CH11: Pharmacology Flashcards
What is “absorption”
the movement of a drug from site of entry into systemic circulation
What is “bioavailability”
the percentage of active drug that is absorbed and available at the target tissue
Most important plasma protein for drug binding
albumin
What is “plasma protein binding”
drugs may attach to proteins (mainly albumin) in the bloodstream. Only the unbound drug is active.
As free drug is excreted, more of the drug is released from binding to replace what is lost.
(2) factors that can affect the amount of free drug that is available
- competition for binding sites by different drugs
- hypoalbuminemia
With plasma protein binding, only the drug that is [bound vs. unbound] is active
unbound
What is the “blood-brain barrier”
Endothelial cells of the capillaries that surround the brain are packed tightly together, which limits passive transport from blood into the cerebral tissue. A drug must be highly lipophilic to pass into the brain.
A drug must be highly _______ to pass into the brain
lipophilic (lipid soluble)
_______ of all drugs taken by the mother pass through the placenta to the fetus to some degree, and they reach steady state levels in the fetus generally between ____% to ____% of maternal concentration
Nearly all drugs
50-100%
(3) factors that affect drug transfer across the placenta
- lipid solubility
- extent of plasma protein binding
- degree of ionization of weak acids and bases
What is “steady state”
when the rate of drug elimination equals the rate of drug availability or absorption
What is “half life”
the time it takes for the plasma concentration of a drug to be reduced by 50%
the half life is used to determine the time required to reach steady state and the dosing interval
What is “volume of distribution”
the apparent volume in which the drug is dissolved. this relates to concentration of the drug in plasma and the amount in the body.
may be used to calculate the loading dose needed to achieve a desired steady state drug level immediately
what is “drug metabolism”
chemical inactivation of a drug by conversion to a more water-soluble compound (metabolite) that can be excreted from the body
the chemical alterations of drug metabolism in the body are mainly produced by ______ in the _______
microsomal enzymes mainly in the liver
What is the “hepatic first pass effect”
An orally-administered (PO) drug goes from the GI tract, through the portal system, to the liver before reaching general circulation. Some metabolism of the drug may occur as it is taken up by the liver’s microsomal enzymes
Drug-drug interactions can affect drug metabolism by enzyme _____ or _____
induction or inhibition
What is a “prodrug”
drugs that must be metabolized to become effective (into their active metabolites).
These drugs were developed to improve stability, increase absorption, or prolong duration of drug activities
Example: valacyclovir is not effective, but it’s active metabolite acyclovir is
What is “drug excretion”
removal of the drug from the body via the kidneys, intestines, sweat and salivary glands, lungs, or mammary glands
What is “enterohepatic recirculation”
some fat-soluble drugs may be reabsorbed into the bloodstream from the intestines and returned to the liver
How is drug absorption affected by pregnancy
not typically significantly affected
How is drug distribution affected by pregnancy
the increase in plasma volume during pregnancy may result in lower serum levels of the drug. a relative reduction in plasma proteins (albumin) may result in higher levels of free/unbound drugs.
How is drug metabolism affected by pregnancy
hepatic enzyme systems (i.e., CYP3A4, CYP1A2) are affected by rising levels of estrogen and progesterone. This may result in either faster OR slower metabolism of some drugs
How is first-pass hepatic metabolism affected by pregnancy
blood flow through the liver is not changed significantly so there is not typically a change in first-pass effects
How is drug excretion affected by pregnancy
the increase in glomerular filtration rate (GFR) in pregnancy may result in faster elimination of drugs that are excreted primarily through the kidneys
What is a “drug receptor”
a cellular protein, enzyme, or membrane that, when bound to a drug, initiates a physiologic response or blocks a response that the receptor normally stimulates
What is a “drug receptor agonist”
a drug that combines with a receptor to stimulate a response
What is a “drug receptor antagonist”
A drug that interferes with receptor action or with other drug agonists present to prevent that response
What is “drug affinity”
The propensity of a drug to bind itself to a given receptor site
What is “drug efficacy”
the ability of a drug to initiate biologic activity as a result of drug receptor binding
What is a “therapeutic range or window”
the plasma concentration of the drug that produces a desired action without toxic effects
What is a “therapeutic index” (TI)
a ratio comparing the dose causing lethal effects in 50% of the population, over the median minimum effective dose in 50% of the population.
