1. Principles of Therapeutics Indiviualization of Dosage Compliance Herbal/Botanical Suppliments Faraza Javed Mphill Pharmacology

2. Therapeutics The treatment and care of a patient for the purpose of both preventing and combating disease or alleviating pain or injury. The term comes from the Greek therapeutikos, which means inclined to serve. OR The branch of medicine concerned with the treatment of disease. 3. Drug A chemical substance of known structure, which, when administered to a living organism, produces a biological effect. 4. Most common parameters evaluated to check the action and therapeutic activity of the drug. Pharmacodynamic Pharmacokinetics Preclinical Study Clinical Trials 5. Pharmacodynamics 6. Pharmacodynamics Study of how drug act on living body. How drug act General Principles: Binding Postulate Such binding leads to cellular response that results in pharmacological effect of drug. 7. How Drugs Act: GeneralPrinciples The Binding Postulate Paul Ehrlich A drug will not work unless it is bound 8. Drug Targets Receptor s Enzyme s IIon Channels Carrier Molecule (Transpo rter) Miscellaneou s 9. Receptors The cellular Assembely which recognizes chemical mediators. Binding Activation Chain of Reaction Physiological Action Affinity Efficacy 10. Enzymes 11. Ion Channels 12. Transporter 13. Miscellaneous: Drugs that act without being bound to any tissue constituent (e.g. osmotic diuretics, antacids and heavy metal chelating agents) may fall in this category. A few other types of protein (plasma proteins) are known to function as drug targets and their exist many drugs with sites of action that are not yet known. e.g Nefopam. 14. Pharmacokinetics 15. Pharmacokinetics Absorption Distribtion Metabolism Excretion 16. Bioassays and Clinical Trials 17. Bioassay Biological testing procedure for estimating the concentration of a pharmaceutical drug substance in a formulated drug product or bulk material. The specific potency of drug is given to animal and then drug response is compared with the standards. 18. Objective Bioassays are commonly applies to characterised: Substance Biological Properties To study a Biological Process To detect the presence and quantity of a substance in a sample To screen for active molecules from a library of molecules 19. Clinical Trials 20. Clinical Trials A rigorously controlled test of a new drug or a new invasive medical device on human subjects; it is conducted under the direction of the FDA before being made available for general clinical use. 21. Phases of Clinical Trials Phase I Phase II Phase III Phase IV 22. Phase I The object of the first clinical trials in humans is to find out if the new drug is safe. These first trials, called "Phase 1 trials, usually involve a small number of individuals (less than 100) who are healthy. 23. Phase II This second phase of testing may last from several months to 2 years, and involve up to several hundred patients. Most Phase 2 studies are randomized trials. One group of patients will receive the experimental drug, while a second "control" group will receive a standard treatment or placebo. Often these studies are "blinded"--neither the patients nor the researchers know who is getting the experimental drug. 24. Phase II trials are aimed at elucidating dose response relationships, safety and efficacy of the compound treating the disease or condition for which it is intended. 25. Phase III In a Phase 3 study, a drug is tested in several hundred to several thousand subjects. This large- scale testing provides more information about the drug's effectiveness, possible side effects, and safety in a broader range of people. 26. Phase IV Phase IV trial is also known as postmarketing surveillance Trial. Phase IV trials involve the safety surveillance and ongoing technical support of a drug after it receives permission to be sold. Harmful effects discovered by Phase IV trials may result in a drug being no longer sold, or restricted to certain uses. Recent examples involve Cerivastatin (brand names Baycol and Lipobay), Troglitazone (Rezulin) and Rofecoxib (Vioxx). 27. Indiviualization of Drug Therapy OR Dosage Indiviualization 28. Dosage Indiviualization Adaptation of the dosage regimen in function of clinical characteristics of the indiviual aiming to achieve the best possible therapeutic efficacy at the lowest risk of unwanted side effects. 29. Factors Factors responsible for variation in drug response: Ethinicity Age Genetic Factor Idiosyncratic Reactions Disease Drug Interaction 30. Ethnicity Pertaining to Race Examples: African-American with heart failure gain a mortality benefits from treatment with a combination of Hydralazine+Nitrates whereas White Americans do not. Overal effectiveness of Gefitinib in treating patients with advanced lung cancer has been disappointing but in 10% of patients, lung tumor shrinks rapidly. Japenese patients are 3 times as likely as whites to fall into this group. 31. Age The main reason that age effect drug action is that elimination is less efficient in new born babies and in old people hence drug produce greater or prolonged effect. 32. Other age related factor like Physiological factors(altered CV reflexes) and Pathological factors(Hypothermia, common in elder people) also influence drug effect. Fat contributing a greater proportion to body mass in elderly with consequent changes in distribution volume of drug. 33. Effect of Age on Renal Excretion of Drug Gentamycin has a plasma half life of 18 hours or greater in new born as compared with 1 to 4 hours for adults. It is therefore necessary to reduce the doses to avoid toxicity. 