Pregnancy Pharmacology Flashcards
(110 cards)
1
Q
What is pharmacokinetics?
A
It describes ‘what the body does to the drug’
2
Q
What are the four basic pharmacokinetic processes?
A
Absorption
Distribution
Metabolism
Excretion
3
Q
During pregnancy, how is the absorption of drugs via the oral route affected? Why?
A
Decreased
This is due to a decrease in gastric emptying and gut motility
4
Q
During pregnancy, how is the absorption of drugs via the intramuscular route affected? Why?
A
Increased
This is due to an increased blood flow
5
Q
During pregnancy, how is the absorption of drugs via the inhalation route affected? Why?
A
Increased
This is due to an increased cardiac output and decreased tidal volume
6
Q
During pregnancy, how is the distribution of drugs affected? Why?
A
Increased
This is due to the fact that there is an increase in plasma volume and fat
7
Q
During pregnancy, how is the fraction of free (active) drugs affected? Why?
A
Increased
This is due to a greater dilution of plasma, decreasing the relative amount of plasma proteins
8
Q
During pregnancy, how is the metabolism of drugs affected? Why?
A
Increased or reduced
This is due to the fact that oestrogen and progesterone can induce or inhibit liver P450 enzymes
9
Q
During pregnancy, how is the excretion of drugs affected? Why?
A
Increased
This is due to the fact that GFR is increased in pregnancy by 50%
10
Q
How do drugs enter fetal circulation?
A
Placenta
11
Q
What are the three factors which affect the placental transfer of drugs?
A
Molecular Weight
Polarity
Lipid Solubility
12
Q
How does molecular weight affect the placental transfer of drugs?
A
The smaller molecular weight molecules cross the placenta more readily
13
Q
How does polarity affect the placental transfer of drugs?
A
The unionised molecules cross the placenta more readily
14
Q
How does lipid solubility affect the placental transfer of drugs?
A
The lipid soluble molecules cross the placenta more readily
15
Q
Why does the distribution of drugs differ in the foetus compared to the mother?
A
Fetal circulation is different, with relatively more blood flow to the brain in comparison to the mother
The fetus also has little fat in comparison to the mother
16
Q
How does the fraction of free (active) drugs differ in the foetus compared to the mother? Why?
A
It is greater in the foetus
This is due to there being less protein binding
17
Q
Why does the metabolism of drugs differ in the foetus compared to the mother?
A
Reduced enzyme activity
The different exhibition of P450 isoenzymes
18
Q
In the fetus, what does enzyme activity increase with?
A
Gestational age
19
Q
How do excretions from the foetus exit? How can this lead to drug toxicity?
A
Excretions exit into the amniotic fluid, which the fetus then swallows
This leads to recirculation, which can potentially lead to drug toxicity in the fetus
20
Q
What is pharmacodynamics?
A
It describes ‘what the drug does to the body’
21
Q
In what two ways does pregnancy affect pharmacodynamics?
A
It affects the site of drug action
It affects the receptor response of drugs
22
Q
Why is it important that medications are reviewed once a patient becomes pregnant?
A
During pregnancy, medications impose a risk of teratogenicity and fetotoxicity
23
Q
When does teratogenicity tend to occur?
A
First trimester
24
Q
When does fetotoxicity tend to occur?
A
Second and third trimester
25
What nine drug classes need reviewed during pregnancy?
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Beta-Blockers
ACE Inhibitors & Angiotensin II Receptor Blockers (ARBs)
Opiates
Anticoagulants
Anticonvulsants
Antipsychotics
Selective Serotonin Receptor Inhibitors (SSRIs)
Retinoids
26
List two examples of NSAIDs
Ibuprofen
Naproxen
27
How do NSAIDs work?
They block the hormone prostaglandins
28
What are the two functions of prostaglandins during pregnancy?
It maintains the ductus arteriosus
It softens the cervix and stimulates uterine contractions at the time of delivery
29
What advice is given regarding NSAIDs during pregnancy?
They are generally avoided, unless really necessary
30
In which trimester is NSAIDs particularly avoided during pregnancy?
Third trimester
31
Why are NSAIDs avoided during pregnancy (two reasons)?
They can cause premature closure of the ductus arteriosus in the fetus
They can delay labour
32
Through which mechanism do NSAIDs produce teratogenic effects? Describe this mechanism
Enzyme mediated teratogenesis
This means that these drugs interact with specific receptors and enzymes to damage fetal development
33
What beta-blocker is most frequently prescribed during pregnancy?
Labetalol
34
What advice is given regarding beta-blockers during pregnancy?
There are certain beta blockers prescribed during pregnancy, however it is important to advice patients of the possible teratogenic effects
35
What are the three teratogenic effects of beta-blockers?
Fetal Growth Retardation
Neonatal Hypoglycaemia
Neonatal Bradycardia
36
How do ACEI and ARBs work?
They block the renin-angiotensin system (RAAS).
37
What are the four teratogenic effects of ACEIs and ARBs?
