2. Pharmacology for Biotech Information taken from Healthcare Science Technology “The difference between a deadly poison and life saving medicine can be very small; In fact, it is sometimes merely a question of dosage.” Dr. R.E. Schultes

3. Pharmacology The study of chemical agents and living organisms and all aspects of their interactions i.e. biological response Xenobiotics: drug substances foreign to the body such as pollutants, food additives, and drugs

4. Pharmacokinetics Pharmacokinetics is the study of the five processes that affect the plasma concentration of drugs. (ADMET)

5. Pharmacokinetics (cont.) Absorption – the process by which a drug enters the plasma.  Oral medications are dissolved in the stomach.  Can be absorbed thru lungs, skin, or the GI tract

6. Pharmacokinetics (cont.) Distribution – where the drug goes after entering the plasma.  Some of the drug binds to the proteins in the plasma; some diffuses into other tissues.  Liberation: the process of drug “release” from dosage form Metabolic transformation – chemical changes in a drug that occur after it has been absorbed into the body.

7. Pharmacokinetics (cont.) Elimination or excretion – the process that removes a drug from the body.  Excreted via skin, lungs, kidneys, intestines Toxicology – the study of poisons and the toxicity of drugs to the body  Worry about toxicity if on an antibiotic too long  A negative concern about taking drugs especially if you will be on them a long time

8. Routes of Administration Routes of Administration (ROA) – the different ways used to get a drug into the tissues of the body.

9. Routes of Administration (cont.) Oral Administration  The most common route. Client swallows a tablet, capsule, or liquid.  Usually requires 30 to 60 minutes before producing an effect, or onset of action.  Analgesics: drugs to reduce pain such as Tylenol as OTC or vicodin or morphine which are much stronger and need Rx

10. Routes of Administration (cont.) Parenteral Administration – all forms of administration, other than oral.  Metered-Dose Inhaler Delivers medications directly to the lungs. Rapid action. Minimal systemic side effects.  Nasal spray, suppository, drops

11. Routes of Administration (cont.)  Transdermal Patch – one of the most consistent and convenient dosage forms. Remove and discard old patch. Select a site for new patch. Apply the patch.  Topical ointments Hormone therapies, nicotine patches Often times this is an anti-itch

12. Routes of Administration (cont.)  Injections – used when a rapid effect is needed. Intravenous (IV) injection – into the vein Subcutaneous (SC) injection – most frequently given in the upper arm, front of thigh, or abdomen. Intramuscular (IM) injection – normally given into relatively large muscles of the shoulder, buttocks, or outer portions of the thigh.

13. Take your best guess! What is the largest volume that can be given with an SC injection? Answer: The largest volume is 1 milliliter (mL).

14. Dosages Dosages are usually based on the weight of an individual.

15. Dosages (cont.) Effects of Individual Differences on Maintenance Doses  Age, body fat, and diseases that affect the liver and kidneys may require altering the dosage of a drug.

16. Apply Your Knowledge List the 5 processes of pharmacokinetics. Answer: 1.Absorption 2.Distribution 3.Metabolism 4.Elimination or excretion 5.Toxicology

17. Systems affected by Drugs! Nervous system Cardiovascular system Gastrointestinal system Endocrine system

18. What diseases / drugs effect each system Endocrine System  Hormone treatments for diseases such as Thyroid disease, human growth hormone levels, etc. Cardiovascular  Heart disease: Digitalis  Atherosclerosis / high BP: Lipitor and diuretics (cause kidneys to excrete more water and salt)

19. What diseases / drugs effect each system Nervous System  Bells Palsy, Cerebral palsy  Parkinson’s or Alzheimer’s disease  Most nervous disorders are not treated with drugs Gastrointestinal System  Ulcers: Pepcid, Zantac  Colon cancer, cirrhosis, hepatitis  Diabetes: insulin

20. How drugs work Receptors – proteins found inside or outside the cell; bind to Ligands Ligands – molecules that bind to receptors i.e. hormones or neurotransmitters  Types of Ligands Agonists – activate receptors Antagonists – de-activate receptors by inhibiting the binding of agonists Inverse agonists – reduce cellular activities

21. How drugs work (cont.) Enzymes – proteins that speed up a chemical reaction Enzyme inhibitors – bind to enzymes and decrease activity i.e. herbicides Enzyme activators – bind to enzymes and increase activity Enzyme inhibitor – block substrate from entering enzyme active site or from catalyzing the reaction, can alter amino acid structure

22. Sources of Drugs Natural Sources  Pharmacognosy is the study of drugs made from natural sources, such as plants and animals.  Plants were the main source of medicine until the early 1900s, when Sir F. G. Banting and Charles Herbert Best extracted insulin from a pancreas and tested it on diabetic dogs.

