M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder Clinical Pharmacy 2 Lab Group 1 Lesson 1: Hormonal Replacement Therapy CASE PRESENTATION ON HRT Synthroid 75 mcg po once daily ● NKDA All ROS Chief Complaint ● ● ● “I have been having hot flashes for the past few months, and I just can’t take it anymore.” (+) hot flashes, occasional night sweats and insomnia, vaginal dryness. (–) for weight gain, constipation. LMP 12 months ago. Physical Examination HPI ● Emma Peterson is a 50-year-old woman who reports experiencing two to three hot flashes per day, occasionally associated with insomnia. She also states she is awakened from sleep about two to three times per week needing to change her bed clothes and linens. Her symptoms began about 3 months ago, and over that time, they have worsened to the point where they have become very bothersome. She states that her mother was prescribed a pill for this, but she is hesitant to take the same thing because she heard on the news and from friends that the medication may not be safe. She also does not want to “get her period back,” if possible. Successfully treated for depression in the past, she is currently controlled on paroxetine therapy. She currently exercises three times a week and tries to follow a low-cholesterol diet. Gen WDWN female in NAD ● BP 128/86, P 78, RR 15, T 36.4°C; Wt 76.2 kg, Ht 5'6'' VS Skin ● ● ● ● WNL Neck/Lymph Nodes Supple, no bruits, no adenopathy, no thyromegaly Lungs/Thorax ● Depression GERD HTN Hypothyroidism Warm, dry, no lesions HEENT PMH ● ● ● ● ● ● CTA bilaterally Breasts ● Supple; no masses ● RRR, normal S1 and S2; no MRG ● Soft, NT/ND, (+) BS; no masses CV FH ● Mother died of stroke at age 67; father died of lung cancer at age 62. Patient has one brother, 52, and one sister, 48, who are alive and well, but both with HTN. Abd Genit/Rect SH ● Married, mother of two healthy daughters, ages 21 and 25. She is an RN in a neighboring physician’s office. She walks on her treadmill three times a week and is trying to follow a dietitian-designed lowcholesterol diet. She does not smoke and occasionally drinks a glass of red wine with dinner. ● Pelvic exam normal except (+) mucosal atrophy; stool guaiac (–) ● (–) CCE; pulses intact Ext Meds ● ● ● Hydrochlorothiazide 25 mg po once daily Omeprazole 20 mg po once daily Paroxetine 20 mg po once daily Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] 1 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder Lab Results ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● Na 136 mEq/L Hgb 12.7 g/dL Ca 9.3 mg/dL K 3.9 mEq/L Hct 39.3% AST 32 IU/L Cl 104 mEq/L WBC 6.5 °x 103/mm3 ALT 30 IU/L CO2 25 mEq/L Plt 208 °x 103/mm3 TSH 2.46 mIU/L BUN 10 mg/dL FSH 87.8 mIU/mL Random Glu 98 mg/dL SCr 0.7 mg/dL UPT (–) Fasting Lipid Profile: T. chol 190 mg/dL ; HDL 50 mg/dL; LDL 132 mg/dL; Trig 180 mg/dL 2. Medical treatment for menopause simply focuses on relieving its manifestations and managing chronic conditions that may occur with aging. Estrogen hormone replacement therapy is the most common and effective treatment for the relief of the signs and symptoms of menopause, especially hot flashes, which the patient is specifically concerned about. Therapeutic Alternatives 3.a. What nondrug therapies might be useful for this patient? The Mayo Clinic suggests different ways to manage signs and symptoms associated with menopause. ● ● Neuro ● Normal sensory and motor levels ● Other ● PAP smear and mammogram: Normal Assessment ● 50-year-old, symptomatic postmenopausal woman considering HRT versus other treatment options QUESTIONS Problem Identification 1.a. Create a list of the patient’s drug therapy problems. ● Omeprazole interacts with Levothyroxine (Synthroid) by increasing gastric pH, lowering the levels of Levothyroxine. Hence, symptoms of hypothyroidism are not addressed. 1.b. What information (signs, symptoms, laboratory values) indicates the presence or severity of this patient’s problems as she begins menopause? ● ● ● ● ● ● ● The patient is in her menopausal age (50 years old) Frequent hot flashes Occasional night sweats and insomnia Vaginal dryness LMP was 12 months ago Mucosal atrophy was observed Elevated FSH (87.8 mIU/mL) Desired Outcome Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] What are the goals of therapy for this patient’s menopausal symptoms? ● To cool hot flashes, it is recommended to know what triggers the flashes so it can be avoided. Aside from these, it is recommended to always have a glass of water and to dress in layers. OTC water-based or silicone-based lubricant can also be used to decrease