Lecture 9 - Nov 18 Flashcards
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emesis
-emesis = vomiting
-ubiquotous and necessary process the body uses to defend itself against real or perceived pathogens
-coordinated by 2 areas of the CNS (both located in the meduccla):
-vommiting centre
-chemreceptor trigger zone
-nerves afferetn (towards) to these areas induce emesis
-nerves efferent (away from) these areas will stimulate the motor nerves to generate the reflex
-retrograde contractions of the small intestine couples with contractions of the diaphragm and abdominal muscles
Vommiting reflex:
-the vomiting reflex is triggered by stimulation of receptos in the upper GI tract and mechanoreceptod in the wall of the GI tract, watch are activated bu both contraction and distension of the gut
-a coordinating centre in the cns controls the emetic response
-afferent nerves to the vomiting centre arise from abdominal splanchnic and vagal nerves and stimulate a structure in the brain called the chemroecpto trigger tonze (CTZ)
-the CTZ senses activation from distenstion and contraction of the gout and can sense hormone variations associated with pregnancy (rising estrogen and progesterone levels) and have histamine receptors
-this activation sets off the vomiting reflex
Nausea and vomiting of pregnancy NVP:
-nvp has a serious impact on th elives of pregnanct people
-47% fell loss of job opportunity, 35% must take time off work
-negative impact on relationships
-results in the feelings of anxiety and worry anout the effects of symptos on the fetus
-severe nvp has been compared to the severity of neasura caused by chemotherapy
-has been cited as a reason for elective termination of prefnancy
-hypermesis gravidarum lies on the extreme nvp - effecting 0.3-2% of pregrnancies
-recognizing and treating nvp in a timely fashion may prevent the progression to HG
Anti-emetics:
-design focuses primarily on the neurotransmitters associated with the vomiting reflex
-each one will be specific to a certain type of nausea an vomiting
-drug used in canada to treat nausea and vommiting of pregnancy NVP is diclectin
-doxylmaine succinate prridoxinne hydrochlorid
-diclectin is the first line therapy for nvp
-best studied drug in pregnany - has been included in 25 epidemiological studies and 2 meta-analyses
-drug class: antihistaine 9doxylamine succinate) and an anti-emetic (pyridoxine-hydrochloride, beloongs to the vitamin b complex group, specifically vitamin B6)
Diclectin and nvp:
-diclectin is a histamine antagonist that binds to hsutamien tupe 1 receptos
-one of the principal recpetos at the ctz are histamin type 1 receptod (H1(
-this reeptor is also expressed throughout the body, specifically in smooth muscles
-H1 antagonists like diclectin reduce or block the actions of hsitamie by reversible competitive bincding to the H1 recpeto (works very poorly at the H2 and H3 receptrod)
-once hound to H1 recpetos, it prevents histamine from bind and directly inhibits the action of histamine at the H1 receptor and decreases stimulation of the vomiting centre
-binding to histamine recpetos on smooth muscles of the stomach, and intestine prevents smooth muscle contraction
Diclectin formulation and dosage:
-tablets have a special coating for delayed release so should not be crushed/chewed/broekn
-contain 10mg of doxylamine and 10mg of pyridoxine
-delayed release works optimally between 4-6 hours agter ingestion
-cleint does not take as needed, but on a dosing sjcdule acocorind to the timing, duration, severity and frequency of symptoms
-typcal dosing is 4 tablets a day
-2 at bedtime - so that form most people when symptoms are worst in morinign, the drug will have appeared in the blood
-1 in the morning to counteract any afternoon symptoms
-1 in the afternoon to counteract any evening symptoms
-this regie can be modified based on clients history and symptoms
Adverse reactions of dicletctin:
-due to anticholinergic properties of antihisatmins, caution should be used when dicelctin is taken concurremtyl with alcohol
-clients with epile[y should conslt their doctors as diclectin can increase the risk of seizures
-no published reports of diclectin use while breastfeeding - but its MW is small, so passged into breast,il should be expected
