Pharmacokinetics Flashcards
What does ADME stand for
Absorption
Distribution
Metabolism
Excretion
Drug definition
A chemical substance of known structure (non nutritional) which produces a biological effect when administered
How are drugs categorised (Anatomical classification system)
Physiological system (target area eg - blood, respiratory system)
Therapeutic group (effect eg - stimulants, contraceptives)
Chemical properties (structure)
Most common/successful drugs
Lisoprinal (ACE inhibitor)
Atorvastatin’s (for high cholesterol)
Penicillin (200mil lives saved)
Major drug failure examples
Thalidomide (treated morning sickness but caused serious birth defects & maternal death
Relentlessly incurable diseases
the Cold, Alzheimer’s, Diabetes I
Common drug administration methods
Oral, Rectal, Intravenous, Nasal, Sublingual, intramuscular, inhalation, Transdermal, intrathecal
How are most small molecule drugs delivered, where is absorption & contributing physiological factors
Orally - absorbed in SI
Gut content, GI motility
How do drugs move across membranes
Simple diffusion (through lipids)
Facilitated diffusion (through aqueous channels)
Carrier protein transport (ATP dependant or independent)
Which conditions aid the movement of drugs
- high conc grad
- low molecular weight
- low degree of ionisation
What is the first pass effect
a large reduction in concentration of orally taken drugs before reaching systemic circulation (reduces bioavailability)
Where does the first pass effect take place and how
The gut or liver - following absorption the drugs maybe travel through the portal vin to the liver where they are metabolised
Bioavailability definition
How much of a orally given drug makes into circulation in is active form
IV vs oral administration (bioavailability)
IV reaches blood much quicker and at greater concentrations (but is also undergoes a rapid elimination process)
Oral bioavailability equation
AUC = area under curve
Oral bioavailability = AUC oral
/ AUC iv
what does Oral bioavailability calculation show (eg for a 50% result)
for a 50% result the dose must be doubled when converting from intravenous to oral route
Oral administration pros/cons
pros - easy to administer
cons - subject to first pass effect
Rectal administration pros/cons
pros - can be used for vomiting patients
cons - bioavailability varies depending on blood supply
Inhalation administration pros/cons
pros - local effect, very fast
cons - not suitable for large molecules (can leak into systemic blood)
Intravenous administration pros/cons
pros - 100% bioavailability
cons - enters tissue rich in blood vessels first
Intrathecal administration pros/cons
pros - cross the blood-brain barrier
cons - difficult to administer
Transdermal administration pros/cons
pros - not subject to first pass effect
cons - bioavailability depends on the subcutaneous muscle/fat
Alcohol absorption (empty stomach)
- Some absorbed in stomach most moves into SI where it is rapidly absorbed
Alcohol absorption (after a meal)
- Pyloric sphincter is closed so alcohol is kept in stomach longer where is it slowly absorbed
By what % can a fatty meal reduce peak blood alcohol concentration
up to 50%
Ethanol key propertires
- Small molecule
- hydrophobic & hydrophilic
- readily cross membranes & protein channels
- moves passively down conc grad
what does the compartmental model refer to
Drugs not being evenly distributed between tissues
What is blood distribution dependant upon
- blood flow for delivery speed
- lipid solubility for tissue accumulation
Pattern of drugs distribution for Oral & IV administration
oral - slow even filling
IV - brain/heart first then redistributed
Movement pathway of drugs through membranes (compartment to compartment)
GI tract -> GI tissue (fenestrae)
Blood -> Liver (loose barrier - pores)
Blood -> CNS/heart (tight barrier)
Lipid solubility relation with drugs
effects measuring of drug in blood
poorly lipid soluble = more drug in blood
highly lipid soluble = more drug in lipid
Alcohol distribution key facts
- restricted to total body water
- doesn’t enter adipose tissue
- can cross the blood/brain barrier leading to cognitive & motor impairment (500mg/100ml = lethal)
Why does alcohol effect different genders differently
males have higher body water content (68% compared to 55%)
Meaning females will have a high BAC when drinking the same amount as males
Phase I metabolism of drugs
Drug goes in primary product comes out
expose or add functional group (oxidation, reduction, hydrolysis)
Phase II metabolism of drugs
Primary drug goes in secondary product comes out
Conjunction (glucuronide, sulphate, methyl, glutathione)
What is drug metabolism doing and why
making a lipophilic drug more hydrophilic
both primary and secondary products are excreted (better if hydrophilic)
How is alcohol metabolised in the liver
Ethanal -> acetaldehyde (ADH enzyme) -> acetic acid (oxidised in the mitochondria)
acetic acid is an inert metabolite and is secreted
Acetaldehyde is toxic metabolite what does it do
causes flushing, ^ HR, headaches, nausea
Alcohol elimination follows zero order kinetics why is this? (a constant amount is eliminated over time regardless of concentration)
no more Alcohol dehydrogenase (ADH) can be produced so metabolism continues at a steady rate and alcohol will accumulate in the bloodstream
What rule does first order elimination kinetics follow
The higher the drug concentration the quicker it is eliminated (high gradient of initial curve on a graph)
a constant fraction is eliminated per time eg 50%
Renal clearance equation = ?
Renal clearance = (Urinary conc x urinary volume) / plasma concentration
Total clearance equation = ?
Total clearance = CLtotal = CLrenal +CLnonrenal
Total clearance = volume of plasma cleared of drug per untie by metabolism & excretion
Non renal clearance pathway examples
Metabolism, sweating, expiration
