General Pharmacology

1. Better living through pharmacology, pharmokinetics, and pharmodynamics, P. Andrews General Pharmacology

2. CAREFUL AND JUDICIOUS USE OF MEDICATIONS CAN TRULY MAKE A DIFFERENCE

3. Things to know about drugs • Pharmokinetics • Pharmodynamics • Generic names • Trade names • Schedules of drugs • FDA approval process • The Harrison Narcotic act of 1914 • Enteral drug administration • Parenteral drug administration • Mechanism of action • Route of administration • Pure food and drug act of 1906

4. Things to know, cont. • The Federal Food, Drug and Cosmetic act of 1938 • The Durham-Humphrey Amendments to the 1938 Act • The Controlled Substance Act of 1970 • OTC medications • Absorption • Six rights of medication administration • Bioavailability • Biotransformation • First-pass effect

5. More things to know! • Blood-brain barrier • Placental barrier • Oxidation • Hydrolysis • Elimination • Agonist • Antagonist • Agonist-antagonist • Extrapyramidal symptoms • Idiosyncratic response • Tolerence • Side effect • Cumulative effect • Synergism • Potentiation • Onset of action • Therapeutic index • Half-life • Minimum effective concentration

6. Historical trends • Ancient health care • Herbs & minerals - 2,000 BC • Pharmacology by end of Renaissance; separate from medicine • Vaccinations 1796 (Smallpox) • Insulin, Penicillin early 20th century • Modern health care • Human insulin • tPA

7. Pharmacology • Chemical name • Precise description chemical composition and molecular structure • Vecuronium Bromide: • Chemical compound: piperidinum, 1-[(2, 3, 5, 16, 17)-3, 17-bis (acetyloxy)-2-(1-piperidinyl)androstan-16yl]-1-methyl-, bromide. • Molecular structure C34H57BrN2O4

8. Genericname – Non-proprietary name • FDA approved • First manufacturer • vecuronium bromide • Trade (Proprietary) name • Registered to a specific manufacturer • Marsam Pharmaceuticals, Inc. • VecuroniumTM • Officialname • Assigned by USP • Vecuronium Bromide USP

9. Drug Sources • Plants • Atropine – Deadly nightshade plant • Morphine – Opium plant • Digitalis – Foxglove • Animals and Humans • Insulin • Glucagon • Minerals • Calcium chloride • Sodium Bicarbonate • Magnesium Sulfate • Synthetics • Bretylium tosylate • Lidocaine • Procainamide

10. Drug Profiles • Names • Classification • Mechanism of Action • Indications • Pharmacokinetics • Side effects/ adverse reactions • Routes of administration • Contraindications • Dosage • How supplied • Special considerations

11. Legal stuff- Federal • Protect the public • Pure Food and Drug Act, 1906 • Improve quality and labeling of drugs • Harrison Narcotic Act, 1914 • Regulating importation, manufacture, sale, use of opium, cocaine, derivatives • Federal Food, Drug, Cosmetic Act, 1938 • Empowers FDA to enforce, set premarket safety standards

12. More Federalstuff • Durham-Humphrey Amendments, 1951 • Prescription drug amendments, 1938 act; requires written or verbal prescription from physician to dispense some drugs • Created OTC category

13. Comprehensive Drug Abuse Prevention & Control Act, 1970 (Controlled substance act) • Replaces Harrison Narcotic Act • Establishes 5 schedules of drugs • Prohibits refilling of Rx for Schedule II drugs, & requires original Rx to be filled within 72 hours

14. Other regulations • Prescription drugs • Designated sufficiently dangerous to require supervision • OTC • Available in small doses; present low risk

15. General issues • Drugs must be secured • State laws vary; generally set scope of practice for EMS • Medical directors can delegate authority to paramedics

16. New Drug Development

17. You Are Responsible! • Know precautions and contraindications • Practice proper technique • Know how to observeand document effects • Establish and maintain professional relationships with other health care providers

19. In disease, all systems are affected • The three systems can’t exist without each other • The actions of one impact the actions of the others • I.e., stress (nervous system) disrupts endocrine system which may respond with glucocorticoid production = suppressed immune response

20. Drug Class Examples • Nitroglycerin • Body system: “Cardiac drug” • Action of the agent: “Anti-anginal” • Mechanism of action: “Vasodilator” • Indications for nitroglycerin • Cardiac chest pain • Pulmonary edema • Hypertensive crisis • Which drug class best describes this drug?

