1. Chapter 30 Pharmacology for the Orthopaedic Physical Therapist

2. Overview Pharmacology is the broad area of study that deals with how chemical substances affect living tissue on a molecular level and how drugs affect specific patient populations The Guide to Physical Therapist Practice identifies clinical pharmacology as an essential component of appropriate patient monitoring, modality delivery, and communication among medical professionals

3. Drug Development and Regulation It is the responsibility of the Food and Drug Administration (FDA) to direct the drug development process and give approval for marketing a new drug or approving a new use for an older drug. FDA approval involves a 4-step process

4. FDA 4-step Approval Process Phase 1: Phase 1: The safety assessment study Phase II: The drug effectiveness study Phase III: Larger study including many more subjects with the disease than in the previous phase, and a much longer duration for the testing Phase IV: Begins when the drug is approved for public use and includes monitoring of the drug for safety on the real-life conditions in large numbers of patients

5. Controlled Substances Control substances are drugs classified according to their potential for abuse. These drugs are regulated under the Controlled Substances Act, which classifies these compounds into schedules from I to V

6. Controlled Substances Schedules I-II: Schedules I-II: –I: –I: Drugs that are available only for research. They have a high abuse potential, leading to dependence without any accepted medical use. Examples include heroine, and LSD – –II: Drugs that also have a high abuse potential but that have accepted medical uses. Examples include amphetamines, morphine, oxycodone

7. Controlled Substances Schedules III-IV Schedules III-IV –III: Drugs with –III: Drugs with lower abuse potential but may still be abused and can result in some physical and psychological dependence. Examples include mild to moderately strong opioids, barbiturates, and steroids. – –IV: less of an abuse potential. No more than five refills within 6 months are allowed within the same prescription. Examples include opioids, benzodiazepines, and some stimulants.

8. Controlled Substances Schedule V Schedule V – –These drugs have the lowest abuse potential and are often available without prescription. Examples include various cold and cough medicines containing codeine.

9. Drug Classifications Specific categories that provide an explanation of the overall pharmacological action on a specific disease process Pharmacological action, e.g., arterial vasodilators and anesthetics Molecular action, e.g., calcium channel blockers Chemical makeup or the source of the drug, e.g., atropine and penicillin

10. Pharmacodynamics The drug’s mode of action The drug’s mode of action –Potency –Efficacy –Tolerance The indications for use of a drug The indications for use of a drug The drug’s safety profile The drug’s safety profile The site of action The site of action

11. Drug Receptors Receptors come in various forms and can be located inside the nucleus of a cell, in the cytoplasm, or on the surface of the cell A number of receptors are recognized and are classified as being either membrane-bound or intracellular

12. Autonomic Nervous System Receptors No discussion about drug receptor sites would be complete without mention of the impact of the autonomic nervous system (ANS) has on drug delivery. Drugs that are used in the treatment of autonomic dysfunction can be subdivided into 3 groups: – –Cholinergic – –Muscurinic – –Adrenergic

13. Pharmacokinetics The study of the physicochemical factors involved as the body absorbs, distributes, metabolizes, and eliminates a drug. – –Bioavailability--refers to the fraction or percentage of active medication that reaches the systemic circulation following administration by any route. – –The volume of distribution (Vd) is used to indicate how a systemic dose of the medication is ultimately dispersed throughout the body. – –Clearance is the rate at which the active form of the drug is removed or eliminated from the body

14. Transport of Drugs Across Cell Membranes When given by most routes (excluding intravenously), a drug must traverse semi- permeable cell membranes (biological barrier) at several locations before reaching the systemic circulation. – –Drugs may cross a biologic barrier by diffusion through the water filled channels or specialized ion channels, passive diffusion through the lipid membrane, carrier-mediated processes that include a facilitated diffusion, active transport, or pinocytosis

15. Drug Absorption and Routes of Administration Absorption is the process by which a drug is made available to the body fluids that distribute the drug to the organ systems. – –A prerequisite to absorption is drug dissolution. The size, shape of the drug’s molecule, and its solubility in water or lipids determine the ability of specific drug absorption.

