F23-Week11-Slides.pdf

VACCINES, SEX HORMONES, & THYROXINE Readings: Ch 21, 25-26 in Pharmacology Revealed © Dr. E. Cates, Fall2021 1 AGENDA • Review from last week • Vaccines • Endocrine System and Endocrine Drugs • Sex Hormones • Thyroxine & Cortisol • Infographic Sharing Presentations © Dr. E. Cates, Fall2021 2...

VACCINES, SEX HORMONES, & THYROXINE Readings: Ch 21, 25-26 in Pharmacology Revealed © Dr. E. Cates, Fall2021 1 AGENDA • Review from last week • Vaccines • Endocrine System and Endocrine Drugs • Sex Hormones • Thyroxine & Cortisol • Infographic Sharing Presentations © Dr. E. Cates, Fall2021 2 VACCINATION • Along with sanitation, one of the 2 most important contributions to public health in the last 100 years • The basis of modern immunology • Built upon the success of Jenner’s smallpox vaccine and Pasteur's cholera vaccine • Early strategy – deliberately cause a mild infection with an unmodified pathogen • Discovered long-lasting protection could be generated against re-infection • E.g., Jenner: Using cowpox (the bovine analog of smallpox) to protect against human smallpox • Hence the term Vaccination (vacca is Latin for cow) • Vaccination now considered a safe and important component of public health Janeway et al. Immunobiology 6th Ed. 2005 © Dr. E. Cates, Fall2021 6 WHAT THIS LECTURE WILL NOT DO: • Address anti-vaccine controversies or the “anti-vaxxer” movement • Discuss vaccine ingredients or perceived toxicity • Address whether “vaccines cause autism” • CAM has put together a package to educate midwives about vaccines and how to provide ICDs about them. You can find it here: Vaccines - CAM ACSF (canadianmidwives.org) © Dr. E. Cates, Fall2021 7 VACCINATION Active Vaccination • Stimulate the immune system to protect the host against subsequent encounters with the infectious agent Passive Vaccination • Introduction of antibodies to the host that will “mop up” problematic antigens © Dr. E. Cates, Fall2021 8 IMMUNOLOGY OF ACTIVE VACCINATION • Vaccines work by stimulating the B & T cells of the immune system • Creation of a lineage of memory cells (Both B and T memory cells) that remain in the body long-term and can fight subsequent infection with less immune stimulation • The next immune response is often strong enough and swift enough that the person does not know they’ve been exposed • Can be achieved with live attenuated organisms, killed organisms, purified components of organisms (epitopes), or their toxins © Dr. E. Cates, Fall2021 9 IMMUNOLOGY OF ACTIVE VACCINATION – B CELLS 1. A vaccine containing the live attenuated virus is injected into the body. The B-cells recognize the epitopes on the virus in the vaccine and become activated. 2. The B cells then give rise to memory B cells and plasma cells. 3. The plasma cells make antibodies specific to the virus. These antibodies stick to the virus and eliminates the virus from body. 4. The memory cells ‘remember’ the virus and if subsequent infection occurs, they can fight off the infection. © Dr. E. Cates, Fall2021 10 IMMUNOLOGY OF ACTIVE VACCINATION – B CELLS © Dr. E. Cates, Fall2021 Image Sourced From: Nature.com 11 IMMUNOLOGY OF ACTIVE VACCINATION – T CELLS • Exposure of T cells to the epitopes activates them • Activated T cells become cytotoxic T cells • These cytotoxic cells will directly attack and kill cells displaying the epitopes so infected cells will be targeted 1. 2. 3. 