vaginal discomfort. It is best to avoid glycerin-containing lubricant to avoid burning or irritation. Staying sexually active can also help increase blood flow in vagina. It is important to practice getting enough sleep regularly, eating a balanced diet, exercising regularly, and avoiding smoking. Some alternative medicines include: ○ Plant estrogens like isoflavones (soybeans, lentils, chickpeas, other legumes) and lignans (flaxseed, whole grains, and some fruits and vegetables). Although these should be consumed carefully since this can interfere with the patient’s high blood pressure. ○ Bioidentical hormones (plant-sourced hormones) ○ Black cohosh ○ Yoga ○ Acupuncture ○ Hypnosis 3.b. What are the benefits and risks of HRT for this patient? HRT can help reduce the symptoms of menopause that the patient is currently experiencing. In addition, it slightly reduces that patient’s risk of bowel cancer, prevents cardiovascular disease, and protects the patient in developing osteoporosis. However, there are increased risk of developing breast cancer, blood clot, and or gallbladder/gallstone problems for patients undergoing HRT. 3.c. What pharmacotherapeutic hormonal therapies are available for the treatment of menopause? The pharmacotherapeutic hormonal therapies available for the treatment of menopause includes Estrogen therapy and Estrogen Progesterone/Progestin Hormone Therapy (EPT). 2 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder ● ● Estrogen therapy - Estrogen is taken alone ○ may be prescribed as a tablet, spray, cream, vaginal ring, gel or spray. EPT - Also called combination therapy, this form of HT combines doses of estrogen and progesterone ● ● ● 3.d. What nonhormonal alternatives may be used to manage menopausal symptoms? Clonidine - might provide some relief from hot flashes. Gabapentin - helps reduce hot flashes and useful for women who can't use estrogen therapy. Low-dose antidepressants - helps in the management of hot flashes and may be useful for women who can't take estrogen for health reasons or for women who need an antidepressant for a mood disorder. To manage menopause non hormonal alternatives can be used like: Optimal Plan 4. What drug, dosage form, dose, schedule, and duration are best for this patient? DRUG INDICATION DOSE FREQUENCY ROUTE TREATMENT DURATION PRICE Premarin Moderate to severe vasomotor symptoms of menopause 0.3 mg once daily PO daily regimen or cyclic regimen (25 days on, 5 days off) Php 39.25 per tab Hydrochlorot hiazide Hypertension 25 mg once daily PO Maintenance Php 6.25 per tab Omeprazole GERD 20 mg once daily PO Maintenance Php 27.50 per cap Paroxetine Depression 20 mg once daily PO Tapered once symptoms improve Php 34.80 per tab Synthroid Hypothyroidism 75 mcg once daily PO Maintenance Php 11.25 per tab Reference https://reference.medscape.com/drug/premarin-estrogens-conjugated-342771 Outcome Evaluation 5. What clinical and laboratory parameters are necessary to evaluate the therapy for achievement of the desired therapeutic outcome and to detect or prevent adverse effects? ● ● ● ● Pelvic exam - examines the organs of the female reproductive system; detects swelling and other abnormalities Mammogram - detects early sign of breast cancer Estrogen test - helps monitor HTR for menopause Blood fats, sugar levels, liver function - help monitor for any unwanted effects of HRT 6. What information should be provided to the patient to enhance adherence to the medication, ensure successful therapy, and minimize adverse effects? The information that should be provided to the patient in order to enhance adherence, ensure successful therapy and minimize adverse effects would be the importance of medication regimen compliance as well as the consequences of non-adherence to the patient’s health and safety. The patient must be advised not to abruptly stop the use of HRT unless otherwise told by her physician. ■ CLINICAL COURSE Reference: https://www.rxlist.com/premarin-drug.htm https://www.medsafe.govt.nz/consumers/cmi/p/premarin.pdf https://medlineplus.gov/lab-tests/estrogen-levels-test/ The patient returns to her physician after taking HRT for 1 year. She reports that her hot flashes, night sweats, and occasional insomnia have significantly decreased and would like to know if she should continue taking the HRT regimen and if so, for how long. Patient Education The patient should continue taking the HRT regimen. The lowest effective dose should be taken for the shortest amount Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] 3 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder of time. Research has supported an acceptable HRT of 2-5 years. On the other hand, long-term use depends on the individual decision between the patient and the doctor, in consideration to the annual assessment. ■ FOLLOW-UP QUESTIONS 1. What is the optimal dose and length of time for a patient to continue on HRT? There is no predetermined period of time for which one should use HRT; it is a decision between a patient and a doctor (The Menopause Charity, 2022). But as much as possible, HRT should be used at the lowest possible dose and for the shortest period of time. Generally, treatment should be initiated with Premarin 0.3 mg. Subsequent adjustments to the dose and duration of treatment should be based upon the individual patient response and reassessment done annually by the healthcare provider (Pfizer, 2023). Reference: https://www.breastcancer.org/research-news/20100708 https://www.themenopausecharity.org/2022/04/19/starting-or-c ontinuing-hrt-many-years-after-your-menopause/ https://www.pfizermedicalinformation.com/en-us/premarin/dosa ge-admin 2. How should HRT be discontinued after successful treatment? Would your recommendation for HRT change if the patient had been complaining of genital symptoms only? Why or why not? Sudden discontinuation of HRT after successful treatment is not recommended. Gradually decreasing HRT dose should be done to prevent recurrence of symptoms. If the patient had only complained genital symptoms, HRT would still be recommended. Physical examination revealed mucosal atrophy which indicates vaginal dryness. Wilson (2018) suggested that HRT should be used to address and relieve this symptom as it can cause inflammation of the vaginal wall. Reference: https://www.nhs.uk/conditions/hormone-replacement-therapy-h rt/# https://www.medicalnewstoday.com/articles/189406#quick_fact s HRT, patients with a history of breast cancer are likely to develop new or recurrent breast cancer. In general, doctors do not recommend HRT if a woman was previously treated for breast cancer. A 2021 analysis found that women who took systemic HRT with a history of breast cancer had a 46% higher risk of recurrence. Current recommendations say that women with a history of breast cancer should not take any type of systemic HRT (Breastcancer.org, 2023). Therefore, HRT would not be recommended for the patient. Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780586/ https://pubmed.ncbi.nlm.nih.gov/19095500/# https://www.cancer.org/cancer/breast-cancer/living-as-a-breast -cancer-survivor/menopausal-hormone-therapy-after-breast-ca ncer.html# https://www.breastcancer.org/risk/risk-factors/using-hormone-r eplacement-therapy 4. What is the use of black cohosh in menopausal women? Black cohosh helps relieve menstrual cramps and menopausal symptoms. Further studies have mentioned that it improves physical and psychological menopausal symptoms, including anxiety, hot flashes, night sweats, and vaginal dryness. Although its safety and effectiveness were poorly evaluated, this dietary supplement is still recommended by some doctors for short-term use (less than 6 months) for the relief of hot flashes. Reference: https://www.mountsinai.org/health-library/herb/black-cohosh# ■ SELF-STUDY ASSIGNMENTS 1. Research non-hormonal therapies that have been studied for the relief of menopausal symptoms and compare the scientific evidence of their efficacy to traditional hormonal medications. · The non-hormonal therapy used for menopause symptoms include Paroxetine, Clonidine, and Gabapentin among others. Compared to hormonal therapies that are primarily used and are first line treatment for menopause symptoms, non-hormonal therapies are less effective but are still useful alternatives. 2. Review the results of the Women’s Health Initiative (WHI) study and provide a summary of the findings regarding HRT and cardiovascular risk and breast cancer risk. 3. Would your recommendation for HRT change if this patient were to have had significant risk factors for CHD or a personal history of breast cancer? Why or why not? HRT increases the risk of heart disease in healthy postmenopausal women. Analyses showed that women who started HRT less than 10 years after menopause remained at increased risk of heart disease on average for about six years. Overall risks of long-term use of hormone therapy outweigh the benefits (Women's Health Initiative, 2010). HRT is not recommended for patients with risk factors for CHD. There is a known link between estrogen levels and breast cancer growth. A clinical trial has shown that with the use of Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] The