Pharmacotherapy: Medication Effects and Physical Therapy

Pharmacotherapy Objectives

• This lecture aims to enable students to state differences between medication names and define concepts like dose-response.
• Students will utilize pharmacokinetics and pharmacodynamics to determine possible physical therapy implications.
• Students will state factors that affect medication distribution and common sources of medication errors.
• The lecture will cover routes of drug administration, elimination pathways, and variations in drug response.
• It will also explore how to identify medication classes using common prefixes/suffixes and differentiate adverse/side effects.

Patient Presentation: Case Study

• A 57-year-old female presents to physical therapy with a pelvic fracture and left humerus fracture.
• The patient's medical history includes being three weeks post-motor vehicle accident (MVA) with fixation and mild concussion.
• Current medications include OxyContin every 12 hours and PRN immediate release oxycodone for breakthrough pain.
• The patient reports fatigue, abdominal discomfort, frequent somnolence, difficulty following directions, and 7/10 pelvic pain.

Possible Causes of Fatigue and Sluggishness in Case Study

• Decreased endurance after hospital stay and muscle strength in lower extremities.
• The patient might have decreased ROM which is decreasing her biomechanical efficiency, depression, anemia, pulmonary disease, heart disease or an infection/fever.
• Consider the medications that she is taking for pain management.

Questions on Medications

• Was the patient addicted to opioids?
• What types of medications is the patient taking?
• Any common side effects?
• How did the medical team determine the appropriate dose?
• What factors did they consider when prescribing the dose?
• When should the patient take her medications in relation to physical therapy sessions?

Need to Study Pharmacology

• Physical therapists need to understand a patient's response to different drugs to optimize patient outcomes.
• Pharmacology can help Physical Therapists provide optimal drug scheduling to facilitate movement and recovery in physical therapy and minimize drug-therapy interactions.
• Understanding drugs will help physical therapists recognize and address adverse drug reactions (ADRs).

Fundamentals of Pharmacology

• Important topics include medication nomenclature and classes, mechanism of action (moa), therapeutic onset time, its effects, and adverse events.
• Dosing fundamentals, lifespan considerations, and polypharmacy are important to know too.

Basic Principles of Pharmacology

• Toxicology is the study of chemicals’ harmful effects on living things.
• Pharmacology studies how chemicals affect living tissue.
• Pharmacotherapeutics (or medical pharmacology) uses specific drugs to prevent, treat, or diagnose diseases.

Pharmacotherapeutics

• Pharmacodynamics analyzes what a drug does to the body including mechanism, effects, and adverse effects.
• Pharmacokinetics analyzes what the body does to the drug, including absorption, distribution, metabolism, and excretion.

Specialty Areas in Pharmacology

• Pharmacogenetics/Pharmacogenomics directs therapeutics according to a person's genotype and examines unexpected reactions to drugs and a form of personalized medicine.
• Pharmacoepidemiology studies the effects of drugs on large populations, examining all factors.
• Pharmacoeconomics is an area of pharmacology that looks at cost:benefit.

Availability of Medications

• There are OTC "over-the-counter" medications (some used to be prescription), as well as herbal and alternative therapies that do not require a prescription.
• Prescription medications include controlled and non-controlled substances, traditional small molecules, biologic medications, specialty pharmaceuticals, and "home" parenteral and compounded medications.

Controlled Medication Classes

• Schedule I drugs have a high potential for abuse and are not approved for non-investigational clinical use (e.g., heroin, hashish, LSD, ecstasy).

• Schedule II drugs have a high potential for abuse and addiction (e.g., cocaine, PCP, methamphetamines, opium, oxycodone).

• Schedule III drugs have less potential for abuse (mild to moderate), for example, high concentration codeine, anabolic steroids, and ketamine.

• Schedule IV drugs have a low potential for abuse, for example, phenobarbital, tranquilizers, seizure medications, Xanax, ambien, and valium.

• Schedule V drugs have the lowest abuse potential, such as opiate drugs at low concentrations in inhalers and cough medicines.

Drug Testing Phases

• Preclinical animal trials take 1-2 years.
• Clinical trials in humans include Phase 1 (healthy volunteers), Phase 2 (people with the disease, small samples), and Phase 3 (people with the disease, large samples), which take 3-5 years.
• FDA considers approval for marketing in Phase 4 with post-marketing surveillance.