The higher (wider) the therapeutic index, the safer the drug
Genetic variations account for approximately ____% of individual differences in drug responses, in general
15-30%
Pharmacokinetic processes affected by genetics occur primarily because of polymorphisms that affect the function of ___________, resulting in variations in metabolism in a given drug
CYP450
What might it mean to be a poor (slow) metabolizer of a given drug
may have significantly elevated plasma levels/concentrations of a drug and a greater risk of toxicity with the same dose compared to other users
alternatively, may not be able to convert pro-drugs into their active metabolites effectively, thereby getting less or no effects from these drugs
What might it mean to be an ultra-rapid metabolizer of a given drug
may have difficulty maintaining therapeutic drug levels
alternatively, may have increased conversion of pro-drugs into their active metabolites causing increased risk of toxicity for these drugs
Why do hypersensitivity drug reactions (i.e., Stevens-Johnsons syndrome) occur
polymorphisms of the histocompatibility complex proteins allow some drugs to bind directly, initiating the hypersensitivity reaction
When is the clinical utility of pharmacogenomic testing the highest?
when prescribing drugs with
- a narrow therapeutic index
- high risk for adverse drug reactions
- consequences of treatment failure are severe
What is a PHARMACOKINETIC drug-drug interaction
from inhibition of absorption, enzyme inhibition, or induction that increases the risk for drug toxicity or that results in reduced drug effect or altered renal elimination
i.e., if one drug is a CYP450 inducer and the other relies on CYP450 for metabolism
What is a PHARMACODYNAMIC drug-drug interaction
additive if two drugs have similar pharmacodynamic effects (i.e., both lower BP)
antagonistic if two drugs have opposing pharmacodynamic effects
(4) factors that affect whether or not a drug will end up in the breastmilk
- pH
- protein binding
- liposolubility
- molecular weight
Age-related _____ in drug metabolism and/or excretion may result in ______ plasma concentrations
decreased metabolism and excretion»_space;
increased plasma concentrations (risk for toxicity!)
(5) examples of drugs/classes to avoid when possible in elderly populations due to increased risks for adverse effects
- long-acting NSAIDs
- benzodiazepines
- anticholinergic medications (i.e., amitriptyline, oxybutynin, dicyclomine)
- muscle relaxants
- diabetic medications with risk for hypoglycemia (i.e., sulfonylureas)
Risks of long-acting NSAIDs in geriatric populations
increased risk for indigestion, stomach ulcers, GI bleeding (they don’t list this in book but also kidney function??)
Risks of benzodiazepines in geriatric populations
increased risk for falls, confusion (especially those with a long half-life)
Risks of anticholinergic drugs in geriatric populations
e.g., dicyclomine (Bentyl), amitriptyline (TCA), and oxybutynin
increased risk for confusion, constipation, urinary retention, blurred vision, and low BP
Risks of muscle relaxants in geriatric populations
Increased risk for falls, confusion, constipation, and urinary retention
Risks of certain diabetes medications in geriatric populations
hypoglycemia
i.e., sulfonylureas (glyburide, chlorpropamide)
Medication class: metronidazole (Flagyl)
nitroimidazole antibiotic, antiprotozoal
Select indications for metronidazole (Flagyl) (5)
- trichomonas
- bacterial vaginosis (BV)
- PID (in combination with other abx)
- pseudomembranous colitis caused by C. diff
- gastric or peptic ulcers from H. pylori
Pharmacokinetics of metronidazole (Flagyl) (absorption, route, half life, metabolism, excretion, pregnancy)
- oral route has excellent bioavailability (>90%)
- intravaginal route is also an option, absorbed systemically with peak serum concentrations <2% of levels achieved with the oral dose
- widely distributed throughout the body tissues and fluids
- mean half-life is 8 hours
- metabolized mostly by the liver
- excreted mostly through the kidneys/urine (some fecal)
- crosses the placenta and does enter breastmilk
Pharmacodynamics (MOA) of metronidazole (Flagyl)
- disrupts DNA and protein synthesis of susceptible organisms
- amebicidal, bactericidal, antiprotozoal
- selectivity for anaerobic bacteria
Adverse reactions with metronidazole (Flagyl) are more common with the [oral vs. vaginal] route
oral
Most common adverse reactions of metronidazole (Flagyl)
- GI upset, nausea, vomiting, anorexia, abdominal cramps
- dry mouth, metallic taste
- headache
- hypersensitivity reaction
- mild leukopenia or neutropenia that should not persist after treatment
- peripheral neuropathy or seizures are possible in high doses or prolonged use
Drug-drug interactions with metronidazole (Flagyl)
- disulfiram (Antabuse) = may cause acute psychosis and confusion if taken within 2 weeks of one another
- alcohol (including medications with alcohol in them) = may cause nausea, vomiting, headache, flushing, abdominal cramps
- warfarin = metronidazole potentiates the actions of warfarin
- cimetidine (Antihistamine/Antacid) = this drug can decrease the hepatic metabolism of metronidazole increasing its serum levels
- phenobarbital and phenytoin = can increase the hepatic metabolism of metronidazole but the clinical significance of this is uncertain
Contraindications and cautions to use of metronidazole (Flagyl)
- hypersensitivity/allergy
- history of drug-induced hematologic dyscrasias
- hematologic diseases
- liver disease
- kidney disease
