Absorption, Distribution (and Drug Delivery Systems) Flashcards
List the factors that affect absorption of a drug from the GI tract
The absorption of a drug from the gastrointestinal (GI) tract depends on several key factors:
Drug Properties:
Solubility: Lipid-soluble drugs absorb more easily than water-soluble ones.
Molecular Size: Smaller molecules are absorbed more efficiently.
Ionization: Non-ionized drugs cross membranes more easily, with absorption influenced by pH and the drug’s pKa.
Formulation: The physical form of the drug (e.g., tablet vs. liquid) impacts absorption rates.
Stability: Drugs may be degraded by stomach acid or enzymes before absorption.
Physiological Factors:
Gastric Emptying: Delayed gastric emptying can slow drug absorption.
GI Motility: Faster motility (e.g., diarrhea) can reduce absorption time, while slower motility (e.g., constipation) may increase absorption.
Food: Food can delay absorption, alter pH, or interact with the drug, enhancing or inhibiting absorption.
Blood Flow: Reduced blood flow (e.g., in shock or heart failure) can decrease absorption efficiency.
Enzymatic Activity: Enzymes may metabolize drugs before they are absorbed (e.g., first-pass metabolism in the liver).
Surface Area: The large surface area of the small intestine aids absorption; diseases or surgery that reduce surface area can hinder it.
Site of Absorption:
Most absorption occurs in the small intestine due to its large surface area and neutral pH, while the stomach is more suited for drugs that require an acidic environment.
Transport Mechanisms:
Active transport proteins and efflux pumps in the GI tract can influence the rate and extent of drug absorption.
Age and Health:
Age: Infants and the elderly may have altered GI conditions affecting drug absorption.
Health Conditions: Conditions like liver disease, gastrointestinal disorders, or infections can impair absorption.
Genetic Factors:
Genetic variations in transporters and enzymes can affect drug absorption and metabolism.
Drug-Drug Interactions:
Certain drugs can enhance or inhibit the absorption of others by altering GI conditions (e.g., pH or motility).
Discuss the medical importance of first pass metabolism.
First-pass metabolism refers to the process where a drug is significantly metabolized in the liver or gut wall before reaching systemic circulation, reducing its bioavailability. This has important medical implications:
Dosage and Route of Administration: Drugs with high first-pass metabolism often require higher oral doses or alternative routes (e.g., sublingual, intravenous) to bypass the liver and achieve therapeutic effects. For example, nitroglycerin is given sublingually because it is extensively metabolized in the liver when taken orally.
Drug Formulation: Drugs subject to first-pass metabolism may be formulated in ways (e.g., extended-release or sublingual forms) to enhance absorption and efficacy.
Liver Dysfunction: In patients with liver disease, first-pass metabolism may be impaired, increasing the drug’s bioavailability and potential toxicity. Conversely, liver enzyme induction (e.g., by alcohol or certain drugs) can speed up metabolism, requiring higher drug doses.
Drug Interactions: Drugs that inhibit or induce liver enzymes can affect the first-pass metabolism of other drugs, altering their effectiveness or risk of toxicity.
Prodrugs: Some drugs are inactive until metabolized in the liver (e.g., codeine, which is converted to morphine), relying on first-pass metabolism for activation.
Discuss the benefits of intravenous, topical and inhaled medication
Intravenous (IV) is ideal for rapid action, precise dosing, and drugs with poor oral bioavailability or in emergency situations.
Topical medications provide localized treatment with minimal systemic side effects, ideal for skin or mucosal conditions.
Inhaled medications offer rapid onset and high local concentration for treating respiratory diseases with minimal systemic side effects.
Describe what is meant by bioavailability and the factors that affect it, including protein-binding
Bioavailability refers to the proportion of a drug that reaches systemic circulation in its active form after administration. It is important in determining the correct dosage and route of administration. Several factors influence bioavailability:
First-pass metabolism: Drugs taken orally are metabolized in the liver before reaching circulation, reducing their bioavailability. IV drugs bypass this and have 100% bioavailability.
Drug properties: Solubility, molecular size, and ionization affect how easily a drug is absorbed in the gastrointestinal tract.
GI factors: Gastric pH, blood flow, and motility influence absorption. Food and other substances can alter these factors.
Absorption: The drug’s ability to pass through the gut wall and enter the bloodstream impacts bioavailability.
Enzymes and transporters: Enzymes in the gut and liver, as well as efflux pumps (e.g., P-glycoprotein), can reduce bioavailability by metabolizing or expelling the drug before it is absorbed.
Protein binding: Drugs bind to plasma proteins (like albumin), and only the free, unbound fraction is active. Low protein levels (e.g., in liver disease) can increase free drug levels, potentially increasing effects or toxicity.
Define the following terms: Cmax, tmax, AUC, zero order, first order, t1/2, Vd, clearance (and recognise their importance in understanding the safety and efficacy of
medications)
Cmax: The peak drug concentration in the bloodstream. High Cmax may indicate potential toxicity, while a sufficiently high Cmax is needed for efficacy.
tmax: The time it takes to reach Cmax. Faster tmax is important for quick onset of action, but delayed tmax may be useful for sustained release formulations.
AUC (Area Under the Curve): Represents total drug exposure over time. A higher AUC indicates greater exposure, which can increase efficacy but also the risk of toxicity.
Zero Order Kinetics: The drug is eliminated at a constant rate, regardless of concentration. Can lead to accumulation and toxicity if dosing is too frequent.
First Order Kinetics: Drug elimination is proportional to its concentration. This allows for more predictable drug levels, supporting consistent efficacy and reducing overdose risk.
t1/2 (Half-Life): The time it takes for the drug concentration to reduce by half. A longer half-life means less frequent dosing, but may increase toxicity if not managed properly.
Vd (Volume of Distribution): Indicates how widely the drug is distributed in the body. A higher Vd means the drug is more tissue-bound, with lower plasma concentration, which may reduce efficacy.
Clearance: The rate at which the drug is removed from the body. Lower clearance (due to liver or kidney dysfunction) can increase drug levels, risking toxicity, while higher clearance may require more frequent dosing.
Understanding these parameters helps clinicians manage drug dosing, predict therapeutic effects, and minimize the risk of toxicity or inefficacy in treatment.
Describe specific barriers to drug distribution (blood-brain, placental, testis)
- Blood-Brain Barrier: Tight junctions between endothelial cells and efflux pumps prevent most drugs from entering the brain. Lipophilic drugs can cross more easily.
- Placental Barrier: The trophoblast layer acts as a filter. Lipophilic drugs and small molecules pass through, while large or highly charged molecules have difficulty crossing.
- Blood-Testis Barrier: Tight junctions between Sertoli cells protect germ cells in the seminiferous tubules, limiting the passage of large molecules or those that are not lipid-soluble.
