Pharmacokinetics / Pharmacodynamics Flashcards
Describe absorption
Peak plasma concentration and time within the body depends
on rate of entry of drug and first pass metabolism
Systemic rate of entry of drugs into the body can depend on: • GI motility • Splanchnic Blood Plow • Molecular Size • pH levels
Define bioavailibility
What can it be affected by
Give an equation to express bioavailibiltiy
amount of drug which reaches the systemic circulation in an unchanged form, relative to that if administered via IV
can be affected by first-pass metabolism, intestinal motility, age, or drug preparation
= Amount of drug reaching systemic circulation /
Total amount of drug administered
Oral bioavailability = AUCoral / AUCintravenous
What are the 4 main stages in pharmacokinetics
Absorption
Distribution
Metabolism
Elimination
Define distribution
What is affected by
refers to a drugs ability to “dissolve in the body”
This is mainly affected by Drug lipophilicity / hydrophilicity:
Lipophilic drugs will mainly distribute throughout the body’s tissues
whereas hydrophilic drugs will mainly stay in the plasma
Also affected by Protein binding:
(Changes can occur in hypoalbuminaemia, pregnancy, renal failure, or displacement by other drugs)
Define volume of distribution (Vd)
The apparent volume of fluid in which total dose of drug distributed @ same conc as in plasma
(a measure stating how well drugs distribute throughout the body compartments)
As a result:
high lipid solubility/low plasma binding = high Vd
low lipid solubility/high plasma binding = low Vd
(Passive movement of drugs between the fluid compartments is
determined mainly by lipophilicity)
Useful in dosing calculations, such as loading dose
normally expressed in L/kg, yet can be
expressed just in litres under the assumption of a health 70kg
individual
When can acute increases of volume of distribution be seen
In sepsis (due to increase in vascular permeability)
Concurrent drugs (binding sites are taken up by other drugs)
Hypoalbuminaemia (amount of unbound drug in the plasma
increases, which moves from plasma to other compartments)
What is the equation to calculate volume of distribution
What does this mean
Vd (L/kg) =
Total amount of drug in body / Plasma Concentration of Drug (at time0)
larger the Vd= more the drug distributes throughout the body.
Vd proportional to t1/2 of the drug
Drugs that are:
confined to the plasma compartment = Vd of around 0.1 L/kg
confined to the extracellular fluid = 0.4 L/kg
throughout the body water = > 1.1 l/kg
Define drug metabolism & describe the two phases
the enzymatic conversion of one chemical entity to another
It can be broken down into:
• Phase I reactions: catabolic (e.g. oxidation, reduction, or hydrolysis), producing products that are chemically reactive (a ‘point of attack’ for the conjugating system)
• Phase 2 reactions: anabolic and involve conjugation,
normally resulting in inactive products produced
Define first pass metabolism
Any metabolism that occurs to the drugs prior to entering the systemic circulation
Mainly occurs via portal system and the liver
Can also occur:
• Within the gut lumen (e.g. Proteolytic enzymes)
• Gut wall (e.g. Efflux pumps)
List some CYP enzyme inducers & inhobitors
Inducers - CRAP GPS: Carbemazipines (anticonvulsant/analgesic) Rifampicin (antibiotic) Alcohol (chronic) Phenytoin (anticonvulsant) Griseofluvin (antifungal) Phenobarbitone (anti-epileptic) Sulphonylureas (anti-diabetic)
Inhibitors - SICK FACES. COM: Sodium valporate (anti-convulsant) Isoniazid (TB: bactericidal) Cimetidine (H2 receptor antagonist) Ketoconazole (antifungal) Fluconazole (antifungal) Alcohol (binge) Chloramphenicol (antibiotic) Erythromycin (antibiotic) Sulfonamines (antibiotic) Ciprofloxacin (antibiotic) Omeprazole (PPI) Metronidazole (antibiotic/antiprotozoal) & grapefruit juice
Elimination: what is clearance affected by
HRH factors:
Heart: CVS factors affecting blood flow to organs
Renal factors: affecting renal clearance
Hepatic factors: affecting hepatic elimination
How are drugs transported from the plasma to the kidneys for clearance
Organic Anion and Cation Transporters (OAT and OCT) act as renal
transporters transporting drugs from the plasma to the nephron
lumen
Define half life & the equation used to calculate it
the amount of time over which the concentration a drug in plasma decreases to once half of the concentration value it had when measured
Also affected also by HRH factors
Half life is calculated as a result by:
tl/2 = 0.693 x Vd / clearance
Define zero order kinetics
Non-linear
Rate of elimination is constant
No t1/2 can be defined
Drug monitoring is essential
Define first order kinetics
Linear
Rate of elimination proportional to drug level
Half life can be defined