Drug Naming Conventions

• Chemical names reflect the chemical structure of the drug, like N-acetyl-p-aminophenol.
• Generic names are nonproprietary and typically derived from the chemical name; they should have similar safety and efficacy to brand name drugs (bioequivalence) and are typically lower priced.
• Trade or brand names are assigned by the pharmaceutical company based on consumer testing.

Morphine Sulfate

• Morphine Sulfate's molecular formula is (C17H19NO3)2·H2SO4,5H2O.
• Its chemical name is Morphinan-3,6-diol, (5α,6α)-7,8-didehydro-4,5-epoxy-17-methyl-, sulfate (2:1) (salt), pentahydrate.
• Synonyms/generic name: Morphine Sulphate and brand names include MS Contin®, Avinza®, Duramorph®, and Kadian®.

Drug Classes

• Drug classes share activities or treat similar diseases.
• Identification relies on common stems or syllables.

Stems and Drug Classes

• Examples of stems and drug class associations: Cort- (Cortisone derivatives), -lol (Beta blockers), -curium (Neuromuscular blocking agents.)
• Further examples: -azepam (Antianxiety Agents), -butazone (Anti-inflammatory analgesics like profen.)

Name that Class

• Metoprolol is indicated for BETA BLOCKER
• Diazepam is indicated for ANTI-ANXIETY
• Nasacort is indicated for Cortisone Derivative
• Amoxicillin is indicated for PENICILLIN
• Lidocaine is indicated for LOCAL ANESTHETIC

Drug Nomenclature

• Drug classes can be classified by Indication such as Anti-infective (Aminoglycosides, Cephalosporin, and Antifungal) and Cardiac Medications (Antihypertensives and Antiarrhythmics).
• Classifications are also named for the type of interaction with the receptor such as Agonist or antagonist, and adrenergic receptor responses may be categorized as alpha (a) or beta (β).

Pharmacodynamics

• The drug's mechanism of action will cause the drug to have an effect on the patient.
• Drug interactions include: Agonist, Antagonist, Agonist/Antagonist

Mechanism Of Action of Antibiotics

• Antibiotics inhibit bacterial cell wall synthesis (e.g., Penicillins, Cephalosporins) , protein synthesis (e.g., Erythromycin, Tetracycline) and organism's metabolism (sulfonamides) and DNA synthesis (Fluoroquinolones).

Drug-Receptor Interactions

• Neurotransmitters: Binds to the receptor site and give pharmacologic response.
• Agonist: Binds to the receptor site and give pharmacologic response.
• Antagonist: Binds to the receptor site and gives no pharmacologic response.

Routes of Drug Administration

• Enteral administration uses the alimentary canal by oral, sublingual/buccal, or rectal.
• Parenteral administration uses non-alimentary routes, this includes inhalation, injection/IV, subcutaneous, intramuscular, intrathecal, topical, and transdermal.

Routes of Administration:

• Oral administration is easy to perform, but absorption is variable and comes with a first-pass effect.
• Sublingual administration has a rapid effect, and does not have a first-pass effect.
• Rectal administration can impact the tissue in the rectum, and is used when oral is not available, but has poor absorption.
• Inhalation has rapid effect, directly effects lung tissue, issue with correct technique and some systemic side effects.
• Injection has a rapid effect with a more direct effect on target tissues, requires hospitalization, and irritation at injection site.
• Topical provides a local effect on the skin, but can't treat deeper layers.
• Transdermal enters the body without breaking the skin and provides steady and prolonged release of medications.

Pharmacokinetics

• Pharmacokinetics is what a patient does to the drug.
• Includes: Absorption, Distribution, Elimination, Metabolism

Absorption

• This is the bioavailability which is the percentage of drug into the bloodstream.
• The drug is absorbed in the GI tract, is sent to the liver via the portal vein, and the liver metabolizes some of the medication.

Bio phospholipid cell membrane

• Water and non-lipid soluble substances enter the cell through pores
  • How well this happens is dependent on shape/size of the molecule and its charge
• Lipid-soluble substances can cross membrane through Diffusion, Osmosis or Active transport
• Medications are manufactured to harness these factors to enhance drug delivery

Distribution

• Drugs are distributed differently throughout the system.
• Factors impacting distribution includes tissue permeability, blood flow and if its binding to plasma proteins.

