Pharmacokinetics: ADME

• Pharmacology involves studying drugs and how they affect living things
• Pharmacology includes pharmacokinetics, pharmacodynamics, adverse effects, therapeutic uses, and drug actions.

Pharmacokinetics

• Pharmacokinetics is what the body does to drugs
• It includes absorption, distribution, metabolism (or biotransformation), and excretion which is often shortened to ADME
• Absorption refers to when a drug enters the bloodstream from where it was administered
• Absorption depends on how the drug is administered, what the drug is made of, blood flow, and gastrointestinal (GI) function
• Bioavailability refers to how much of a drug reaches the blood stream
• Intravenous drug administration results in 100% bioavailability
• Distribution refers to when the drug spreads throughout the body
• Distribution depends on blood flow, tissue binding, and the drug's physical and chemical traits
• Volume of distribution (Vd) is a theoretical volume for how much a drug distributes
• A large Vd value means the drug spreads into tissues more, while a small Vd means it stays in the bloodstream
• Metabolism (biotransformation) means the body is chemically modifying a drug
• The liver is the primary location of drug metabolism
• Enzymes, like cytochrome P450 (CYP450) enzymes, are important for drug metabolism
• Metabolism can activate, inactivate, or change the toxicity of a drug
• Prodrugs are inactive until metabolized
• Excretion is the body removing a drug or its metabolites
• Kidneys are key excretion organs
• Drugs can also be excreted through bile, feces, sweat, and breath
• Clearance is the rate of removing a drug from the body
• Half-life (t1/2) refers to how long it takes for a drug's plasma concentration to decrease by 50%
• Half-life determines dosing intervals and time to reach steady state
• Steady state is reached after about 4-5 half-lives

Pharmacodynamics

• Pharmacodynamics refers to what drugs do to the body
• It involves how the drug works on target cells, tissues, and organs
• Receptors are cellular macromolecules that drugs bind to for an effect
• Agonists bind to a receptor and activate it, causing a response
• Antagonists bind to a receptor but do not activate it, and they block agonists
• Affinity is the measurement of how strongly a drug binds to a receptor
• Efficacy is the maximum effect a drug can produce
• Potency refers to how much of a drug is needed for a given effect
• A more potent drug creates an effect at a lower dose
• Dose-response relationships describe how the dose of a drug relates to the effect
• Therapeutic index (TI) measures a drug's safety
• It is calculated as the toxic dose to the effective dose ratio (TD50/ED50)

Adverse Effects

• Adverse effects are unintended and undesirable effects of a drug
• Side effects are predictable and often unavoidable effects that occur at therapeutic doses
• Toxic effects come from excessive doses or prolonged drug use
• Allergic reactions are immune-mediated responses to a drug
• Anaphylaxis is a severe, life-threatening allergic reaction
• Idiosyncratic reactions are unpredictable and unusual drug responses
• Drug interactions occur when one drug affects the activity of another drug
• Interactions can be pharmacokinetic (affecting ADME) or pharmacodynamic (affecting drug action)
• Teratogens are drugs that can cause birth defects

Therapeutic Uses

• Therapeutic uses are the conditions a drug treats, prevents, or diagnoses
• Indications refer to the specific conditions a drug is approved to treat
• Contraindications are conditions where a drug should not be used
• Off-label use refers to using a drug for a non-approved condition
• Tolerance is a decreased response to a drug over time, requiring higher doses for the same effect
• Dependence is when the body requires a drug to function normally
• Withdrawal symptoms appear when the drug is stopped after prolonged use

Drug Actions

• Drug actions refer to how drugs create their therapeutic effects
• Drugs can affect receptors, enzymes, ion channels, and transport proteins
• Receptor agonists stimulate receptors, like endogenous ligands
• Receptor antagonists block receptors, preventing endogenous ligands or agonists from binding
• Enzyme inhibitors block enzymes, reducing the production of certain molecules
• Ion channel blockers block the flow of ions through ion channels and affect cellular excitability
• Transport protein inhibitors block molecules across cell membranes
• Some drugs directly interact with DNA or other cellular components
• Placebo effects are psychological or physiological effects from taking a placebo
• Nocebo effects are negative effects from taking a placebo or expecting a negative outcome