Extra Pharm

Question 1

What factors are unique about neonatal devo pharmacokinetics?

Answer 1

• Slower GI, but faster IM absorption
• More body water than lipid in early life
• Limited protein binding
• Larger liver/body weight ratio (and brain/body weight)
• Immature enzymes
• Higher BBB permeability
• Immature renal function

Question 2

How can drug 1/2 lives vary in neonates/young children?

Answer 2

• Half-lives are longer in the neonate than the young child or adult
• Dose adjustment may be necessary on an ongoing basis: ex of Phenytoin pharmacokinetics changing as the neonate ages, even over a period of days

Question 3

How should drugs be adjusted for neonates?

Answer 3

• Based on weight or surface area ratio to adults

Question 4

How does breast milk affect drug transfer to the infant?

Answer 4

• Acidic pH and high fat content, so will concentrate bases and lipid-soluble drugs
• Lower transfer of highly protein-bound drugs
• Drugs with shorter half-lives preferred; dose immediately after feeding, allowing levels to decline
• Most cautious in early post-partum -> alveolar cells in breast milk buds mature in response to prolactin, reducing drug transfer to milk

Question 5

Breastfeeding: Chloral hydrate

Answer 5

Drowsiness if fed at peak concentrations

Question 6

Breastfeeding: Chloramphenicol

Answer 6

• Antimicrobial
• Grey baby syndrome if given directly to infant: vomiting, grey skin, hypotension, CV collapse, etc.
• Blood dyscrasias and bone marrow suppression if exposed via breast milk

Question 7

Breastfeeding: Diazepam

Answer 7

Sedation; accumulation in neonates

Question 8

Breastfeeding: Heroin

Answer 8

Can produce narcotic dependence

Question 9

Breastfeeding: Iodine (labeled)

Answer 9

Thyroid suppression

Question 10

Breastfeeding: Lithium

Answer 10

Avoid unless levels quantitated

Question 11

Breastfeeding: Methadone

Answer 11

Withdrawal if drug interrupted

Question 12

Breastfeeding: PTU

Answer 12

Thyroid suppressed

Question 13

Oxytocin

Answer 13

• Most common drug used to induce labor
• Half-life 10-12 minutes; discontinuation of the drug an effective way to alleviate adverse effects (MC: uterine hyperstimulation)
• Excessive doses can predispose to post-partum bleeding
  1. Can also cause hyponatremia due to anti-diuretic effect

Question 14

Dinoprostone

Answer 14

• PGE2: timed-release suppository left in place for 12 hours -> can be removed if hyperstimulation occurs
• Cervical ripening
• GI side effects and fever uncommon with vaginal administration
• Can start Oxytocin 30-60 min after removal

Question 15

Misoprostol

Answer 15

• PGE1
• Intravaginal tablets Q3-6 hrs
• Oxytocin should NOT be given within 4 hours of last dose

Question 16

Carboprost tromethamine

Answer 16

• PGF-2-alpha
• Oxytocic properties (labor induction), and can reduce post-partum bleeding

Question 17

Magnesium sulfate

Answer 17

• Parenteral: anti-convulsant that depresses the CNS and blocks peripheral neuromuscular transmission
• To treat hypomagnesemia
• Prevent/control preeclampsia/eclampsia; contraindicated in women with Myasthenia Gravis
• IV: immediate effect, lasting 30 minutes
  1. IM: onset in 1 hour, and lasts around 4 hours
• Crosses placenta, and excreted into breast milk, but no reported problems
• Renal excretion: Mg reabsorbed -> impaired renal function can lead to toxicity, characterized by flushing, nausea, blurry vision, headache, hypotension, and pulm edema
• Orally: laxative effect

Question 18

Indomethacin

Answer 18

• Non-selective COX INH: delays/prevents premature parturition
• Loading dose, followed by more doses Q6hrs
• Maternal side effects: related to GI tract (N/V, gastritis, reflux), platelet dysfunction
• Fetal side effects: premature closure of ductus arteriosus, oligohydramnios
• Seems to be safe and effective as a tocolytic when used for a short period of time

Question 19

Menotropin

Answer 19

• From urine of post-menopausal women
• Contains FSH, LH (IM injection) -> INFERTILITY TX
• Recombinant FSH also used subq

Question 20

How does estrogen affect protein synthesis?

Answer 20

• INC synthesis of several hepatic proteins: TBG, transcortin, SHBG, clotting factors

Question 21

Ethinyl estradiol

Answer 21

• Synthetic estrogen -> ethinyl groups greatly reduce hepatic metabolism (can’t give native estrogens orally)

Question 22

Clomiphene/Fulvestrant

Answer 22

• Ovulation induction for infertility in anovulatory women
• Anti-estrogens (SERD’s)
• Act on ER’s in the hypothalamus to block feedback INH of natural estrogens and stimulate release of GnRH, which stimulates pituitary to INC LH and FSH secretion, leading to ovulation
• Can be used to treat PCOS

Question 23

Minipill

Answer 23

• Low-dose progestin: blocks ovulation in 60-80% of cycles
• Impairs sperm transport by thickening cervical mucus
• DEC motility of ovules in oviduct, altering endo to impair implantation
• Taken daily and continuously
• Best for women who are breastfeeding or over 35 and smoke
• May cause acne and weight gain

Question 24

How can combo pills be used to treat PCOS?

Answer 24

• Used “off-label”
• Reduced dysfunctional uterine bleeding, and dysmenorrhea
• Menstrual regularity, INC hemoglobin
• Raise SHBG, DEC androgens, so less hirsutism and acne

Question 25

Who can't use the transdermal combo patch?

Answer 25

- Women \>90kg because too much adipose tissue

Question 26

Depo-provera

Answer 26

- Progesterone only =\> usually medroxyprogesterone - _Injected every 3 months_ - Amenorrhea common, but irregular bleeding can occur - AE's: weight gain, headache, _DEC bone density_ - Discontinue after 2 years, unless no other alternative -\> _6-12 mo delayed fertility_

Question 27

Copper IUD

Answer 27

- 10-15 years - Spermicidal -\> fertility quickly restored upon removal - FDA-approved for dysmenorrhea bc \< blood loss - AE's: copper may cause cramping

Question 28

Mifepristone

Answer 28

- Blocks binding of progesterone to its receptor - FDA-approved for termination of pregnancy - Main side effect is abdominal cramping

Question 29

Spironolactone

Answer 29

- Primarily used as an aldosterone antagonist for the tx of primary or secondary hyperaldosterism or as an antihypertensive (diuretic) - Competes for testosterone receptor - Used as a treatment for hirsuitism in women