4. © Dr. E. Cates, Fall2021 A vaccine containing the live attenuated virus is injected into the body. The T-cells recognize the epitopes on the virus in the vaccine and become activated. Activated T cells become cytotoxic cells and memory T cells Cells that are infected with the virus display a special ‘kill’ tag on their cell surfaces. These kill tags are then recognized by the cytotoxic T cells. The cytotoxic T cells then secrete granzymes and perforins which perforate the infected cells. The holes created cause water to flow into the cell, lysing the infected cell. 12 IMMUNOLOGY OF ACTIVE VACCINATION – T CELLS © Dr. E. Cates, Fall2021 13 Image Sourced From: http://drjosephtm.blogspot.ca PASSIVE IMMUNIZATION © Dr. E. Cates, Fall2021 14 VACCINES ON THE 884/93 • Hepatitis B immune globulin • Hepatitis B vaccine • Measles-mumps-rubella virus vaccine (MMR) • RhD Immune globulin • Varicella Zoster immune globulin © Dr. E. Cates, Fall2021 15 MMR VACCINE • The MMR vaccine is to be offered in the immediate post-partum for people with low or no rubella antibodies (not to be given in pregnancy, as risk to the fetus is unknown) • Why do we do it? • To protect the person from a rubella infection in a subsequent pregnancy as this can lead to congenital rubella syndrome in the newborn • 2 brands: M-M-R II and PRIORIX © Dr. E. Cates, Fall2021 Slide modified from: B. Wainman, McMaster University 16 CONGENITAL RUBELLA SYNDROME • Occurs with maternal exposure in the first trimester • Almost always a primary exposure, but cases of CRS have been reported after re-exposures • Risk of congenital anomalies = 90% when maternal exposure occurs before 11w GA, drops to 0% after 16w • Fetal growth restriction appears to be the only sequela of 3rd trimester infection Dontigny et al., JOGC 2008;30(2) © Dr. E. Cates, Fall2021 17 CONGENITAL RUBELLA SYNDROME © Dr. E. Cates, Fall2021 Dontigny et al., JOGC 2008;30(2) 18 CONGENITAL RUBELLA SYNDROME Congenital Cataracts Blueberry Muffin Rash ©©Dr. Dr. E. Cates, Cates,Fall2023 Fall2021 Images Sourced From: Indian Journal of Pediatric Dermatology 19 New England Journal of Medicine http://pediatric-house-calls.djmed.net/numbered-diseases-childhood-third-disease-rubella/ MMR VACCINE • Mode of action: • The measles vaccine contains a live attenuated version of the measles (rubeola), mumps and rubella viruses • The weakened viruses should stimulate the immune system but not cause significant disease • There is a similar vaccine which also includes the varicella zoster virus (chickenpox) vaccine called MMRV • The CDC reports that about 90% will be immune to rubella with one dose of MMR vaccine (>90% will be immune from measles but only 80% from rubella) • The majority of the remaining 20% will experience a greatly reduced form of rubella if they are infected but 15% of vaccinees will have no protection with one dose © Dr. E. Cates, Fall2021 Slide modified from: C. Beites, Laurentian University 20 MMR VACCINE DURING PREGNANCY • The SOGC states that rubella immunization should not be administered in pregnancy • What if a person receives the MMR vaccine, not knowing they are pregnant? Will this harm the baby? • Probably not. In very rare instances, a person who receives the rubella vaccine will develop the illness. Because of this very small but possible risk it is recommended that a person waits 28 days after receiving the vaccine to become pregnant. However, there is information on a large number of pregnancies where the MMR vaccine was received during pregnancy and no babies were born with Congenital Rubella Syndrome and there was not an increase in the rate of birth defects. Dontigny et al., JOGC 2008;30(2):152-158 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5049a5.htm http://www.otispregnancy.org/files/mmr.pdf © Dr. E. Cates, Fall2021 Slide modified from: C. Beites, Laurentian University 21 MMR VACCINE – ADVERSE EFFECTS • It is expected that there will be pain, irritation, and redness at the site of injection in the first 1-3 days • 7-12 days post vaccination some will have a fever and/or rash that occurs • After 1-3 weeks swollen enlarged lymph nodes and a transitory arthritis/ arthralgia occur in about 25% of adults and as much as 40% of women because of the rubella vaccine in MMR • Pain, stiffness and swelling at injection site tend to last about 1-3 days • Individuals who have had a serious allergic (particularly anaphylactic) reaction to neomycin, gelatin or MMR vaccine are at risk • There is no risk of allergy or anaphylactic reaction if the person has an egg allergy