23. Sources of Drugs (cont.) Natural Sources (cont.)  Problems associated with naturally occurring drugs: Some are broken down very quickly by the body. Some are poorly absorbed into the bloodstream. Isolating a drug from a plant or animal can be slow, expensive, and may result in harmful impurities in the drug. Naturally occurring products can be extremely scarce.

24. Sources of Drugs (cont.) Microbial organisms  Penicillin, isolated by Sir Alexander Fleming in 1928, was one of the first drugs that did not come from a plant or animal.  Large scale manufacture in what year? 1943

25. Sources of Drugs (cont.) Synthetics and Bioengineering  Medicinal chemistry modifies natural products by producing them synthetically or by creating new products.  Aspirin, synthetically produced today, was once an extract of willow bark.  Insulin was the first drug to be produced from genetically altered bacteria (recombinant)

26. Sources of Drugs (cont.) Natural Sources (cont.)  Genetically modified E-coli used to make insulin Bacterial Chromosome Plasmid containing human insulin gene Plasmid has been inserted into the bacterial cell Cell ACell B

27. Pharmacotherapeutics Examines the mechanism of action (MOA) of drugs. Describes the effects produced by a drug. Determines what dose of a drug is needed to produce a desired effect. Determines what dose of a drug produces toxic effects.

28. Pharmacotherapeutics (cont.) Mechanisms of Action (MOA)  Drugs with the same MOA are said to belong to the same therapeutic class.  Binding occurs when a drug combines with a chemical in the body.  MOA operates on a “lock and key” principle. The drug is considered the key and the body chemical the lock.

29. Pharmacotherapeutics (cont.) Mechanisms of Action (cont.)  Binding to and Stimulating a Receptor in the Body Receptors – proteins found in cells. Click for Picture

30. Binding to and Stimulating a Receptor in the Body Epinephrine receptors on cell membranes of the respiratory passages. When epinephrine binds to these receptors, the respiratory passages dilate. Epinephrine Many of the drugs used to treat asthma work by binding to and stimulating epinephrine receptors. Bronchodilating drug Mechanism of Action Back

31. Mechanisms of Action (cont.)  Binding to and Blocking a Receptor in the Body Some drugs, called antagonists or blockers, bind to a receptor without causing a response, thus preventing the naturally occurring key from binding. Pharmacotherapeutics (cont.) Click for Picture

32. Binding to and Blocking a Receptor in the Body Histamine receptors on a cell membrane Allergic signs and symptoms occur when the histamine binds to histamine receptors. When a person is exposed to something they are allergic to, they produce histamine. Histamine Antihistamines bind to the histamine receptor without causing allergic signs & symptoms. As a result, fewer receptors are occupied by histamine and signs are less severe. Antihistamine Mechanism of Action Back

33. Pharmacotherapeutics (cont.) Mechanisms of Action (cont.)  Inhibiting an Enzyme Enzyme inhibitors increase or decrease the concentration of an enzyme. Click for Picture

34. Inhibiting an Enzyme Building blocks The enzyme lines up building blocks. The building blocks react with one another, forming a chemical bond. The enzyme releases the newly built compound. Enzyme Products are released from the enzyme. The enzyme breaks a chemical bond in the compound. The substance to be broken down binds to the enzyme. Mechanism of Action Back

35. Pharmacotherapeutics (cont.) A side effect is any effect produced by a drug that is not the desired effect.  Local Side Effects Occur before a drug is absorbed into the bloodstream.

36. Pharmacotherapeutics (cont.)  Systemic Side Effects Take place after being absorbed into the bloodstream. May take the form of an allergic reaction, since drugs are not a “natural” part of our body. Most occur because the drug affects cells other than the target cells.