- preexisting seizure disorder
Considerations on the use of metronidazole (Flagyl) in pregnancy and lactation
- considered SAFE in all trimesters of pregnancy
- recommend interrupt nursing for 12-24 hours after the drug dose to allow for excretion of the drug before breastfeeding
Patient education points in prescribing metronidazole (Flagyl)
- taking with food may decrease GI upset
- avoid alcohol during and for 48 hours after treatment
- chew gum or suck on ice or candy to reduce dry mouth or metallic taste
- may cause a darkening of the urine, this is normal
- report any CNS symptoms
- if taking for trichomonas, refrain from sex until self and partner treatment is complete
Medication class: fluconazole (Diflucan)
triazole antifungal, azole derivative
Select indications for the use of fluconazole (Diflucan)
- candidiasis (yeast infection) of the oropharynx, esophagus, and vulva/vagina
- fungal meningitis caused by cryptococcosis, candida species, and histoplasmosis
Pharmacokinetics of fluconazole (Diflucan) (absorption, route, half life, metabolism, excretion, pregnancy)
- oral administration is rapidly absorbed in the GI tract with bioavailability >90%
- is widely distributed in the body tissues and fluids
- drug concentrates in the vagina and saliva — vaginal secretion, saliva, and sputum concentrations are about 10x that of plasma concentrations
- mean half-life is 30 hours
- metabolized by the liver via CYP450 with NO first-pass metabolism effect
- mostly excreted through the urine (60-80%) as unchanged drug
- distribution into breastmilk and across the placenta is unknown
Pharmacodynamics (MOA) for fluconazole (Diflucan)
- highly selective inhibitor of fungal CYP450 enzymes
- alters fungal cell membrane function and cell-wall synthesis
- broad spectrum of antifungal activity
- there is emerging resistance to this by non-Candida albicans species
Common adverse reactions to fluconazole (Diflucan)
- headache
- GI upset including nausea or abdominal pain
Drug-drug interactions with fluconazole (Diflucan)
- carbamazepine (Tegretol) = increases antiseizure med levels and decreases fluconazole levels
- phenytoin (Dilantin) = nystagmus and ataxia
- sulfonylureas = hypogylcemia
- warfarin = increases warfarin levels
- theophylline = increases theophylline levels
- cyclosporine (immunosuppressant after transplant) = can cause nephrotoxicity
- cisapride (Propulsid; Prokinetic GI motility agent) = can cause prolonged QT interval
Contraindications and cautions to the use of fluconazole (Diflucan)
- history of heart arrhythmia
- liver disease
- kidney disease
- hypersensitivity/allergy
- multiple drug interactions
Considerations on use of fluconazole (Diflucan) in pregnancy and lactation
- recommend topical treatment for vulvovaginal candidiasis in pregnancy x7 days to be safe. however, the available human data do not suggest an increased risk of congenital anomalies following a single oral maternal dose of 150mg
- considered compatible with breastfeeding. however, distributed in breastmilk at concentrations similar to that of maternal plasma
Patient counseling points for prescription of fluconazole (Diflucan)
- symptoms should start to disappear ~24 hours after taking medication
- it may take several days for the symptoms to go away completely.
- notify your HCP of all medications because several drug-drug interactions are possible.
- avoid overuse and unnecessary use of antibiotics (which can cause yeast infection)
Medication class: acyclovir
antiviral, nucleoside analogue
Select indications for the use of acyclovir
- herpes simplex virus (HSV)
- herpes genitalia (genital HSV)
- herpes zoster (shingles)
- varicella (chickenpox)
Pharmacokinetics of acyclovir (absorption, route, half life, metabolism, excretion, pregnancy)
- poorly absorbed from oral administration with 15-20% bioavailability; however, this is adequate for therapeutic levels to be achieved
- widely distributed throughout the body
- mean half life is 3-4 hours
- metabolized mostly in the liver
- excreted 90% by the kidneys (urine) as unchanged drug
- known to cross the placenta and enter breastmilk
Pharmacodynamics (MOA) of acyclovir
- selectively activated in infected cells
- inhibits viral DNA synthesis
- only effective against rapidly replicating herpes virus, does not eliminate the latent herpes virus
Common adverse reactions from acyclovir
- GI upset including n/v, diarrhea
- headache
- skin rash
- acute kidney failure (rare with PO administration)
Drug-drug interactions for acyclovir
- increased risk for renal toxicity with other nephrotoxic drugs
Contraindications and cautions to the use of acyclovir
- renal disease
- liver disease
Considerations around use of acyclovir in pregnancy and lactation
- generally considered SAFE
- the acyclovir registry has not found any increase in birth defects in pregnant folks who use this drug
- it can be used to treat a first episode of genital herpes or severe recurrent herpes
- may also consider its use in late pregnancy to reduce the frequency of recurrence at term
- may be used as indicated during lactation, although there is some excretion into the breastmilk
Patient education points with prescription of acyclovir
- take with a full glass of water
- space doses evenly
- start at the first sign of a recurrent herpes episode
- provide additional information if using for suppressive regimen
The other nuceloside analogues (famciclovir, valacyclovir) have the same indications, MOA, adverse reactions, and contraindications as acyclovir. What are some of their differences?
