Flashcards in 243 Pregnancy Deck (71)
How may pregnancy effect drug absorption?
Morning sickness- a tablet may not stay down in the stomach long enough to be absorbed.
Progesterone slows gastric emptying and can therefore leas to slower absorption and lower peak concentration.
This is a bigger problem for SINGLE doses rather than long term meds- these will build up over time
How could we overcome the problem of morning sickness effecting absorption?
Change the timing of the dose
Can also give with an anti-emetic
What does total body water increase by in pregnancy?
By About 81
What does increasing total body water mean for drugs in preggers women?
It should dilute the concentration of any drug, but as serum albumin falls and pregnancy steroids displace drugs from their binding proteins "free drug" levels may rise.
Example of drug effected: Thyroxine
Also assays are needed for anti-epileptic drugs
How does pregnancy effect enzymes? An example of a drug involved?
Pregnancy effects metabolism of drugs acting through cytochrome p450 enzymes
An important example is the enzyme which inactivates lamotrigene. This is induced by pregnancy.
So doses of lamotrigene need to be increased to get the same effect
How does pregnancy effect drug excretion?
A higher cardiac output (51 becomes 71) leads to an increase of 50% in GFR
Renally excreted drugs like penicillin are excreted faster
(Therefore in pregnancy we will use 500mg ampicillin tds not 250mg tds)
The increased GFR in pregnancy due to increased cardiac output causes physiological __________.?
Causes physiological glycosuria
(Excretion of glucose in the urine)
Beta Blockers are less likely to cause _______ because of the tachycardia which exists in pregnancy. This is due to physiological changes in pregnancy.
Less likely to cause bradycardia because it's cancelled out by the tachycardia
Calcium channel blockers are less likely to decrease the total ________ resistance because this is already reduced in pregnancy.
Total peripheral resistance
What is teratogenesis?
Where a baby is born with a congenital abnormality (means a defect present at birth)
This can be induced by a drug
1-2% of babies are born with a congenital abnormality
Under 1 in 20 of these can be due to drugs
What two drugs, if they are given to a pregnancy woman, will result in the majority of fetuses being born with birth defects.
Most congenital abnormalities are multi-factorial, what does this mean?
A lot of drugs risk of teratogenicity is small.
(Example Valproate is linked with NTD's in 1-2%)
Therefore if a baby is born with an abnormality it's usually die to another factor such as Folate deficiency being a cofactor for NTDs.
How do most drugs cross the placenta into the baby?
By simple diffusion.
This depends on concentration gradient and molecular weight.
Most drugs given to a mother will reach the fetus.
What's one drugs that won't eventually reach the foetus when given to the mother?
Too big to cross into the foetus.
What drugs accumulate in the fetus due to fetal metabolism, therefore should be avoided in pregnancy?
Gets concentrated in fetal thyroid
Accumulates in amniotic fluid of the baby
When is the maximum susceptibility period in pregnancy for teratogenic effects to occur?
Between 3-11 weeks of pregnancy, this is during organogenesis (when a mass of cells turn into organs)
Why does glucose tolerance decrease with advancing gestation? (Diabetes)
Because of the anti-insulin effects of the placentas substances:
lactogen, glucagon and cortisol
Increased oestrogen levels in pregancy increase serum levels of Globulin, which binds_______,________ and ______?
Note: free levels of hormone do not change
Why is it important to control diabetes In pregnant women?
Poorly controlled diabetics have a high incidence of congenital abnormalities
HOW can we optimise blood glucose control in pregnant diabetic women?
Using either more frequent doses of insulin OR Metformin
Usually over 4 daily injections of insulin is required.
Increase the frequency of Blood sugar monitoring
What abnormality can Phenytoin use cause in ?
Eg cleft lip / palate
What two epilepsy drugs are most likely to cause NTDs?
What epilepsy drugs are most likely to cause cardiac defects in ?
Valproate and phenytoin
The risks of epilepsy drugs causing abnormalities increases with polypharmacy.
___% likely for just one AED
___% likely for two AEDs
___% likely for three AEDs
6-7% for one
15% for two
Up to 50% for three
For what AED is the risk of causing abnormalities dose dependent?
Can you tell me some of the minor abnormalities associated with use of anti-convulsants in preganancy?
Low set ears
Broad nasal bridge
Hypoplastic nails and digits
But then again, even UNTREATED epilepsy is associated with an increased risk of congenital abnormality!!
What must women on epilepsy treatment receive pre-conception due to the mechanism of AEDs causing abnormalities being folate deficiency?
Must receive 5mg folate daily for at least 3 months pre-conception
Especially if any of the ones mentioned eg valproate, phenytoin, carbamazepine must be used
So, if these AEDs are causing abnormalities, should we take women who are pregnant off them and potentially not control their epilepsy?
Overall benefit of treatment outweighs the risk eg woman fitting and rolling over onto stomach damaging baby.
Newer anti-epileptics such as lamotrigene and gabapentin do not appear so risky but they aren't entirely risk free!!
What are the hepatic enzyme inducing drugs to watch out for in pregancy?
Drugs such as carbamazepine, phenytoin, and phenobarbitone