What instance would require brand prescription over generic prescription?
When bioavailability of drugs differs significantly.
What is a black triangle drug?
Drug being intensively monitored for adverse effects
What is pharmacokinetics?
What body does to drug
What is pharmacodynamics?
What drug does to the body
What is pharmacogenetics?
Effect of genetic variability on pharmacokinetics of a drug on an individual
What are the 4 pharmacokinetic processes?
Absorption, Distribution, Metabolism, Elimination
What is bioavailability?
Fraction of a dose which finds its way into the circulation
What is the bioavailability percentage of IV infusions?
In this picture, how would you calculate the total drug exposure? How would you calculate oral bioavailability?
Area under the curve = total drug exposure
Oral bioavailability = AUC oral / AUC iv
What 5 factors affect the bioavailability of a drug?
- Drug formulation
- Food - lipid soluble or water soluble drug
- Vomiting or malabsorption
- First pass effect
What is the advantage of modified release over immediate release drug?
modified release spends more time in the therapeutic window than immediate release
What circulation proteins do these drugs bind to:
a) acidic drugs
b) basic drugs
b) lipoproteins and/or acid glycoproteins
What 4 factors affect protein binding of drugs?
- renal failure
- displacement by other drugs
How does protein binding displacement by drug B affect drug A which is usually bound to the protein?
Preferential binding of protein to drug B means drug A is displaced and results in greater concentration of drug A in plasma, can have serious consequences.
How are drugs differently distributed in the body?
Some drugs bound to tissues, others remain only in circulation AKA volume of distribution
How does volume of distribution relate to half life?
Larger volume of distribution means longer half life because drug resides in tissues and has to diffuse into plasma to be eliminated
How many half lives does it take for a drug to reach steady state?
4-5 half lives
What 3 processes determine renal excretion of drugs?
- Glomerular filtration
- passive tubular reabsorption
- active tubular secretion
How does reduced GFR affect clearance rate of drugs?
Reduced GFR results in reduced clearance which increases half life
Explain zero order and first order kinetics
First order - Half lives. Most drugs display first order kinetics unless high doses are given in which case they display zero order
Zero order - Set amount of drug eliminated per unit time.
Which drugs are more likely to be toxic? first order or zero order and why?
zero order as it has a fixed rate of elimination. Small dose changes can lead to toxicity and large increments in dose
limitations of phase 1 to 3 trials
small number of patients, controlled nature of trials, exclusion of patients at greater risk of ADRs
Freq of adverse events of v common, common, uncommon, rare, v rare
v common - 10
common - 100 then goes up in x10
ADR types A to E
A - causally related to drug pharmacology. common
B - idiosyncratic response. rare
C - chronic
D - delayed e.g. steroid and osteoporosis
E - end of treatment effects
When should ADRs be reported via yellow card scheme?
All ADRs - if associated with new med (black triangle) or with child (below 18) or pregnent
established drug - serious illnesses or death
Pros and cons of yellow card scheme
pros - low cost, generates ADR hypothesis
cons - poor compliance, absence of control groups, coincidence or causal relationship?
legal requirements for prescription
legible, signed and dated, 2 forms of pt ID
where does 1st pass metabolism occur
gut wall, lumen, liver
Grapefruit - cranberry, omeprazole, metronidazole, isoniazide, cimetidine, sodium valproate
how is T1/2 differnet in children
longer as Vd is lower as more of their body is ECF