-side effects include drowsiness, stomach upset, diarrhea and headache
-s&sx of overdose are reslestness, dry mouth, dialted pupils, sleepiness, dizziness, mental confusion, and rapid heartbeat
-treatment for OD = gastric lavage or activated charcoal
Treatent algorithm:
CHECK SLIDE
-pyridoxine monotherpy of doxylamine/pyridoxine combination therapy = first line of treatment of nvp
-ther H1 receptor antaognsirs (ex gravol and benadryl) are considered safe in pregnanc and can be added
-dopamine receptor antagonists and serotonin antagnsts can be considered as adjunct therapies
Prochlorperazine:
-an anttimetic/antihsitamine.antipsychotic in the phenothiazine class
-formualted as 5mg or 10mg for PO use or 10mg rectal suppositiories
-believed to be post-synaptic dopamine D2 recepto antagonisrs in the mesolimbic tract of the brain - but exact mechanism is unknown
-antiemetic effet comes from blockade of D2 receptors in the CTZ as well as anti-muscarning and anti-histamine properties
-5-10mg q6-8h PO or PR
-onset of action: 30-40 min PO, 60min rectal
-significantlt metabolzied by the liver with amy significant durg interactions (including alcohol and many medications used for anxiety and depression)
Prochlorperazine precautions:
Contraindications:
-many listed dont apply to clients who qualify for midwifery care
-hypersenitivity
-severe depression
-lower respiratory tract sympotosm of asthma or COPD
Use with caution:
-prolactin-dependt tumors
-cardiovasular disease (can cause QT prolongation)
-can result in photosensitivty - advise sunscreen use
-can cause constipation
-avoid use near term in pregnnat individuals
-in pregnacny, short-term use, at the lowest possible doses appear safe
Ondansetron (zofran):
-an antiemtic that is a 5-HT3 (seretonin) receptor antagonist
-formulated as 4mg/8mg tabs for PO use, 4mg/8mg dissolving tabs for SL use or 4mg/ml solutinton strawberry fluid
-for IV use: 2mg/ml solution for injection
-believed to block a serotonin-mediated vomiting reflex in the small intestines via on the vagal afferents as well as serotonin-mediated mechanisms in the CTZ but exact mechanism is unknown
-peak plasma levels reaced at about 1.5hr after an 8mg dose, t1/2 = 3-4 hours
-extensivley metabolzied by the liver
-recommended dose for NVP: 8mg q 12h PO or 4mg PO, PRN
Ondansteron precautions:
Contraindications:
-many listed dont apply to clients who qualify for midwifery care
-hypersesntiivty
Use with caution:
-cardiovascular diseas (can cause QT prolongation)
-can increase large-intestine transit tie - cause constipation
-not recommended for use in pregnnacy
-in early pregnanc, has been associated with a small increase in orofacial malformations (clefts) data are conflcuting, limitations in study methodologies
Reflux:
-the back flow of stomach acid into the esophagus and throat
-common in regnanct d/t reduced tone of the LES
-commonly opens when it should be closed
-increased upward pressure on the stomach by the gorwin uterus
-symtpoms includeL regurgitation, burning noncardiac chest pains, nausea, sore throat, asthma-like symptoms (ex chroic cough)
-asssociated with NVP
-often managed well with OTC antacids (ex TUMS)
Omperazole (pirlosec, losec);
-formulated as 20mg capsules for PO use
-acute treatment of sympotmatic reflux esophagitis: 20mg once daily (syptom control and/or healing of esophagela iritation usually complete within 4w)
-t1/2 = 40 min
-extensively metaolzied by the liver
Contraindications:
-hypersensitivyt
Use with caution:
-interactions with antiretrovirals (nature and clinical relevance unknown)
-safety not established in pegnancy
Rantidine (ZANTAC):
-antihistamine
-histamine h2-recpetor antagonist
-reduces gastri acid secretion by blocking the effects of histamine on the H2 recpetos on the parietal cells of the stomach
-canada currently facing a drug shortage due to recalls from 2019 (potential impuritey - NDMA = cardinogen)
-formualted as 150mg or 300mg tablters for PO use
-acute treatment of refleux: 300mg once daily at bedtime or 150mg twice daily (morning and bedtime) for up to 8w
-peak plasma oncetraions 1-3h, t1/2 = 2-3h
-excreted by the kidneys, has the potential to affect the renal excretion of other drugs
Contraindications:
-many listed dont apply to clients who qualify for midwifery are
-hypersentitivyt
Use with caution:
-vitamin b12 deficientu
