Pharmacology Drug Absorption Quiz

General Pharmacology

• Pharmacology is the science of drugs.
• Drugs are substances used to prevent, diagnose, and treat diseases.

Pharmacokinetics

• Pharmacokinetics describes what the body does to a drug.
• This includes absorption, distribution, metabolism, and excretion (ADME).

Absorption

• Absorption is the passage of a drug from the site of administration to systemic circulation.
• Mechanisms of drug absorption include passive diffusion.
  • Passive diffusion is the most common and important mechanism by which drugs cross biological membranes. This involves movement of water-soluble drugs across aqueous pores and lipid-soluble drugs across the cell membrane.
• Other mechanisms of drug absorption include carrier-mediated transport.
  • Facilitated diffusion: This process does not require energy, and the drug moves along a concentration gradient, assisted by a carrier protein.
  • Active transport: Energy (ATP) is needed, and the drug moves against a concentration gradient, using a carrier protein.
• Another mechanism for absorption is endocytosis and exocytosis, where a drug of high molecular weight binds to the cell membrane and gets enclosed for movement into or outside the cell.

Factors Affecting Absorption (Patient-Related)

• Route of administration: IV and inhalation are faster than IM, SC, oral and topical.
• Absorbing surface: Skeletal muscle has higher vascularity than subcutaneous tissue, while the intestine has more surface area than the stomach.
• Pathological conditions: Conditions like diarrhea can decrease oral absorption.

Factors Affecting Absorption (Drug-Related)

• Water and lipid solubility: More lipid-soluble drugs are absorbed easier.
• Valency: Ferrous iron (Fe++) is absorbed better than ferric iron (Fe+++).
• Nature: Inorganic compounds are generally absorbed better than organic compounds.
• Pharmaceutical preparations: Different dosage forms like solutions are better absorbed than suspensions or tablets. Excipients like calcium (Ca++) can decrease absorption of some drugs.
• Ionization of the drug: Unionized drugs are more lipid soluble and absorbed easily.

Factors Affecting Absorption (Additional)

• Systemic circulation: Shock can decrease absorption.
• Specific factors: Intrinsic factor is crucial for vitamin B12 absorption.
• Coadministration factors: Other drugs and food can affect absorption, including adrenaline, which can reduce local anesthetic absorption and calcium reducing tetracycline absorption

The Effect of pH on Drug Ionization

• Most drugs are weak acids or bases.
• Weak acids are better absorbed in acidic environments (low pH), while weak bases are better absorbed in alkaline environments (high pH).
• The pH at which the ionized and unionized forms of a drug are equal is the pKa.
• A smaller pKa value indicates a stronger acid, while a larger pKa value indicates a weaker acid.

Bioavailability

• Bioavailability is the percentage of a drug reaching systemic circulation and available for biological effect.
• Factors affecting bioavailability include:
  • Extent of drug absorption
  • Route of administration (e.g., IV has 100% bioavailability)
  • First-pass effect (metabolism of a drug before it reaches systemic circulation, e.g., in the liver or intestines)

Drug Distribution

• After absorption, drugs are distributed to one or more body compartments.
• Compartments include vascular, vascular and interstitial, and vascular, interstitial, and intracellular compartments.
• Factors affecting drug distribution involve:
  • Blood flow – delivery to an organ is proportional to blood flow
  • Lipophilicity – affects the ability of drug to cross cell membranes
  • Plasma protein binding – drugs exist in bound (inactive) and free (active) forms, impacting distribution
  • Binding to tissues – drug accumulation in particular tissues like the thyroid

Blood-Brain Barrier (BBB) and Placental Barrier

• BBB: Only lipid-soluble drugs can pass due to the structure of capillaries in the brain. Inflammation can increase permeability.
• Placental barrier: Drugs that pass the barrier can affect the fetus during pregnancy (teratogenicity) or during labor (neonatal asphyxia).

Drug Metabolism (Biotransformation)

• Key importance of metabolism is converting unionized drugs into ionized, water-soluble metabolites for easier excretion.
• The liver is the primary organ, but metabolism can also occur in other organs like lungs, kidneys, and intestines.
• Consequences of drug metabolism include:
  • Converting active drugs to inactive metabolites.
  • Converting inactive prodrugs to active drugs.
  • Converting active drugs to active metabolites.
  • Converting drugs to toxic metabolites (e.g., paracetamol to hepatotoxic epoxides).

Factors Affecting Biotransformation

• Physiological changes (age, sex)
• Pathological factors (e.g., liver cell failure)
• Enzyme induction/inhibition

Drug Excretion

• The kidney is the primary organ for drug excretion, with excretion happening via glomerular filtration, proximal convoluted tubules (PCT), and distal convoluted tubules.
• Other sites of excretion include bile and lungs.

Elimination Half-Life

• Elimination half-life (t1/2) is the time it takes for the plasma concentration of a drug to reduce to half of its initial concentration.
• The importance of half-life relates to determining dosing intervals. Short half lives result in frequent dosing, whereas long half-lives allow for less frequent dosing.