Option D: Medicines and Drugs

1. Option D: Medicines and Drugs Section D.1: Pharmaceutical Products pp 405-410 (Green and Damji)

2. Objectives B.1.1: List the effects of drugs and medicines. B.1.2: Outline the stages involved in research, development and testing of new pharmaceutical products. B.1.3: Describe the different methods of administering drugs. B.1.4: Discuss the terms lethal dosage (LD50), tolerance, and side effects.

3. Any chemical (natural or synthetic) • that does one or more of the following… • … altersmood or emotions • … alters incoming sensory sensations • … altersa physiological state including • consciousness, • activity level, or • co-ordination What exactly is a medicine? a drug ?

4. … improve health … assist the body’s natural healing process …‘placebo affect’ Why do people use medicines / drugs?

5. … helpful or harmful … natural or synthetic … legal or illegal … Medicines and drugs can be…

6. How are new drugs developed in USA? • Research • Disease is selected • Vulnerable targets are identified • Potential lead molecules are considered • Lead molecule is selected

7. How are new drugs developed? (2) Preclinical trials • in vitro (lab environment) • in vivo (living organisms) • cell cultures / animals • usu 3 species ) • rats, mice, guinea pigs • purpose – identify lethal dose, effective dose, potential side effects

8. How are new drugs developed? (3) Phase 1 trials – initial clinical trials • small numbers • healthy volunteers • terminally ill patients (with their consent) • purpose: assess toxicity, effective dose, side effects

9. How are new drugs developed? (4) Phase II trials – clinical trial • several hundred • ill patients • treated with drug or placebo • ‘blind’ test or ‘double-blind’ test • statistical study • purpose: determine dosage and administration; eliminate bias

10. How are new drugs developed? • Phase III trials – extended clinical trials • thousands • ill patients • treated with drug and closely monitored • purpose: adjust dosage and monitor side effects

11. How are new drugs developed? (6) Drug launched (7) Phase IV trials • Post-launching • purposes: new formulation, new dosage, new application, product extension

12. Drug Development… • takes a long time and a lot of money… Time – as much as 10-15 years Cost – up to $800 million 

13. Why does drug development require such an exhaustive process?... • to protect users from harmful side-effects and/or death • drugs that make it through the approval process have a reasonable risk/benefit ratio • most proposed drugs never make it through the process

14. What is thalidomide and why was it such a problem?... • non addictive sedative available in Europe 1958-1963 • given to pregnant women to treat ‘morning sickness’ – (which it did)

15. Structure of Thalidomide Thalidomide exists as a racemic mixture of TWO stereoisomers – each with their own special impact on the body! Source: http://www.k-faktor.com/contergan/thalidomide.gif

16. Why was thalidomide such a problem?... •  babies born dead or with birth defects: • no arms &/or legs, • short arms &/or legs • missing bones • Intestinal abnormalities • 460 cases in UK • 3000 in former West Germany

17. What about thalidomide now?   As a result of the impact, thalidomide was initially banned, but • is currently available (under another name) to treat severe leprosy in Brazil, Mexico, USA • special warnings provided • and is being considered for other applications (i.e. cancer treatment)

18. When are medicines/drugs considered hazardous? When they pose a risk to the • Physical • Mental • Social well-being of the user.

19. What are main vs side effects? • Main effect = desired response • Side effect = the unwanted response to the use of a medicine or drug • Ex: Morphine – prescribed for pain • Main impact = pain relief • Side effect = constipation • Ex: Morphine – prescribed for diarrhea • Main impact = induced constipation • Side effect = pain relief

20. What are side effects? • NO drug is free of side effects… • range from trivial to serious – even death • allergies (over-reaction of immune system) • Mild skin rashes… to fatal shock • penicillin • damage to liver &/or kidney • often long term • alcohol damages liver • users of one drug over a long time… or of multiple drugs often have periodic liver / kidney function test

21. What is toxicity? • TOXICITY: • LD50value • Lethal dose of a substance that kills off 50% of a population • Not humans – numbers extrapolated from animal studies • Molecules with small LD50 numbers are the most toxic

22. Some interesting LD50

23. Some interesting LD50

24. Some interesting LD50

25. Some interesting LD50

26. What is tolerance? • User needs increasing amounts of a drug to get the same physiological effect. • Due to use over time and with regular use • Maximum daily tolerance • amount that can be taken into the body without undesirable symptoms occurring

27. Why is tolerance a problem? • Body may become tolerant to the positive effect, not NOT to the harmful effect(s) • User needs more of the drug… and this intensifies the harmful effect(s). • Barbituates – users develop a tolerance to sedative but not to its effect on breathing (slows it down) – so they take so much of the drug their breathing stops.

28. Why is tolerance a problem? • Tolerance changes after the user stops using… • Body’s tolerance decreases with time and non-use • User begins using again… but at former dose (which was increasingly higher with time…) • User experiences more intense side effect(s) • Overdose may occur

29. What is dependence? • A person is ‘drug-dependent’ when an individual continues to use a drug because s/he does not feel ‘right’ without it • Dependence can be • Physical • Without the drug, user experiences physical symptoms • Mild discomfort…. Convulsions • ‘withdrawal’ • Psychological • Intense craving for the drug and its effects • difficult to stop using • Drug Addiction

30. What is a therapeutic window? • Measure of the relative margin of safety of the drug for a particular treament. • Ratio of LD50 to ED50 • ED50 is the therapeutic dose – the effective dose for 50% of the population. • If the window is WIDE, the effective dose is below toxicity – so there is a safe margin • If the window is NARROW, small doses need to be administered for successful treatment.

31. How are medicines/ drugs administered? (1) Oral • Through the mouth • Tablet / capsule • Syrup • adv: self-administer, easy • disadv: must be able to survive the digestive system

32. How are medicines/ drugs administered? (2) Rectal • suppository • adv: self-administer, efficiency • disadv: yuck factor

33. How are medicines/ drugs administered? (3) Inhalation •  by breathing (i.e. via an inhaler) • adv: rapid • disadv: drug must be for the lungs – or able to be absorbed through the lungs

34. How are medicines/ drugs administered? (4) Injections • intravenous – into blood stream (quick, but spreads out dose) • subcutaneous – into body fat (good for fat-soluble molecules) • intramuscular – into muscle tissue • adv: put directly where it is needed, requires reduced dose, reduces chance of altercation by body • disadv: requires trained person, people don’t like shots

35. How are medicines/ drugs administered? (4) Injections • intravenous – into blood stream (quick, but spreads out dose) • subcutaneous – into body fat (good for fat-soluble molecules) • intramuscular – into muscle tissue • adv: put directly where it is needed, requires reduced dose, reduces chance of altercation by body • disadv: requires trained person, people don’t like shots

36. How are medicines/ drugs administered? • Patches • Molecules absorbed through the skin barrier – gradually • Adv: continuous and controlled rate; people like them; can receive a strong medication without IV • Disadv: patch may come off; takes up to 72 hours for drug to saturate the body; heat (from fever or use of heating pad) may increase side effects