study sponsored by National Heart, Lung, and Blood Institute (NHLBI) called the Women’s Health Initiative (WHI), was a long-term study to assess how some diseases affect post-menopausal women. It was found that post-menopausal 4 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder women who takes hormone therapy had an increased risk for cardiovascular diseases and breast cancer. ● https://www.womenshealth.gov/30-achiev ements References: ● https://www.health.harvard.edu/womenshealth/nonhormonal-treatments-for-meno pause Subjective Objective Demographics ● Emma Peterson ● 50-year old female. Medication list ● Hydrochlorothiazide 25 mg po once daily ● Omeprazole 20 mg po once daily ● Paroxetine 20 mg once daily ● Synthroid 75 mcg po once daily Chief complaint ● Hot flashes associated with insomnia ● Her sleep is disrupted 2-3 times per week. ● The patient does not want to get her period back PMH ● ● ● ● Depression GERD Hypertension Hypothyroidism ● ● Mother died of stroke at 67 Father died of lung cancer at 62 Brother is 52 y/o and has hypertension Sister is 48 y/o and has hypertension Vital signs ● ● ● ● ● ● ● SH ● ● ● ● Married Have 2 healthy daughters ages 21 and 25 She is a registered nurse She exercises thrice a week and follows a low-cholesterol diet Allergy ● No known drug allergy (NKDA) Review of systems ● ● ● (+) hot flashes, occasional night sweats, insomnia, and vaginal dryness. (–) weight gain, constipation. Last Menstrual Period- 12 months ago. Lab results ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 50-year-old, symptomatic postmenopausal woman considering HRT versus other treatment options Drug interaction BP= 128/86 RR= 15 bpm PR= 78 bpm T= 36.4C Wt= 76.2kg Ht= 5’6” FH ● Assessment Na 136 mEq/L Hgb 12.7 g/dL Ca 9.3 mg/dL K 3.9 mEq/L Hct 39.3% AST 32 IU/L Cl 104 mEq/L WBC 6.5 °x 103/mm3 ALT 30 IU/L CO2 25 mEq/L Plt 208 °x 103/mm3 TSH 2.46 mIU/L BUN 10 mg/dL FSH 87.8 mIU/mL Random Glu 98 mg/dL SCr 0.7 mg/dL UPT (–) ● The Omeprazole being taken by the patient interacts with the prescribed Levothyroxine by increasing gastric pH and decreasing the levels of Levothyroxine which will make the hypothyroidism treatment ineffective. Plan Pharmacologic Treatment ● Hormone replacement therapy (HRT) may be used to manage the signs and symptoms of menopause, especially the hot flashes that are bothering the patient. ● The patient may take Premarin tablets at 300 mcg-1.25mg daily as prescribed by a physician. ● Non hormonal alternatives may also be used such as Clonidine, Gabapentin and low-dose antidepressants for the patient’s condition. Non-Pharmacologic Treatment ● Use of OTC water-based or silicone-based lubricant to reduce vaginal discomfort ● Sexual activity may also help by increasing blood flow in vagina ● Ensure enough rest and sleep as well as a healthy and balanced diet ● Yoga and exercise ● Acupuncture and hypnosis ● Black cohosh and plant-sourced hormones Medical Examination/Follow Up ● Physical examination including pelvic and breast should be done ● Periodic check-ups are recommended Fasting lipid profile: ● ● ● ● T. chol 190 mg/dL ; HDL 50 mg/dL; LDL 132 mg/dL; Trig 180 mg/dL Physical ● Well-developed, well- nourished (WDWN) and no abnormality detected (NAD) HEENT ● Within normal limits (WNL) Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] 5 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder Lymph nodes ● Supple, no bruits, no adenopathy, no thyromegaly CTA bilaterally Breasts ● Supple; no masses ● Regular rate&rhythm (RRR), normal S1 and S2, no murmur, rubs, or gallops (MRG) CV Abdomen ● Soft, NT/ND (non tender/non distended), (+) Bowel sound (BS); no masses Genit/ Rect ● Pelvic exam normal except (+) mucosal atrophy; (–) stool guaiac Extremities (–)Cyanosis, Clubbing, Edema (CCE); pulses intact Neuro ● Normal sensory and motor levels ● Normal PAP smear and mammogram Other References: https://www.mayoclinic.org/diseases-conditions/menopause/diagnosis-treatment/drc-20353401 https://www.drugs.com/medical-answers/after-taking-levothyroxine-omeprazole-3562259/# https://www.medicines.org.uk/emc/product/2900/smpc# Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] 6 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder Lesson 2: Contraception The group assigned for this activity should prepare a case presentation (following either a SOAP/FARM format) in a power point presentation. All members should actively collaborate with the team and shall present this in our virtual meet. Make sure all the information and questions have references that are properly