P1: Journey of a drug: The pharmacokinetic phase Flashcards
What is the journey of a drug?
Mouth –> Oesophagus –> Stomach –> Small intestines –> Liver –> Circulatory system –> Target
What must an oral drug be able to do?
- Dissolve
- Survive a range of pHs ( 1.5-8)
- Survive intestinal bacteria
- cross membranes
- survive liver metabolism
- avoid excretion by kidneys.
- Partition into target organ
- avoid partition into undesired places (eg brain, foetus)
What are the phases of drug action?
- Pharmaceutical phase: (drug dissolved)
- Pharmacokinetic phase (action of body on drug).
- Pharmacodynamic phase (action of drug on body)
What are the four basic components of the pharmacokinetic phase?
Absorption
Distribution
Metabolism
Excretion
ADME
What does absorption need for drugs to do?
Needs to be soluble in body fluids.
Needs to cross the cell membrane.
For efficient absorbption, drug molecules need to have correct balance between hydrophobic and -philic groups.
What do drugs need to be to get through cell membrane?
Neutral
What does a drug need to be to be able to absorb through the stomach?
Low pH (1.5)
Not a significant absorption site unless the drug is highly hydrophobic or unionised at low pH (acidic drugs)
What does a drug need to be to be able to absorb through the small intestine?
pH = 7-8
Most important site of oral drug absorption
What happens in distribution?
Transport of drugs from blood to site of action.
Distributed to all tissues.
Competition w/ other sites reduces bioavailability at the site of action.
Hydrophobic drugs - low serum levels.
Hydrophilic drugs - high serum availability.
What do barbiturates act on?
CNS (anaesthetics)
Fat soluble
Very diff to estimate does- obese ppl need more but released slowly later.
Where are places that take up drugs quickly?
Well perfused tissues - eg kidney, liver, heart, brain.
Where are places that take up drugs slowly?
adipose tissue and muscle tissue.
What factors affect distribution?
Plasma protein binding.
Blood brain barrier.
Placental barrier
What happens in plasma protein binding that can affect distribution?
Blood has proteins: albumin and globulins.
Drugs can bind to these proteins to varying degree.
Protein binding decreases conc of free drug circulation.
Limits amount of drug available to travel to site of action.
Bound drugs = pharmacologically inactive.
What is an example of a drug that binds to plasma proteins?
Warfarin (prevents blood clotting- prevents strokes).
Binds to albumin.
How does the blood brain barrier affect distribution?
Brain capillaries - less permeable.
Most drugs can’t pass BBB eg penicillin.
Drugs that do cross = very lipid soluble.
How does the placental barrier affect distribution?
Placental membrane = liquid in nature = readily allows non-ionized, lipid soluble drugs to pass.
Alcohol, nicotine, cocaine and barbiturates can pass through
What does metabolism do to drugs?
Process by which the drug changes the chemical structure of a drug to another from called metabolite (biotransformations).
Body treats drug as foreign.
Water soluble (polar) drugs excreted by kidneys.
Metabolite is generally more water soluble than original drug.
What organ participates in drug metabolism?
Liver
What are the two phases of drug metabolism?
I (functionalisation reactions)
II (Conjugation reactions)
What are the different parts that make up phase I metabolism?
Oxidation
Hydrolysis
Reduction
What experiences oxidation in phase I metabolism?
Alkyl groups
Carbon centres next to sp and sp2 carbons are activated and more likely to be oxidised.
Dealkylations of amines, ethers and thioethers.
What catalyses the hydrolysis in phase I metabolism?
Esterase and peptidases
What catalyses the reduction in phase I metabolism?
Enzymes in liver
