Pcl 7

Pharmacology Concepts

Agonists and Antagonists

  • Agonist: An agent that activates a receptor, producing an effect opposite to that of an agonist.

  • Efficacy: Refers to the maximum effect a drug can produce regardless of dose.

    • Example: A highly potent drug may have low efficacy if it is rapidly metabolized, while a drug with lower potency may achieve higher efficacy if it absorbs quickly with minimal first-pass metabolism.

Potency

  • Potency: The concentration or dose of a drug required to produce 50% of its maximum effect.

    • Highly potent drugs (e.g., morphine) elicit a greater response at low concentrations.

    • Lower potency drugs (e.g., ibuprofen, aspirin) evoke smaller responses at low concentrations.

Drug Interactions

  • Synergism: The combined effect of two drugs is greater than the sum of their individual effects (e.g., 2+2=4).

    • Example: Barbiturates with anesthetics enhance CNS depression.

    • Additive Effect: The combined effect of two drugs equals the sum of their individual effects (e.g., 2+2=4).

    • Example: Aspirin combined with paracetamol.

    • Potentiation: When one drug increases the effect of another drug that has little or no effect on its own (0+2=2).

      • Requires the drugs to act on different receptors (e.g., bisostigmine enhances acetylcholine).

Selectivity and Specificity

  • Selectivity: The ability of a drug to bind to a specific receptor over others, often associated with specificity.

    • Example: Propranolol interacts with both beta 1 and beta 2 receptors, while metoprolol is more selective for beta 1.

  • Specificity: The capacity of a receptor to respond to a single ligand.

    • Low specificity can lead to unintended physiological responses, resulting in side effects.

    • Specific drugs like atropine and valbutamol act on specific receptors, whereas non-specific drugs like nothiazine affect multiple receptors.

Dose and Concentration Relationships

  • Concentration: Represents the weight of drug per volume (e.g., mg/ml).

  • Dose: Refers to the amount of drug administered (e.g., g or mg/kg).

    • Therapeutic doses vary per individual.

    • Effective doses are used in experimental settings, e.g., treatment for roundworms with piperazine.

Types of Doses

  • Daily Dose: The total quantity of drug to be taken within 24 hours.

    • Example: 1 g of erythromycin per day.

  • Loading Dose: A large initial dose designed to rapidly reach effective plasma concentrations, usually followed by a maintenance dose.

    • Example: 600 mg chloroquine for malaria followed by lower doses.

  • Maintenance Dose: The continued dose to maintain stable plasma drug concentration.

Drug Response Types

  • Graded Response: The response increases proportionally with the dose or concentration. The threshold dose is the minimal amount needed to observe a measurable effect.

  • Quantal Response: Indicates a binary outcome where each unit responds maximally, and the overall response is measured against the drug concentration.

    • Helps determine therapeutic index (TI) using median effective dose (ED50) and median lethal dose (LD50).

Therapeutic Index and Safety

  • Therapeutic Index (TI): Reflects the safety of a drug, calculated as the ratio of LD50 (lethal dose for 50% of the population) to ED50 (effective dose for 50% of the population).

    • A higher TI indicates a safer drug.

    • Drugs with low TI: digoxin, insulin, warfarin.

    • Drugs with high TI: penicillin and most antimicrobials.

Understanding Dosing Parameters

  • Median Therapeutic Dose (ED50): The dose causing the specified effect in 50% of individuals.

  • Median Toxic Dose (TD50): The dose causing toxicity in 50% of subjects.

  • Median Lethal Dose (LD50): The dosage required to kill 50% of the test subjects.

  • Therapeutic Range/Window: The dosage range in which a drug is effective for most patients without reaching toxicity.

Pharmacology Concepts

Agonists and Antagonists

  • Agonist: Activates a receptor, producing an effect opposite to an antagonist.

  • Antagonist: Blocks or dampens the effect of an agonist.

Efficacy and Potency

  • Efficacy: Maximum effect a drug can produce, independent of dose.

  • Potency: Dose required to achieve 50% of the maximum effect. (e.g., morphine vs. ibuprofen).

Drug Interactions

  • Synergism: Combined effect is greater than individual effects.

  • Additive Effect: Combined effects equal the sum of individual effects.

  • Potentiation: One drug increases the effect of another with little to no effect on its own.

Selectivity and Specificity

  • Selectivity: Ability of a drug to bind to specific receptors.

  • Specificity: Capacity of a receptor to respond to a specific ligand.

Dosing Parameters

  • Daily Dose: Total quantity within 24 hours.

  • Loading Dose: Initial large dose to quickly reach effective levels.

  • Maintenance Dose: Continued dosage to maintain drug concentration.

Drug Response Types

  • Graded Response: Response increases proportionally with dose.

  • Quantal Response: Binary outcome measuring max response against concentration.

Therapeutic Index (TI)

  • TI reflects drug safety, calculated as LD50/ED50. A higher TI indicates safer drugs.