L6 - Pharmacokinetics (Flipped) Flashcards
What is pharmacokinetics?
The study of what the body does to a drug
Drug effects depend on…
Pharmacokinetics and pharmacodynamincs
Pharmacodynamics is the….
mechanism of action and effects on cellular functions: eg. receptors, ion channels, enzymes, transporters.
What do the physiochemical properties of a drug affect in phramacokinetics?
Concentration - ADME
Absorption, Distribution, Metabolism, Excretion
What is the diffusion coefficient?
Proportional to 1/sqrt
What is the relationshop between drug size and diffusion coefficient?
The smaller the drug the higher the diffusion cefficient, and the faster it diffuses.
What are some of the barriers in drug absorption?
- The plasma membrane
- epitheilial cells, gastrointestinal mucosa or renal tuble (all consit of a layer of tightly connected cells)
What prevents potentially harmful molecules from leaking from the blood into the organs?
Periendothelial cells or pericytes
What type of transport is important for small molecule drugs?
Diffusion through lipid and carriers, as they dont fit through pores.
What is important for transfer or macromolecules across the BBB?
Pinocytosis.
What in the liver and kidneys can be used for the elimination of drugs?
Carriers involved in the elimination of toxic materials.
Physiochemical properties of a drug that affect absorption
- Lipid Solubility
- Diffusivity
- Diffusion coeffcient
What molecules can move freely in lipids and penetrate cell membranes?
Non-polar/ucharged molecules.
What are 4 routes of drug administration?
- Intravenous - most direct route
- Subcutaneous/Intramuscular - next
fastest route - Intrathecal - A lumbar puncture used to
produce regional
anaesthesia. - Oral - Most absoprtion happens in the gut
by passive diffusion.
What is bioavailability?
How well the fraction of ingested dose gain access to circulation.
Low if absorption is incompleted or drug is metabolised in the gut or by the liver.
What is the OCT2?
Organic Cation Transporter
- A uniporter in proximal tublular cells of
the kidney.
- Also a solute carrier
What drugs does the OCT2 deal with?
Nephrotoxic drugs such as Cisplatin (anticancer drug)
What are the main sites where SLCs (solute carriers) such as OCTs and OATs act?
- The BBB
- The renal tubule
- The GI Tract
- The Biliary tract
- The placenta
What does the effectiveness of a drug depend on?
- Affinity/Efficacy
- Pharmacokinetics
How the drugs is processed in the body depends on?
- Absorption
- Metbolism
- Distribution
- Excretion
What is distribution of a drug dependant on?
permability and lipid solubility.
What is Volume of distribution (Vd)?
- A measure of the volume of fluid that would be required to hold the amount of drug in the body as measured in the plasma.
Vd = Dose/ concentration in plasma.
What molecules can cross the BBB easily
Lipid soluble molecules such as caffine and ethanol.
How are drugs metabolised in the body?
In the liver by 2 biochemical phases
What are the 2 phases of drug metabolism?
Phase 1 - catabolic reactions - can produce
a more reactive compound.
Phase 2 - Syntheic (anabolic) reactions -
involve conjugation to produce
an inactive product.
What does the metabolism of paracetamol produce?
Hepatotoxic molecules
What does the metabolism of Benzodiazapines produce?
long-lived active metabolites
What may products of phase 1 reactions have?
Increased toxicity and carcinogenity.
How are drugs excreted from the body?
- Through urine
- Excretion in milk
- Excretion in air
- Renal excretion - glomerular filtration
- active tubular secretion
- Passive diffusion
What are saturation kinetics?
when the velocity of the reaction increases to a maximal value (plateau) as the concentration of the reactant is increased.