cited. Attach the PDF file copy of your report on the quiz question. Meds ● ● All ● ROS ● M3L2 WHILE TASK Chief Complaint ● “My fiancé and I are getting married soon, and we’re not ready for kids just yet.” HPI ● Madeline Macy is a 24-year-old graduate student who presents to the Family Medicine Clinic for contraceptive counseling. She and her fiancé, Fritz, are planning to be married in approximately 3 months. Madeline states that she and Fritz have been in a monogamous sexual relationship for the past 2 years, and that their primary method of contraception has been via the inconsistent use of male condoms. She is here today to be evaluated for the use of hormonal contraceptives. The patient states she began menses at age 14, with irregular cycles of 25–36 days in length. Her last menses was 2 weeks ago. The patient states she has heard about contraceptive options that “keep you from having a period,” and she wants to know more about those options, and if they would be okay for her to try. NKDA (No known drug allergy) Menstrual periods are the most irregular during exam times. Migraine headaches are not accompanied by aura or focal neurologic symptoms, and have been well controlled on prophylactic medication. (Patient states she has not had a migraine for more than 6 months; however, prior to being placed on propranolol for migraine prophylaxis, she reported experiencing menstrual-related headaches in addition to frequent migraines.) Physical Examination Gen ● WDWN (well developed, well nourished) female in NAD (No abnormality detected) ● BP 116/74, PR 66, RR 14, T 37°C; Wt 56 kg, Ht 5'6'' VS Skin ● Mild facial acne HEENT ● PMH ● Propranolol LA 160 mg po once daily for migraine prophylaxis Naproxen 220 mg, one to two tablets po Q 8 h PRN menstrual cramps Migraine headaches without aura or focal neurologic symptoms; well controlled for the past 6 months on prophylactic therapy PERRLA (pupils equal, round, and reactive to light and accommodation); EOMI (extra-ocular motion intact); TMs (tympanic membrane) intact; oral mucosa clear Neck/Lymph Nodes ● Supple without lymphadenopathy or thyromegaly FH ● ● ● ● Mother, age 52, has HTN and osteoporosis. Grandmother died from complications of breast cancer, which was diagnosed at age 60. Father, age 53, has osteoarthritis, hypothyroidism, and hyperlipidemia. Grandfather died at age 74 of MI. Lungs ● CTA (Clear to Auscultation), no wheezing CV ● NSR (Normal sinus rhythm); no MRG (Murmur, gallops or rubs) SH ● Currently lives in a house on campus, which she rents with three other graduate students. Once she and Fritz are married, they plan to rent an apartment together until she finishes graduate school. She admits to occasional social use of tobacco and alcohol (“a few drinks and a couple of cigarettes at parties on the weekends”). Otherwise, she denies regular smoking or alcohol use during the week, and she denies illicit drug abuse. Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] Breast ● Equal in size without nodularity or masses, nontender Abd ● Soft, NT (Non tender), no masses or organomegaly Genit/Rect ● Normal vaginal exam w/o tenderness or masses 7 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder MS/Ext ● Normal ROM (Range of motion); normal muscle strength ● ● Neuro ● Labs ● NHS website. (2021, November 18). Complications. nhs.uk. https://www.nhs.uk/conditions/migraine/complications/ Shearman RP. Oral contraceptives. Aust Fam Physician. 1984 Sep;13(9):685-91. PMID: 6508652. A & O (alert and oriented) x 3 Negative Pap smear and UPT (Urine pregnancy test) Assessment ● Young, generally healthy, sexually active female with a history of migraine headache disorder that has been well controlled with prophylactic medication is requesting hormonal contraceptives for birth control. 1.c. What medical problems are relative contraindications to hormonal contraceptive use, and do any of these apply to this patient? ● Smoking and her irregular spontaneous menstruation are the medical problems that are relatively contraindicated to hormonal contraceptive use that apply to the patient. Problem Identification Reference: ● Shearman RP. Oral contraceptives. Aust Fam Physician. 1984 Sep;13(9):685-91. PMID: 6508652. 1.a. Create a list of the patient’s potential drug therapy problems. 