Pharmacokinetics - Absorption Quiz

Study Notes

Drug movement from administration site into blood occurs via passive diffusion
Influencing factors include concentration gradient, drug size, and lipid solubility
Membrane permeability:
- Uncharged, hydrophobic drugs readily diffuse across lipid bilayers
- Weak acids (HA) dissociate into H+ and A-
- Weak bases (B+) combine with H+ to form BH+
- pH and pKa determine drug form (charged or uncharged)
- Only uncharged forms cross membranes
- pH = pKa + log ([unprotonated form]/[protonated form])
- Example: Antacids (like Tums) raise pH, affecting drug absorption/action

Amount of drug reaching systemic circulation unchanged
F = (amount of drug in systemic circulation) / (amount of drug administered)
IV administration (intravenous) has F = 1 (100% bioavailability)
Oral administration (oral) cannot have F = 1 as GI tract (gastrointestinal tract) can absorb, metabolize, or degrade drug and liver further metabolizes.

Almost all organs metabolize drugs, primarily the liver
Biotransformation makes drugs more polar, allowing easier excretion in urine.
Phase 1: Cytochrome P450 (CYP) enzyme induction/inhibition:
- Enzyme families that add or remove polar groups.
- Enzymes can be induced or inhibited (impact metabolism rates) due to drugs, foods, pregnancy, or disease
- Major cause of drug interactions; adjust dosing may be required
Phase 2: Conjugative enzymes (non-CYP):
- Add large, polar molecules to metabolites (making them easier to excrete)
- Crucial for excretion.
Pregnancy alters P450 enzymes; impact on drug metabolism and effect on fetus.
Placenta has little effect on drug metabolism.
Fetal liver has oxidation reactions only.

Drugs and metabolites are excreted via:
- Bile/feces: Drugs/metabolites secreted into bile ducts, then duodenum
- Breast milk (minor): significant for babies (lower pH than blood)
- Kidneys: Major route for excretion of many polar metabolites.

Specific concentration needed for proper response
Response magnitude depends on dose
Pharmacological effects (e.g., blood pressure changes, pain relief) show drug action.
Plasma drug levels determine duration and toxic effects
Onset of action: time until minimum effect is reached.

Types of response:
- Predictable: desired actions, side effects
- Iatrogenic: unintentional effects
- Unpredictable: drug allergy, hypersensitivity, idiosyncratic reaction
Tolerance: Decreased response to same drug amount
- Cross-tolerance: tolerance to other drugs
- Tachyphylaxis: Rapid tolerance
- Dependence
Drug interactions: Effects of one drug altered by another. Examples involve:
- Antagonism: One drug blocks another's effects
- Summation: Additive effects from multiple drugs
- Synergism: Effects greater than sum of individual drugs
- Potentiation: One drug enhances another's effects
- Interference: Direct biochemical interaction, changing another drug's effect

Age, sex, body mass, environmental milieu, pathological state, genetic factors, and psychological factors.

Variables: intestinal absorption, competition for plasma protein binding, drug metabolism/biotransformation, and renal excretion
Influences from food (e.g., grapefruit juice) and other drugs, altered enzyme activity from smoking/drinking alcohol

Receptors determine drug action and activity (concentration) needed
Receptor-drug coupling involves drug-receptor interactions
Allosteric molecules can affect receptor function without changing agonist concentrations.
Quantitative: Receptors determine the relationship between drug dose and effect (dependent on affinity and number)
Selective: Receptor shape/charge determine drug binding (agonists vs antagonists)
Different receptor types (Lipid soluble drugs acting w/ intracellular receptors, interactions with transmembrane ion channels, interactions with intracellular enzymes) have different functions.

Recognition of signals (typically in target tissue) triggers transduction.
Receptors (proteins) activate signaling cascades, leading to cellular responses.
Signal transduction can be short-term/fast or long-term/slow.

Humans vary in their ability to metabolize drugs.
Drug-drug interactions affect metabolism.
Drug metabolism in humans differs among species.
Drug metabolism phases (phases 1 & 2):
- Phase 1: Introduces functional groups, increasing water solubility; may activate/deactivate drug.
- Phase 2: Modifies the drug to form a more water-soluble conjugate/metabolite, leading to more efficient excretion.
Key enzymes in each phase: CYP’s, FMO’s, UGT’s, SULT’s, GSTs
Drug elimination and excretion are affected by metabolic efficiency and half-life.