Perinatal and Pediatric Pharm Flashcards
at which stages in pregnancy are we most concerned for the teratogenic effects of medications
teratogenic effects most detrimental during week 4-17 as this is when most growth of somatic orgin is occuring
Damange during week 4-17 = will result in malformations of the fetus (impacting organogenesis)
Teratogenicity
- defined the capibility of producing fetal malformations
- results in cahracterisitics, sets of malformation sydnromes
- a dose-dependnet phenomenon: more use = more effect
- only 3% of tertogenicity is meds: but we can control for these!!!
How do drugs make their way across the placenta
drug aspects which impact delivery across the placenta
Delivery Across Placenta
- passive diffusion is the most common way
other ways include
- active transport
- faciliated diffusion
- phagocytosis
- pinocytosis
Drug-Drug Factors Infleunce
- molecular weight
- lipid solubility
- polarity
- degree of protein binding
how do the certian drug factors impact placental crossing
Molecular Weight
- smaller molecules = more likely to pass
- those > 3000 are unlikely to pass
Lipid Solubility
- those more lipid soluable: hydrophobic, lipophilic will cross
- this is because the placenta is a lipid bylater
Polarity
- non-polar molecules more likely to pass
- Fetal environementmore aciding: so those which are polar if they cross may get trapped
Protein Bounding
- those which are higly protein bound are less likely to cross
- becuase free = active!
how does pregnancy physiology affect drugs action in the body (ADME)
absorbtion
Absorbtion
- morning sickness: likely to expel meds before they get absorbed
- increased gastric pH: stomach becomes more basic: thus things which rely on a more acidic environment are likely to be altered
- gastic and GI motility decrese in pregnancy: thus meds stick around much longer int eh GI tract: less excretion and more time to be absorbed
how does pregnancy physiology affect drugs action in the body (ADME)
Distribution
Distribution of drugs in preganncy
Plasma Volume
- increased plasma volume in pregnancy: albumin amt. stays relatively the same: thus a false dilution effects: need to measure free drug amounts rather than total or bound!
Cardiac Output
- increased HR and stroke vlume
- thuse a decrease in systemic vascualr resistance, decreased BP
Increased Total Body Water
- expanded intravascualr volume but ALSO increased extravascular volume (third spacing)
- increased Vd of the hydrophilic drugs: the water-loving meds will be disburused further throughout the body
Increased Total Body Fat
- thuse there is a increase in the Vd of the hydropohbic drugs too
- more fat, more spread of fat loving meds
how does pregnancy physiology affect drugs action in the body (ADME)
Metabolism
Metabolism
pregnancy alters the enzyme activity in the body: specifically the liver CYPs
CYP: 3A4, 2C9, 2D6 all increase in activity = thus medications which get metabolized by these will ahve increased metabolism and “leave” faster
CYP2C19 = decreased activity
clincially: monitor medications which pass and metabolie by teh CYP pathways more frequently
how does pregnancy physiology affect drugs action in the body (ADME)
Excretion
Excretion of Medications
in pregnancy there is an increase in glomeular fileration rate (GFR) = thus there is an increase in renal clearnace of meds which will be excreted renally
NOTE
- there is no reliable way to estimate crcl in pregnancy; as excretion is also influenced by secretion and reabsorbtion
increased GFR = increased clearance
specfically: lithium, lamotrigine, cefazolin
Drug use in Lactation
how do meds pass into breastmilk
similar to how drugs pass through the breast milk:
- through a lipid bilayer
- through passive diffusion
Strategy for Mitigating the Risks of med use while breastfeeding
DRug factors infleuncing ability to pass the breastmilk
select medications which are safe for use in infants
Protein bounding: highly bound meds = less likely to pass
Moleular weight: higher weight = less diffusion (smaller = will diffuse)
Lipid soluabiltiy = lower lipid soluability = less diffusion (more lipid soluable = will pass)
Lower oral bioavailability = not absored by the infant even if it transfers into breast milke
- same as low bioabal. in mom , same in baby
Options for Meds in Breastfeeding: Chronic Medications
Options
- if able, can choose not to treat mom during this time (just monitor condition) = not really possible sometimes
- treat mom with normal medication & monitor infant effects whilte breastfeeding
- treat mom with an alternative medication if possible& monitor mom /baby
Options for Meds in Breastfeeding: Acute Conditions
Acute Conditions: Options
Trreat mom with an agent that is least likely to pass or least likely to cause adverse effects & continue breast feeding
Treat mom with normal agent and recommend stopping breast feeding for a short period of time
- “pump and dump” & used sotred breat milk/frozen for baby in mean time
Timing Strategies for Delivery of Meds to decrease risks associated with Breastfeeding
Breastfeeding & Medication Delivery Timing
Pump & Dump: only appropriate if acute duration of treatment