1.d. What other information should be obtained before creating a pharmacotherapeutic plan? ● ● Prescribing combined pills and contraceptive patches are not usually recommended if the patient is taking propranolol or other medicines for high blood pressure. Naproxen interacts with drospirenone-containing birth control pills. Health problems, especially heart problems, are observed with concurrent use of these drugs due to induced hyperkalemia. Reference: ● The Pill | Penn State Student Affairs. (n.d.). https://studentaffairs.psu.edu/health-wellness/medical -services/health-information-resources/pill ● NHS website. (2022, September 1). Propranolol. nhs.uk. https://www.nhs.uk/medicines/propranolol/ 1.b. What medical problems are absolute contraindications to hormonal contraceptive use, and do any of those conditions apply to this patient? ● ● The medical problems that are absolutely contraindicated to hormonal contraceptive use that apply to the patient are active migraine and potentially having breast cancer since the patient has a family history of having one. With her family history of cardiovascular disease and hyperlipidemia, she is also not advised to take combined contraceptive pills. Reference: ● Judge CP, Zhao X, Sileanu FE, Mor MK, Borrero S. Medical contraindications to estrogen and contraceptive use among women veterans. Am J Obstet Gynecol. 2018 Feb;218(2):234.e1-234.e9. doi: 10.1016/j.ajog.2017.10.020. Epub 2017 Oct 27. PMID: 29111146; PMCID: PMC5807130. Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] ● ● ● Specifically, when do they plan to have a child? Is the patient taking supplements or vitamins? Does the patient undergo STD screening? 1. What are the goals of pharmacotherapy in this case? ● To prevent pregnancy following sexual intercourse. ● To ascertain the best option of contraception for the patient that will not put her at risk of developing other pressing diseases such as breast cancer and cardiovascular disease among others. 2. What pharmacotherapeutic alternatives are available for prevention of pregnancy in this patient? Therapeutic Alternative ● Opting for progestin-only pills rather than combined hormonal oral contraceptives. ● Use of progestin implants or Depo medroxyprogesterone acetate (DMPA) injectables instead of peroral pills. ● Utilizing intrauterine devices (IUD) to deliver the progestin levonorgestrel. Non-Therapeutic Alternative ● Hormone-free contraception through ParaGard IUD which utilizes copper to prevent pregnancies. ● Natural family planning ○ Body temperature ○ Cervical mucus ○ Calendar (Most successful when intercourse takes place from 2 days before ovulation to the day of ovulation) 8 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder ● Withdrawal Method Reference: ● Barhum, L. (2022, November 8). What to know about non-hormonal birth control. https://www.medicalnewstoday.com/articles/320213 ● https://americanheadachesociety.org/wp-content/uplo ads/2021/01/AHS-First-Contact-Hormones-Contrcepti ve-Options.pdf 3. What contraceptive method, dose, and schedule are best for this patient? ● The contraceptive method that is the best for the patient is by using progestin-only “minipills” to prevent unwanted pregnancy. One tablet is to be taken daily for 28 consecutive days. Each subsequent pack is started immediately after finishing the previous pack. The interval between two pills should be 24 hours. It is best to take the medication after evening meals or before going to sleep. Patients may continue taking the pill as long as they want to avoid pregnancy. The patient has an option to choose between: ○ Cerazette (Desogestrel) 75 mcg ■ Tablet-taking has to start on day 1 of the woman's natural cycle (day 1 is the first day of her menstrual bleeding). ■ Starting on days 2-5 is allowed, but during the first cycle a barrier method is recommended for the first 7 days of tablet-taking. ○ Exluton (Lynestrenol) 500 mcg ■ Tablet-taking has to start on day 1 of the woman's natural cycle (day 1 is the first day of her menstrual bleeding). ■ Starting on days 2-5 is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking. ○ Daphne (Lynestrenol) 500 mcg ■ Tablet-taking has to start on day 1 of the woman's natural cycle (day 1 is the first day of her menstrual bleeding). ■ Start any day as long as the patient is not pregnant but use a back-up method such as condom for the next seven days as a Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] precaution pregnancy. to avoid Reference: ● Cerazette Full Prescribing Information, Dosage & Side Effects | MIMS Philippines. (n.d.). https://www.mims.com/philippines/drug/info/cerazette ?type=full ● Exluton Full Prescribing Information, Dosage & Side Effects | MIMS Philippines. (n.d.). https://www.mims.com/philippines/drug/info/exluton?ty pe=full ● Daphne Full Prescribing Information, Dosage & Side Effects | MIMS Philippines. (n.d.). https://www.mims.com/philippines/drug/info/daphne?t