Pharmacodynamics 2

Upon completion of this session, students should be able to:
- Describe drug response relationships
- Discuss predictable adverse responses to drugs

Pharmacodynamics: The study of how drugs affect the body.
Drug response relationship: The correlation between drug dosing and ensuing physiological responses.
Plasma concentration-time profile of a drug: The measurement of drug levels in the blood over time following administration.
Half-life: The time required for the plasma concentration of a drug to halve.
Therapeutic range: The plasma concentration range that yields the desired pharmacological effect without causing toxic effects.

Age: Younger and older populations may metabolize drugs differently.
Body mass: Variations in body weight can influence drug distribution and effect.
Gender: Biological differences can affect drug efficacy and metabolism.
Environmental factors: External factors such as diet and lifestyle can alter drug metabolism.
Time of administration: Circadian rhythms may impact drug effectiveness.
Pathological state: The presence of concurrent conditions can affect drug responses.
Genetic factors: Genetic polymorphisms influence drug metabolism and efficacy.
Psychological factors: Mental state can affect perceptions of drug effects and compliance.

Onset of action: The period before the drug begins to exert its effects.
Peak concentration: The highest concentration of the drug in the plasma following administration.
Duration of action: The time frame during which the drug is effective.
Termination of action: The process by which the drug's effects cease.

Drug action: Involves cellular and chemical interactions between the drug and the targeted cells.
Therapeutic response: The body’s physiological reaction to the drug that leads to the desired outcome.

Oral Administration:
- The drug is absorbed from the gastrointestinal tract, increasing plasma concentration until elimination equals absorption.
Intravenous (IV) Administration:
- Results in immediate peak plasma concentration, with subsequent decline reflecting elimination.
Peak Plasma Level: The highest achieved concentration after a single dose.

This relationship is dependent on the plasma concentration-time profile.
Monitoring plasma drug levels can ensure maintenance within a therapeutic range.

The biological half-life is the time required for plasma concentration to decrease to half its initial value due to metabolism and excretion.
Typically takes 3-5 half-lives to achieve a steady-state concentration.
Elimination: 97% of a drug is eliminated after 5 half-lives, regardless of dosage or route.

Half-life: A critical measurement indicating the rate of drug clearance from the body.
Dosing Interval: Usually matches the half-life to maintain effective treatment
Loading Dose: A sizable initial dose followed by smaller, regular maintenance doses for drugs with long half-lives.

A steady-state concentration is essential for maintaining therapeutic effects.
Achieved through:
- Continuous IV infusion.
- Multiple dosing via other administration routes.

Peak Concentration: Highest point after dosing.
Trough Concentration: Lowest point before the next dose.
Steady-State Concentration: Fluctuates within a twofold range around average concentration throughout dosing intervals.
Example: A drug with a half-life of 4 hours taken every 4 hours achieves steady state within 3-5 half-lives.

Important considerations for maintaining therapeutic efficacy following a missed dose.

Minimum Effective Concentration (MEC): The lowest plasma concentration at which a therapeutic response occurs.
Minimum Toxic Concentration (MTC): The lowest plasma concentration at which toxic effects may develop.

The therapeutic range is indicative of drug safety; a wider range indicates a safer drug.
Formula: Therapeutic Range = MTC - MEC.

Definition (WHO, 1984): "Any response to a drug which is noxious, unintended, and which occurs at doses normally used for therapy."
Preference for the term “adverse effect” over “side effect” due to implications of undesired outcomes possibly linked to dosage.
Adverse Drug Event: Refers to injury associated with drug use that is not necessarily caused by the drug itself, such as prescribing or administration errors.

Type A (Augmented): 80% of reactions;
- Dose-related, predictable, usually mild, rarely fatal.
- Example: Hypoglycemia caused by insulin.
Type B (Bizarre): 20% of reactions;
- Unpredictable, unrelated to dosage, may be severe, potentially fatal.
- Example: Allergic reactions.
Type C (Chronic): Related to long-term use and dosage.
Type D (Delayed): Responses that occur after a latency period.

Polypharmacy: Involves potential interactions, including drug-herb and drug-food interactions.
Pharmacodynamic interactions:
- Example: Warfarin combined with aspirin increases bleeding risk due to both acting on clotting.
Pharmacokinetic interactions:
- Example: Other drugs taken with morphine may delay peak plasma concentration.
- Example: Grapefruit juice inhibits enzymes, affecting the metabolism of various drugs, resulting in increased bioavailability.

Essential notes on risk factors associated with adverse drug reactions and methods for prevention.

Associated with Pharmac and the Ministry of Health.
Focus on Pharmaco-vigilance: Documenting and reporting all adverse effects to enhance public safety and medication monitoring.
Emphasis on better communication as a fundamental aspect of effective monitoring.

Bryant, B., Knights, K., Darroch, S. & Rowland, A. (2019). Pharmacology for health professionals. (5th ed.). Chatswood, NSW, Australia: Elsevier.