34. Drugs Neonates Adults Elders Gentamycin 10-18 2 4 Digoxin 200 40 80 Diazepam 25-100 15-25 50-150 Mean Half Life of some Drugs(h) 35. Genetic Factors/Pharmacogenomics The study of genetic variation that influence indiviual response to the drug. Cytochrome P450(CYP) Genes 36. Clopidogrel(Plavix) R It is a Platelet inhibitor used in the treatment of no. of CV diseases. However, despite of Clopidogrel treatment, upto one quarter of patients experience a sub therapeutic antiplatelet response, resulting in higher risk for an ischemic event. Clopidogerl is a prodrug, its antiplatelet properties exerted once it is converted to an active metabolite. A Cytochrome P450 enzyme CYP2C19 mediate the conversion of clopidogrel into its active metabolite. 37. Patients who carry certain variations in CYP2C19 are considered poor metabolizer and show decreased ability to convert clopidogrel into its active metabolite resulting in a diminshed antiplatelet effect. Hence Patient are more likely to have an ischemic event following clopidogrel therapy. Approx. 2-20% of patients are likely to carry CYP2C19 variations. 38. Idiosyncratic Reactions An IR is abnormal and usually harmful drug effect that occurs in a small proportion of individuals. Reaction may occur with low doses Genetic factor may be responsible Cause is poorly understood 39. Examples Chloramphenicol causes Aplastic Anemia in approx. 1 in 50,000 patients. Primaquine, Dapsone, Doxorubicin and some Sulfonamide cause Hemolysis leading to severe anemia in 5-10% of Afrocarribean men. 40. Effect of Diseases Impaired Renal or Hepatic function predispose to toxicity causing unexpectedly intense or prolonged drug effect as a result of increased drug conc. Hypothermia markdely reduce the clearance of many drug. 41. Drug Interactions Polypharmacy in case of chronic diseases may interact and results in toxicity. The risk of bleeding specially from stomach caused by Warfarin is increased by drugs that cause bleeding by different mechanism like Aspirin. Sulfonamide prevent the synthesis of folic acid by bacteria and other MCOs. Trimethoprim Inhibits its reduction to THF. Given together, drugs have synergistic action in treatig Pneumocystis carinii. 42. Compliance 43. Compliance It is the act of taking medication on schedule or taking medication as prescribed. 44. Resons for Medication Non Compliance 45. Outcomes Unnecessary disease progression and complication Reduced functional abilities and quality of life An additional medical cost and physician visit 46. Botanical and Nutritional Suppliments 47. Botanicals Botanicals are plant preparations which have become widely available in the form of food suppliments. Examples: Ginkgo Green Tea Ephedra St. John Wort Ginseng 48. Natural does not mean It is Safe! Botanicals are safe.. Consumer tend to believe that because they are natural, Botanicals are safe. But interaction b/w herbal substances and conventional drugs have been reported. 49. Green Tea Green Tea has a relationship with metabolism of lipids. It is a natural and useful aid to maintain normal body weight. It regulate cholesterol and boost your immunity. 50. Ginkgo(Ginkgo Biloba) Ginkgo has been used to treat circulatory disorders and enhance memory, specially effective in treating Dementia. Studies have shown that ginkgo improves blood circulation by dilating blood vessels and reduce the platelet activity. 51. Hence, Ginkgo may increase the effect of some blood thining medicine including Aspirin. People taking blood thining medication should ask their doctors before using Ginkgo. 52. St. Johns Wort(Hypericum Perforatum) Well known for its anti-depressent effect. Effective treatment for mild to moderate depression. Interact with a variety of medications including antivirals. Take it only under the guidance of Health Care Provider. 53. Epedra Uses: Bronchial asthma, Athletic Performance Enhancer Likely safe in low doses for 7 days Likely unsafe in higher doses for longer periods, associated with MI, stroke, seizures and death Interact with drugs including MAO inhibitors, SSRIs, Glycosides and Caffeine. Banned by FDA in February 2004. 54. 140 Events, 1/3 definitely-related to supplement, 10 deaths, 10 strokes, 13 permanent disabilities 55. Conclusion Polypharmacy is common among supplement users Many assume herbs and supplements are safe Many pharmacological actions but dangerous side effects and interactions exist 56. Future of Herbal Medicine In some countries of Europe, herbs are classified and regulated as drugs. While still not widely accepted, but herbal medicine is being taught more in medical or pharmacy schools. Researchers will be looking at their health effects and in particular their anti-oxidant, anti-diabetic and memory mediating activities, which, it is hoped, will contribute to the development of new food and supplimentation offering a +ve effect on the maintenance of health. 57. References Rang H. P., & Dale M. M. (2007). Rang & Dales Pharmacology (6th Edition). London, United Kingdom. Katzung B. G., & Masters S. B. (2012). Basic & Clinical Pharmacology (12th Edition). Califonrnia, San Francisco. Dietary Supplementation Health and Education Act of 1994. Natural Medicines Comprehensive Database 2006.