General Pharmacology

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

2. Case # 1

3. Case 1, cont.

4. Case 1, cont.

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

6. 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 Things to know about drugs

7. 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 Bioequivalence Six rights of medication administration Absorption Bioavailability Biotransformation First-pass effect Things to know, cont.

8. 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 More things to know!

9. 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

10. 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

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

12. 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 Drug Sources

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

14. 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

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

16. 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

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

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

19. Standards • Assay • Determines amount & purity • Bioequivalence • Relative therapeutic effectiveness of chemically equivalent drugs • Bioassay • Attempts to ascertain drugs availability in biological model

20. New Drug Development

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

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

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

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

26. 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

27. 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?

28. 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 • Beta blockers: metoprolol • ACE inhibitors: lisinopril • Alpha blockers: prazosin • Calcium-channel blockers: verapamil • 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

29. 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?

31. Sources of drug information • AMA Drug Evaluation • Physician’s Desk Reference (PDR) • Hospital Formulary • Drug Inserts • Other sources

32. 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, Meperidine, Dilaudid, Oxycodone, Cocaine, Codeine, Opium, Methadone

33. 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, lorazepam, Phenobarbital

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

35. 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

36. 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

37. 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

38. FDA Pregnancy Categories

39. FDA Pregnancy Categories, cont.

40. 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

41. 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

42. 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

43. 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

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

45. 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

46. 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

47. 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

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

49. 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.

50. Case #2 • You are dispatched to a report of a possible suicide attempt. You arrive to find a 50 year old woman CAO PPTE. She is crying, and says that she wants to die. She admits to taking pills about ½ hour pta. PMH: Vascular H/A. • Her B/P is 140/90, P 100, RR 28, Skin PWD, PERL. BBS =, clear. Wt. ~ 60 kg.