Pharmacokinetics Quiz

Drug Action and Handling

• Drug action and handling is covered in Chapter 2.

Characterization of Drug Action

• Drug response or action is measured using terms like dose-response curves, log dose-effect curves, potency, and efficacy.

Dose-Response Curve

• A simple model where increasing the dose increases the response (e.g., pinching your ear harder hurts more).
• The intensity of the response increases proportionally with the dose.

Log Dose Effect Curve

• A more complex model showing the relationship between the drug dose and the resulting response.
• The curve shows a gradual increase in response as the log dose increases.
• The curve plateaus at the maximum response which is the ceiling effect.

Therapeutic Range & Maximum Response

• Therapeutic range: the dose range where the response increases sharply; the desired dose is in this zone.
• Maximum response: the point on the curve showing the highest response possible from administering more of the drug.

Potency

• Potency is the amount of drug needed to produce an effect.
• Higher potency means a smaller dose is needed for the same response.
• Drug A is more potent than Drug B if it produces an effect with a lower dose.

Efficacy

• Efficacy is the maximum response a drug can produce, regardless of dose.
• Increasing the dose does not increase efficacy; if the maximum response is reached, increasing the dose has no further effect.
• Increasing a drug does not increase efficacy—it just increases the probability of side effects.

Therapeutic Index

• TI (Therapeutic Index) is the ratio of the median lethal dose (LD50) to the median effective dose (ED50).
• A higher TI indicates a safer drug.
• A TI close to 0 suggests careful monitoring of the drug's administration is necessary.

TI Examples

• Drug A: LD = 200mg, ED = 20mg, TI = 10
• Drug B: LD = 300mg, ED = 100mg, TI = 3

Mechanism of Action of Drugs

• Drugs do not create new functions.
• They produce the same action as endogenous agents.
• Drugs can replace or block the action of endogenous agents.
• Drugs bind to the receptor site on the cell's membrane to have a desirable effect.
• Adverse effects result from unintended drug actions on non-target organs.

Agonists and Antagonists

• Agonists have affinity for a receptor, bind to it, and produce an effect.
• Antagonists counteract the action of agonists by binding to receptors.
• Drugs with stronger affinity bind to more receptors and are more potent.
• More potent drugs will require a smaller dose to produce the same effect.

Pharmacokinetics ADME

• Pharmacokinetics is the study of how a drug enters, circulates in, and is removed from the body.
• Absorption, distribution, metabolism, and excretion are the key processes.

Pharmacokinetics: Drug Absorption

• Absorption is the transfer of a drug from the administration site to the bloodstream.
• Physicochemical properties, site of absorption, drug solubility, dose form, and blood flow at site of injection influence absorption rate.
• IV (intravenous) administration bypasses this step

Pharmacokinetics: Drug Distribution

• Distribution is the passage of drugs into various body fluid compartments (plasma, interstitial fluids, intracellular fluids).
• Drugs distribute to organs with higher blood flow.
• Factors affecting distribution include organ size, blood flow to organs, drug solubility, plasma protein-binding, and barriers like the blood-brain barrier and placenta.

Pharmacokinetics: Drug Metabolism

• Metabolism, also called biotransformation, is the body's way of changing a drug molecule to excrete it more easily.
• The liver is the primary site of metabolism.
• Metabolism mechanisms include converting active drugs to inactive forms, inactive drugs to active forms, and active to active forms.
• Impaired liver function and other substances can affect drug metabolism.

Pharmacokinetics: Drug Excretion

• Excretion is the removal of drugs from the body through various pathways (renal, lungs, saliva, bile, gastrointestinal tract, sweat, milk).
• Drug elimination ends the effects of the drug.

Clinical Pharmacokinetics: Half-Life

• Drug half-life is the time it takes for the drug concentration to decrease by half.
• 4-5 half-lives are needed for a drug to be largely eliminated.
• This is important for determining dosing schedules.
• Example: Azithromycin (Zithromax) half-life is approximately 68 hours.

Half-Life First-Order Kinetics

• Drug elimination in first-order kinetics is proportionate to the drug's plasma concentration.
• The drug's concentration decreases by a constant percentage over a given time.

Half-Life Zero-Order Kinetics

• In zero-order kinetics, drug elimination is constant for a given time period, regardless of drug concentration.
• This occurs because elimination mechanisms are saturated; they can't keep up with a large dose.
• Aspirin and alcohol have zero-order kinetics in some conditions.

Altering Drug Effects

• Patient adherence, psychological factors, pathologic state, time of administration, route of administration, gender, genetic variation, drug interactions, age and weight, environment, and other factors can alter drug effects.

Routes of Administration

• Onset: The time it takes for a drug to start having an effect.
• Duration: The length of time a drug's effect lasts.
• Enteral routes place drugs directly into the gastrointestinal tract (e.g., oral, rectal).
• Parenteral routes bypass the gastrointestinal tract (e.g., intravenous, intramuscular, subcutaneous).

Oral Route of Drug Administration

• Advantages: large absorbing area in the small intestine, slower onset of action, safest, least expensive, most convenient.
• Disadvantages: nausea, vomiting, drug inactivation by GI tract acidity or enzymes, drug interactions, requires patient cooperation, first-pass effect (drug metabolized when first passing through the liver).

Rectal Route of Drug Administration

• Advantages: used if patient is vomiting or unconscious, produces local or systemic effects.
• Disadvantages: drugs are poorly and irregularly absorbed, poor patient acceptance.

Intravenous Route of Drug Administration

• Advantages: most rapid drug response, more predictable blood levels, can be used in emergencies.
• Disadvantages: phlebitis (inflammation of a vein), drug irretrievability, allergy, side effects related to high plasma concentrations.

Intramuscular Route of Drug Administration

• Advantages: increased tolerance for irritating drugs, can administer suspensions resulting in a sustained effect.
• Disadvantage is not listed.

Subcutaneous Route of Drug Administration

• Method of injecting drugs into the subcutaneous areolar tissue.
• Insulin and local anesthetics are often administered this way.
• Disadvantages: irritating solutions may cause sterile abscesses or hematomas.

Other Routes of Drug Administration

• Intradermal: Injection into the epidermis (e.g., tuberculin test).
• Intrathecal: Injection into the spinal space.
• Intraperitoneal: Injection into the body cavity.

Inhalation Route of Drug Administration

• Examples: asthma inhalers, general anesthetics, nitrous oxide/oxygen.
• Advantages: rapid onset of action, avoids needles.
• Disadvantages: often leads to drug abuse.

Topical Route of Drug Administration

• Advantages: systemic side effects are rare.
• Disadvantages: increased risk of systemic side effects if surfaces are large and/or inflamed.
• Some topical anesthetics can be absorbed into the bloodstream.
• Most effective on non-keratinized surfaces.

Topical Drug Examples

• Creams, ointments, gels (epicutaneous)
• Transdermal patches (fentanyl)
• Sublingual tablets (NTG)
• Buccal tablets
• Subgingival (atridox, periochip)