Basic Pharmacology Concepts

PHARMACODYNAMICS (how a drug exerts it effect on the body)

Drug-receptor theory (a fundamental concept)

• Each drug binds to a specific receptor on or in the cell (i.e. drugs from other classes won't bind)
• Binding of the receptor results in a specific response (each and everytime)
• The degree of response is proportionate to the receptors bound (until it reaches a maximum)

Receptors

• Receptors are typically protein molecules with a specific conformation (shape)
• Receptors are constantly recycled and synthesised
• Drug-receptor fits like lock and key.

Important terms

• Agonist = drug that when binds to the receptor activates a response
• Antagonist = drug that when binds to a receptor prevents a response occurring
• Competitive (reversible) antagonist = antagonist that does not bind permanently to receptor
• Non-competitive (irreversible) antagonist = antagonist that binds permanently to receptor (until that receptor is metabolised)


• Efficacy = the potential for a drug to exert maximal response
• Potency = the amount of drug required to exert its maximal response
• Full agonist = a drug that is able to elicit a maximal response (if given in adequate dose) = high efficacy
• Partial agonist = a drug that is only able to elicit a sub-maximal response (even with adequate dose) = low/moderate efficacy

Secondary messengers

• A set of biochemical pathways that are activated when a drug binds a receptor
• Maintains and amplifies the signal because the components are recycled even though the receptor remains bound
• The final pathways results in activation of the physiological response
  
  Examples - cAMP, GMP, DAG-IP3

Types of side effects (adverse drug reaction)

• Pharmacological - an extension of the pharmacologic effect of the drug
• Idiosyncratic - occurs only in isolated individuals and often unpredictable
• Allergic - due to a hypersenstivity immune reaction

PHARMACOKINETICS (what happens to the drug after it is administered)

Four major processes

• Absorption - from site of administration (oral, intramuscular, intravenous etc)
• Distribution - to different organs and tissues
• Metabolism - into (usually) inactive metabolites
• Excretion - of drugs and metabolites out of the kidney

Drug related

• Molecular weight (small molecules cross membranes more easily)
• Charge / Ionisation / Lipid solubility (uncharged, lipid soluble molecules cross membranes easier)
• pKa (the pH of body fluids will affect how much of that drug is ionised)

Body related

• Blood flow to the site (more flow = ^rate of drug movement)
• Lipid content of the site (e.g. fat > muscle)
• Organ function / health

Clinical examples

• Absorption: inadequate blood flow to the gut may slow the absorption and rapidity of drug entering the body, some drugs bind to food and may not be absorbed adequately
• Distribution: some drugs will be distributed unevenly to different organs initially before their concentration equalise. Toxic effects may occur if the dose is administered too quickly.
• Metabolism: liver disease is a common cause of slowed metabolism of medication and may require a dose adjustment to prevent toxicity
• Excretion: kidney disease may result in accumulation of drug since this is a common route of excretion