ype=full Outcome Evaluation 1. What clinical and laboratory parameters are necessary to evaluate the therapy for efficacy and adverse effects? ● Prior to Prescribing: Blood pressure, BMI, Lipid levels, Liver enzymes, Bimanual examination and cervical inspection, Clinical breast examination, Glucose levels test, Hemoglobin, and Thrombogenic mutations. ● Monitor blood pressure during the course of use to ensure that it is maintained within normal range. Reference: Progestin-only Pills. (2017, February 1). Centers for Disease Control and Prevention. https://www.cdc.gov/reproductivehealth/contraception/mmwr/sp r/progestin.html. 1. What information should be provided to the patient to enhance adherence, ensure successful therapy, and minimize adverse effects? ● Tell the patient not to skip on taking the pill even if there is a brief pause from sexual activity. Regularity in taking the pill is very important because contraceptive efficacy is reduced if a pill is delayed for 3 hours. ○ If the user is less than 3 hours late in taking any tablet, the missed tablet should be taken as soon as it is remembered and the next tablet should be taken at the usual time to avoid premature withdrawal bleeding. ○ If she is more than 3 hours late, she should follow the same advice but also additionally use a barrier method for the next 7 days of tablet-taking. ○ If tablets were missed in the very first week of use and intercourse took place in the week before the tablets were missed, the possibility 9 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder of a pregnancy should be considered. Patients should only stop taking the pill after finishing a pack; otherwise bleeding may start. The patient should also stop smoking to prevent or reduce breakthrough bleeding. Drinking alcohol should also be ceased since it precipitates vomiting. Vomiting and persistent severe diarrhea can interfere with the absorption of the pill. ● Reference: ● Cerazette Full Prescribing Information, Dosage & Side Effects | MIMS Philippines. (n.d.). https://www.mims.com/philippines/drug/info/cerazette ?type=full ● Exluton Full Prescribing Information, Dosage & Side Effects | MIMS Philippines. (n.d.). https://www.mims.com/philippines/drug/info/exluton?ty pe=full ● Daphne Full Prescribing Information, Dosage & Side Effects | MIMS Philippines. (n.d.). https://www.mims.com/philippines/drug/info/daphne?t ype=full ● ● ● ■ CLINICAL COURSE Madeline returns to the clinic in 2 months complaining of worsening acne and breakthrough bleeding. ■ FOLLOW-UP QUESTIONS 1. What medical conditions can be the cause of breakthrough bleeding? If breakthrough bleeding is not caused by an underlying medical condition, how can it be managed? ● Breakthrough bleeding is a prevalent side effect of “minipill” or the progestin-only pills. This is usually common during the first months of starting with oral contraceptives and the bleeding may go away on its own. When compared to combined birth control pills, the sudden bleedings are also more unpredictable in the progestin-only type. In order to manage this problem, it is advised for the patient to take the medication at the same time everyday. If the patient is more than 3 hours late taking the progestin-only pill, take the missed dose right away and use a backup method of contraception (such as a condom) for the next 2 days. Another factor is smoking which is linked to higher rates of menstrual irregularities and breakthrough bleeding. Therefore, it is also suggested for her to cease smoking. Reference: Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] ● 2. Santos-Longhurst, A. (2021, October 13). What You Need to Know About Breakthrough Bleeding on Birth Control. Healthline. https://www.healthline.com/health/womens-h ealth/breakthrough-bleeding-on-the-pill Salvaggio HL, Zaenglein AL. Examining the use of oral contraceptives in the management of acne. Int J Womens Health. 