Basics of Pharmacology Study Notes

Basics of Pharmacology

General Areas of Study

• Pharmaceutics

  • Definition: The science of preparing drugs for administration.

  • Concept: "Dosage Forms."

• Pharmacokinetics

  • Definition: The study of the absorption, distribution, metabolism, and elimination of drugs.

  • Concept: "What the body does to the drug."

• Pharmacodynamics

  • Definition: The study of the action or effects of drugs on living systems.

  • Concept: "What the drug does to the body."

General Properties of Drugs

• Modification of Existing Functions:

  • Replace:

  • Example: Iron in anemia, hormones.

  • Interrupt/Block:

  • Example: Adalimumab (Humira®), anticoagulants.

  • Potentiate/Enhance:

  • Example: Stimulant laxatives, epinephrine.

• Multiple Effects of Drugs:

  • Example: Bupropion functions as an antidepressant and aids in smoking cessation.

• Interaction Requirement:

  • Drugs typically interact with target sites to exert an effect.

Levels of Drug Activity

• Body Systems: Interaction at a systemic level.

• Component Tissues: Interaction at the tissue level.

• Cellular Level: Interaction at the cellular level.

• Molecular Level: Interaction at the molecular level.

Beta-Blockers

• Body Systems Activity:

  • Effect: Reduces pulse rate.

• Component Tissues Activity:

  • Effect: Negative chronotropic effect.

• Cellular Level:

  • Effect: Prevents elevation of cAMP (cyclic adenosine monophosphate).

• Molecular Level:

  • Mechanism: Competitive antagonism of norepinephrine at cardiac beta1 receptors.

Basic Receptor Pharmacology

Receptor Binding - Agonism

• Agonism Definition:

  • Process: Production of a molecular/cellular response when a molecule interacts with and activates a receptor.

  • Agonist: Can be either a drug or an endogenous ligand.

• Full Agonist:

  • Definition: An agonist that can produce a full biological effect.

  • Concept: Increasing concentrations lead to a biological effect up to an intrinsic activity of 1.

  

  • Y-Axis: Biological Effect (% effect)

  • X-Axis: Concentration.

  • 1 to 100% Activation plotted.

• Partial Agonist:

  • Definition: An agonist that results in a biological response <1.

  

  • Y-Axis: Biological Effect (% effect)

  • X-Axis: Concentration.

  • Shows limited activation compared to full agonist.

Log Dose of Opioid Receptor Activation

• Graphical Representation: Comparison between Full Agonist (e.g., Methadone) and Partial Agonist (e.g., Buprenorphine).

  • Discusses receptor activation levels in relation to drug concentrations.

Receptor Binding - Antagonism

• Definition:

  • The binding of a drug to a receptor that does not activate the receptor, thereby blocking any response to an agonist.

• Types of Antagonism:

  • Competitive Antagonism:

  • Definition: Antagonist binds to the same site as the endogenous agonist.

  • Effect: Prevents agonist binding and receptor activation.

  • Nature: Can be reversible or irreversible depending on the bond.

  • Noncompetitive Antagonism:

  • Definition: Antagonist binds to an allosteric site, altering the receptor shape, preventing agonist binding.

• Graphical Representation:

  • Showing effects of competitive antagonists on receptor activation in relation to agonists such as Methadone and Buprenorphine.

Pharmacologic Antagonism vs. Effect Antagonism

• Discusses differences and implications in pharmacological theory.

Post-Receptor Effects

• Examines events occurring after receptor binding and the biological outcomes.

Ligand-Gated Ion Channels

• Description:

  • Example: Sodium channels with binding sites for ligands (e.g., acetylcholine).

  • Mechanism: Binding of acetylcholine opens the channel.

Enzymes in Pharmacology

• Definition: Proteins that accelerate chemical reactions within cells.

Routes of Administration

Enteral Administration

• Mouth:

  • Characteristics: Thin lining, rich blood supply, employed via sublingual and buccal routes.

