Pharmacokinetics 2 Flashcards
Describe Phase 1 metabolism in the liver?
- It is generally oxidation, reduction or hydrolysis, introducing or revealing a reactive chemical group (functionalisation). Products are often more reactive
Describe Phase 2 metabolism in the liver
Hydrophilic, inactive compounds generated by changing the chemical properties. This makes the body more likely to get rid of it.
How are hydrophilic compounds excretes?
in urine via the kidneys
What enzymes mediate phase 1 metabolism?
Cytochrome P450 enzymes (mixed function monooxygenases)
What are the functions of Cytochrome P450 enzymes?
Describe the metabolism of paracetamol
It can be conjugated with sulphate or glucoronide (main ways) or some of it is metabolised by cytochrome P450 enzymes.
Describe the metabolism of paracetamol via cytochrom P450 enzymes
The enzymes turn it into a toxic metabolite which will combine with glutathione if there are normal levels which then gets conjugated and excreted. If there are depleted levels of glutathione it will combine with hepatic proteins and become toxic.
Describe the interaction between Warfarin and Phenobarbital
Phenobarbital increases the expression of Cytochrome P450 and Warfarin is metabolised by cytochrome P450 so it will decrease the effect of warfarin
Describe the effects of grapefruit juice on statins
It prevents the metabolism of statins by blocking the enzyme that metabolises it. (CYP3A4)
What is the importance of drugs being metabolised differently?
It allows for patient-specific choices to be made, for example Vecuronium is metabolised by the liver so this drug wouldn’t be suitable for a patient with poor liver function.
Metabolism can affect what?
The bioavailability of drugs
How are drugs eliminated?
(Not in terms of route)
Either unchanged or as metabolited. Hydrophilic drugs are eliminated more readily than lipophilic except for in the lungs
What are the possible sources of excretion?
Breath, Urine, Saliva, Perspiration, Feces, Milk, Bile and hair
What is the minimum effective concentration
The min plasma conc that needs to be achieved before evidence of a therapeutic effect could be observed.
What is the minimum toxic concentration?
The min plasma conc required to observe unwanted or toxic effects of the drug
What is the theraputic window? how can you calculate it from a graph
The gap between the minimum effective concentration and the minimum toxic concentration. Calculated by drawing a line at both values and the space in between is therapeutic window
What is the onset of action? How can u calculate it on a graph?
How long it takes the drug plasma conc to reach the min effective conc. Draw line at value for min effective conc and where the curve breaches that line is the onset of action
How can you calculate on a graph the duration of action?
Draw line at the min effective concentration. Mark when the curve breaches the line and then another mark when it descends back below the line.
What is Cmax?
The peak plasma concentration achieved after administering the drug
What is Tmax?
The time taken to reach the Cmax
What is the plasma clearance half life (elimination half life)? How is it calculated?
How quickly the drug is removed from the body. Start at Tmax and work out how long it takes for 50% of Cmax to be reached (towards the right of Tmax)