Timing
mom taking 1x daily med: take it right before the childs longest sleep time (time to get through moms system)
mom taking multiple times a day : take the med immediately after breastfeeding
Medication Considerations for Allergic Rhinitis
- what is safe
- what is to avoid
for pregnancy and BF
intranasal corticosteroids
intranasal antihistamines
oral antihistamines
decongestants
Intranasal Corticosteroids
- considered safe in preganancy and breastfeeding
Intranasal Antihistamines
- pregnancy: low risk
- lactation: probably low risk
Oral Antihistamines
- pregnancy: first generations are preferred (diphenhydramine) ;
- the 2nd gens; avoid in first trimester (if you HAVE to: cetirizine and loraditine)
lactaion: are safe, but the drowsy side effects can be seen in baby
Decongestants
- AVOID IN PREGNANCY: alter blood flow
- potential risk in lactation: avoid
Asthma Medications in BF and Pregnancy
all inhalers are safe in pregnancy and lactation
uncontrolled asthma is associated with adverse pregnancy complications: treat to improve
DM medications in pregnany and BF
insulin
metformin
sulfonyureas
Pregnancy
- insulin is preferred
- metformin and sulfonyureas are low risk
Breastfeeding
- insulin is safe; as the molecule is large and wont pass
- metformin : safe
- sulfonyureas: probabbly safe; otehr classes is unknown
Hypertension medications
BF and Preganancy
Preganancy
ABSLOUTELY AVOID ACE, ARB, DIRECT RENINs
- anything whic directly acts on the kidneys and renin system: need to avoid
- preferref agents labateolo, nifedipine, methyldopa are ok
Lactaion
- most meds are safe
- labetalol and nifedipine are usually just continued from pregnancy
Depression Meds and Pregnancy/breasfeeding
Pregnancy
SSRIs: some are safe and some are to be avoided; if you can swap to the preferred agents, do
- want to start these and continue to avoid MDD and deveoping depression during pregnancy
- preferred agents: sertaline, citalopram & escitalopram
- AVOID: paroxetine, fluoxetine,
- AVOID: bupririon, velafaxine
Lactation
- preferred: sertraline, paroxetine
- avoid: citalopram and fluxoetine
not recommended to use venlaxfaxine, bupriprion
if you can avoid SSRIs during 3rd tri its good
Epilepsy Medications in Pregancy and BF
Pregnancy
- the benefit for mom to be on the med outweighs the risk of damage for phenytonin, carbamazepine and lamotrigine (lamotrigine is least teratogenic)
Risks= phenobarb and topiramate
AVOID: valproic acid = teratogenic
alwasy ensrue theyre taking folic acid!!!
Lactation
- phenytoin and carbamazepine are okay
- avoid: phenobarb. lamortrigine, valproic acid and toperimate
Definitions for Pediatrics and Neonates
preterm: those more before 37 weeks gestation
term: those borns 37 weeks + gestation
neomate = 0-28 days
infant = 1month -12 months
child = 1-12 years old
adolsecent = 12-21 years
Physiological Differences in Peds: Absorbtion
Absorbtion
the gastric pH
- at birth is 6-8 (alkaline)
- the normal adult pH is not acheived until 2 years old
Gut Motility
- neonates: slower (6-8 hours slower) thus more absorbtion occurs
- first few days of life, increased
- adult gastric transit time: by 6 months
skin/muscle composition
- immature epidermis and high hydration
- higher ration of BSA to body mass: impacts topical meds
Physiological Differences in Peds: Distribution
Distrubution of Meds
plasma proteins
- lower concentration of plasma proteins
- lower binding affinity of these protines
- thus you see more free drug and therfore more active drug
- increased competition for the binding sites: increase bilirubin: displaces drugs which may have been bound
Blood Brain Barrier
- not fully developed so more CNS ADE possible
- incomplete CNS myleination and elss efflux pumps able to remove things from teh CNS
- increased CNS side effects
Body Componsition
- Neonates: higher total water composition: 75-85%
- they have a greter amout of extracellular fluid
- less fat tisseu!!
Physiological Differences in Peds: Metabolism
CYP Development
- not fully developed until about 1-2 years old
Sulfation: developed at birth
Glucurondation takes until3 years
Acetlyaion
- developed until 2-4 years
Physiological Differences in Peds: Excretion
Estimating Renal Function
Excretion
newborn kidneys are anatomically and functionally immature!! : there is reduced blood flow and GFR
not fully matrued GFr unitl age 2
Tubular Function
- excretion: reduced until about 15 months
- reeaborsbtion: the last function of the renal system to mature
Estimating Renal Function in those 1week -18 years old
Schwartz Equation : for 1 week old - 18 year olds
CrCL = (length in cm x k)/SCr
Scr varies by length and age of child
How is Neonatal dosing determined
Neonatal Dosing
depends on PCA: post-conception age - aka age from gestation + age since birth
if not doing PCA: PNA (post-natal age aka from birth) is used
Pediatrid Drug Dosing
Oral Formulations
- exisit to allow for easy administeration
- IV, IM and subQ avalible
Pearls
- weight base dosing: 2.2 lbs. = 1 kg
- refer to the package, double check math
- never use trailing 0, only starting
- always include ptweight with rx. so pharmacist can double check!