16. Drug Absorption and Routes of Administration The primary routes of administration include: – –Oral – –Buccal – –Sublingual – –Rectal – –Parenteral – –Topical – –Inhalational

17. Bioavailability In pharmacology, the term bioavailability is used to describe the rate and extent of a therapeutically active drug that reaches the systemic circulation and is available at the site of action

18. Controlled-Release Drug Forms Controlled-release dosage forms are designed to reduce dosing frequency and to reduce fluctuation in plasma drug concentration, providing a more uniform therapeutic effect. – –Less frequent dosing is more convenient and may improve patient compliance.

19. The Effects of Exercise on Pharmacokinetics The effects of exercise on drug distribution are complex and is dependent on factors that pertain to the characteristics of each drug as well as exercise-related factors such as exercise intensity, mode, and duration

20. The Effects of Physical Agents on Pharmacokinetics Similar to exercise, physical therapy modalities have the potential to alter the pharmacokinetics of locally and systemically administered drugs, primarily by affecting blood flow and tissue kinetic and metabolic activity

21. Distribution of Drugs The distribution of a drug refers to the movement or transport of a drug to the site of action.

22. Metabolism of Drugs Metabolism refers to the process of transforming a drug into a compound that can be excreted Metabolism refers to the process of transforming a drug into a compound that can be excreted

23. Drug Elimination Drugs are eliminated from the body by a variety of routes including elimination in fluids (urine, breast milk, saliva, tears, and sweat), through the GI tract in the feces, and expelled in exhaled air through the lungs. – –The kidney is the primary organ for excretion of drugs that have been inactivated by the liver

24. Drug Half-life The half-life is the rate at which a drug disappears from the body, through metabolism, excretion, or a combination. – –It is the amount of time required for half of the drug that is in the body to be eliminated.

25. Musculoskeletal Pharmacology Opioid Analgesics Opioid Analgesics – –Most of the narcotics used in medicine are referred to as opioids, as they are derived directly from opium or are synthetic opiates

26. Non-Opioid Analgesics Nonopioid analgesics comprise a heterogeneous class of drugs including the salicyclates (aspirin and diflunisal), paraaminophenol derivatives (primarily acetaminophen), and the nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, Naprosyn, Motrin, and many others.

27. Nonsteroidal antiinflammatory drugs (NSAIDs) NSAIDs are distinguished from true steroid agents such as cortisone, prednisone, and from the opiate-derived analgesics NSAIDs also seem to promote the inhibition of the release of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and the synthesis of prostaglandins at an injury site

28. Corticosteroids Corticosteroids are natural anti- inflammatory hormones produced by the adrenal glands under the control of the hypothalamus. Synthetic corticosteroids (cortisone, dexamethasone) are commonly used to treat a range of immunological and inflammatory musculoskeletal conditions.

29. Skeletal Muscle Relaxants Skeletal muscle relaxants are thought to act by decreasing muscle tone without causing impairment in motor function and by acting centrally to depress polysynaptic reflexes.

30. Micronutrients Vitamins and minerals are essential for efficient nutrient metabolism and numerous bodily functions affecting functional activity and athletic performance

31. Vitamins Fat-soluble vitamins: – –Include vitamins A, D, E, and K. – –After being absorbed by the intestinal tract, these vitamins are stored in the liver and fatty tissues Water-soluble vitamins: – –Include the B complex, vitamin C, biotin, choline, and folacin (folic acid). – –Water-soluble vitamins are not stored in the body in any significant amount, which significantly reduces the incidences of toxicity, but requires that they be included in the diet on a daily basis

32. Minerals Minerals, like vitamins, are important nutrients found in foods. The main difference is that vitamins are organic substances (meaning that they contain the element carbon) and minerals are inorganic substances