Term
| Changes in Pregnancy and How it Impacts Drugs |
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Definition
50% increase in plasma volume and body water
-Drugs (especially water soluble ones) are diluted more than in the nongravid state
-Drug dosage may need to be increased.
-May be offset by other pharmacokinetic changes of pregnancy
Increased weight and body fat
-Drugs (especially lipid soluble) are distributed more widely.
-Durgs that are distrubted to fat tend to stay in the body because they are slowly released from fat stores
Decreased serum albumin. The rate of albumin production is increased.
-Serum levels fall because of plasma volume expansion
-Many plasma protein binding sites are occupied by hormones that increase during pregnancy.
This leads to higher levels of free or unbound drugs
Because of decreased protein binding, a given drose of drug is likely to produce greater effects than it would in the nonprgenant state
-Dexamethasone, Diazepam, Lidocaine, meperidine, Phenobarbital, Phenytoin, Propranolol, Sulfisoxazole
Increased renal blood flow and increased GFR due to increased cardiac output
-Increased exretion of drugs by the kidneys (penicillins, digoxin, and lithium)
In late pregnancy, the increased size and weight of the uterus may decrease renal blood flow in the supine position |
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Term
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Definition
A-Adequate studies demonstrate no risk
B-Animal studies indicate no risk, but there are no adequate studies in pregnant women or animal studies show adverse effects but adequate studies in humans have not demonstrated a risk
C-A potential risk, usually because animal studies have either not been performed or indicated adverse effects, there are no data from human studies (drugs may be used when benefits outweigh risks)
D-Evidence of human fetal risk but benefits may be acceptable despite the potential risk (Seizures)
X- studies in animals or humans or adverse reaction reports or both have demonstrated fetal abnormalities. The risk of use in the pregnant patient outweighs any possible benefit |
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Term
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Definition
Most likely to occur in 1st trimester
In 2nd or 3rd trimester, adverse effects are manifested as growth retardation, respiratory problems, or bleeding |
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Term
| Teratogenicity of ACE Inhibitors |
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Definition
All trimesters
Cause renal damage |
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Term
| Teratogenicity of Androgens |
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Definition
2nd and 3rd trimesters
Masculinization of female fetus |
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Term
| Teratogenicity of Carbamazepine |
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Definition
1st trimester
Neural tube defects
Used for seizures |
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Term
| Teratogenicity of Cocaine |
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Definition
Increased risk of:
Spontaneous abortion
Abruption placentae
Premature labor
Neonatal cerebral infarction
Abnormal development
Decreased school performance |
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Term
| Teratogenicity of Diethylstilbestrol |
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Definition
Female offspring:
Vaginal adenosis
Clear cell vaginal adenocarcinoma
All trimesters
Indications: threatened miscarriages in 70s |
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Term
| Teratogenicity of Ethanol |
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Definition
All trimesters
Fetal alcohol syndrome and alcohol-related neurodevelopmental defects |
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Term
| Signs of Fetal Alcohol Syndrome |
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Definition
Retarded body growth
Microcephaly
Underdevelopment of midfacial region
Minor joint abnormalities |
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Term
| Teratogenicity of Isoretinoin |
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Definition
All trimesters
Extremely high risk of CNS, face, ear, and other malformations
Ear malformations most prevalent
External ear is malformed
Ear canal is absent (child is deaf) |
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Term
| Teratogencity of Phenytoin |
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Definition
All trimesters
Fetal hydantoin syndrome |
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Term
| Signs of Fetal Hydantoin syndrome |
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Definition
Congenital malformations:
Cleft lip/palate
Heart malformations
Microcephaly and mental deficiency |
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Term
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Definition
All trimesters
Intrauterine growth retardation
Prematurity
SIDS
Perinatal complications |
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Term
| Teratogenicity of Tetracycline |
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Definition
All trimesters
Discoloration and defects of teeth and malformation of bone
Contraindicated in small children as well |
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Term
| Teratogenicity of Thalidomide |
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Definition
Category X
First trimester
Phocomelia (shortened or absent long bones) and many internal malformations
Given as sedative in Europe (now used in treating cancers and leprosy) |
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Term
| Teratogenicity of Valproic Acid |
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Definition
All trimesters
Neural tube defect |
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Term
| Teratogenicity of Warfarin |
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Definition
1st trimester: hypoplastic nasal bridge, chondrodysplasia
2nd: CNS malformations
3rd: Risk of bleeding (discontinue one month before delivery)
Can use subq heparin instead |
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Term
| % Risk of Neonatal Abnormality in Absence of any teratogenic exposure |
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Definition
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Term
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Definition
IM absorption is erratic due to decreased muscle mass and poor peripheral perfusion
GI absorption- decreased gastric acid secretion, prolonged gastric emptying
Intestinal peristalsis is slow and irregular (increases drug absorption)
GI enzyme activity is diminished
Decreased concentrations of bile acids which may decrease the absorption of lipid soluble drugs |
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Term
| % Total body water at various stages |
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Definition
Small preterm neonate 85%
Full term neonate 70-75%
Adult 50-60%
For water soluble drugs such as aminoglycosides, the size of the extracellular water compartment is important in determining concentration of drug |
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Term
| % Total Body Fat at various stages |
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Definition
Preterm infants 1%
Full term infants 15%
Lipid soluble drugs will accumulate to a smaller degree in the preterm infant |
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Term
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Definition
Protein binding of drugs is reduced in the neonate
Therefore the concentration of the free (active) drug is increased
Some drugs compete with bilirubin for binding to albumin
-Sulfonamide antibiotics can cause hyperbilirubinemia
-Avoid in first 4-6 weeks of life
-Will displace bilirubin |
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Term
| Hepatic Metabolism in Infant |
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Definition
Glucuronidation pathway not fully mature until age 3-4
Neonatal cytochrome P450 pathways operate at 50-70% of adult levels |
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Term
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Definition
Decreased GFR of adult values
-Drugs which depend on renal function for elimination are cleared very slowly
-Penicillins are cleared at 17% of the adult rate based on BSA
Amoxicillin/Ampicillin is dosed less |
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Term
| Drug that speeds closure of Patent Ductus Arteriosus |
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Definition
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Term
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Definition
Elixir- alcoholic solutions, no shaking required
Suspension- contain undissolved particles that must be shaken to distribute
Chewable tabs- accurate dosing, no need to refrigerate |
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Term
| Drugs with significant effect on Nursing Infant |
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Definition
Chloral hydrate (sedative)
Diazepam
Ethanol
Narcotics
Radioactive iodine
Lithium
PTU
Tetracycline
Barbiturates |
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Term
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Definition
Dose = adult dose x age (years)/age+ 12
Dose = adult dose x weight (kg)/70
Dose = adult dose x weight (lb)/150 |
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