Pharmacokinetics Flashcards
What is pharmacokinetics?
Pharmacokinetics is the study of what the body does to the drug, encompassing absorption, distribution, metabolism, and excretion (ADME).
What does the PK-PD correlation describe?
It describes the relationship between plasma drug concentration and drug effects, including pharmacological and adverse effects.
What are the routes of drug administration?
Enteral (GI-related): Oral, sublingual, rectal.
Parenteral: Intravenous (IV), intramuscular (IM), subcutaneous, transdermal, inhalation, nasal, topical.
How is bioavailability (F) calculated?
What factors affect drug absorption?
Drug factors: Physicochemical properties, dosage form.
Patient physiology: Gastric emptying rate, GI motility, disease state.
Other factors: Food or drug interactions.
Why are small intestines the main site for absorption?
hey have a large surface area, good blood flow, and long residence time (~4 hours).
What is the apparent volume of distribution (Vd)?
Vd is the theoretical volume in which a drug disperses. It influences drug dose and is calculated as A/C0 where A is the drug dose and C0 is initial plasma concentration.
What factors affect drug distribution?
Body size.
Lipid solubility of the drug.
Tissue vs. plasma protein binding.
Disease states.
What are the two types of drug binding?
Plasma protein binding: Extends action duration; affected by drug interactions (e.g., valproic acid as a displacer).
Tissue binding: Slows elimination; occurs in fat and muscle.
Where does most drug metabolism occur, and what is first-pass metabolism?
The liver is the major site. First-pass metabolism occurs when orally administered drugs are metabolized before reaching systemic circulation.
Distinguish between Phase I and Phase II metabolism.
Phase I: Functionalization via oxidation, reduction, or hydrolysis.
Phase II: Conjugation with endogenous molecules like glucuronic acid.
What are the effects of drug metabolism?
Metabolic inactivation: Converts active drugs to inactive metabolites (e.g., phenobarbital).
Metabolic bioactivation: Converts prodrugs to active drugs (e.g., L-DOPA to dopamine).
Metabolic toxicity: Produces toxic metabolites (e.g., NAPQI from paracetamol).
What is the role of cytochrome P450 enzymes?
Family of enzymes (e.g., CYP1, CYP2) responsible for biotransformation.
Exhibits genetic polymorphisms affecting drug metabolism.
How can drug metabolism be altered?
CYP enzyme inhibition: Fluoxetine inhibits CYP2D6, increasing propranolol levels.
CYP enzyme induction: Rifampicin induces CYP3A4, reducing midazolam levels.
Influenced by genetics, age, and liver pathology.
What are the major and minor routes of drug excretion?
Major: Urine (renal), bile (hepatobiliary), feces (fecal), expired air (pulmonary).
Minor: Sweat, saliva, milk, tears.
How does renal clearance (CLR) work, and how is it calculated?
Renal clearance refers to the volume of plasma cleared of a drug by the kidneys.
CL R = C/(U×V)
where
U is urine concentration
V is urine volume/time
C is plasma concentration.
What is drug elimination half-life (t1/2), and how is it calculated?
It is the time for plasma concentration to drop by 50%.
t1/2 = 0.693 x (Vd/CL) .
What are the renal processes involved in drug excretion?
Glomerular filtration: Passively filters drugs <40,000 Da. Protein-bound drugs are not filtered.
Active secretion: Actively transports drugs (e.g., penicillin).
Passive reabsorption: Non-ionized drugs are reabsorbed; polar metabolites are not.
What assumptions are made in the one-compartment model?
The body is a single, homogeneous compartment with instantaneous and even drug distribution.
What type of drugs is the one-compartment model applicable to?
Hydrophilic drugs like aminoglycosides.
What are the uses of compartment models in PK?
They describe drug distribution and elimination patterns mathematically.
What influences dosing frequency?
Clearance (CL), which combines renal, hepatic, and other organ-specific clearances
CLtotal = CLR + CLH + CLothers
When is drug elimination considered complete?
After 4-5 half-lives.
