to (I.M) administration of drugs because of poor peripheral circulation. N.B. :- Drugs injected (I.V) are placed directly into the circulatory system leading to rapid drug absorption.

43. 4-Solubility of the drug -In order to be absorbed drug must be soluble in solutions. The more soluble the drug, the more rapidly it will be absorbed. N.B: Chemicals and minerals that form insoluble precipitates in the G.I.T or drugs that are insoluble in water or lipids can’t be absorbed. - Parenterally غير معويadministered drugs(injections ) prepared in oily vehicle will be more slowly absorbed from the muscle than drugs dissolved in water or isotonic sodium chloride solution.

44. 5-Influence of pH Drugs that are acidic (e.g. Aspirin) the medical substance becomes relatively undissociated ( remain active) in an acidic environment such as the stomach , and therefore can readily diffuse across the intestinal cell membrane into the circulation. In contrast, an alkaline drugs (antacid) tends to dissociate (inactivated) in the stomach acid environment and not absorbed through the gastric mucosa.

45. 5-Influence of pH The reverse occurs when these drugs are in an alkaline media. ( like Duodenum). N.B. : The unionized (undissociated ) drug in water is lipid soluble readily diffuses across the cell membrane of intestine , while the ionized water soluble (dissociated ) drug is lipid insoluble and nondiffusable across the cell membrane of intestine .

46. 6-Drug concentration Drug administered in high concentration tend to be more rapidly absorbed than drugs administered in low concentration. In certain situations, drug may be initially administered in large doses that temporarily exceeds the body capacity for exertion of the drug High concentration tend to be more rapidly absorbed than drugs administered in low doses. In this way (high concentration) the active drug therapeutic levels are rapidly reached at the receptor site.

47. 6-Drug concentration Once active drug level is established by such cumulating effects, smaller doses of the drug can be administered to replace only the amount of the drug excreted since the previous dose. N.B. :- The initial large dose temporary overloading doses of the drug are Priming or Initial doses, while the smaller daily doses are Maintenance doses .

48. Distribution of drugs Is defined as the transport of a drug in body fluids from the blood stream to various tissues of the body and ultimately to its site of action. Most of drugs are distributed initially to organs that have rich blood supply as the heart, liver and kidney. Delivery of the drug to extremities, skin and adipose tissue is slower due to poor blood supply. The distribution phase can be extremely slow for drugs that bind strongly to serum proteins, because the drug- protein complex is unable to pass out of the plasma to different tissues due to its large size.