and gets MMR vaccine • MMR vaccine should not be given to people who are planning to get pregnant within 4 weeks of vaccination since there is a small chance that the mild form of the disease will be enough to cause developmental defects © Dr. E. Cates, Fall2021 Slide modified from: C. Beites, Laurentian University 22 VARICELLA-ZOSTER VIRUS (VZV) • A member of the herpes virus family, which includes HSV • One of the most communicable diseases • VZV causes: • Chickenpox (varicella) in children and adults • Can re-emerge as herpes zoster (shingles) – primarily in older adults (>45y) • Same virus, given a different name… I know… confusing… © Dr. E. Cates, Fall2021 23 VARICELLA-ZOSTER VIRUS (VZV) • Presents a serious risk to both the pregnant person and the fetus In the Pregnant Person • A primary VZV infection is associated with potentially life-threatening pneumonitis In the Fetus • May cause congenital varicella syndrome • If infection occurs in the first 2 trimesters (particularly 13-20w) • Affects 1-3% of fetuses • • • • • Damage to brain: encephalitis, microcephaly, hydrocephaly Damage to the eye: microphthalmia, cataracts Other neurological disorder: damage to cervical and lumbosacral spinal cord Damage to body: hypoplasia of upper/lower extremities, anal and bladder severe malformations Lifelong issues In the Newborn • Exposure to the virus just before or during delivery can result in neonatal varicella – can be fatal • Neonatal infection occurs primarily when maternal symptoms occur less than 5d before to 2d after delivery JOGC 2012; 34(3):287-292 © Dr. E. Cates, Fall2021 24 VARICELLA –ZOSTER VIRUS IMMUNE GLOBULIN (VZIG) • VZIG is given within 96 hours of exposure • It may not prevent the disease, but it will likely decrease the severity • VZIG is also given to neonates at risk of varicella infection • The VZIG is isolated from pooled human plasma samples with known high titers of VZIG • Artificially acquired passive immunity • The IgG will bind to the VZV and will inhibit the virus from binding to live cells and starting the infection • The normal route of administration will be IM in the deltoid or anterolateral thigh • The antibodies should be detectable in the blood after 2 days and the t1/2 is >24 days © Dr. E. Cates, Fall2021 Slide modified from: C. Beites, Laurentian University 25 VZIG – ADVERSE EFFECTS • There are no preservatives in the product • Pain at the injection site is common because of the volume injected intramuscularly and the inflammation due to immune stimulation however headache (<10%) and rash (5%) have been reported © Dr. E. Cates, Fall2021 Slide modified from: C. Beites, Laurentian University 26 VZIG – DRUG INTERACTIONS • If the person has taken VZIG it would be theoretically unwise for them to have vaccines soon afterwards since the immune globulin would inhibit the ability of the attenuated virus to cause an immune response. • If the person is unwilling to take VZIG there are antiviral drugs (e.g., acyclovir) which are effective at decreasing the severity of the disease, but they are not currently on the 884/93. • It is recommended that VZIG be administered to infants whose parents have the onset of varicella 5 days or less before delivery or in the first 48 hours after delivery © Dr. E. Cates, Fall2021 27 FREQUENTLY ASKED VACCINE QUESTIONS Influenza Vaccine “The Flu Shot” • The National Advisory Committee on Immunization (NACI) recommends the flu shot to pregnant people • • • • More likely to be in a hospital setting More likely to be providing care to young children Higher risk of influenza-related complications http://www.phac-aspc.gc.ca/naci-ccni/flu-2015-grippe-eng.php#iii3 Pertussis Vaccine • NACI recommends vaccination against Bordetella pertussis (Tdap) to all pregnant people between 27 and 32w GA irrespective of their vaccination history • Tdap immunization can be provided from 13w up until the time of delivery in view of programmatic and unique patient considerations Rationale • Cases of pertussis in Canada have been on the rise since 2012 • To protect infants via maternal Ab transfer, as morbidity and mortality is greatest in the first 6m of life • Infants are highly susceptible to infection – immunization in pregnancy is safe and provides infants with protection until they are able to receive the pertussis vaccine at two months of age. • The cycles of pertussis vary in Canada – routine vaccination in pregnancy is preferable to outbreak control • Update on immunization in pregnancy with Tdap vaccine - Canada.ca Neither of these vaccines are currently captured in the midwifery drug legislation ©©Dr. Dr. E. Cates, Cates,Fall2023 Fall2021 28 SELF-STUDY HepB Treatments • What is given? • When? • Prepare drug card/resource on this RhD Iummunoglobulin • What is given? • When? • Prepare drug card/resource on this • Study the SOGC guideline RE: Hepatitis B and pregnancy& alloimmunization in pregnancy posted under “Additional Resources” on A2L to understand these treatments • THIS IS TESTABLE MATERIAL • Share your thoughts/questions with each other on A2L. Laiba and I will pop on and answer questions as needed. © Dr. E. Cates, Fall2021 29 THE ENDOCRINE SYSTEM • A group of glands throughout the body • Regulates bodily function via blood-borne hormonal messages • Steroids, peptides, amines • Peptides are most common Corpus Luteum (menstrual cycle, first ½ of pregnancy • Release of endocrine hormones regulated by circulating levels of chemicals and nervous system connections • Many commonly prescribed drugs are endocrine modulators Image Sourced From: www.medicalnewstoday.com © Dr. E. Cates, Fall2021 31 SEX HORMONES • All sex hormones are steroids (derivatives of cholesterol) • Primarily made in the gonads • However, during pregnancy, the placenta makes most of the steroids • The main sex hormones are: • Estrogens • Estriol, 17β-estradiol, estrone • Progesterone • Androgens • In females, progesterone and the estrogens are the most important sex hormones, although there is a role for testosterone © Dr. E. Cates, Fall2021 32 ESTROGENS • 3 natural estrogens: 17β-estradiol (most abundant, potent, menstrual cycle, reproductive events), estriol (placenta), estrone (postmenopausal) • Estrogens stimulate fat-deposition during maturation, bone deposition; development of uterine endometrium and thin, elastic cervical mucus (menstrual cycle); increases production of clotting factors and inhibits antithrombin III production; stimulates breast tissue/glands in pregnancy • Why are pregnant people at risk of deep vein thrombosis with high amounts of estrogen? • Synthetic = ethinyl estradiol: half-life 6-12 hrs © Dr. E. Cates, Fall2021 Slide modified from: C. Osepchook, Ryerson University 33 PROGESTOGENS • Progesterone most abundant; made by corpus luteum and placenta • Inhibits myometrial contractions and maintenance of endometrium in pregnancy • Progestins are synthetic progestogens; orally active; half-life 11-45hrs • Antagonists include mifepristone and ulipristal acetate (available in Canada as PrELLA™) • Progesterone receptor antagonists: cause breakdown of decidual layer of endometrium → what are their uses? ©©Dr. Dr. E. Cates, Cates,Fall2023 Fall2021 34 MIFEGYMISO • 2-drug combination treatment – providing a non-surgical option for early abortion • Up to 63 days of gestation as measured by LMP with a 28d cycle • Available to Canadians as of January 2017 • Currently cannot be prescribed by midwives • Provided as a composite package containing: • 200mg mifepristone tablets • 200mcg misoprostol tablets • How the medication is to be dispensed and where is to be ingested needs to be determined on a case-by-case basis • SOGC Accredited Medical Abortion Training Program for care providers (i.e., currently physicians and NPs; webbased course) wishing to prescribe this medication ©©Dr. Dr. E. Cates, Cates,Fall2023 Fall2021 35 SELF-STUDY: “BIRTH CONTROL WITH SEX STEROIDS” • Read this section in your text • Sex steroids are