Pharmacokinetics, Pharmacodynamics, and teratogenesis Flashcards
(42 cards)
Define bioavailable
The amount of drug that reaches the systemic circulation unchanged
IV drugs = 100% bioavailability
Oral drugs loose a lot of bioavailability because of first pass metabolism
Define volume of distribution
The amount of water the drug would need to be dissolved into in order to make it same conc as in blood
Fat soluble drugs = V large volume of distribution since little of it is in blood.
Water soluble drugs = Little volume of distribution
Describe phase 1 of hepatic metabolism, Also describe the 3 types of production you can end of after phase 1 of hepatic drug metabolism
Phase 1 = Metabolis in liver by reduction/oxidation/hydrolysis with the cytochrome p450 enzyme complex
There are 3 types of products drugs can become after this first phase
1) Inactive = Vast majority of drugs will be this. Biologically inert
2) Active = The metabolism itself turns the drug active. Like enalapril and diazepam
3) Toxic = Rare. Some drugs turn toxic and require an additional step to be broken down. So can cause problems in overdose, like paracetamol.
Describe phase 2 of hepatic metablicm and the 3 different conjugation agents that can be used
Phase 2 = The chemical breakdown drug is made more soluble with conjugation to another compound
Three examples
1) Glucoronate = For basic drugs like paracetamol and morphine
2) Acetate = For acidic drugs like hydralazine, procainamide, ioniazide
3) Sulphate = For oral contraceptive.
What determines whether drug is excreted in urine or liver
Urine = Most things filtered from afferent blood flow and go out in urine
Bile = If molecular weight greater then 300Da goes into faeces.
Describe enterohepatic circulation, and an example drug
If excrete in faeces through bile = Some drugs can be reabsorbed through lower GI tract before final excretion
Example = COCP
Describe the 2 processes by which drugs are filtered within the nephrons of kidney
1) Can be active in the PCT = This relies on transporters
- Anion transporters = For acidic drugs
- Cation transporters = For basic drugs
2) Or passive = In descending loop of Henle.
How are highly protein bounded drugs different in terms of their renal excretion and why
These drugs are bound to negatively charged protein carriers.
They therefore are slightly repelled by the glomerular basement membrane. So they are filtered less overall in kidneys.
Describe 6 ways in which pharmacokinetics are altered in pregnancy.
1) Large 40-50% increase in circulating volume
2) Concomitant large increase in renal blood flow and consequent GFR
3) Increased third space = Amniotic fluid and peripheral oedema
4) Relatively increased fat content as laying down maternal fat. This effects Vd
5) Reduced albumin and other binding proteins due to overall plasma dilutional effect
6) Progressive insulin resistance
Describe how clearance of most drugs changes in pregnancy and give 3 classes of drug that commonly need their doses changed as a result
There is increased clearance of must drugs.
1) Anticonvulsants often need higher drug doses
2) Mood stabalisers = Esp like lithium where close titrations of levels are needed
3) Thyroxine
Most drugs in pregnancy will have reduced levels because of the Pk changes described earlier. But 2 types of drugs may not, or be affected less. What are these
1) Highly protein bound drugs = Because the active conc is affected less. This is because of reduced albumin levels, so less binding. Example is warfarin
2) Fat solubel drugs = because there is increased fat reservoir in pregnancy and can be stored there. Example is chloroquine.
How does ampicillin cause drug interactions? Esp with COCP
It alters bacterial gut flora = Meaning reduced entero-hepatic recirculation of oestrogens
Therefore can impair effect of COCP
Name some enzyme inhibitors
Valproate (all other antiepileptics are inducers).
Also Sulphonamide drugs = like sulphonylureas, certain diuretics, and antiretrovirals
Name some enzyme inducers
Phenytoin and other barbiturates, carbemazepine, rifampicin, spirnolactone
Give some general rules for using medication in pharmacy
1) Avoid drugs in the first trimester wherever possible
2) Use smallest effective dose as possible. And use drugs for the shortest time possible
3) Choose drugs with the most extensive experience in human pregnancy
4) Avoid polypharmacy where possible
The FDA has a drug categorisation for the teratogenicity of drugs in pregnancy, what are the categories and what do they mean
A = No risk in controlled human studies. Adequate human studies B = No risk in other studies = No risk in animal studies OR risk in animal studies, but no risk in human studies. C = Risk not ruled out = Animal studies show risk. But potential benefits may warrant use of drug despite these risks D = Positive evidence of risk = Positive human evidence of risk. But again benefits may outweight risks X = Contraindicated in pregnancy = Cannot use. Risks always overweigh benefits N = Not yet classified by FDA
When is the ‘all or nothing’ effect in regards to teratogenicity and when is it
Pre-embryonic stage up to day 17 = All of conceptus is totipotent cells
So here you either get = Death or survival.
So if there is drug exposure here and pregnancy continues = Can reassure mum
How long can retinoids last before you can get pregnancy
2 years
How long can methotrexate last before you can get pregnant
3 months
At what point during pregnanct is there the most risk of teratogenesis and why
The embryonic stage from day 18-55 = Organogenesis is occuring here from weeks 2-8.
Biggest potential for structure damage.
The earlier the exposure the more marked the damage is likely to be
What sort of teratogenic effects occur in the post-embryonic period and when is this
Post-embryonic period = From 8 weeks on
Effect = Often causing IUGR eg. beta blockers.
Also some organs are still developing like kidneys = So ACE-I cause reduced renal function
What is the way to remember the main classes of teratogens. There are 8 of these name them
ALL THE A’S = There are 8 groups
Anticonvulsants Antibiotics Anticoagulants Antimetabolites Antipsychotics Androgens Acne drugs ( or Vitamin A) Alcohol
There are 4 types of drugs that may result in miscarriage what are these
1) Ergotamine = Vasoconstrictor for migraines/cluster headaches
2) Misoprostol = Prostoglandin used in termination and to start labour
3) Mifepristone = Antiprogesterone use with misoprostol in terminations
4) Thrombolytics = Like alteplase as a tissue plasminogen activator
Which antiepileptic to use in pregnancy? and why
Lamotrigine = Shows no extra risk above baseline.
