Drug absorption Flashcards
How many people are harmed by healthcare?
1 in 10
Pharmaceutical
Get drug into the patient
Pharmacokinetic
Get drug to site of action - what body does to the drug
Pharmacodynamic
Produce correct pharmacological effect - what drug does to the body
Pharmacokinetics 4 letters
Absorption
Distribution
Metabolism
Excretion
What does pharmacokinetics allow the understanding of?
Dosage, drug handling, harm potential, drug administration and patient variability
Absorption
Blood must enter the bloodstream and be distributed to site of action to have biological action
The process of movement of unchanged drug from site of administration to systemic circulation
Oral
Always consider purpose and site of drug, effects, speed, reliability etc
IV
Small volume and depends on blood flow to site, right into blood
Subcutaneous
For example an insulin injection
Intramuscular
Vaccines in deltoid and water soluble better
Avoid 1st pass metabolism
Other GI
Rectal, sublingual - under tongue to avoid 1st pass metabolism
Inhalation and nasal
Better for volatile agents
Metabolism in lungs
5-10% absorbed
Transdermal
Avoids first pass metabolism but few substances well absorbed eg nicotine patches
Plasma concentration and therapeutic response
Always a correlation
Therapeutic range
Drug active over a range if concentrations
What is above the therapeutic range?
Toxicity
What is below the therapeutic range?
No or insufficient pharmacological action
Therapeutic index
Range at which a drug is safe and active
Tmax
Time to peak concentration ( rapid rate of absorption decreases this)
Cmax
Peak concentration ( increase dose increase c max)
What does AUC show?
Area under the curve equivalates to the amount of drug reaching the systemic circulation
Bioavailability
Amount of drug in system/circulation which is ready for action
IV = 100%
First pass metabolism
Metabolism of any drug prior to reaching systemic circulation and is a limit for the oral route
Metabolism by acid/enzyme in lumen gut wall and liver
Formulation
Slow release preparations
GI effect
Food
Illness - malabsorption and diarrhoea eg coeliac disease, migraine reduce stomach emptying
Gut motility - gastric absorption
Pass physiological barrier
Particle size
Lipid solubility
pH and ionisation
Ionisation (4 points)
- Most drugs do not completely ionise in water
- Most drugs are weak acids or bases
- Ionised drugs DO NOT cross the membrane
- Unionised distribute until equilibrium
What does the degree of dissociation depend on?
Environmental pH
Ion trapping
Acidic drug will be more concentrated in the compartment with high pH
What do proton pump inhibitors do?
Reduce the amount of acid made in the stomach
What do antacids do?
Neutralise the acid made by the stomach?
Lipid solubility
Drug must be in solution and lipid soluble
Lipid - water partition co efficient
Ability of drug to diffuse across lipid barrier
Ratio of amount of drug dissolve lipid: water phase
Lipid soluble reach brain, testes, liver, ovaries
Not lipid soluble not absorbed eg gentamicin
What does passive diffusion depend on?
Lipid solubility and degree of ionisation
Not saturated as no proteins used to occupy
Active absorption
Specific, unusual, saturable and requires a carrier +energy
Eg iron upake by brain
Drugs must resemble naturally occurring compound
Facilitated diffusion
No energy needed but carrier is so is saturable
Filtration/bulk flow
Channels in membrane - low molecular size
Pressure differences across membrane drives it
Usually water soluble drugs eg ammonia, water
Real excretion, remove drug from CSF and enter the liver
