Drug therapy in pregnancy Flashcards
Discuss classification of teratogenic risk
Pregnancy Category A
Have been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.
Pregnancy Category B1
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.
Pregnancy Category B2
Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Pregnancy Category B3
Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
Pregnancy Category C
Have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible.
Pregnancy Category D
Have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.
Pregnancy Category X
Have such a high risk of causing permanent damage to the fetus that they should NOT be used in pregnancy or when there is a possibility of pregnancy.
Discuss transfer across the placenta
Usually occurs via passive diffusion or protein transport. A thin layer of trophoblastic cells is all that separates maternal from fetoal circulation
The degree to which a drug gains access to foetal circualtion depends on
- molecular size - less than 5kDA readily diffuses
- Anionic substances diffuse through the lipid layer more readily
- free drugs diffuse more readily than bound
- As foetal ph is slightly more alkalotic than maternal weak organic acids may become ion trapped in the foetal circualtion increasing feotal exposure
Discuss transfer during lactation
Generally drugs taht are ingested or injected by the mother digguse passively into milk and then back int the matenral ciruclation for excretion.
The amount of drug diffusing into milk depends on
- lipid solubility
- amount of bound vs free
Wether a substance is concentrated in maternal milk or note the neonate gnerallys is able to detoxify it wiht no adverse effects and only a few drugs pose serious danger to breast feeding infant
Discuss high risk times of gestation
The foetus is ost vulnerable to toxic insults during the time of organogenesis days 21-56 of fetal life
Functional development of the CNS is affected when it is exposed to a CNS teartogen during the 10th to 17th week of pregnancy
Discuss anagelsia use in pregnancy
Acetaminophen is widely used in pregnancy and has not been associated with congenital malformations.
NSAIDS - (C in first and second, D in third)
- taken in the first trimester have been linked to an increased risk of spontaneous abortions and a slight increase in cardaic septal defects, oral clefts and gastroschisis
- when used in the third trimester inhibit labour and have been historically used as a tocolytic.
- When used in later pregnancy leads to premature closure of the ductus
Aspirin (C in first and second, D in third)
- increased risk of gastroschisis in the first trimester, IUGR
- increased risk of both foetal and maternal hemorrhage in the third trimester
- Also associated with post maturity, prolonged labour neonatal hypoglycaemia, permature duct closure causing primary pulmonary htn.
- Low dose aspirin may be beneficial in pregnancy complicated by SLE with antiphospholipid antibodies and those at risk for gestationl htn and preeclampsia
- excreted in breast milk and its use is discouraged
Opiates (Codeine C, Oxy B, Morph C)
- In general short term episodic use of opiates are safe in pregnancy
- There use near term howevere may result in severe resp depression in the neonate
- Long term use can lead to feotal addiction , low birth weight and neonatal abstinence syndrome characterised by CNS hyperirritability, ANS dysfunction and high infant mortality
Discuss RSI drugs in pregnancy
Limited data primarily been obtained from animal studies and retrosepctive human data
- None of the agents has been consistently associated with congenital malformations.
- The effect of nondepolarising neuromuscular blockade on organogenesis is not know but are not thought to pose a significant risk as very little crosses the placents
Discuss anticoagulants in pregnancy
Low molecular weight heparin (B) is recommended for those requriing anticoagulation for all but the final weeks of pregnancy becuase they are effective, easier to administer and produce a more predictable anticoagulant response than unfractionated. Less risk of HITS
If patient at risk of HITS, fondaparinux, argatroban and danaparoid all appear to be safe
Warfarin (Class D) should be avoided as it crosses the palcenta and is a known teratogen - signficiant risk for wide range (corpus collusum agenesis, hypolasia of the nasal bones, midline dysplasia, optic atrophy and blindeness and feotal osteogenesis, CNS malformation)
Oral direct anticoagulants are avoided due to absence of information on efficacy and feotal saftey
Discuss antibiotics treatment in pregnancy
Penicillins, cephalosporins and macrolids remain the drugs of choice in pregnancy.
- Aminoglycosides (D)
- Associated with ototoxcicity and nephrotoxicity
- Do not appear to have any structural teratogenic effects in humans
- Nil reports linking in utero exposure to gentamicin with oto or neprho toxicity and is likley compatable with breast feeding
Cephalosporins (B)
- Safe although no controlled studies examining their saftey
Clindamycin
-not asscoiated with any birth defects in humans or animal studies
FLuroguinjolones (c)
- Numerous toxic effects on bone and cartilage growth in animal models and are discouraged from use during bpregnancy particularly during the first trimester.
- Can use in breast feeding
Macrolides (B)
-Safe
Metronidazole (B)
- Mutagenic and carcinogenic in mice and rats
- multiple studies in humans have failed demonstrate association between its use and teratogenicity
Nitrofurantoin
-near term use is associated with haemolytic anaemia
Penicillins
all safe
Sulfonamides (D)
- Increase risk of neural tube defects and other congenital abnormalities such as cleft palate
- a number of obervation studeis also demonstrate an increased risk of CVS adn urinary tract malfomration
- also cause kernicterus near term
Tetracyclines (D)
- Readily cross the placenta
- associated with development of fatty liver
- it also chelates clacium causing abnormalitles in bone growth and staining of decidual teeth
Discuss antifungal use in pregnancy
Nystatin has a long saftey profile during pregnancy and with lactation it is poorly absorbed from skin and mcuous memrans – is the antifungal of choice for the treatment of mucocutaneous fungal infection.
Clotrimazole, miconazole and ketoconazole all appear safe during pregnancy and lactation. There has been a minor increase in the incidence of hypolastic left ventricle - ketokonazole is tetatogenic in rates. For these reasons the above are second line
Fluconazole is teratogenic in high doses and has been associated with an increased incidence of craniofacial and cardiovascular defects in offspring
Discuss Anti TB drugs and pregnacny
Untreated TB places the mother and foetus at greater risk than the use of anti TB drugs.
Rifampin has been associated with haemorrhagic disease of the newborn but is still first line
Go nutzzzzzzzzzzzz
Discuss the use of antiviral drugs in pregnancy
Antiherptic drugs - aciclovir and valcyclovir all g
Anti flu -
-oseltemavir - use likley outweighs ris
Anit HIV drugs
-All G
Discuss the use of antiarythmics during pregnancy
Adenosine - safe
Amiodarone (D)
- associated with congential goiter and transietn neonatal hyperthyroidism and hypothyroidism
- linked to many congential abnormalities including structural cardiac
Dig - safe as houses
B/Blockade ok
Discuss the use of antiHTN
ACE inhibtiors/ARB (D) -
- Embryocidal in animals and increase the rate of stillbirths in some animal species
- most significant adverse affect occurs in the second and third trimesters including (oligohydraminios, anuria, renal agenesis, IUGR)
B/Blockade - first line in treatment of htn emergencies in pregnant ladies
Ca channel also appear to be safe