-safety not established in pregnnacy - animal studies show no evidence of harm
human lactation slide
Domperidone (motilium):
-dopamine receptor antagonist
-deginsged to improve gastric motiltuy and decrease nausea
-its effects on lactation are side-effects
-domperidone as a galactagogue is an off-label use
-concrns about the effect of domperidone on heart aryhtmias particularly QT interval prolongation which could lea to ventricular tacharrythmia
-led to a black box warning against domperidone
-evidence based response in support of domperdone written by a group of MDs and IBCLCs
Domperidone mechanism:
-dopamine receptor antagonist
-blcoks the effect of dopamine (prolactin-inhibiting hormone) on the prolactin-producing cells in the anterior putriary
-this disinhibiton increases prolactin secretion
-increase in prolactin secretion enhance milk production
Domperidone effects:
-increase in millk production is normally seen in 3-5 days but can take 2-3 weeks to see maximal effect
-prescription is normally for at least 3 weeks (3-8 weeks is standard)
-to stop, dose must be slowly decreased (ddecrease by tablet every 2-5 days)
-if there is no effect on milk production, decrease by another tablet every 2-5 days but if milk production is decreased from reduction, return to effect dose and once milk supply is reestablished try decreasing dose agin in 2wks
Domperidone metabolism and excretion:
-the drug is rapidly absorbed orally and metabolised in the liver
-extensive fist-pass metabolism - oral bioavilabiblty is only 13-17%
-becasue of extensive liver metabolism of the drug, it should not be given to clients with sigigcant hepatic impairment
Domperidone adverse effects:
-very few side effects of domperidone (except ventriuclar tachyarrhythmia)
-many organziations consider domperiodne compatible with breastfeeding
-infant exposure from breast milk is minla - aout 1% of maternal dose
-domperidne is given to infants in nicu for refex (GERD) so safe even at higher doses
-dystonia possible sife effects in infants
Domperidone drug interactions:
-domperidone is metabolzied by CYP3A4
-strong inhibitors of CY3A4 such as eryhtromic and azole-antmycotics affect metbaolsim of domperidone
-ketaconzale is a potent CY3A4 inhibto which increase the half lfie of the domperudone and increases the likelihood of overdose; about a 3x increase in circualting levels of domperidone are seen with co-adminsitarion of oral/IV ketaconazole
-topically applied ketaconazloe is reported as not appearing in the blod in measurable quantities
Cabergoline (dostinex):
-dopamine receptor agonist
-used to treat hyperprolactinemic disorders (ex pituitary adenomas)
-inhibition of physiological lactation
-stillborn, neonatal death, or any other condition where human milk feeding is not possible
-not indicated for the supresion of already established post partum lactation
-acts by direct stimulation of the D2-dopamine receptos on the pituiaty lactotrophs → inhibiting prolactin secretion
-decreae in prolactin secession reduce milk production
Cabergoline:
-for the inhibition of lactation: 1mg (2x0.5mg tablets), PO< given as a single dose on the first day postpartum - best taken wth food
-largely excreted in urine unchanged
-elimiantion t1/2 is long, 63-68 hours
Contraindicatins:
-uncontrolled hyypertenson
-hypersitintity
-history of pulmonary, pericardial or retroperitoneal fribrotic disorders
Precautions:
-should not be used in people with pregnnacy induced hypertension (unless benefit outweighs risk)
-inital doses higher than 1mg may result in hypotension
-use with caution in people with raynauds syndrome
-avoid pregnancy for at least 1 month after treatment
The endocrine system:
-a group of glands throughout the body
-regulates bodily functions via blood-borne hormonal massages
-steroids, peptides, amines
-peptides are most common
-release of endocrine hormones regulated by circualitng levels of chemicals and nervous system connections
-many commonly prescribed drugs are endocrine modulations
Thyroid hormones:
-critical to the maintenance of metallic homeostasis
-increase metabolic rate, protein synthesis and fat breakdwon - influcen the function of all major organs
-during fetal development, thyroid hormones essential for normal develop,ent