37. Apply Your Knowledge Where do drugs come from? Answer: 1.Natural sources such as plants and animals. 2.Microscopic organisms such as bacteria, fungi, and molds. 3.Synthetics and bioengineering.

38. Therapeutic Classes of Drugs Drugs in a therapeutic class produce their effect in the same way. Examples are listed on the following slides.

39. Therapeutic Classes of Drugs (cont.) Angiotensin Converting Enzyme Inhibitors  Angiotensin is a naturally occurring protein in the body. An enzyme called angiotension converting enzyme (ACE) activates angiotensin, which, when overactive, causes high blood pressure, or hypertension.  ACE inhibitors reduce the production of angiotensin.  Representative drugs: Accupril ®, Lotensin ®, Prinivil ®, Vasotec ®, and Zestril ®.  Common side effects include headache and dizziness.

40. Therapeutic Classes of Drugs (cont.) Beta-1 Blockers  Bind to beta-1 receptors without stimulating them, preventing epinephrine (adrenalin) and norepinephrine from binding.  Representative drugs: Lopressor ®, Tenormin ®, Toprol ®.  Indications: hypertension, tachycardia or rapid heartbeat.  Common side effects: dizziness, drowsiness.

41. Therapeutic Classes of Drugs (cont.) Beta-2 Agonists  These drugs bind to beta- 2 receptors on the smooth muscle cells of the bronchioles, causing dilation. Representative drugs: Ventolin ®, Proventil ®, Serevent ®, Alupent ®, Brethine ®.  Indications: asthma, emphysema.  Common side effects: tremors, increased heart rate, and insomnia.

42. Therapeutic Classes of Drugs (cont.) Antihistamines  Antihistamines bind to histamine receptors, without stimulating them.  Representative drugs: Allegra ®, Benadryl ®, Claritin ®, Zyrtec ®.  Indications: itching, nasal congestion, seasonal allergies such as hay fever.  Common side effects: dry mouth and drowsiness.

43. Therapeutic Classes of Drugs (cont.) H 2 Antagonists  Bind to H 2 receptors, found only in the stomach, to decrease the amount of hydrochloric acid produced.  Representative drugs: Tagamet ®, Pepcid ®, Zantac ®.  Indications: gastroesophageal reflux disorder, gastric ulcers, duodenal ulcers.  Common side effects: diarrhea, headache.

44. Therapeutic Classes of Drugs (cont.) Proton Pump Inhibitors  Drugs that turn off the proton pumps in the stomach, which reduces stomach acid.  Representative drugs: Prilosec ®.  Indications: gastroesophageal reflux disorder, gastric ulcers, duodenal ulcers.  Common side effects: diarrhea, headache.

45. Therapeutic Classes of Drugs (cont.) Narcotic Analgesics  Drugs that bind to and stimulate the endorphin receptors in the spine which inhibit nerve cells that carry pain to the brain.  Representative drugs: morphine, codeine, Demerol ®, Vicodin ®, Percodan ®.  Indications: severe pain.  Common side effects: drowsiness, slow and shallow breathing, constipation.

46. Therapeutic Classes of Drugs (cont.) Nonsteroidal Anti-inflammatory Drugs  Nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the enzyme prostaglandin synthase, which makes prostaglandins.  Representative drugs: aspirin, Motrin ®, Advil ®, Relafen ®, Naprosyn ®, Aleve ®.  Indications: mild to moderate pain, inflammation, fever.  Common side effects: stomach irritation.

47. Therapeutic Classes of Drugs (cont.) Reverse Transcriptase Inhibitors  Inhibit the activity of the enzyme reverse transcriptase, which is needed to convert RNA to DNA.  Representative drugs: AZT, Combivir ®, Sustiva ®, Retrovir ®.  Indications: HIV infection.  Common side effects: anemia, fever, rash, headache, lack of energy, nausea, vomiting, diarrhea, stomach pain, cough, shortness of breath, sore throat.

48. Apply Your Knowledge What type or class of drugs are used to relieve pain?  Analgesics such as Tylenol or morphine What type or class of drugs is given for an allergic reaction  Anti histamines What type or class of drug is given for an ulcer?  Proton pump inhibitor such as Prilosec or  H 2 antagonist such as Zantac