Chapter 30Chapter 30

Pharmacology for the Pharmacology for the Orthopaedic Physical Orthopaedic Physical TherapistTherapist

OverviewOverview

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

Drug Development and Drug Development and RegulationRegulation 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

FDA 4-step Approval FDA 4-step Approval ProcessProcess 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

Controlled SubstancesControlled 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

Controlled SubstancesControlled 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

Controlled SubstancesControlled Substances

Schedules III-IVSchedules 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.

Controlled SubstancesControlled Substances

Schedule VSchedule V– These drugs have the lowest abuse

potential and are often available without prescription.

Examples include various cold and cough medicines containing codeine.

Drug ClassificationsDrug 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

PharmacodynamicsPharmacodynamics

The drug’s mode of actionThe drug’s mode of action– PotencyPotency– EfficacyEfficacy– ToleranceTolerance

The indications for use of a drugThe indications for use of a drug The drug’s safety profileThe drug’s safety profile The site of actionThe site of action

Drug ReceptorsDrug 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

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

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

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

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.

Drug Absorption and Routes of Administration The primary routes of administration

include: – Oral– Buccal– Sublingual– Rectal– Parenteral– Topical– Inhalational

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

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.

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

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

Distribution of DrugsDistribution of Drugs

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

Metabolism of DrugsMetabolism of Drugs

Metabolism refers to the process Metabolism refers to the process of transforming a drug into a of transforming a drug into a compound that can be excretedcompound that can be excreted

Drug EliminationDrug 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

Drug Half-lifeDrug 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.

Musculoskeletal Musculoskeletal PharmacologyPharmacology Opioid AnalgesicsOpioid Analgesics

– Most of the narcotics used in medicine are referred to as opioids, as they are derived directly from opium or are synthetic opiates

Non-Opioid AnalgesicsNon-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.

Nonsteroidal antiinflammatorydrugs (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

CorticosteroidsCorticosteroids

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.

Skeletal Muscle Skeletal Muscle RelaxantsRelaxants 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.

MicronutrientsMicronutrients

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

VitaminsVitamins

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

MineralsMinerals

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