Intro to Pharmacokinetics + Absorption PK1 Flashcards
What is pharmacokinetics (PK)?
The study of what the body does to the drug, including absorption, distribution, metabolism, and excretion (ADME).
What is pharmacodynamics (PD)?
The study of what the drug does to the body, including its biochemical and physiological effects.
How do PK and PD differ?
PK = Drug movement in the body (ADME).
PD = Drug action and effect on the body.
Give an example of PK and PD using paracetamol
PK: Absorbed in 30 minutes, 30% bound to plasma proteins, metabolized in the liver, excreted in urine.
PD: Acts as an analgesic (pain reliever) and antipyretic (reduces fever) by inhibiting prostaglandin synthesis.
What is drug absorption?
The process of the drug moving from the site of administration into the bloodstream
What factors affect drug absorption?
Drug-related factors:
Molecular weight (100-400 is ideal).
Lipophilicity (more lipophilic = better absorption).
Ionization (non-ionized drugs cross membranes easier).
Patient-related factors:
pH of GI tract.
Gastric emptying time.
Blood flow to absorption site.
How does the route of administration affect absorption?
Intravenous (IV): No absorption step, direct into blood.
Oral: Absorbed in the GI tract, slower onset.
Topical/Inhalation: Local or systemic effects.
What is drug distribution?
The process of the drug moving from the bloodstream into tissues and organs.
What factors affect distribution?
Blood flow to tissues (e.g., liver, kidneys, brain = high; fat, muscle = low).
Plasma protein binding (e.g., albumin binds acidic drugs).
Lipid solubility (lipophilic drugs cross membranes easier).
What is the volume of distribution (Vd)?
A theoretical value that describes how widely a drug is distributed in the body.
Low Vd = Drug stays in blood (e.g., warfarin).
High Vd = Drug enters tissues (e.g., amiodarone).
What is drug metabolism?
The process of converting drugs into more water-soluble metabolites for easier excretion.
Where does metabolism occur?
Liver (primary site).
Intestines, kidneys, lungs (secondary sites).
What are Phase 1 and Phase 2 reactions in metabolism?
Phase 1 (Functionalization reactions): Oxidation, reduction, hydrolysis (e.g., cytochrome P450 enzymes).
Phase 2 (Conjugation reactions): Glucuronidation, sulfation, acetylation (makes drugs more water-soluble).
What is first-pass metabolism?
When an orally administered drug is metabolized in the liver before reaching circulation, reducing its bioavailability.
Solution? Use IV, sublingual, or rectal routes to bypass the liver.
What is drug excretion?
The removal of drugs from the body, primarily via the kidneys (urine) or liver (bile/feces)
What are the main routes of excretion?
Renal (kidneys): Filtration, secretion, reabsorption.
Hepatic (bile/feces): Some drugs are excreted via bile into the intestines.
Lungs: Volatile drugs (e.g., anesthetics).
What factors affect renal excretion?
Glomerular filtration rate (GFR) (low GFR = less excretion).
Urine pH (acidic urine favors excretion of basic drugs, and vice versa).
What is the plasma concentration-time curve?
A graph showing drug levels in blood over time
Define these key terms:
*cmax, Tmax,MEC, MTC and therapeutic window
Cmax: Maximum plasma concentration of a drug.
Tmax: Time taken to reach Cmax.
MEC: Minimum effective concentration (lowest level needed for effect).
MTC: Minimum toxic concentration (lowest level causing toxicity).
Therapeutic window: The range between MEC and MTC.
What is onset time, duration of action, and intensity?
Onset time: Time to reach MEC (lag period).
Duration of action: Time between MEC and drug falling below MEC.
Intensity: Strength of drug effect (proportional to Cmax).
What are the four main mechanisms of drug transport across membranes?
Passive diffusion (no energy, high → low concentration).
Facilitated diffusion (carrier-mediated, no energy).
Active transport (carrier-mediated, requires ATP, moves against gradient).
Endocytosis (large molecules engulfed by the cell)
What are influx and efflux transporters?
Influx transporters: Move drugs into cells (help absorption).
Efflux transporters: Pump drugs out of cells (reduce absorption, e.g., P-glycoprotein).
What is the partition coefficient (P)
A measure of a drug’s lipophilicity (how easily it crosses membranes).
What does log P tell us?
High log P (>5) = Too lipophilic, poor water solubility.
Low log P (<1) = Too hydrophilic, poor membrane permeability.
Ideal range (1-5) = Good balance for oral drugs
What drug-related factors affect absorption?
Molecular weight (small drugs absorbed better).
Ionization (non-ionized drugs cross membranes easier).
Lipophilicity (more lipophilic drugs cross membranes easier).
What patient-related factors affect absorption?
Gastric pH (acidic pH affects drug stability).
Gastrointestinal motility (slower motility = slower absorption).
Food intake (some drugs need to be taken with/without food).
What is the relationship between increasing P?
by increasing the lipophilicity of a molecule will facilitate its penetration through
membrane barriers and increase its concentration in the blood stream (hence higher absorption)