- famciclovir = converted to its active form via first-pass metabolism meaning it has better biavailability
- valacyclovir = is a prodrug that is converted to acyclovir causing better bioavailability and less frequent dosing requirements
Medication class: alendronate (Fosamax)
bisphosphonate
Select indications for use of alendronate (Fosamax)
- prevention of osteoporosis in postmenopausal females
- treatment of osteoporosis in postmenopausal females
- treatment of osteoporosis in males
- treatment of glucocorticoid-induced osteoporosis
- treatment of Paget’s disease of the bone
Pharmacokinetics of alendronate (Fosamax) (absorption, route, half life, metabolism, excretion, pregnancy)
- reaches maximum concentration in the bone at 3-6 months
- systemic bioavailability is low, with little exposure to tissues other than the bone. approximately 50% of the oral dose binds to the exposed bone surface
- bioavailability is greatly affected by meals; reduced by 40% when taken with food, and by 60% when taken with coffee or orange juice.
- estimated half life from bone is >10 years
- given high affinity for bone, no evidence of metabolism in the liver
- 50% of the dose that remains after it binds to bone is excreted unchanged in the urine
Pharmacodynamics (MOA) of alendronate (Fosamax)
- reduces bone resorption by inhibiting the activity of osteoclasts
- no direct effects on bone formation
Adverse effects of alendronate (Fosamax)
- local irritation of the upper GI mucosa
- esophagitis, esophageal ulcers, esophageal erosions
- hypocalcemia
- severe and occasionally incapacitating bone pain, joint pain, or muscle pain
- osteonecrosis of the jaw (rare, tends to be related to dental work and IV administration)
- atypical (low-impact) fractures of the femoral shaft (rare, more common with longterm use)
- hypersensitivity reactions/allergy
Drug-drug interactions with alendronate (Fosamax)
- antacids containing calcium, magnesium, or aluminu are likely to reduce absorption of alendronate if taken together
Contraindications and cautions for alendronate (Fosamax)
- abnormalities of the esophagus that may delay esophageal emptying
- inability to follow directions for standing or sitting upright for 30 minutes after oral administration
- hypocalcemia
- kidney disease
- hypersensitivity/allergy
Considerations for the use of alendronate (Fosamax) during pregnancy and lactation
- there are no well-designed studies of use during pregnancy in humans, although small studies and case reports have shown no increase in the rate of birth defects or long-term health concerns
- there is limited evidence to suggest that breastfeeding after stopping a long-term bisphosphonate treatment appears to have no adverse effects on the infant
- there is no data available on active use during breastfeeding. given the poor maternal systemic absorption,, the amount in breastmilk is likely small
Patient counseling points for prescription of alendronate (Fosamax)
- take in the morning on an empty stomach with 8oz of plain water
- do not eat food, drink fluids, or take any other medications for at least 30-60 minutes after taking
- remain sitting or standing upright for at least 30-60 minutes after taking
- if taking any calcium supplements or antacids, separate by at least 2 hours
Medication class: oxybutynin
antimuscarinic, anticholinergic
Select indications for the use of oxybutynin
treatment of overactive bladder (OAB; including frequency, urgency, nocturia) and urge urinary incontinence
Pharmacokinetics of oxybutynin (absorption, route, half life, metabolism, excretion, pregnancy)
- rapid absorption, reaching maximum concentration within 1 hour
- bioavailability is low, approximately 6%
- widely distributed in body tissues
- mean half-life is 2-3 hours
- metabolized by the liver via CYP3A4 enzyme
- extensively metabolized by the liver, with less than 0.1% of the dose excreted unchanged in the urine
Pharmacodynamics (MOA) of oxybutynin
- targets M1 and M3 receptors to reduce the muscarinic action of acetylcholine on smooth muscle
- acts as a mild antispasmodic - increasing bladder capacity and diminishing the frequency of uninhibited contractions of the detrusor muscle
Adverse reactions from oxybutynin
- systemic anticholinergic side effects, including dry mouth, blurred vision, constipation, tachycardia, urinary retention, drowsiness, impaired sweating, confusion (all common reasons for discontinuation)
- transdermal patch administration may decrease serum levels of the active metabolite and thus reduce anticholinergic side effects
- warning: heat stroke is possible in hot climates if sweating is impaired
Drug-drug interactions with oxybutynin
- inhibitors of CYP3A4 enzyme may cause increased plasma concentrations of oxybutynin
- oxybutynin may enhance the effects (additive) of other anticholinergic drugs
- may enhance (additive) the sedative effects of opioids or other sedative agents
Contraindications and cautions for use of oxybutynin
- hypersensitivity/allergy
- uncontrolled narrow-angle glaucoma
- gastric retention
- urinary retention
- concomitant use of other anticholinergic drugs
- esophageal disease