Renal Dysfunction
Growth Retardation
Hypocalvaria
Oligohydramnios
38
What is hypocalvaria?
It is incomplete skull bone formation
39
Can opiates cross the placenta?
Yes
40
Does opiate misuse interfere with pregnancy or labour?
No
The effects occur after delivery
41
What is the teratogenic effect of opiates?
They can cause withdrawal symptoms in the neonate after birth
This is referred to as neonatal abstinence syndrome (NAS)
42
When does neonatal abstinence syndrome (NAS) present?
Between 3 – 72 hours after birth
43
What are the four clinical features of neonatal abstinence syndrome (NAS)?
Irritability
Tachypnoea
High temperature
Poor feeding
44
When does heroin withdrawal occur in the neonate?
Immediately after delivery
45
When does methadone withdrawal occur in the neonate?
Three weeks after delivery
46
What anticoagulant is particularly avoided during pregnancy?
Warfarin
47
What are the three teratogenic effects of Warfarin?
Fetal Loss
CNS Malformations
Haemorrhage
48
What three anticonvulsants are particularly avoided during pregnancy?
Sodium valproate
Carbamazepine
Phenytoin
49
What advice is given regarding anticonvulsants during pregnancy?
They are strictly avoided in women of childbearing age unless there are no suitable alternatives
In cases, where they are prescribed, there are strict guidelines to ensure that these patients don’t become pregnant
50
What are the two teratogenic effects of anticonvulsants?
Neural tube defects
Developmental delay
51
Through which mechanism do anticonvulsants produce teratogenic effects? Describe this mechanism
Folate antagonism
Folate metabolism is a key process in DNA formation and new cell production. However, anticonvulsant drugs block enzymes in this metabolic pathway and thus cause fetal malformations.
52
What antipsychotic is particularly avoided during pregnancy?
Lithium
53
What advice is given regarding lithium during pregnancy?
It is avoided in pregnant women or those planning pregnancy, unless other options have failed
If Lithium is prescribed, close monitoring is required
Lithium also enters breast milk and is toxic to the infant, so should also be avoided in breastfeeding
54
How often should lithium levels be monitored during pregnancy?
Every four weeks
Weekly from 36 weeks
55
In which trimester should lithium be particularly avoided?
First trimester
56
What is the teratogenic effect of lithium?
Congenital cardiac abnormalities, specifically Ebstein’s anomaly
57
What is Ebstein's anomaly?
A condition in which the tricuspid valve is set lower on the right side of the heart, causing a bigger right atrium and a smaller right ventricle
58
What are the most commonly prescribed antidepressants during pregnancy?
SSRIs
59
What advice is given regarding SSRIs during pregnancy?
Despite there being teratogenic effects associated with these drugs, the benefits of treatment outweigh risks
60
What is the teratogenic effect of SSRIs during the first trimester?
Congenital heart defects
61
What is the teratogenic effect of SSRIs during the third trimester?
Neonatal pulmonary hypertension
62
What is the teratogenic effect of SSRIs in neonates?
Withdrawal symptoms
63
Which SSRI has a strong association with congenital malformations in the first trimester?
Paroxetine
64
What retinoid is particularly avoided during pregnancy?
Isotretinoin (Roaccutane)
65
What advice is given regarding roaccutane during pregnancy?
It is a highly teratogenic drug, which requires women to be on reliable contraception before, during and one month after taking this medication
66
What are the six teratogenic effects of retinoids?
Aortic Arch Anomalies
Ventricular Septal Defects
Craniofacial Malformations
Oesophageal Atresia
Pharyngeal Gland Abnormalities
Miscarriage
67
Through which mechanism do retinoids produce teratogenic effects? Describe this mechanism
Neural crest cell destruction
Neural crest cells are cells induced at the border of the neural plate, which differentiate into multiple cell types contributing to the peripheral nervous system and the cranio-facial structure
68
Through which mechanism do methotrexate and trimethoprim produce teratogenic effects? Describe this mechanism
Folate antagonism
These drugs block the conversion of folate to tetrahydrofolate by binding irreversibly to the tetrahydrofolate reductase enzyme
69
What are the three teratogenic effects of methotrexate and trimethoprim?
Neural tube defects
Cranial-facial defects
Limb defects
70
Do drugs consumed by the mother present in breast milk?
Yes
71
How do we determine generally if a drug is safe during breastfeeding?
Drugs licenced and safe in paediatric use, especially in those under the age of two, are thought to be safe in breastfeeding
72
What advice is given in regards to drugs during breastfeeding?
In some cases, it is possible to postpone drug treatment until the baby is weaned
If there are no alternatives and the drug needs to be prescribed, then we advise the mother to take the medication immediately after feeding the baby and to avoid breastfeeding during peak drug effect.
It is also advised that clinicians prescribe drugs with pharmacokinetic properties that reduce infant exposure
73
What three pharmacokinetic properties reduce infant exposure to drugs during breastfeeding?
