Transcript Chapter 16 Cholinesterase Inhibitors

Drug Therapy During
Pregnancy and
Breast-Feeding
1
Clinical Goal
Provide effective treatment for
mother while avoiding harm to
fetus or nursing infant
2
Basic Considerations
● Availability of data
● Drug use during pregnancy
● To treat or not treat conditions in the mother
● Avoid drug therapy if at all possible
3
Physiological Changes during
Pregnancy
• Renal blood flow
• Hepatic metabolism
• Tone & motility of the bowel
4
Example
• Seizure disorder – can the mother go without
controlling the condition?
– No, unsafe
• Which drug to use? Least teratogenic
– carbamazepine
• What are the pharmacokinetic considerations for
achieving therapeutic effects?
– Hepatic metabolism increased (enzyme
induction)
– Increased plasma vol = lower concentrations
5
Placental Drug Transfer
• Same pharmacokinetics as before
– if lipid soluble, cross easily
– If ionized, highly polar, cross with
difficulty
• Assume that any drug taken during
pregnancy will reach the fetus
6
Adverse Reactions during
Pregnancy
Examples – if woman is on:
Pain relievers -  resp in neonate
ASA – can suppress contractions in labor; 
risk of bleeding
Dependence-producing drugs – infant will go
through withdrawal syndrome
Heparin – causes osteoporosis
• Greatest concern - teratogenesis
7
Teratogenesis
• Incidence and causes of congenital anomalies
• Gross malformations, behavioral and biochemical
anomalies
• Teratogenesis and stage of development
– Preimplantation/presomite (conception – wk 2)
– Embryonic (wk 3 – wk 8)
– Fetal period (wk 9 – term)
• Identification of teratogens
8
Figure 9-1 Effects of teratogens at various stages of development of the fetus. (From
Moore KL: The Developing Human: Clinically Oriented Embryology, 5th ed. Philadelphia: WB
Saunders Company, 1993. With permission.)
9
Teratogenesis
Identification of teratogens
Why so difficult? – page 89
Classification of a teratogen
10
FDA pregnancy risk categories
The FDA has established five categories (A, B, C, D, and X) to indicate a drug's
potential for causing teratogenicity.
A - Controlled studies in women fail to demonstrate a risk to the fetus in the first
trimester, and the possibility of fetal harm appears remote.
B - Animal studies do not indicate a risk to the fetus and there are no controlled
human studies, or animal studies do show an adverse effect on the fetus but
well-controlled studies in pregnant women have failed to demonstrate a risk to
the fetus.
C - Studies have’ shown that the drug exerts animal teratogenic or embryocidal
effects, but there are no controlled studies in women, or no studies are available
in either animals or women.
D - Positive evidence of human fetal risk exists, but benefits in certain situations
(e.g., life-threatening situations or serious diseases for which safer drugs cannot
be used or are ineffective) may make use of the drug acceptable despite its
risks.
X - Studies in animals or humans have demonstrated fetal abnormalities or there is
evidence of fetal risk based on human experience, or both, and the risk dearly
outweighs any possible benefit.
11
Teratogenesis
• Minimizing the risk of teratogenesis
• Responding to teratogen exposure
12
Case
Sherri - 28 y/o F. At primary care for referral to
antepartum care. Positive home pregnancy test, LMP
6 weeks ago.
• PMH: seasonal asthma, hypothyroidism,
depression.
• Medications:
– Thyroid hormone, 125 mcg daily, for hypothyroid
– Albuterol MDI, 1-2 puffs PRN for asthma
– Flovent (fluticasone) MDI, 1 puff/day for asthma
– Zoloft (sertraline) 150 mg/d for depression
– Ibuprofen, 400 mg, PRN, for headache
13
Drug Therapy During
Breast-Feeding
• Extent of drug entry into breast milk
varies
• If drugs need to be used:
– Dose immediately after breast-feeding
– Avoid drugs that have a long half-life
14
Principles of Therapy During
Breastfeeding
• Is the drug therapy necessary?
• What is the safest option for the infant?
• If there’s the possibility of harm, monitor
infant blood levels of the drug.
• Minimize infant exposure.
– American Academy of Pediatrics
15
Examples to consider
• Immune suppressants (e.g.,
cyclosporine. methotrexate)
• Amiodarone & antithyroid drugs
• Benzodiazepines, anticonvulsants,
antihistamine – watch for sedation
• Caffeine – high infant exposure =
irritability
16
Drug Therapy in Pediatric
Patients
17
Pediatric Patients
Respond differently to drugs
Drug sensitivity results from organ
system immaturity
Why insufficient drug info?
18
Pharmacokinetics: Neonates and Infants
• Drug levels differ between infants and adults
•
•
•
•
Absorption
Distribution
Hepatic metabolism
Renal excretion
19
Pharmacokinetics:
Neonates and Infants
• Absorption
– Oral administration
• Gastric emptying time
• Gastric acidity
– Intramuscular administration
– Percutaneous absorption
20
Pharmacokinetics:
Neonates and Infants
• Distribution
– Protein binding
– Blood-brain barrier
• Hepatic metabolism
• Renal excretion
21
Pharmacokinetics: Children
Aged 1 Year and Older
22
Adverse Drug Reactions
23
Dosage Determination
• Approximate dosage for a child =
Body surface area of the child × adult dose
1.73 m²
24
Promoting Adherence
Effective education is critical. The following
issues should be addressed:
•
•
•
•
•
Administration timing and dose
Administration route and technique
Treatment duration
Drug storage
Nature and time course of desired
responses
• Nature and time course of adverse
responses
25