Pharmacokinetics + Pharmacodynamics Flashcards
Define zero order elimination:
Constant amount of drug eliminated per unit time = Non-linear (conc of reagent has no effect on reaction rate)
- Cannot calculate half-life
- Unpredictable
- Dangerous
- Require careful monitoring
Define first order elimination:
Constant fraction of drug eliminated = Linear (^conc of reagent = ^reaction rate)
- Can calculate half-life
- Predictable
Define oral bioavailability:
The fraction of an oral administered drug that reaches systemic circulation.
What factors can affect the oral bioavailability of a drug?
- Drug formulation
- Age
- Food (lipid-/water-soluble)
- Vomiting/malabsorption
- 1st pass metabolism
Define ‘distribution’ of a drug:
The ability of a drug to move between compartments within the body
The distribution of a drug is determined by which factors?
- Protein binding
- Volume of distribution of the drug
What factors affect the protein binding of a drug?
- Hypoalbinaemia
- Pregnancy
- Renal failure
- Displacement by other drugs (precipitant drugs)
How do you calculate the volume of distribution of a drug?
Dose / Peak plasma conc of drug (@ time = zero)
In a typical 70kg man, how many litres of fluid is in each compartment?
- Intracellular = 23 L
- Intravascular = 5 L
- Interstitial = 14 L
The tissue distribution of a drug can be influenced by what factors?
- Disease states
- Lipid solubility
- Active transport
- Regional blood flow
- Specific receptor sites in tissues
- Drug interactions
Which phase of metabolism is dependent on the activity of the CYP450 enzymes?
Phase 1
Phase 1 of metabolism is dependent on which enzyme?
CYP450
How does a CYP450 inducer affect the activity of other drugs metabolised by this enzyme?
A CYP450 inducer would REDUCE the activity of other drugs metabolised by this enzyme
- EXCEPT PRODRUGS - an inducer will cause exaggerated effects of prodrugs
Name some CYP450 inducers:
- Phenytoin
- Carbamazepine
- Barbiturates
- Rifampicin
- Chronic alcohol use
- Sulphonylureas
- St Johns Wort
How does a CYP450 inhibitor affect the activity of other drugs metabolised by this enzyme?
A CYP450 inhibitor would INCREASE the activity of other drugs metabolised by this enzyme
- EXCEPT PRODRUGS - an inhibitor will cause reduced activity of prodrugs
Name some CYP450 inhibitors:
- Erythromycin
- Omeprazole
- Cimetidine
- Grapefruit juice
- Disulfiram
- Amiodarone
- Co-trimoxazole
- Sodium valproate
- Isoniazid
- Ciprofloxacin
- Sulphonamides
- Amiodarone
- Fluconazole
- Fluoxetine
- Paroxetine
- Metronidazole
- Ritonavir
- Co-trimoxazole
- Clarithromycin
- Diltiazem
- Itraconazole
- Ketoconazole
- Nefazodone
- Telithromycin
- Verapamil
Generally, what can affect the activity of CYP450 enzymes?
- Enzyme inducers
- Enzyme inhibitors
- Age
- Liver disease
- Hepatic blood flow
- Cigarette consumption
- Alcohol consumption
Where in the body can you find CYP450 enzymes?
- Liver (mainly)
- Gut
- Lung
Describe phase II metabolism:
Conjugation with a polar molecule to make drug water soluble, enabling rapid elimination
- conjugation with glutathione, glucoronic acid, sulphate, or N-acetyl
What are the possible routes of drug elimination?
- Kidney
- Lungs
- Sweat
- Tears
- Breast milk
- Genital secretions
- Bile
- Saliva
What factors determine the renal excretion of drugs?
1) GFR - filtration of unbound drugs ie Gentamycin
2) Active tubular secretion ie Penicillin
3) Passive tubular reabsorption ie Aspirin
Define drug clearance:
The ability to excrete the drug, mostly = GFR
What is the relationship between clearance and half-life of a drug?
Half-life is inversely proportional to clearance
- As clearance decreases, half-life increases
Which of zero order and first order elimination can be saturated?
Zero order
Constant amount of drug eliminated = non-linear
