Pharmacokinetics Flashcards
What must happen before drug absorption?
Administration
What is drug absorption?
The passage of a drug from the site of administration into the bloodstream.
The faster the drug crosses the membrane, the better the drug absorption.
Determining how much of the drug gets into the bloodstream.
What must the drug cross to get absorbed in the body?
cellular barriers, specifically lipid membranes.
What is simple(passive) diffusion in drug absorption?
Drug moves from an area of high concentration to an area of lower concentration through a semi-permeable membrane.
What are the main factors determining the rate of passive diffusion?
lipid solubility
concentration gradient
What are the properties of carriers in facilitated diffusion?
Carriers are selective
saturable
do not require energy
What facilitated diffusion in drug absorption?
Drug moves by binding to carriers and moves from high concentration to a low concentration.
What is Pharmacokinetics?
The study of effect of living systems or the body on drugs.
What are the four main processes involved in pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
What is active transport in drug adsorption?
Drugs move by binding to specific carriers and can move against a concentration gradient
What are the properties of carries in active transport?
Carries are selective
saturable
need energy
What is endocytosis in drug absorption?
Engulfment of the drug by the cell membrane
Transported into the cell by pinching off a drug-filled vesicle.
needs energy
What factors influence drug absorption?
1.Effect of pH on the drug
2. Blood flow to the absorption site
3. Total surface area available for absorption
4. Rate of gastric emptying
How does pH affect drug absorption?
Acidic drugs are better absorbed in an acidic environment (e.g., stomach).
Alkaline drugs are better absorbed in an alkaline environment (e.g., intestines).
The state of ionization (charge) determined by pH affects absorption, with uncharged/non-ionized drugs diffusing across lipid membranes more readily.
How does blood flow to the absorption site affect drug absorption?
Higher blood flow to a specific site increases absorption. For example, the intestines have higher blood flow compared to the stomach, making absorption more efficient in the intestines.
How does the total surface area available for absorption affect absorption?
Higher surface area of absorption site leads to more absorption. For example, the intestine has a surface area 1000 times greater than the stomach, making absorption more efficient in the intestine.
What is gastric emptying and how does it affect the drug absorption?
The rate of gastric emptying is how quickly stomach contents move to the small intestines.
It is affected by various factors such as drugs (e.g., metoclopramide speeds up gastric emptying) and viral infections.
What is bioavailability?
The fraction of the ingested dose of a drug that gains access to the systemic circulation.
Fraction of unchanged drug reaching the systemic circulation following administration by any route
What is drug distribution?
Reversible transfer of a drug between the blood and extravascular fluids and tissues of the body. (e.g. fat, muscle, brain)
where are lipid insoluble drugs mainly confined?
plasma and interstitial fluid
What factors affect drug distribution?
Regional blood flow
Capillary permeability
Drug properties (lipophilicity, volume of distribution, binding to plasma protein)
where do lipid soluble drugs distribute?
they reach all compartments and may accumulate fat
what is volume distribution?
the proportionality factor between the amount of drug in the body and the amount of drug in the plasma
what are the major compartments for drug distribution?
Plasma (5% of body weight)
Interstitial fluid (16%)
Intracellular fluid (35%)
Transcellular fluid (2%)
Fat (20%)
what types of drugs are mainly confined to the plasma compartment?
lipid-insoluble, large molecular weight, and highly protein-bound drugs (e.g. heparin)
what types of drugs pass into the interstitial fluid?
drugs with low molecular weight and hydrophilic properties (e.g. gentamicin)
what types of drugs move into the intracellular fluid?
drugs with low molecular weight and lipophilic properties (e.g. ethanol)
What is drug metabolism?
chemical alterations in the drug structure by specific enzymatic processes in the body(biotransformation)
what are the objectives of drug metabolism?
Transform lipophilic drugs into more polar, readily excretable products.
Produce drug metabolites that are more ionized and easily excreted.
where can drug metabolism occur?
liver (main site)
kidneys
muscle tissue
intestinal wall
lungs
skin
blood
what reactions are involved in phase 1 metabolism?
oxidation, reduction and hydrolysis reactions
what is first pass metabolism?
the process where an orally administered drug enters the liver and undergoes extensive biotransformation, reducing its bioavailability
what reactions are involved in phase 2 metabolism?
conjugation reactions, glucuronidation, acetylation and sulfation.
what is enterohepatic circulation?
some conjugated drug products are excreted via bile, reactivated in the intestine by bacteria and the reabsorbed.
what is drug excretion?
the process whereby drugs or metabolites are irreversibly transferred from the internal to external environment through renal or non-renal routes.
what are the types of drug excretion?
renal excretion
biliary excretion
pulmonary excretion
salivary excretion
mammary excretion
skin/dermal excretion
gastrointestinal excretion
what is the half-life (t1/2) of a drug?
The time taken for the concentration of a drug to decrease to half (50%) of its starting dose in the body.
why is the half-life of a drug important?
it helps determine how frequently a drug should be administered, as different drugs have different half-lives.
what is first-order kinetics?
A chemical reaction where the rate of elimination is directly proportional to the concentration of the drug?
what is the onset of action?
the time interval from when the drug is administered to when its therapeutic effects begin
what is zero-order kinetics?
drugs undergo constant elimination regardless of the plasma concentration
what is the duration of action?
the length of time that a drug produces its therapeutic effect
what is the peak effect?
the maximum concentration of a drug that is reached in the body
what is the therapeutic index?
the ratio of the dose that exerts a toxic effect in 50% of the population (TD50) to the dose of a drug that exerts a therapeutic/ effective response (ED50) to 50% in the population (TI=TD50/ED50)
What does the therapeutic index represent?
It represents the safety margin of a drug for clinical use. A higher therapeutic index is better, indicating a wide margin between effective and toxic doses. Drugs with a narrow therapeutic index have a higher risk for toxicity.