used in form of combination contraceptive, progestin-only contraception, or postcoital contraceptive • Combination contraceptives: ethinyl estradiol and a progestin • Estrogen and progestin inhibit ovarian follicle maturation and LH surge • Progestin causes thick, dry cervical mucus and atrophic endometrial environment to decrease chances of implantation • E.g., oral tablets (COCPs), skin patch (Ortho Evra), vaginal ring (NuvaRing) • Failure rates equal to or less than 1 per 100 women-years • Progestin-only: oral pills, IUD (Mirena), injectable (Depo-Provera), implants (polymer rods, not available in Canada) • Do not reliably suppress ovulation but keep cervical mucus thick and endometrium in atrophic state • Depo-provera still available in Canada, but no-longer recommended due to longterm women’s health concerns • Loss of bone mineral density, early onset osteopenia, osteoporosis, fragility fractures • Nation-wide class action settlement in 2021 • Postcoital contraception: high dose of progestin levonorgestrel within 72 hrs • Side effects: nausea, abdominal pain, fatigue, headache, menstrual changes ©©Dr. Dr. E. Cates, Cates,Fall2023 Fall2021 36 GLUCOCORTICOIDS • Produced and released in the adrenal cortex • Main glucocorticoid in humans is cortisol – released in response to stress • Glucocorticoids stimulate gluconeogenesis (from protein and fat catabolism), hepatic glucose secretion, immunosuppression, an increase in systemic blood pressure • Glucocorticoids inhibit the effects of insulin, the growth of muscles, and tissue repair • From a pharmacological perspective, the anti-immune activities of glucocorticoids are a useful feature © Dr. E. Cates, Fall2021 37 GLUCOCORTICOIDS • Synthetic glucocorticoids have potent anti-inflammatory and immunosuppressive actions • Main immunosuppressive effect results from the inhibition of neutrophils • An important part of the innate immune response • Anti-inflammatory effects also mediated by the inhibition of phospholipase A2 • Therefore, prostaglandins can’t be made • Used in a wide variety of conditions that require suppression of inflammatory symptoms • Relevant to midwifery care are the treatment of inflammatory dermatoses • E.g., OTC low concentration (0.5%) hydrocortisone cream for eczema or polymorphic eruption of pregnancy (pruritic urticarial papules and plaques of pregnancy – PUPPs) • Itchy, bumpy rash that starts in the stretch marks of the abdomen in the last 3 months of pregnancy then clears with delivery © Dr. E. Cates, Fall2021 38 GLUCOCORTICOID CLASSES Class 1 • very potent, 600x as potent as hydrocortisone • e.g., betamethasone dipropionate Class 2 • potent, 100-150x hydrocortisone • betamethasone valerate • What is effect of long-term use of high-potency GC cream? Class 3 • moderate, 2-25x hydrocortisone Class 4 • Mild • e.g., hydrocortisone 0.5-2.0% solution © Dr. E. Cates, Fall2021 39 THYROID HORMONES • Critical to the maintenance of metabolic homeostasis • Increase metabolic rate, protein synthesis, and fat breakdown – influence the function of all major organs • During fetal development, thyroid hormones essential for normal development • Thyroid gland makes thyroxine (T4) and triiodothyronine (T3) in response to thyrotropin-releasing hormone (TRH) from the hypothalamus and thyroid stimulating hormone (TSH) from the anterior pituitary • Thyroid hormone production regulated via a negative feedback loop • Why is TSH high in hypothyroidism? © Dr. E. Cates, Fall2021 40 HYPOTHYROIDISM • Low levels of thyroid hormones from inadequate thyroid gland function • S&S: weight gain, fatigue, amenorrhea, depressed lactation, constipation, mental sluggishness, and dry, thick skin • Associated with infertility • Fetus relies on maternal thyroid hormone until 12 wks gestation • Treatment is levothyroxine (SYNTHROID) - > TSH monitored closely in pregnancy and medication may be adjusted by physician © Dr. E. Cates, Fall2021 Slide modified from: C. Osepchook, Ryerson University 41