Pharmacology Notes for Physical Therapists

Introduction to Pharmacology

• Kevin Koons PharmD, BCPS, discusses pharmacology to assist Physical Therapists.

The CAPRIE Trial

• Compared Aspirin versus Clopidogrel (Plavix®).
• Primary outcome: Myocardial Infarction (MI), Ischemic stroke, vascular death.
• Population: Patients with prior MI, Ischemic stroke, Peripheral Artery Disease (PAD).
• Follow up: 1-3 years.
• Overall: 8.7% Relative Risk Reduction (RRR) (P=0.043).

Concept #1: Drugs are (probably) good

• Drugs may:
  • Save lives.
  • Prevent strokes.
  • Alleviate pain.
  • Prevent serious infections.
  • Help with breathing.
  • Fight cancer.
  • Prevent heart attacks.
  • Prevent hip fractures.

Concept #2: Drugs are (probably) bad

• Drugs may:
  • Cause death.
  • Cause disability.
  • Induce nausea.
  • Cause headaches.
  • Damage the liver.
  • Damage the kidneys.
  • Cause Rhabdomyolysis (muscle breakdown).
  • Lead to abuse, dependence, and addiction.
  • Cause dizziness, falls, and fractures.

Therapy Selection

• Risk versus Benefit: Weighing the potential harm against the potential benefit of a medication.
• Prioritize:
  • SAFETY
  • TOLERABILITY (including adherence)
  • EFFICACY
  • PRICE

CAPRIE Trial Breakdown

• 5.32% of patients on clopidogrel experienced the primary outcome.
• 5.83% of patients on aspirin experienced the primary outcome.
• RRR (Relative Risk Reduction): ((0.0583 - 0.0532) / 0.0583) * 100 = 8.7%.
• ARR (Absolute Risk Reduction): 0.0583 - 0.0532 = 0.0051 or 0.51%.
• NNT (Number Needed to Treat): 1 / 0.0051 = 196.
• NNH (Number Needed to Harm) for GI Bleed = 50.

Risk Reduction Calculations

• Relative Risk Reduction (RRR): (CER - EER) / CER .

• Absolute Risk Reduction (ARR): CER - EER .

• Number Needed to Treat (NNT): 1 / ARR .

  • CER = Control Event Rate
  • EER = Experiment Event Rate

• Statistical significance ≠ Clinical significance

Concept #3: Things can and will go wrong

• Medication misadventures: Lead to ER visits, hospital admissions, prolonged stays, and readmissions.
  • Cost: ~$150 billion.
  • Types:
    • Medication errors
    • Adverse drug events
    • Adverse reactions (5% of hospital admissions)
    • Drug interactions
    • Non-adherence

Medication Errors

• Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer (NCCMERP definition).
  • Most common error: Wrong dose (e.g., Ropinirole 0.25mg vs. 2.5mg).
  • Look-alike/Sound-alike drugs: Aripiprazole vs. rabeprazole.
  • Resources: ISMP.org.
  • Other errors: Wrong patient, wrong drug, wrong route.

Adverse Drug Reaction

• A noxious and unintended response to a drug at doses normally used for prophylaxis, diagnosis, or therapy.
  • Example: Augmentin® (amoxicillin/clavulanate) causing diarrhea (9% vs. <1% with placebo).
  • Anaphylaxis: Type I reaction.
  • Diphenhydramine: Can cause sedation (sometimes used advantageously).

Types of Adverse Drug Reactions

• Augmented: Expected (e.g., steroid-induced hyperglycemia).
• Bizarre: Unpredictable (e.g., steroid-induced psychosis).
• Chronic: Due to prolonged exposure (e.g., steroid-induced Cushing’s).
• Delayed: Remote from treatment (e.g., steroid-induced osteoporosis).
• End of treatment: Due to sudden discontinuation (e.g., steroid-induced adrenal suppression).

Drug Interactions

• Pharmacological result (desirable or undesirable) of drugs interacting with other drugs, chemical agents, or components of the diet.
  • Drug:Food: Examples include Atorvastatin (Lipitor) + Grapefruit = Myopathy, and Warfarin + Kale = Stroke (decreased anticoagulation).
  • Drug:Drug: Examples include Ketoconazole + Ranolazine = Arrhythmia, and Simvastatin + Diltiazem = Myopathy.
  • Drug:Diagnostic testing agents: Example includes Metformin + Contrast media = Renal failure.

Types of Interactions

• Additive: 1 + 1 = 2 (e.g., Alcohol + Lorazepam).
  • Two substances with similar effects.
• Synergistic: 1 + 1 = 5 (e.g., Cocaine and propanolol).
  • Significant enhancement of activity.
• Antagonistic: 1 + 1 = 0.
  • One increases metabolism of another (e.g., Carbamazepine and estradiol (Birth control)).
  • One blocks effect of another (e.g., Vitamin K and Warfarin).

Concept #4: Optimal patient care needs team work and communication

Impact on Society

• ~10% of healthcare expenditures are for medications.
  • $374 billion in the United States in 2014 → $419.4 billion in 2015.
  • Dramatic increase of >10%/year.
• Percentage of persons using at least one prescription drug in the past 30 days: 48.7% (2009-2012).
• Percentage of persons >65 using one or more prescriptions in the last 30 days: 90% (www.cdc.gov).
• 2015 US Prescriptions filled: 4.4 billion.
• Percent of visits involving drug therapy: 75.1%.
• Most frequently prescribed therapeutic classes:
  • Analgesics
  • Anti-hyperlipidemic agents
  • Antidepressants (AJHP May 2016).

Why Physical Therapists Should Care

• You will be a trusted healthcare provider.
• You will likely have patients on medication.
• You will likely have patients helped by medication.
• You will likely have patients hurt by medication.
• Medications will probably impact your ability to provide care.
• You will likely recognize a medication problem and help.

Patient Presentation Example

• A 68-year-old male presents with changes in presentation (tired, confused).
• Consider medications as a potential cause.
• Questions to ask the patient and/or spouse to investigate.

Learning Pharmacology

• Even pharmacists can't know it all.
• Start with generalities, then learn exceptions.
  • Generalities will cover 90% of cases.
  • Antihypertensive example.
• As of 2013, the FDA estimated 1,453 new molecular entity approvals.

Pharmacowhat?

• Critical definitions:
  • Drug: Typically a known chemical structure.
  • Biological agents: Proteins, sugars, not easily identified.
  • Pharmacology
    • Pharmacotherapeutics: Use of drugs to treat, prevent, diagnose disease.
    • Pharmacokinetics (ADME): Drug absorption, distribution, metabolism, elimination.
    • Pharmacodynamics: Systemic and cellular effect of the drug (mechanisms).
    • Toxicology: Poisons and their effects.

Drug Nomenclature

• Potentially confusing.

• Each drug has 3 names:

  • Chemical name: Specific compound structure.
  • Generic name: Official or nonproprietary name.
  • Trade name(s): “Brand” or proprietary name.

• Example:

  • Chemical Name: 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one
  • Generic Name: Diazepam
  • Trade Name: Valium

Where Do Drugs Come From?