Session 1 - Intro and Pharmacokinetic concepts Flashcards
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?
ADME
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?
100%
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
- Age
- 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
c) hormones
a) albumin
b) lipoproteins and/or acid glycoproteins
c) globulins
What 4 factors affect protein binding of drugs?
- Hypoalbuminaema
- pregnancy
- 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
CYP inhibitors
G-COMICS
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
Monophasic and multiphasic COCP?
monophasic - same dose of oest and prog on each of 21 days
COCP ADRs
increase risk of PE, stroke, DVT, headache, depression
decrease risk of ovarian cancer, endometrial and colorectal
high ldl effects on blood?
increase platelet aggreg therefore atherogenic
obesity effects on lipids in blod
increase cholesterol and TG, decrease HDL
why acei different in blacks and older ppl
dye to reduced RAS activity
what is type A and B ADR according to pharmacogenetics
A - polymorphism in affected structure increase or decrease effect
B - presence of gene leads to abnormal interaction e.g. hepatic porphyria induced by alcohol
MoA of corticosteroids
binds with intracellular receptor and complex forms dimer with another one then binds to clucocorticoid response element (GRE) in nucleus and modulats transcription
effects of glucocorticoids (GC) and in excess
increase blood glucose, AAs, and TGs
excess - atrophy, increase bone resorption (osteoporosis), DM (prolonged increase glucose)
how are GCs elminated in liver
what is steroid sparing drug
how monitor steroid usage
phase 1 and 2
DMARD
peak flow, ALT, CRP
how should GCs be stopped?
gradually tapered off to prevent adrenal insufficiency
symptoms of mineralocorticoud deficiency?
hy[ptension, dehydration, hypoNa, hyper K+
what is time dependent and conc dependent killing
time dependent - requires drug exceed a certain conc for a prolonged period of time to work
conc dependent - needs to exceed certain conc to kill bacteria
severe asthma and life threatening asthma criteria
severe - unable to complete sentences, HR 110+, RR 25+, PEFR 33-55% of best
life threatejning - less than 33% PEFR
how treat acute asthma
O2, nebulised salbutamol, oral prednisolone
what is autacoid and eg.
ocal hormones e.g. No, histamine
schedule 2 and 5 drugs
2 - storage and locked, prescription and destruction conditions
5 - just keep invoice of prescription
difference unfractionated and LMWH
unfractionated more effective but needs more monitoring. APTT monitor
nephrotoxic drugs
ACEi, NSAIDs, metformin, aminoglycosides
MANA
ADRs of aspirin
ASPIRIN
asthma, salicyalism, peptic ulcer disease, intestinal bleeding, reyes syndrome, idiosyncracy, noise (tinnititus)
parkinson drugs
SALAD - selegeline, anticholinergics, L-DOPA + DCT, amantadine, dopamine agonist
sodium valproate ADR
VALPROATE
vomiting, alopecia, liver toxic, pancytopenia, retention of fats (weight gain), oedema, appetite increase, teratogen, enzyme inducer
steroid ADRs
CUSHINGOID
cataracts, ulcers, skin straie, hypertension and hyperglyc, infections, n.., g..,osteoporosis + obesity, immunosuppression, diabetes + depression
WPW pathophysiology
reentry through bundle of kent