- liver disease
- kidney disease
- myasthenia gravis
- cardiac disease
- HTN
- older age
- dementia
Considerations for the use of oxybutynin in pregnancy and lactation
- there is no evidence of impaired fertility or harm to animal fetus however the safety in pregnant women has not been established
- it is not known whether oxybutynin is excreted in the breastmilk
Patient education points for prescription of oxybutynin
- take with a full glass of water at the same time every day
- may be taken with or without food
- avoid becoming overheated or dehydrated during exercise or in hot weather d/t risk for heat stroke s/t impaired sweating
Medication class: atorvastatin (Lipitor)
HMG-CoA reductase inhibitor, statin
Select indications for use of atorvastatin (Lipitor)
first-line treatment in the reduction of low-density lipoprotein (LDL) levels
Pharmacokinetics of atorvastatin (Lipitor) (absorption, route, half life, metabolism, excretion, pregnancy)
- rapid absorption with maximum concentration within 1-2 hours
- low systemic bioavailability of approximately 14% due to extensive first-pass metabolism, which is a benefit since the liver is a target organ for the drug
- half life is 14 hours
- metabolized by the liver via CYT3A4
- eliminated primarily in the bile, and does not appear to undergo enterohepatic recirculation, extensively metabolized by the liver so only minimally (<2%) excreted in the urine
Pharmacodynamics (MOA) of atorvastatin (Lipitor)
- reduces cholesterol production in the liver through inhibition of HMG CoA, an enzyme that is involved in cholesterol synthesis
- stimulates the upregulation of LDL receptors in the liver, which bind the LDL and increase it’s extraction from the plasma
- some statins cause a decrease in triglycerides and increase in HDL secondary to LDL reduction
- improves plaque stability while reducing endothelial inflammation
Common adverse reactions with atorvastatin (Lipitor)
- muscle pain, soreness, and muscle cramps (may resolve with switching to a different statin)
- rhabdomyolysis is a rare effect of skeletal muscle breakdown that may cause renal dysfunction (check CK level if there is significant muscle pain or weakness, or dark-colored urine)
- GI upset including abdominal pain, constipation, diarrhea, or nausea
- asymptomatic elevations in LFTs
Drug-drug interactions with atorvastatin (Lipitor)
- with warfarin, causes increased anticoagulation effect
- with digoxin, can slightly increase digoxin levels
- concurrent use of drugs that may increase serum levels of statins will increase the risk for myopathy and rhabdomyolysis
- CYP3A4 enzyme inhibitors may increase serum statin levels by decreasing its metabolism (examples = macrolide antibiotics, SSRIs, ketoconazole, protease inhibitors, rifampin, calcium channel blockers, cimetidine, grapefruit juice)
- concurrent use with other antilipid drugs (e.g., gemfibrozil, niacin) increases the risk for myopathy and rhabdomyolysis
Contraindications and cautions for use of atorvastatin (Lipitor)
- do not use in pregnancy
- do not use with active liver disease and elevated liver enzymes
Considerations for the use of atorvastatin (Lipitor) in pregnancy and lactation
contraindicated in pregnancy & breastfeeding - NOT SAFE!
Can cause adverse fetal outcomes, CNS and limb deformities found in animal studies
Patient education points with prescription of atorvastatin (Lipitor)
- follow a heart-healthy diet and regular exercise along with taking a statin
- report promptly any unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or a fever
- report promptly any symptoms that may indicate liver injury including fatigue, anorexia, RUQ pain, dark urine, or jaundice
Medication class: tamoxifen
selective estrogen receptor modulator (SERM)
Select indications for the use of tamoxifen
- treatment of ER-positive breast cancer
- prevention of ER-positive breast cancer in high-risk individuals
Pharmacokinetics of tamoxifen (absorption, route, half life, metabolism, excretion, pregnancy)
- peak plasma concentration within 5 hours
- mean half-life is 5-7 days
- pro-drug is metabolized to more active forms by various CYP450 enzymes in the liver
- excreted primarily in the feces
Pharmacodynamics (MOA) of tamoxifen
anti-estrogen effects in the breast, pro-estrogen effects in the uterus and bone
binds to estrogen receptors. For estrogen-antagonist effects, prevents estrogen from binding, thereby blocking its action at select sites like the breast tissue. In other sites, it acts like an estrogen to those receptors (uterus, bone)
Adverse reactions with tamoxifen
- VTE
- endometrial cancer
- hot flashes
- nausea
- menstrual irregularities
- vaginal dryness
- weight gain
- bone loss in premenopausal women (but prevents bone loss in postmenopausal women)
Drug-drug interactions with tamoxifen
- may cause a significant increase in effect of warfarin (Coumadin)-like anticoagulants
- increased risk for thromboembolic events when cytotoxic agents are used in combination with tamoxifen
- anastrazole (AI) decreases concentrations of oral tamoxifen
- strong inhibitors of CYP2D6 may cause lower blood levels of the active metabolite of tamoxifen
