Exam PK Q Flashcards
Define pharmacokinetics
Pharmacokinetics is the study of what the body does to the drug, how the drug is handled as it moves through the body
absorption
(Movement of a drug into the blood stream)
The rate of absorption depends on….
- route of administration (IV, IM, PO, sub cut, PR, buccal, topical, transdermal, inhalation)
- Permeation (how does the drug get into the systemic circulation)
The 4 main mechanisms of permeation are….
- Aqueous diffusion
- Lipid diffusion
- Facilitated diffusion
-Pinocytosis
What is Bioavailability?
Bioavailability is a term used to describe the proportion of drug reaching the systemic circulation.
IV drugs have 100% bioavailability because they avoid first pass metabolism.
Bioavailability says nothing about the drugs effectiveness
What is first pass metabolism?
First pass metabolism prepares the blood to go back into the circulation and filters out foreign bodies.
The main site is the liver but it can also be gut wall (Parkinson’s medication), hepatic portal vein and vena cava
What is half life?
Half life refers to the time taken for the concentration of the drug to fall by half (50%) of its original value.
What is steady state?
Steady state is when the value of the drug input is equal to the rate of elimination.
It takes 5 half lives to reach steady state
A loading dose may be required to rapidly achieve therapeutic response if a drug has a long half life (eg Phenytoin)
Distribution
(Transportation of a drug to its target site)
Measured as Vd (volume distribution) How far will a drug go? The further it is distributed the longer it will take to be eliminated
Large Vd 1-10l/kg - wide/extensive - (digoxin/ethanol)
Small Vd - 0.1-1 l/kg - implies limited to vascular space - more affinity to plasma proteins (Warfarin/gentamicin)
Diffusional characteristics and ability to cross hydrophobic barriers vary between drugs
Factors influencing distribution are?
- Protein binding (drug inactive when bound to protein)
- blood flow (good blood flow= good Vd)
- Membrane permeation (lipid soluble)
- Tissue soluble (PH and ionisation)
- Molecular size (small molecules)
- High to low concentration
The most important factor influencing distribution is protein binding:
- a drug can only exert its effect when not bound to protein
- some drugs may be displaced from proteins by highly bound drugs causing toxicity (eg valproate displaces diazepam from binding site)
- patients with low albumin may be at greater risk of toxicity because they have less protein for drugs to bind to
Metabolism
(The body’s ability to build up and break down substances by enzyme conversion)
The liver is the main organ for metabolism but other tissues are able to metabolise some drugs (GI tract, lungs, skin and kidneys)
Factors influencing metabolism:
- Genetics
- Age (over 50 and immature liver)
- Gender (males metabolise faster)
- Liver size and function
- circadian rhythms
- body temperature (cold metabolise slower)
- Nutritional weight (distribution of inbound drug with low albumin)
- Environmental factors (smokers metabolise faster)
Drug metabolism involves 2 phases:
Phase 1 - mainly oxidation - metabolic reaction caused by enzyme p450 produce toxic metabolites.
Phase 2 - mainly conjugation - performed by various enzymes. H2O is added to make it less toxic and easier to excrete.
Pro drugs are drugs that are inactive until metabolised (eg codeine - morphine)
Excretion
(How the drug leaves the body)
There are 5 routes if excretion:
- Kidneys (urine) - relies on GFR and tubular secretion. The kidneys are the main route of excretion.
- Liver - drugs secreted in bile would be active so can be re absorbed (enterohepatic re uptake)
- GI tract - excreted in faeces
- Lungs - gaseous anaesthetics
- minor routes - sweat, saliva and breast milk
Zero order excretion…
- rate of excretion of a drug is independent of its concentration
- can’t speed up excretion
- non linear kinetics
- only 5% of drugs
- example - ethanol
