Chapter 16 Cholinesterase Inhibitors

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Transcript Chapter 16 Cholinesterase Inhibitors

Drug Therapy During
Pregnancy and
Breast-Feeding
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Clinical Goal
Provide effective treatment for
mother while avoiding harm to
fetus or nursing infant
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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
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Physiological Changes during
Pregnancy
• Renal blood flow
• Hepatic metabolism
• Tone & motility of the bowel
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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
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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
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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
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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
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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.)
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Teratogenesis
Identification of teratogens
Why so difficult? – page 89
Classification of a teratogen
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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.
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Teratogenesis
• Minimizing the risk of teratogenesis
• Responding to teratogen exposure
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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
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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
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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
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Examples to consider
• Immune suppressants (e.g.,
cyclosporine. methotrexate)
• Amiodarone & antithyroid drugs
• Benzodiazepines, anticonvulsants,
antihistamine – watch for sedation
• Caffeine – high infant exposure =
irritability
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Drug Therapy in Pediatric
Patients
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Pediatric Patients
Respond differently to drugs
Drug sensitivity results from organ
system immaturity
Why insufficient drug info?
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Pharmacokinetics: Neonates and Infants
• Drug levels differ between infants and adults
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Absorption
Distribution
Hepatic metabolism
Renal excretion
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Pharmacokinetics:
Neonates and Infants
• Absorption
– Oral administration
• Gastric emptying time
• Gastric acidity
– Intramuscular administration
– Percutaneous absorption
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Pharmacokinetics:
Neonates and Infants
• Distribution
– Protein binding
– Blood-brain barrier
• Hepatic metabolism
• Renal excretion
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Pharmacokinetics: Children
Aged 1 Year and Older
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Adverse Drug Reactions
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Dosage Determination
• Approximate dosage for a child =
Body surface area of the child × adult dose
1.73 m²
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Promoting Adherence
Effective education is critical. The following
issues should be addressed:
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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
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