Distribution & Blood-Brain Barrier

• The endothelial cells of the blood vessels in the brain form tight junctions that prevent most medications from getting to the brain.
• Tight junctions allow for better control and regulation of the environment in the brain
• Reduces the number of medications that can be used to treat issues of the brain.
• Small lipid soluble medications can cross the BBB

Storage

• Medications are stored in fat, muscle, bone, liver, and kidneys primarily
• Storage can mean that the availability of certain medications is variable

Elimination

• Metabolism involves enzymatic alterations of drug, changing the structure to an inactive form

• Includes the Hepatic Renal, Gastrointestinal, and Circulating Enzymes

• Excretion involves elimination often of water soluble chemicals.

• Includes the Renal, Gastrointestinal, Pulmonary, and Dermal systems

Half-Life

• Half-life is the amount of time it takes for half (50%) of the drug to get eliminated from the body
• Most drugs follow this rule called "first order kinetics."

Dosing Schedules

• The goal is to reach a therapeutic dose, avoid the toxic dose, and provide a relatively stable amount in the bloodstream, by IV to yield a stable dose.
• Most other medications produce vacillations in plasma dose: higher amounts (peaks) and lower amounts (troughs).
• Extended dose or Extended release medications still produce peaks and troughs, but they are less than other types of non-IV meds.

Pharmacokinetics meets Pharmacodynamics

• Cumulative Dose includes the -Median Effective Concentration/Dose (MEC) and the -Median Toxic Concentration/Dose (MTC)
• Therapeutic Range •Doses at which medication is effective without adverse events

Pharmacokinetics Chart

• The amount of a drug in the blood stream over time is shown in this graph.
• The aborption phase shows an uptrend, while the elimination phase shows the downtrend.
• Important measurements are: Cmax (Highest concentration of drug in blood), AUC (Area Under the Curve)/Overall drug exposure, t1/2 (Half-life) at which drug has lost half its maximum concentration and Cmin which is the Lowest concentration of drug in blood.

Factors Affecting Pharmacokinetics

• Age, disease process, genetics, gender, body composition, diet, and physical factors.

Aging Effects on Medication

• Liver and kidney function is altered with older age, which affecting medication metabolization with elimination meaning medication is higher concentrations

• Weight changes in older age affect storage of lipid-soluble medications, increased body fat.

• Polypharmacy has increased chances of interactions.

• Pediatrics has a different effect on drugs because they dont have full enzymes needed to metabolize drugs, so need to alter drug doses during early childhood.

Genetics effect on Medication

• Genetic variability can result in missing or reduced levels of certain enzymes needed for metabolism
• Example: there is a genetic polymorphism in a gene that results in a change in enzymes that help degrade a drug called Warfarin increased bleeding risk in those that have this polymorphism.
• Genetic polymorphisms are being identified and could eventually act as targets for a drug (or non drug) intervention.

Gender effects on medications

Men and women may have different ways, which influences how the distribution occurs, as well as other key pharmacokinetics. Hormonal fluctuations influence pharmacokinetics; alcohol absorption is faster in women than in men due to alcohol dehydrogenase.

Body Compostion and Diet Effects

• Some food-drug interactions can result in a negative drug uptake or effect.
• Example is that Grapefruit inhibits enzymes in some drugs and increases drug levels.
• Obesity affects the Permeability of GI System
• Therapeutic dose is altered because of lower drug penetration of tissues,

Physical Therapy session considerations

• Consider: time to peak onset , half-life of medication
• Heat, exercise, and massage during physical therapy may increase distribution/absorption
• Conversely, cold can affect distribution/absorption
• Observe for adverse drug reactions
• PTs contribute to understanding how medication impacts function, movement, and cognition.

Safety and Errors Related to Medications

• Adverse effect: unintended pharmacological effects
• Side effect: is a secondary unwanted or unintended that are generally known about the medication and is a risk with taking medicine
• Be aware of look alike, sound a like drugs

Medication error abbreviations to avoid

• Do not use "u" for unit, rather write out "unit"
• Do not use "qd" for every day, write "daily"
• Do not use "qod" for every other day, rather write out "every other day"
• Do not use trailing or leading zeros

General concerns with medications

• Cost
• Culture
• Compliance problems
• Self-medication
• OTC drugs
• Alteration of regimen