-thyroid gland makes thyroxine (T4) and triiodothyronine (T3) in the response to thryptropin releasing hormone TRH from the hypothalmus and thryid stimualitng hormone TSH from the anterior pituiaty
-thryd homrine production regulated via a negative feedback loop (why is TSH high in hypothyroidism)
Hypothyroidism:
-low levels of thyroid hormones from inadequate thyroid gland functions
-S&S: weight gain, fatigue, amenorrhea, depressed lactaion, contipation, mental sluiggshness and dry/thick skin
-asscoaite with infetitliy
-fetus relies on maternal thyroid hormone until 12w gestation
-treatment us levothyroxine (synthroid) → TSH moinitoed cleosly in pregnancy and medication may be adjusted by physician
Sex hormones:
-all sex hormones are steroids (derivaes of cholesterol)
-priamrly made in th egonads - however drign pregnnacy, the placenta makes most of the steorids
-the main sex hormones are
-esteognes - estriol, 17beta-estradiol, estrone
-progesterone
-androgens
-in females, progesterone and the estrogens are the msot important sex horones alhtough there is a role for testoseterone
Estrogens:
-3 natural esteogens: 17beta-estradils (most abundant, potent, menstrual cycle, reproductive events) estriol (placenta), estrone (postmenopausal)
-estrogens stimulate fat depostion during maturation, bone deptosion, development of uterine endometriun and thin, elasic cervical mucus (mesntual cycle), increase production of clotting factors and inhibits antithrombin 3 production, stimulates breast tisue/glands in pregnancy
-why are pregnancy people at risk of deep vein thrombosis with hugh amounts of estogen
-syntehic = ethinyl estradiol: half life 6-12 hrs
Progestogens:
-progesterine most abundant; made by corpus luteum and placenta
-inhibits myometriaal contractions and maintenance of endometrium in pregnancy
-progestins are synthetic progestoens; orally active, half life 11-45hrs
-antagonists include mifeprristone and uliprristal acetate (available in Canada as Prella)
-progesterone receptor antaognsrts: cause breakdown of decidual layer of endometrium → what are their uses
MifeGymiso
-2 drug combinaiotn treatment - providing a non-surgical option for early abortion
-up to 63 days gestation as measured by LMP with a 28d cycle
-availel to canadians as of januray 2017
-provided as a composite package containing:
-200mg mifeprristone tablets
-200ncg misoprostol tablets
-how the medication is to be dispensed and where is to be ingested needs to be determine on a case by case basis
-SOGC accredited medical abotion training program for care providers (web-based course) wishing to precribe this medication
Slide 38 review birth control with sex steroids
Reccomendations:
-advise poeple of the wider variety of options available. Including LARC
-refer appropriately if someone at your practie is not skilled in IUD/iplant insertion
-options should consider the lielhood of epxosure to STI, other lifestyle facotds and contraceptive protperies
-contraceptive cunselling should include typical use failure rates and the importance of using ones chose route correctly
-midwives typically discuss family-planning options with clients at the 6w dishcagre visit
-include pregnancy spacing based on OB-Hx (ex tolac)
-include fertility rates associated with ageing
Example LARC hormone releasing IUD (MIRENA):
-t shaped device with 52mg of levonorgestrel on arms and stem
-progestin released at rate of 20mcg/day (becomes 10mgd/d after 5y), thought to thicken cervical mucous to create barrier for sperm entry, may stop ovulation and thin uterine lning
-prevents fertilization
-lasts 5-7 years once placed
-reversible if removed
Example hormone releasing IUD:
good:
-dont have to remember daily pill, removable, low risk to STI, helps with jeavy bleeding, can be inserted at anytime
contradiciton: pregnancy, various complications
Example combined oral contraceptive pill
-suppresion of ovulation, changes in cervical mucous
Example seasonique/levonorgestrel-ethinyl estradiol
-days 1-84 is hugher dose of ethinyl estradiol and levonorgestrel
day 85-91 are only ethinyl estradiol and av maller dose of it
-4 periods a year
good: if you want to take a pill daily, can be disconitued, low sti risk, fewer period, lessens heavy bleeding
bad: hypersensitity to any ingredient, pregnancy, clotting disorders, heart/liver issues