Contraindications and cautions to use of tamoxifen
- hypersensitivity/allergy
- history of a VTE
- pregnancy
Considerations for use of tamoxifen in pregnancy and lactation
generally. …. not safe
- there are no adequate or well-controlled studies of use in pregnant people and there are small number of reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal deaths
- has been reported to inhibit lactation
- it is unknown if the drug is excreted in the breastmilk
Patient counseling points for use of tamoxifen
- can be taken with or without food
- report any signs or symptoms that may indicate a blood clot
- report any irregular or unusual vaginal bleeding
medication class: oxytocin (Pitocin)
uterotonic (high alert medication)
select indications for the use of oxytocin (Pitocin)
- induction of labor
- augmentation of labor
- active management in the third stage of labor
- postpartum hemorrhage treatment
- contraction stress test
pharmacokinetics of oxytocin (Pitocin) (absorption, route, half life, metabolism, excretion, pregnancy)
- excellent systemic absorption per IV route with immediate onset (3-4 minutes) and duration dependent on the duration of administration. reaches steady state within 30-40 min. effects will subside within 1 hour once discontinued (half life 6-10 minutes)
- good absorption via IM route with delayed onset and duration of action 2-3 hours
- metabolism occurs rapidly in the liver and kidneys
- only small amounts are excreted in the urine
- minimal amounts cross the placenta
pharmacodynamics (MOA) of oxytocin (Pitocin)
- increases intracellular calcium ions which promotes motility of the uterine muscle
- exerts effects via an agonist action - uterotonic effect is mediated by receptor function
- receptors on the myometrium are upregulated in pregnancy, peaking in early labor. hence, the response is highly individualized as it depends both on the dose given and the receptor concentration
- with prolonged exposure, receptors can be downregulated
- will have diuretic effect in large quantities
adverse reactions with oxytocin (Pitocin)
adverse effects are more common with excessive dosing or prolonged exposure
- anaphylaxis
- postpartum hemorrhage
- cardiac arrhythmia
- fatal afibrinogenemia
- nausea, vomiting
- pelvic hematoma
- subarachnoid hemorrhage
- hypertensive episode
- uterine rupture
- severe water intoxication leading to convulsions, coma, or maternal death
- fetal effects including bradycardia, cardiac arrhythmia, brain damage, fetal death, neonatal seizures, low Apgar scores, neonatal jaundice, neonatal retinal hemorhage
drug-drug interactions for oxytocin (Pitocin)
drug-drug interactions are rare.
- it is a vasoconstrictor so when administered with caudal block anesthesia may cause severe hypertension
- when administered with cyclopropane anesthesia, may result in hypotension or sinus bradycardia
contraindications and cautions to the use of oxytocin (Pitocin)
- hypersensitivity/allergy
- uterine tachysystole
- abnormal fetal heart rate pattern
- requiring fluid restriction
- at risk for pulmonary edema
- use caution if patient has a history of previous c-section
patient education points for use of oxytocin (Pitocin)
- may be best used once the cervix is ripe
- external (and sometimes internal) monitoring of uterine contractions and fetal HR is required during administration of oxytocin (Pitocin) in labor
- low-dose protocols can be used for safe administration
- if administered postpartum via IM injection, there may be pain at administration site
- report any headache, nausea, or muscle cramps
medication class: nitrous oxide (Nitronox)
analgesic, anxiolytic, inhalent
select indications for the use of nitrous oxide (Nitronox)
management of pain and anxiety for:
- labor
- repair of perineal laceration
- third stage labor management PRN
- other procedures such as IV placement, catheter placement, vaginal examination, IUD insertion
pharmacokinetics of nitrous oxide (Nitronox) (absorption, route, half life, metabolism, excretion, pregnancy)
- per inhalation route, is self-administered by the patient. tasteless odorless gas mixed with oxygen and inhaled by a mask, 50/50 concentration of nitrous oxide + oxygen
- onset of action is 1 minute or less
- rapid elimination with residual effects resolving within 5 minutes
- readily crosses the placenta but is quickly eliminated
- not metabolized, though is reduced by intestinal bacteria
- excreted primarily by the lungs (exhale), and a minimal amount is diffused through the skin
pharmacodynamics (MOA) of nitrous oxide (Nitronox)
MOA is not well understood
- noncompetitively inhibits the N-methyl-d-aspartate subtype of excitatory glutamate receptors is one theory
adverse reactions with use of nitrous oxide (Nitronox)
- neuroapoptosis at high, prolonged doses
- loss of consciousness, which is not common as long as self-administered
- nausea, vomiting
- megaloblastic anemia in the presence of a vitamin B12 deficiency
- myocardial risk at high doses
- diffusion hypoxia at high, prolonged doses followed by a lack of high-concentration oxygen thereafter
