Special Populations - Pregs and Kiddos

CO, GFR, renal blood flow, Creatine clearance, uterine blood flow (exponentially)

Which physiological mechanisms INCREASE in pregnancy?

speed of gastric emptying slows, intestinal motility

Which physiological mechanisms DECREASE in pregnancy?

total body weight, total fat mass, total body water, RBC volume

Which anatomical and functional changes in pregnancy INCREASE?

Hematocrit, albumin (acidic drugs), AAG (basic drugs)

Which anatomical and functional changes in pregnancy DECREASE?

Hepatic blood flow

Which anatomical and functional changes in pregnancy have no significant change?

Inhibits

How does estrogen affect CYP enzymes

induces

How does progesterone affect CYP enzymes

decreased protein binding, fetoplacental growth

What leads to the increased Vd in pregnancy?

Increased Vd, Decreased compliance, slowed oral absorption, enzyme induction/inhibition, Increased renal blood flow

How is Drug concentration clearance affected in pregnancy?

N/V (common in 1st trimester), acid reflux (antacids, Al-containing antacids), prenatal vitamins (Fe), Delayed gastric emptying, decreased intestinal motility

How is oral absorption affected in Pregnancy?

Increased CO and hyperventilation, increased alveolar uptake (decease doses of general anesthesia)

How is pulmonary absorption affected in pregnancy?

Decreased blood flow to lower extremities, Increased peripheral vasodilation (increase transdermal)

How are IM/SC/transdermal absorption affected in pregnancy?

CYP enzymes (affected by progesterone and estrogen) and efflux pumps (PgP)

What are the natural protection mechanisms at the placenta?

Lipid soluble (weak bases), unbound, small drugs

What type of drugs can cross the placenta?

meperidine, propranolol, lidocaine, morphine

Examples of weak bases that get trapped in the fetal blood stream (baby is more acidic)

Heparin or LMWH (BIG molecules)

What is the anticoag of choice for pregnancy?

Insulin

What is the anti-glycemic of choice for pregnancy?

3-11 weeks (1st trimester - avoid the big, bads here)

When is the greatest risk of teratogenesis?

Statins, ACEIs, ARBs, ARNI, warfarin, EtOH, tobacco, Barbiturates, Carbamazepine, phenytoin, valproic acid, tetracyclines, NSAIDs

What are some examples of teratogens?

gross structural malformations, permanent alterations in function, affects placenta, stimulates forceful uterine contractions (misoprostol)

Teratogenic effects

Thalidomide (sedative used for morning sickness - led to phocomelia)

What is was the 1st documented teratogen?

A (human evidence that is safe), B (animal evidence that is safe), C (animal evidence for harm), D (human evidence of harm), X (for sure a no go)

OG teratogenic classifications

Puts the decision back into the provider and patient’s hands → use risk/benefit analysis

How does the new labeling for pregnancy and lactation work?

Effect on fetus vs. untreated maternal, placenta barrier, use the smallest dose and titrate

When treating pregnant women, what do we need to think about in terms of risk vs. benefit?

HIV drugs (prevent perinatal transmission), Digoxin (fetal tachyarrythmias)

Examples of fetal therapeutics (give mom drug to affect baby)

1st 4 weeks (<31 days)

How old are neonates?

1-12 months

How old are infants?

1-12 years

How old are children?

12-18 years

How old are adolescents?

65+

How old is considered elderly?

unionized, lipid soluble, unbound drugs move by passive diffusion

How are drugs transferred into the breast milk?

no drugs (if possible) 4 hours before feeding, feed right before taking the dose, think about things with long T1/2 (norfluoxetine, normeperidine, morphine 6G)

How can breast-feeding mothers decrease drug exposure to the infant?

6-8 months

Kids have delayed gastric emptying until

Increased absorption of acid labile drugs (PCN)

Since kids have a lower pH, how does this affect drug absorption?

Elixir, Suspension (mix before hand), IM (0.5 ml for infants, 1 ml for child)

What route of administrations are better for kids?

Water soluble drugs have higher Vd that will decrease with maturity (vice versa for lipids)

As we age we lose water and gain fat, how does this affect Vd?

Competitive binding from bili (displacement leads to CNS entry and kernicterus)

Since newborns have decreased plasma proteins, what are we worried about?

CYP activity matures by 6 months (risk of overdose and then underdose), glucuronidation formation reaches adult by 3-4, Liver metabolism is rapid compared to an adult, tubular secretions doesn’t reach adulthood until 6-7 months

Why is it important to titrate doses to therapeutic effects in kids?

they have decreased muscle mass so renal function may be worse than it appears

Why is Serum Creatinine a bad indicator for GFR in kids?

CNS depressant effects (less PgP at BBB)

Neonates are more sensitive to ________.

A guessitmate based on weight (child weight/70 kg) x adult dose

What is Clark’s rule?

A guessitmate based on age (under 2); [Age/(age+12)] x adult dose

What is Young’s rule?

A guessitmate based on Body surface area; (Child BSA/1.76) x adult dose

What is Catzel’s rule?