21. Understandpharmacokinetics, pharmacodynamics • Have current references available • Takecareful drug histories • Evaluate compliance, dosage, adverse reactions • Consult with medical direction when appropriate

22. SIX RIGHTS OF MEDICATION ADMINISTRATION • Right medication • Right dose • Right time • Right route • Right patient • Right documentation • AND SEVEN – Right to refuse

24. Cells talk to each other • Three distinct languages • Nervous system • neurotransmitters • Endocrine system • hormones • Immune system • cytokines

25. Another way to classify drugs • Mechanism of Action • Drugs in each category work on similar sites in the body and will have similar specific effects/side effects • Example: beta blocker actions and impacts • Suppress the actions of the sympathetic nervous system • Prehospital administration of epinephrine may not produce as dramatic effects with a patient taking a drug in this class

26. Prehospital example: Hyperglycemics • Dextrose 50% and glucagon • Both will raise blood glucose • Mechanism of action • Glucagon: hormone that works in the liver to convert stored chains of carbohydrate to glucose • Dextrose 50%: ready-made simple sugar that is ready to enter into the cell • Which drug is considered first-line for hypoglycemia? Why? • What are some limitations for glucagon in the presence of severe hypoglycemia?

27. Sources of drug information • On-line - be cautious of source • Pharmacy.com • Medline.com • AMA Drug Evaluation • Physician’s Desk Reference (PDR) • Hospital Formulary • Drug Inserts • Other sources

28. Controlled substances • Schedule I. High potential for abuse; no accepted medical indications • Heroin, LSD, Crack, Marijuana • Schedule II. High potential for abuse, but have accepted medical indications • Morphine, Fentanyl, meperidine, Dilaudid, Oxycodone, Cocaine, Codeine, Opium, Methadone

29. Schedule III. Less potential for abuse, and accepted medical indications • Tylenol #3, Vicodin • Schedule IV. Low potential for abuse, but may cause physical or psychological dependence. • diazepam, midazolam, butorphanol, lorazepam, Phenobarbital

30. Schedule V. Low potential for abuse, but have small quantities of narcotics • Cough medicine (Vicks 44)

31. Standardization of Drugs • A necessity • Techniques for measuring a drug’s strength and purity • Assay • Bioassay • The United States Pharmacopeia (USP) • Official volumes of drug standards

32. Medical Control • Medication administration is ALS skill • Medical Director • Actively involved in and ultimately responsible for all clinical and patient care. • We are extension of physician’s license

33. Special Considerations- Pregnant patients • Evaluate benefit vs. risk to fetus • FDA has a scale (A,B,C,D,X) to indicate drugs that may have documented problems • Many drugs are unknown to cause problems • Drugs may cross placental barrier or through lactation

34. FDA Pregnancy Categories

35. FDA Pregnancy Categories, cont.

36. Special Considerations – Pediatric patients • Based on weight or BSA • Length-based resuscitation tape (Broslow’s) • Absorption of oral meds less due to differences in gastric pH, emptying time, low enzyme levels

37. Pediatrics, cont. • Unexpected toxicity common in topically applied meds • Drugs that bind to protein have higher availability • Neonates have much higher % of extracellular fluid – may require higher doses • Lower metabolic rate & hepatic system ; higher risk for toxicity

38. Figure 6-1 A Broselow tape is useful for calculating drug dosages for pediatric patients.

39. Special Considerations - Geriatric patients • MULTIPLE MEDS A PROBLEM • Physiological effects of aging can lead to altered pharmacodynamics and pharmacokinetics. • Absorb oral meds slower • Distribution altered • Lipid soluble drugs have greater deposition • Drug action delayed or prolonged

40. Pharmacology • The study of drugs and their interactions with the body • Drugs do not confer any new properties on cells or tissues – only modify or exploit existing functions • Given for local or systemic action

41. Pharmacokinetics • The study of the basic processes that determine duration and intensity of a drug’s effect

42. Transport • Active transport • Requires energy to move a substance • ATP ADP • Sodium – potassium pump • Facilitated diffusion • Binds with carrier protein, configuration of cell membrane changes, allows large molecule to enter body • I.e., Insulin increases glucose transport from 10-20 fold

43. Transport, cont • Passive transport movement of substance without energy • Diffusion • Movement of solute in solvent • Osmosis • Movement of solvent • Filtration • Molecules move across membrane down pressure gradient

44. Absorption • IM faster than SC • Enteral administration; must survive digestive process • Enteric coating; dissolve in duodenum • Many drugs ionize • Ionized drugs don’t absorb across cell membranes • Most drugs reach equilibrium • pH affects ionization

45. Concentration affects absorption • Loading dose – maintenance dose • Bioavailability • Amount of drug still active after reaching target tissue

46. Distribution • Some drugs bind to proteins in blood and remain for prolonged period • Therapeutic effects due to unbound portion of drug in blood • Drug bound to plasma proteins can’t cross membranes • Changing blood pH can affect protein-binding action of drug. • TCA’s are strongly bound to plasma proteins.