- alterations in hypoxic drive when combined with sedatives or opioids - advise patients to breathe more deeply if necessary
- no significant fetal effects - there is no effect on fetal heart rate or contractions, no negative effects on Apgar scoring, neurobehavioral scores, or sucking behavior
Drug-drug interactions with nitrous oxide (Nitronox)
drug-drug interactions are rare
- specifically, sedatives or opioids may produce a more pronounced respiratory depression when used together
contraindications and cautions to use of nitrous oxide (Nitronox)
- recent trauma
- certain respiratory conditions (COPD, pneumothorax, emphysema, pulmonary hypertension)
- acute alcohol or drug intoxication
- reduced level of consciousness
- increased intracranial pressure
- bowel obstruction
- recent vitreoretinal or ear surgery
- acute vitamin B12 deficiency (safe to use if the deficiency is resolved)
- use caution in case of occupational exposure for potential effects on female fertility at higher doses…. scavenging system required to mitigate
Considerations for use of oxytocin (Pitocin) in pregnancy and lactation
yes, this is explicitly used in the third trimester or later in pregnancy
Considerations for use of nitrous oxide (Nitronox) in pregnancy and lactation
safe, typically used in labor or immediately post-partum
Patient education points in prescription of nitrous oxide (Nitronox)
- must be able to self-administer
- promotes a physiologic labor and birth
- to use effectively, breathe deeply and slowly at the start of or just prior to a contraction and stop once the contraction has passed
- may be used as an anxiolytic between contractions
- it is a relatively safe analgesic or anxiolytic for use throughout the entire labor, third stage, or repair
- no monitoring (i.e., pulse ox) is required
- discontinue in the event of fetal or maternal compromise, for side effects that persist, or if no longer desired
- report any nausea, vomiting, or vertigo
medication class: betamethasone (Celestone)
corticosteroid
select indications for use of betamethasone (Celestone)
promoting fetal lung maturity in instances of preterm labor where preterm birth is anticipated (including for those with ruptured membranes and multiple gestation)
pharmacokinetics of betamethasone (Celestone)(absorption, route, half life, metabolism, excretion, pregnancy)
- via IM route most commonly, two 12-mg doses given 24-hrs apart. may give an additional rescue course if the initial course occurred 7-14 days prior AND less than 34weeks gestation
- possible to also give via intra-amniotic and intravenous routes, but these are less common
- the greatest benefit is shown at 2-7 days after the initial dose
- half-life if >72 hours
- metabolism occurs through the liver
- excretion is through the kidneys
- easily crosses the placenta when given IM or IV
pharmacodynamics (MOA) of betamethasone (Celestone)
- promotes lung maturity by stimulating surfactant synthesis
- increases compliance of lung tissue
- reduces vascular capillaries
- lacks mineralocorticoid activity with short-term use
- relatively weak immunosuppressive activity with short-term use
Adverse reactions to betamethasone (Celestone)
maternal:
- glucose intolerance with transient hyperglycemia (without diabetes)
- increased insulin requirements (with diabetes)
- increased risk for pulmonary edema, which is higher if used concurrently with other beta-adrenergic drugs for tocolysis or for those with multiple gestation
fetal:
- fetal heart rate has a biphasic response, initially mild elevation, followed by decreased variability on days 2-3 post-administration
long term effects on the HPA axis is possible but unclear (?)
drug-drug interactions with betamethasone (Celestone) when used for fetal lung maturity
rare
contraindications or cautions to use of betamethasone (Celestone) when used for fetal lung maturity
- serial courses are not recommended due to potential for maternal and fetal harm
- may be harmful for certain fetuses that are growth-restricted
Considerations for the use of betamethasone (Celestone) in pregnancy and lactation
safe for use in pregnancy – can improve newborn outcomes in the setting of preterm birth
Patient education points for prescription of betamethasone (Celestone)
- antenatal corticosteroid therapy is one of the most important treatments for preterm neonates and can significantly reduce the risks of:
- respiratory distress
- intracranial hemorrhage
- necrotizing colits
- neonatal death
the benefit to the fetus and neonate typically outweighs any maternal risk
medication class: magnesium sulfate (MgSO4)
anticonvulsant (high alert medication)
select indications for magnesium sulfate (MgSO4)
- maternal seizure prevention and treatment for preeclampsia and eclampsia
- fetal neuroprotection with anticipated preterm birth (<32 weeks gestation)
- short term (<48hrs) tocolytic
pharmacokinetics of magnesium sulfate (MgSO4) (absorption, route, half life, metabolism, excretion, pregnancy)
- via IV route, excellent absorption systemically with immediate onset. duration depends on the duration of administration. subsides within 1-2 hours after discontinuation.
- loading dose is 4-6g in 100mL over 20-30 minutes.