Short half-life
Highly protein bound
Low lipid solubility
74
What are eleven drugs should be avoided during breastfeeding?
Tetracycline
Isoniazid
Barbiturates
Diazepam
Methadone
Iodine
Propylthiouracil
Amiodarone
Lithium
Radioiodine
Coedine
75
What is the teratogenic effect of tetracycline during breastfeeding?
Permanent tooth staining
76
What is the teratogenic effect of isoniazid during breastfeeding?
Pyridoxine deficiency
77
What are the three teratogenic effect of barbiturates during breastfeeding?
Lethargy
Sedation
Poor Suck Reflexes
78
What is the teratogenic effect of diazepam during breastfeeding?
Sedation
79
What is the teratogenic effect of methadone during breastfeeding?
Withdrawal symptoms
80
What are the two teratogenic effects of iodine during breastfeeding?
Thyroid suppression
Cancer risk
81
What is the teratogenic effect of propylthiouracil during breastfeeding?
Thyroid suppression
82
What is the teratogenic effect of codeine during breastfeeding?
Infant opiate toxicity
83
What two ingredients contained in herbal medicines pose a risk to the infant?
Fenugreek
Comfrey
84
What ingredient contained in herbal medicines poses a risk to the infant and mother?
Pyrrolizidine alkaloids (PAs)
85
What is the first line treatment option for nausea and vomiting during pregnancy?
Antihistamines (cyclizine)
Phenothiazines (prochlorperazine)
86
What is the second line treatment option for nausea and vomiting during pregnancy?
Ondansetron
Metoclopramide
87
What is the first line treatment option for hypertension during pregnancy? What class of drug is this?
Labetalol
Betablocker
88
What is the second line treatment option for hypertension during pregnancy? What class of drug is this?
Nifedipine
Calcium channel blocker
89
What is the third line treatment option for hypertension during pregnancy? What class of drug is this?
Methyldopa
Alpha-2 adrenergic agonist
90
What is the first line treatment option for epilepsy during pregnancy?
Lamotrigine
91
What other drug do we prescribe epilepsy patients during pregnancy, apart from anti-epileptics?
These patients also require a higher dose of folic acid (5mg) compared to other pregnant patients
92
What advice is given in regards to treating diabetic patients during pregnancy?
All oral antidiabetic drugs, except metformin, should be discontinued before pregnancy and substituted with insulin therapy
93
What advice is given in regards to treating diabetic patients with metformin during pregnancy?
Diabetic patients can be treated with metformin as an alternative to insulin in the preconception period and during pregnancy
It can be continued immediately after birth and during breast-feeding
94
What advice is given in regards to treating diabetic patients during breastfeeding?
Insulin and metformin can be prescribed
All other antidiabetic drugs should be avoided while breastfeeding
95
What is the first line treatment option for thromboembolism during pregnancy?
Low molecular weight heparin (LMWH)
96
What advice is given in regards to treating asthma patients during pregnancy?
Asthma medications can be used as normal, and patients should be counselled about the importance and safety of taking their medications to maintain good control
97
What asthma medication requires close monitoring during pregnancy? Why?
Theophylline
Due to its potential toxicity
98
What is the first line treatment option for migraines during pregnancy?
Paracetamol
99
What is the second line treatment option for migraines during pregnancy?
Sumatriptan
Ibuprofen
100
When can ibuprofen be considered as a second line treatment option for migraines during pregnancy?
It should only be considered as a treatment option in the first and second trimesters
101
What is the first line treatment option for depression during pregnancy?
Selective serotonin receptor inhibitors (SSRIs)
102
What advice is given regarding penicillin antibiotics during pregnancy and breastfeeding?
They are generally considered safe
However, it is important to check with the patient that they haven’t encountered an allergic reaction to penicillin in the past
103
What advice is given regarding cephalosporin antibiotics during pregnancy and breastfeeding?
They are generally considered safe
104
What advice is given regarding macrolide antibiotics during pregnancy and breastfeeding?
Erythromycin is the only macrolide antibiotic considered safe
105
What advice is given regarding tetracycline antibiotics during pregnancy and breastfeeding?
Tetracycline antibiotics should not be prescribed, unless absolutely necessary
106
What are the two teratogenic effects of tetracycline antibiotics?
Skeletal development defects
Discolouration of teeth
107
What advice is given regarding sulphonamide antibiotics during pregnancy and breastfeeding?
Sulphonamide antibiotics should not be prescribed, unless absolutely necessary
108
What are the teratogenic effects of sulphonamide antibiotics? In which trimester are they particularly harmful?
They act as folate antagonists, causing neural tube defects, cranio-facial defects and limb defects
First trimester
109
What advice is given regarding aminoglycoside antibiotics during pregnancy and breastfeeding?
Aminoglycoside antibiotics should not be prescribed, unless absolutely necessary
110
What are the teratogenic effects of aminoglycoside antibiotics?
They have damaging effects on the auditory and vestibular nerves
