Introduction

1. Introduction Instructor :MScIkhlasJarrar

2. Pharmacology • Science that study study of drug action • Has two main areas • Pharmacodynamics • Pharmacokinetics • Phamacotherapeutics • Pharmacology has many divisions :

3. Drug • Chemical or biological agent that affect the biological systems • May be used to : • treat, cure, prevention, diagnosis of disease ,and enhance physical or mental well-being • Drug may be derived fro natural sources or may be synthetic

4. Every drug have 3 names chemical,generic and trade name • Chemical name describes the atomic molecular structure(seldom used • Generic name =scientific name • The best used to avoid confusion • Trade name =brand name • may differ according to company • Followed by symbol R means registered and restricted

5. Paracetamol 500mg

6. How is the drug developed marketing In vitro study Animal testing Clinical study New drug application Generics availabl Phase 3 Phase 4 Phase 1 Phase 2 0 2 4 8-9 20 yr

7. Clinical study • On human • Composed of 4 phases • Phase I • Small number of normal people • Pharmacokinetic of the drug is studied • Phase II • Moderate number of normal and ill patients • The goal is to see whether the drug works in the ill patients

8. Clinical study • Phase III • Larger number of people • Phase IV • After marketing • Study of toxicity of the drugs

9. Areas of pharmacology • Pharmacokinetic • What the body do to the drug • ADME • Pharmacodynamics • What the drug do to the body

10. Pharmacokinetic • Action of the body on the drug • Composed of: • Absorption (A) • Distribution (D) • Metabolism (M) • Elemenation (E)

12. Absorption • Rate and extent to which the drug moves from its site of administration

13. What does the rate and efficacy of absorption depend on? • Route of administration • Blood flow • Surface area available • Solubility of a drug • Drug-drug interactions • pH

14. Routes of administration • The path by which a drug, fluid, poison, or other substance is taken into the body • 4 types: • Enteral • Parentral • Inhalation • Others

15. 1.enteral • Desired effect is systemic,administration through GIT .Includes: • Oral • The most common • Include tablet,capsulesyrup,suspension • What is the difference btw them? • Advantage : • Good patient cmpliance • Easy to take • Disadvantage : • First pass metabolism

16. 1.Alimentary • Buccal • Between gum and cheeks • Advantage: • Avoid first pass metabolism by passing directly into superior vena cava • Disadvantage : • Not all drugs can formulated as it

17. 1.Alimentary 3. Sublingual • Under the tongue • Advantage: • Avoid first pass metabolism by passing directly into superior vena cava • Disadvantage : • Not all drugs can formulated as sublingual

18. 1.Alimentary 4. Rectal • Suppository ,fleet enema • Advantage : • Useful when oral route is unavailable due to vomiting • Less first pass effect than oral • Disadvantage : • Patient compliance • Inconvenient when patient has diarrhea

19. Routes of administration • Enteral • Parentral • Topical • Others

20. 2. Parentral • Desired effect is systemic, substance is given by routes other than the digestive tract • Intravenous • Direct injection into the vascular system • Advantage: • Rapid effect • Potent • No first pass effect bec. 100% of the drug enter circulation • Disadvantage • Need specialized persons like you • Painful

21. 2. Parentral 2. Intramuscular (IM) • Usually given in gluteus maximus • Advantage : • More rapid than PO and less rapid than IV • No first pass metabolism • Disadvantage : • Painful

22. 2. Parentral 3. Subcutaneous (SC) • Like insulin injections

24. 2. Parentral 4. Intrathecal • Injection into the spinal subarachnoid space • Advantage : • In cases of acute CNS infection and spinal anesthesia • Avoid first pass metabolism • Disadvantage : • Personal error may lead to disablity to walk

25. 2. Parentral 5. Epidural injection • Injection of drugs through a catheter placed into the epidural space • In your opinion which is safer epidural or intrathecal?

27. Epidural injection

28. Routes of administration • Enteral • Parentral • Topical • Others

29. Topical • Substance is applied directly where its action is desired • Like: • Inhalation • Ear drops • Eye drops • Creams • Ointments

30. Inhalation • Commonly drugs that affect lung but there are exceptions • Inhalers and nebulizers

31. Inhaler Nebulizer

32. 5. Transdermal • Medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream.

33. In what way does the pH of a drug affect the charge? • Drugs are either weak acids or bases • Acidic drug are uncharged when protonated HA H+ A- NOT ABSORBED

34. In what way does the pH of a drug affect the charge? • Basic drugs are charged when protonated BH+ H+ B NOT ABSORBED

35. CHARGE = Not pass through site of administration لا تعبر الحدود

36. Deprotonated forms A- and B predominate Protonated forms HA and BH+ predominate pH less than pKa pH more than pKa pH 3 4 5 6 7 8 9 10 11 pH=pKa HA=A- BH+=B

37. Bioavailability (BA) • Fraction of administered drug that reach its site of action • BA for IV =100% • BA for for a medication given as tablet is less 100%

38. Factors affect bioavailability • First –pass metabolism • All factors that affect absorption

39. First pass metabolism • Biotransformation that occurs before the drug reaches its site action • Commonly occurs in liver • Also happens in other sites but to a lesser extent like: • Small intestine • Kidney

40. Bioequivalence • the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study • Panadol and sedamol are not bioeqivalent.what does that mean?

41. Distribution • Process by which the drug leaves the bloodstream and enters the interstitium or the cells of the tissues

42. Types of transport

43. How the drug absorbed into the cells? • Simple diffusion • Concentration gradient • High conc. Low conc. • No energy consumed • Most common mode of drug transport • Facilitated diffusion • Transport by special carrier proteins • No energy consumed • Active transport • Need of protein • Need energy ATP

44. Factors affect distribution • Blood flow • Capillary permeability • Binding to plasma protein • Acidic drugs binds to albumin more efficiently than basic ones • Ex:aminglycoside are basic drugs so their binding to albumin is…………………… • Drug structure • Lipophilic drugs cross cell membrane • Polar molecule doesn’t cross cell membrane

45. Biotransformation • Lipophilic molecules modified to more polar molecule to enhance their elemination • May activate or inactivate drugs • Composed of 2 phases • Phase I • Phase II

46. Phase I lipophilic molecule Oxidation Reduction hydrolysis May be active or inactive Polar molecule

47. Phase II • Formation of covalent linkage between functional groups on the parent drug and another substrate • Glucoronate , acetic acid ,glutathione,sulfate are major groups added • Usually the drug become inactive

48. What is the main site of biotransformation? • Liver • Small intestine ,kidney play a little role

50. Where do these reaction occurs on a cellular level? • Phase I reaction in cytochrome P450 system • Phase II reaction occurs in cytosol by group of enzymes called transferases