Drugs and Medications: Action, Effects, and Tolerance

• Notes on lectures about drugs and medications, including drug action, effects, pharmacokinetics, tolerance, and related concepts.

Drug Action and Effects

• Drug Action: Molecular changes from a drug binding to a specific receptor or target site.
• Drug Effect: Physiological and psychological changes resulting from drug action.
• Therapeutic Effects: Desired physical and behavioral changes caused by drug-receptor interactions.
• Side Effects: Unintended effects produced by drug-receptor interactions.
• The distinction between therapeutic and side effects depends on the intended drug outcome.
• Example: Amphetamine-like drugs may have increased alertness (therapeutic effect), with side effects of insomnia, increased heart rate, and decreased appetite.

Specific vs. Non-Specific Drug Effects

• Specific Drug Effects: Based on the drug's physical and biochemical interactions with a target site in living tissue.
• Non-Specific Drug Effects: Depend on individual differences, including: Personal history of drug use. Expectations about the drug's effects. Perception of the drug-taking situation. Attitude toward the person administering the drug.

Placebo Effect: Possible Explanations

• Placebo Effect: Explained by: Classical Conditioning (Pavlovian Model): Unconditioned stimulus (e.g., effective drug) leads to an Unconditioned response (symptom relief). Conditioned stimulus (e.g., placebo pill) leads to a Conditioned response (symptom relief). Conscious Expectation: Believing that the drug will work influences the actual effects. Social Learning: Observing others or trusting medical authority enhances the placebo effect.

Pharmacokinetics (PK) and Pharmacodynamics

• Pharmacokinetics (PK): What the body does to the drug.
• Pharmacodynamics: How the drug affects the body, which are the drug's direct effects on the body.

Drug Administration Routes

• Systemic: Drugs distribute throughout the body, reaching the target tissue through general circulation. Enteral Methods: GI system (i.e., oral/rectal) - E for eating Parenteral methods: Bypass the GI system (i.e., IV)
• Central: Relates to the CNS, and bypasses the BBB

Additional Factors Affecting Drug Absorption

• Lower pKa = Stronger acid gives up H⁺ easily, ionizes more in water.
• Higher pKa = Weaker acid that holds onto H⁺ longer, ionizes less.
• Weak acids absorb better in acidic (low pH) environments.
• Weak bases absorb better in basic (high pH) environments.

Vestibule Region

• Localized effect

Respiratory Epithelium

• Systemic effect
• Indirect path to the brain

Olfactory Epithelium (Main Pathway)

• Direct path to the brain
• Olfactory sensory neurons
• Olfactory nerve pathway
• Trigeminal nerve

Drug Depots

• Drug depots or silent receptors are Inactive sites where drugs accumulate
• Depot binding: Binding of drug to inactive sites

Drug Elimination

• Drugs are eliminated from the body through: Drug inactivation or biotransformation: Metabolism (liver) Liver Microsomal enzymes: Liver enzymes responsible for metabolizing exogenous substances (i.e., drugs) Excretion through the urine/feces (kidneys)

Enzyme Induction and Inhibition

• Enzyme Induction: Repeated drug use leads to more liver enzymes being produced, resulting in faster metabolism, and can lead to tolerance & cross-tolerance.
• Enzyme Inhibition: Food/drug blocks enzyme activity leading to elevated blood levels of drugs metabolized by enzymes, and the potential for dangerous side effects.

Drug Competition and Clearance

• Drug Competition: Two drugs using the same enzyme compete, slowing metabolism and resulting in higher bioavailability, which could be dangerous.
• Drug Clearance: First-order kinetics: Steady exponential clearance of a drug with more drug resulting in faster clearance (most common). Zero-order kinetics: A drug is cleared at a constant rate, regardless of concentration with all drugs eliminated after 6t1/2

Therapeutic Index (TI)

• Measures drug safety: TI = TD50 / ED 50 TD = Toxic dose ED = Effective dose Higher TI = Safer drug. Narrow TI = Greater risk of toxicity.

Drug Categories

• Stimulants increase arousal, alertness, and well-being.
• Depressants reduce CNS activity, therefore causing relaxation and sedation.
• Analgesics reduce pain perception.
• Hallucinogens induce sensory distortions and altered perception.
• Psychotherapeutics treat mood and behavioral disorders.

Receptors and Ligands

• Receptors = Protein molecules that bind to specific ligands (e.g., hormones, drugs).
• Ligand = Any molecule that binds selectively to a receptor and triggers a biological response.

Agonists and Antagonists

• Agonist: A drug that binds to a receptor and activates it.
• Affinity: The chemical forces that cause a drug to bind to a receptor (higher affinity = more potent).
• Efficacy: The ability of a drug to produce a biological response once bound.
• Antagonist: A drug that binds to a receptor but does NOT activate it (blocks the receptor from other ligands)

Types of Agonists and Antagonists

• Partial Agonist: Binds to a receptor but only partially activates it (lower efficacy than a full agonist).
• Inverse Agonist: Binds to a receptor and produces the opposite effect of an agonist.
• Competitive Antagonist: Competes with agonists for the receptor, reducing the agonist effect.
• Non-Competitive Antagonist: Binds to a different part of the receptor, blocking the agonist effect regardless of dose.
• Physiological antagonism: Two drugs act on different receptors or pathways but produce opposite effects, reducing each other's effectiveness.

Types of Tolerance

• Tolerance: Decreased drug response with repeated use.
• Cross-tolerance: Reduced response to similar drugs in the same class.
• Sensitization (Reverse Tolerance): Increased drug response with repeated use.
• Drug disposition tolerance: Repeated drug use increases the body's ability to metabolize the drug, leading to lower drug levels at the target site and reduced effectiveness (through liver microsomal enzyme induction).

Receptor Downregulation and Upregulation

• Receptor Downregulation (Desensitization): Fewer receptors = Less drug effect, the body reduces the number of receptors to prevent overstimulation, resulting in more drug needed to get the same effect (tolerance)
• Receptor Upregulation (Supersensitivity): More receptors = Increased sensitivity, the body adds more receptors to compensate for reduced activity, the body becomes hypersensitive to the drug once it's taken again.

Dose Response

• Dose-response curve: Biological change in relation to a given dose
• Threshold: Dose that produces the smallest response
• Potency: Amount of drug necessary to produce a specific effect If drug A requires less dosage to achieve the same effect as drug B (with a higher dosage), drug A is more potent

Certain Safety Factor Index (CSFI)

• Dose that is lethal to 1% vs dose that is therapeutically effective in 99% LD1/ED99 Higher CSF = Safer Drug Lower CSF = Riskier Drug

Explore drug action and effects, focusing on molecular and physiological changes. Understand therapeutic versus side effects and specific versus non-specific drug effects. Learn about pharmacokinetics, tolerance, and individual responses to medications.