• Stomach:

  • Characteristics: Moderate surface area, rich blood supply, low pH (acidic), short residence time.

• Small Intestine:

  • Characteristics: High surface area, rich blood supply, neutral to slightly basic pH.

• Rectal:

  • Characteristics: Smaller surface area, rich blood supply, basic pH.

Parenteral Administration

• Advantages:

  • Applicable for poorly absorbed drugs (e.g., Vancomycin <10% absorbed).

  • Immediate onset of action (e.g., intravenous opioids).

  • Sustained effects from injections (e.g., antipsychotics).

  • Concentration of drug at targeted sites (e.g., corticosteroids in joints).

  • More predictable pharmacodynamic responses (e.g., antibiotics in septic patients).

  • Titrable dosages (e.g., Heparin infusions).

• Disadvantages:

  • Pain upon administration.

  • Irreversibility: Cannot remove once administered.

  • Risk of contamination/infection.

  • Potential issues such as extravasation or phlebitis.

Types of Parenteral Administration

• Intravenous

• Intra-arterial

• Intramuscular

• Epidural

• Intrathecal

• Subcutaneous

• Intra-articular

Topical Administration

• Skin:

  • Forms: Ointments, creams, patches; both local and systemic effects.

• Eyes:

  • Delivery through drops or ointments for local effect.

• Ears:

  • Local distribution through drops.

• Intranasal:

  • Delivery through spray or drops; can have local and systemic effects.

• Inhalation:

  • Delivers medication to lungs; effects can be local or systemic.

• Vaginal:

  • Administration through local forms.

Oral Dosage Forms

Pharmaceutical Phase

• Disintegration: The breakdown of dosage forms into smaller particles.

• Dissolution: The process by which particles dissolve in a solvent.

• Types of Oral Dosage Forms:

  • Dissolved Liquid: Examples: elixirs, syrups.

  • Suspensions

  • Powders

  • Capsules

  • Tablets

  • Coated Tablets

  • Enteric-Coating

  • Sustained-Release forms.

Pharmacokinetics

Pharmacokinetic Phase

• Absorption: Movement of drug molecules into the systemic circulation.

  • Diffusion Mechanisms:

  • Passive versus facilitated diffusion.

  • Absorption influences onset of action, duration of action, and intensity of response.

Variables Affecting Absorption

• Nature of Absorbing Surface: Comparison between intestinal epithelium and skin.

• Surface Area: Different areas such as the small intestine vs. large intestine influence overall absorption rates.

• Blood Flow: Blood flow to the site can greatly affect how drugs are absorbed, for instance, peripheral IV administration during shock scenarios.

• pH: Environmental pH can significantly impact absorption processes.

Drug Elimination and Biotransformation

• Hepatic Metabolism:

  • Mechanism: Involves cytochrome P-450; processes include oxidation/reduction and conjugation.

• Tissue Enzymes: Present in various tissues such as GI tract, lungs, and kidneys contributing to metabolism.

Excretion Mechanisms

• Primary Excretory Organs:

  • Kidneys

  • Lungs

  • Sweat Glands

  • Salivary Glands

  • Mammary Glands

  • GI Tract

Concentration-Time Curve

• Graphical Representations: Shows drug concentration levels over time as administered, with indicated ranges in mcg/ml.

Individual Response to Medications

Variables Affecting Dose/Response

• Body Weight: Larger doses may be required for patients with greater weight or body mass index (BMI).

  • Distribution variables include muscle, adipose tissue, and body water.

• Age: Metabolic and excretion capacities can decline, especially in young and elderly populations.

• Gender: Differences in body composition and hormonal levels may influence pharmacokinetics.

• Genetics: Variations in enzymatic activity can lead to differences in drug effect magnitudes, possibly causing therapeutic failure or toxicity.

• Tolerance: A phenomenon where larger doses are needed to achieve the same effect; often seen in opioid usage.

• Psychological Factors: Placebo effect can alter perceived drug effectiveness.

• Comorbid Conditions: Other medical conditions can affect pharmacokinetics and pharmacodynamics.