- maintenance dose is 2g/hr for at least 12-24 hours
- reaches steady state within 12 hours when given IV
- there is no metabolism
- excreted through the kidneys
- crosses the placenta and is found in limited amounts in breastmilk
- IM route is not preferable and there is variability in producing effective concentration levels
pharmacodynamics (MOA) of magnesium sulfate (MgSO4)
MOA is poorly understood
- blocks neuromuscular transition, depresses CNS
- acts on vascular smooth muscle to cause vasodilation
adverse reactions to magnesium sulfate (MgSO4)
- flushing
- palpitations
- feeling of warmth/heat
- lethargy
- muscle weakness
- dizziness
- nausea, vomiting
- respiratory depressant
- pulmonary edema
drug-drug interactions with magnesium-sulfate (MgSO4)
calcium channel blockers
contraindications and cautions for the use of magnesium sulfate (MgSO4)
- concurrent use of calcium channel blockers
- should not use longer than 5-7 days due to increased risk of fetal and neonatal bone demineralization and fracture
- toxic effects at serum level >7mg/dL
- calcium gluconate reverses the effects of mag toxicity
reversal agent for magnesium sulfate (MgSO4) toxicity
calcium gluconate
considerations for the use of magnesium sulfate (MgSO4) in pregnancy and lactation
yes, specifically used in pregnancy, typically in 2nd and 3rd trimesters and PRN post-partum for preeclampsia and eclampsia
Patient education points for the prescription of magnesium sulfate (MgSO4)
- short-term controlled used is safe in pregnancy when indicated
- urine output and magnesium levels will be monitored
- report any difficulty breathing, lethargy, weakness, dizziness, nausea, vomiting, or palpitations
- for mag levels that are too high, a calcium gluconate injection will be given
- plans to breast or chest-feed should proceed
medication class: RhoGAM
immune globulin, blood product
select indications for use of RhoGAM
prevention of Rh anti-D isoimmunization in pregnant person who is Rh negative
- prevention during pregnancy
- birth of an Rh positive baby
- antepartum hemorrhage (suspected or known)
- pregnancy loss or termination and ectopic pregnancies
- transfusion of Rh positive blood products
- external cephalic version
- invasive procedures such as amniocentesis, chorionic villus sampling
pharmacokinetics of RhoGAM (absorption, route, half life, metabolism, excretion, pregnancy)
- IM route has good absorption and is effective for up to 12 weeks after administration
- available in 2 doses, 50mcg or 300 mcg with multiple doses being given PRN depending on blood loss and gestational age
- maximum concentration is reached within 4 days
- mean half-life is 30 days
- nonspecific metabolism
- excreted via feces and urine
- crosses the placenta only minimally in a way that is not clinically significant
pharmacodynamics (MOA) of RhoGAM
MOA is unknown
- creates passive anti-D immunity, which promotes clearance of anti-D-coated fetal red blood cells in maternal circulation
- inhibits maternal immune response to anti-D, which is protective of future pregnancies
- not effective if Rh alloimmunization has already occurred
adverse reactions from RhoGAM
- injection site reaction
- rash
- low grade fever
- allergy (rare)
drug-drug interactions with RhoGAM
interactions are rare
- may inhibit the efficacy of live vaccines when given together
- theoretical risk of contamination just as with any other blood product
contraindications or cautions for use of RhoGAM
do not use in Rh positive individuals or in neonates themselves (only maternal)
considerations for the use of RhoGAM in pregnancy or lactation
yes, specifically used in pregnancy. typically used at 26-28 weeks gestation and also postpartum. safe to use throughout pregnancy.
if birth occurs within 3 weeks of the previous dose, the postpartum dose may be withheld pending a normal Kleihauer-Betke test (<15mL of RBCs) for fetal-maternal hemorrhage
toxic level of magnesium sulfate (MgSO4) in the serum
> 7mg/dL
patient education points regarding use of RhoGAM
- necessary to reduce the risk of Rh sensitization
- most common risk is reaction at the site of the injection
- although an allergic reaction is rare, should report any symptoms such as hives, itching, tightness in the chest, or wheezing
- postpone any live vaccines (with the exception of rubella or MMR) if needed, until 12 weeks or after the administration of RhoGAM due to possible decreased efficacy
- reevaluate rubella titer 3 months after administration if given postpartum with RhoGAM to ensure successful immunity
Rx for pyridoxine (B6) for nausea in pregnancy
pyridoxine (vitamin B6) 10-25mg PO 3-4x daily
maximum daily dose 200mg/day
Rx for pyridoxine + doxylamine (Diclegis) for nausea in pregnancy
pyridoxine (vitamin B6) 10mg + doxylamine 10mg PO
- 2 tablets QHS before bed
- max 4 tablets daily: may have 1 tablet in AM, 1 tablet in afternoon, and 2 tablets before bed if severe
Rx for metoclopramide (Reglan) for nausea in pregnancy
metoclopramide 5-10mg PO Q6-18 hours
Rx for promethazine (Phenergan) for nausea in pregnancy
promethazine 25mg Q4 hours per rectal suppository
Recommendations for ginger for nausea in pregnancy
up to 1g per day in divided doses
Pharmacotherapy options for nausea that are safe in pregnancy
- pyridoxine (vitamin B)
- doxylamine (antihistamine) (with B6 is called Diclegis or Bonjesta)
- metoclopramide (Reglan; dopamine antagonist)
- promethazine (Phenergan; antihistamine)
- ondansetron (Zofran) is increasingly used but there is not adequate data on its safety or efficacy, contains a BBW on this drug and per FDA should not be used in pregnancy
Can pregnant folks being treated for TB still breastfeed?
yes, breastfeeding is not contraindicated with TB treatment
