Pharmacology - Basic Principles

Introduction

Pharmacology is the study of drugs. Though many are not typically prescribed by physiotherapists/physical therapists, knowledge of this field is pertinent to the care of patients and clients. Knowledge of drugs, drug metabolism, the impacts of various patient diagnoses and their and their effects on various body systems enhances a clinician's ability to clinically evaluate a patient, monitor responses to activity, provide education, and engage in interprofessional discussions with pharmacists, physicians, etc.

Additional Definitions

• Drug: any substance taken that can alter or modify one or more body functions
• Pharmacotherapeutics: the pharmacology branch which uses drugs to prevent, treat, or diagnose disease
  • Pharmacodynamics: how the drug affects the body
  • Pharmacokinetics: how the body affects the drug

Drug Nomenclature

A drug is a substance taken that can alter or modify one or more functions when introduced to the body. These substances are referred to by multiple names, as follows:

• Chemical Name (scientific name) - primarily used by chemists, named for the position and type of atoms which compose the medication
  • An example chemical name for metoprolol succinate is 1-(isopropylamino)-3-[2-(2-methoxyethyl) phenoxy]propan-2-ol
• Generic Name (nonproprietary name) - generated by the United States Adopted Names Council, the World Health Organization's International Nonproprietary Names expert group, and the manufacturer of a medication. Follows a set of criteria and principles that generate a useful name for healthcare providers.
  • Word stems: used to identify a class of medications (e.g., -olol for beta-blockers)
  • Metoprolol is a generic name, which can be further specified as metoprolol tartrate and metoprolol succinate (used for different dosing parameters/needs)
• Trade Name/Brand Name (proprietary name) - made by the pharmaceutical company and approved by the regulating organization. Must be pronounceable and distinct from other medications (including generic names).
  • Lopressor and Toprol XL are examples of brand names for metoprolol in the United States.

Drug Efficacy

Drug dosing principles are often based off of a "range" related to the dose-response curve and bioavailability

• Dose-response curves identify the threshold dose of a drug beginning to have effects, and the ceiling effect where adding more of a drug does not change the effect
  • The Median Effective Dose (ED50) is the dose where 50% of a population responds to a specific drug in a certain manner
  • The Median Toxic Dose (TD50) is the dose where 50% of a population exhibits adverse effects
  • The Therapeutic Index (TI) is derived from the following formula:
    • TI = TD50/ED50
    • Provides information on the safety of a drug (the higher the TI, the safer)

Non-specific dose-response curve

• Bioavailability indicates the amount of drug that is administered versus the amount reaching systemic circulation, which depends on
  • Ability to enter/exit the cell
  • Dependent on the route of administration

Common Routes of Drug Administration

• Enteral routes of administration utilize the GI tract. They are as follows:
  • Oral - most commonly used route of administration
    • Drug absorption primarily occurs in the small intestine
      • Greatly affected by the first-pass effect (large portion of drug is metabolised in the liver, reducing the concentration of the drug)
  • Sublingual (under the tongue) and buccal (through the cheek)
    • sublingual tissue is more permeable than buccal, allowing for faster drug absorption
    • Circumvents first-pass effect
  • Rectal
    • partially bypasses first-pass effect (50% absorption in the liver)
• Parenteral
  • Intravenous (IV): injection into peripheral veins, typically in the upper extremity
    • Upper extremity IVs have decreased incidence of Thrombophlebitis and Thrombosis compared to the lower extremity
  • Intramuscular
  • Subcutaneous: administered to the cutis (below dermis and epidermis)
    • slow, sustained absorption due to minimal vasculature
  • Intra-arterial: not commonly used for medications, used for contrast injections for angiography studies and chemotherapy
• Other
  • Transnasal: utilizes drug absorption via passive diffusion into systemic circulation
  • Inhalation: rapid delivery to respiratory tract epithelium
  • Topical: remains on surface of local application
  • Transdermal: penetrate into skin layers, local application of a drug

Drug Metabolism, Elimination, Excretion, and Metabolism

The process of drug metabolism is called biotransformation, which details the chemical changes occuring after administration

• Most biotransformation occurs in the liver, but may also occur in the lungs, kidneys, Gastrointestinal (GI) epithelium, and skin
• The rate of biotransformation is impacted by the efficiency of the enzymes the drug interacts with; enzymatic efficiency can ultimately lead to drug tolerance
• Drug metabolism is impacted by genetics, disease, age, and additional drug interactions (including supplements, herbal medicines, and certain foods)

Drug excretion is performed primarily by the kidneys, as well as the lungs, GI tract, and through sweat, salivary, and mammary glands

Drug elimination rates are determined by an organ's ability to eliminate a drug.

• Expressed as half-life, the amount of time required for 50% of a drug remaining in body to be eliminated

Drug-Receptor Interactions

In order for a drug to have an effect, it must act on a receptor either on a cell membrane or on a subcellular component. This is driven by the shape, size, attraction, and polarity of medications. The following are key definitions which are related to drug-receptor interactions

• Affinity: amount of attraction between a drug and receptor
• Allosteric modulator: regulates the affinity of a receptor for a drug
  • activator: enhances drug's effect
  • inhibitor: decreases drug's effect
• Selectivity: the more selective a drug, the fewer cells or tissues it can act upon, producing a specific response with minimal side effects
  • Agonist: The drug has affinity for a receptor, and activates the receptor to change cellular functions
  • Antagonist: The drug has an affinity for a receptor, but blocks the cell from changing function
• Regulation of interactions
  • Desensitization: a receptor becomes less sensitive to a drug
  • Down-regulation: less receptors are available to an agonist after prolonged exposure (leads to tolerance)
  • Up-regulation: decreased receptor stimulation leads to increased sensitivity

The following video provides a brief overview of drug-receptor interactions:

Resources

Common Drug Suffixes

This video details common drug and food interactions that a clinician may need to educate patients about: