Untitled Quiz

Pharmacokinetics

• Pharmacokinetics describes what the body does to a drug.
• Four pharmacokinetic properties determine drug action: speed of onset, intensity, and duration.
• Drug administration through various routes leads to absorption, distribution, metabolism, and elimination.

Absorption

• Absorption is the transfer of a drug from its administration site to the bloodstream.
• Absorption rate and efficiency depend on the drug's properties and the route of administration.
• IV drug delivery results in 100% bioavailability.
• Other routes may result in only partial absorption .

Mechanisms of Absorption

• Passive diffusion: Drug movement from high to low concentration across a membrane. Water-soluble drugs go through channels, lipid-soluble drugs cross lipid bilayers.
• Facilitated diffusion: Special transmembrane carrier proteins facilitate drug or molecule passage across cell membranes. It doesn't require energy.
• Active transport: Energy-dependent transport against a concentration gradient using specific carrier proteins that span the membrane.
• Endocytosis / exocytosis: Transport of exceptionally large molecules across the cell membrane.

Factors Influencing Absorption

• Blood flow to absorption site (intestine has a higher blood flow than stomach).
• Total surface area available for absorption (intestine has a much larger surface area).
• Contact time at absorption surface. Fast transit times impair absorption.
• Expression of P-glycoprotein (reduces drug absorption).

Bioavailability

• Bioavailability is the fraction of administered drug reaching systemic circulation.
• Important for calculating drug dosages in non-intravenous routes.
• Affected by administration route and drug properties.

Determination of Bioavailability

• Measured by comparing plasma drug levels after different routes with intravenous injection.
• Area under the curve (AUC) is calculated after plotting plasma concentrations versus time.

Factors Influencing Bioavailability

• First-pass hepatic metabolism.
• Solubility of the drug.
• Chemical instability.
• Nature of the drug formulation (e.g., particle size, salt form, coatings).

Drug Distribution

• Drug distribution is the movement of a drug between intravascular and extravascular compartments (blood/plasma, interstitial fluid, and cells).
• Drugs exist in bound or free form within each compartment.
• Drugs are metabolized and excreted by the liver and kidneys.
• IV administration bypasses drug absorption and immediately enters the distribution phase.

Understanding Drug Distribution

• The amount of drug available at the target organ is crucial.
• Drug distribution to other organs can cause adverse reactions.
• Loading doses account for drug distribution into non-target organs.

Phases of Drug Distribution

• Initial Phase: Drugs first distribute into highly vascular organs (e.g. brain, liver).
• Second Phase: Drugs distribute to less vascular organs (e.g.muscle, skin, fat).

Redistribution

• Movement of a drug from an area of high to low blood flow.
• Lipid solubility of the drug affects redistribution rate (faster for more lipid-soluble).

Factors Affecting Drug Distribution

• Cardiac output and blood flow.
• Capillary permeability.
• Plasma protein binding.

Plasma Protein Binding

• Some drugs bind to plasma proteins (e.g., albumin, alpha-1-acid glycoprotein).
• Only unbound drug can leave the vascular system.
• The concentration of bound and unbound drug influences distribution.

Tissue Binding

• Drugs can bind to tissue proteins and phospholipids acting as reservoirs.
• Prolongs drug half-life and can lead to tissue toxicity.

Volume of Distribution (Vd)

• Represents the ratio of total amount of drug to plasma concentration.
• aVd (apparent volume of distribution) indicates how a drug distributes within the body compared with plasma concentration.

Factors Affecting Volume of Distribution

• Drug factors: molecular size, charge, pKa, affinity to tissue proteins, lipid solubility, aqueous solubility.
• Patient factors: age, gender, pH, protein levels, displacement, pregnancy, edema.

Effect of Vd on Drug Half-life

• Larger Vd implies more distribution to tissues, resulting in a longer half-life.
• The rate of drug elimination in some cases depends on which organs it is delivered to.

Estimating the Loading Dose

• Apparent volume of distribution helps determine the loading dose.
• Drugs with larger volumes of distribution often require higher loading doses.

Drug Distribution to Fetus/Newborn

• Drug distribution to the fetus/newborn depends on lipid solubility, plasma protein binding, and pKa of the drug.
• Fetal pH is lower than maternal, and weak bases can accumulate in the fetus.

Drug Distribution to Breast Milk

• pH and lipid concentration of breast milk can influence drug distribution.
• The drug's pKa, plasma protein binding, and molecular weight are factors influencing distribution.

Metabolism

• Metabolism is the chemical alteration of a drug by various bodily systems.
• Creates compounds that are more easily excreted (metabolites).
• Occurs in liver, kidneys, lungs, etc.

Phases of Metabolism

• Phase I: Converts lipophilic drugs to hydrophilic drugs by adding polar functional groups (e.g., hydroxylation, oxidation).
• Phase II: Conjugates hydrophilic drugs with larger polar molecules (e.g., glucuronidation, sulfation) to increase water solubility.

Types of Metabolites

• Active: Have therapeutic effects.
• Inactive: Have no therapeutic or toxic effect.
• Toxic: Can have harmful effects.

Factors Influencing Drug Metabolism

• Age: P450 activity and enzyme production reduce with age.
• Gender: Males generally metabolize faster.
• Liver size and function: Liver disease or smaller liver reduce metabolism.
• Body temperature: Fever reduces the activity of metabolizing enzymes.
• Diet: Food can induce or inhibit P450 enzyme activity.
• Genetics: Polymorphisms in drug metabolism genes can affect drug metabolism.
• Environmental factors: Exposure to certain substances like pesticides and smoke alters metabolism.

Drug Clearance

• Elimination of drugs can be through metabolism and excretion.
• Kidney clearance is a main method for drug removal.

Renal Elimination

• Drugs enter through renal arteries and form capillaries.
• Small molecular weight, unbound drugs are filtered.
• Active secretion and passive reabsorption in the proximal and distal tubules.

Hepatobiliary Elimination

• Drug metabolites and larger compounds are eliminated via the liver's biliary system.
• Drug glucuronide is an example.
• Enterohepatic recirculation may exist.

Clearance by Other Routes

• Feces, lungs, and milk (nursing mother) can be routes of elimination.
• Excretion of drugs into sweat, saliva, tears, hair, and skin is minimal.

Clinical Situations Affecting Clearance

• Changes like decreased liver or kidney function impact drug clearance resulting in dosage adjustments.

Kinetics of Elimination

• Drugs are removed in first-order or zero-order kinetics.
• Half-life is the time it takes for drug concentration to decrease by half.
• Some drugs can exhibit variable kinetics.

Important Formulas

• CL = 0.693 * Vd / t1/2

• This formula is important for calculating drug clearance, given the half-life and volume of distribution(vd) in the body. Vd is typically constant for many drugs and the equation can be used to estimate how quickly a drug is removed from the body.