2010 Aug 9;2:69-76. doi: 10.2147/ijwh.s5915. PMID: 21072299; PMCID: PMC2971728. familydoctor.org editorial staff. (2020, July 6). Progestin-Only Birth Control Pills. familydoctor.org. https://familydoctor.org/progestin-only-birth-c ontrol-pills/ What recommendations can be made to address this patient’s complaint of worsening acne? ● Increase in acne could also be attributed to her use of progestin-containing pills. Unlike combined oral contraceptives that decreases androgen levels, these “minipills” cause fluctuations or rise in these male hormones leading to increased sebum production and acne. To address this complaint, the following products could be recommended to reduce hormonal acne: benzoyl peroxide (topical acne treatment), Tretinoin (topical retinoid), and salicylic acid (chemical exfoliant). Other tips to manage acne are to cleanse your face twice daily with a gentle cleanser, use moisturizer, and go for non-comedogenic products to avoid pore-clogging. Lastly, the help of dermatology experts is highly suggested. Reference: ● Dunn, J. (2022, August 12). How Do Birth Control Pills Help with Acne. Scripps. https://www.scripps.org/news_items/7002-how-do-birt h-control-pills-help-with-acne#:~:text=Birth%20control %20pills%20that%20contain,%E2%80%9D)%20can %20make%20acne%20worse. ● Sanghvi, S. (2021, December 20). Contraceptive pill and acne. Lloyds Pharmacy. https://onlinedoctor.lloydspharmacy.com/uk/contracep tion/the-pill-and-acne#:~:text=The%20progestogen%2 Donly%20pill%2C%20or,oily%20skin%2C%20resultin g%20in%20acne. ● Curology team. (2022, August 16). Fact vs. fiction: Does progesterone cause acne. Curology. https://curology.com/blog/fact-vs-fiction-does-progeste rone-cause-acne/. ■ SELF-STUDY ASSIGNMENTS Compare the costs of each method of birth control and prepare a report that contains your conclusions as to 10 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder which method provides the best efficacy at the most reasonable cost. ● ● ● ● Cerazette (Desogestrel) 75 mcg ○ 620.00 pesos per box Exluton (Lynestrenol) 500 mcg ○ 189.25 pesos per box Daphne (Lynestrenol) 500 mcg ○ 147.50 pesos per box ParaGard IUD ○ Anywhere from 10,000 to 15,000 pesos on average The three mini pills above provide the same efficacy, but in terms of money and flexibility, Daphne (Lynestrenol) 500 mcg was the most reasonable cost and the medication that can easily be terminated in terms of contraception. Since the couple still plans to have kids in the future, ParaGard IUD is the least recommended contraception because it is costly and its effect could last up to 10 years. Reference: ● Watsons Philippines.com ● Quesada, F. A. (2022, February 2). IUD Available in the Philippines: Is It Right For You? Learn More Here. Hello Doctor. https://hellodoctor.com.ph/sexual-wellness/contracepti on/iud-philippines/ Subjective Objective Assessment Plan Demographics ● Madeline Macy ● 24-year old female Vital Signs ● Weight= 56 kg ● Height= 5’6” ● Blood Pressure= 116/74 mmHg ● Respiratory Rate= 14 bpm ● Pulse Rate= 66 bpm ● Temperature= 37C Young, generally healthy, sexually active female with a history of migraine headache disorder that has been well controlled with prophylactic medication is requesting hormonal contraceptives for birth control. Non-Pharmacologic Treatment ● Hormone-free contraception through ParaGard IUD which utilizes copper to prevent pregnancies. ● Natural family planning ● Body temperature ○ Cervical mucus ○ Calendar Intercourse takes place from 2 days before ovulation to the day of ovulation ● Withdrawal Method Chief Complaint ● Does not want to have kids Past Medical History ● Migraine headaches without aura or focal neurologic symptoms; well controlled for the past 6 months on prophylactic therapy Allergy ● NKDA Medication List ● Propranolol LA 160 mg po once daily ● Naproxen 220 mg, one to two tablets po Q8h PRN Skin ● Family History ● Mother, age 52, has HTN and osteoporosis. ● Grandmother died from complications of breast cancer, which was diagnosed at age 60. ● Father, age 53, has osteoarthritis, hypothyroidism, and hyperlipidemia. ● Grandfather died at age 74 of MI. Social History ● Engaged ● A graduate student ● Smokes and drinks alcohol occasionally ● She denies illicit drug abuse Review of Systems ● Irregular period ● Migraine headaches are not accompanied by aura or focal neurologic symptoms ● Menstrual-related headaches prior to propanolol treatment Mild facial Acne Physical ● WDWN ● NAD HEENT ● PERRLA ● EOMI ● TMs intact ● Oral mucosa clear Neck/Lymph Nodes ● Supple without lymphadenopathy or thyromegaly Lungs ● CTA, no wheezing Cardio Vascular ● NSR ; no MRG Breast ● Equal in size without nodularity or masses, nontender Abdomen ● Soft, NT (non tender); no masses, no acromegaly Genit/ Rect ● Normal vaginal exam w/o tenderness or masses Musculoskeletal & Extremities ● Normal ROM ● Normal muscle strength Neuro ● Alert and Oriented x 3 Laboratory data ● (-) Pap smear and Urine pregnancy test Pharmacologic Treatment ● Opting for progestin-only pills rather than combined hormonal oral contraceptives. ○ Daphne (Lynestrenol) 500 mcg ○ 1 tablet is to be taken daily Q24h for 28 consecutive days. ○ Preferably, take it after evening meals or before going to sleep. ○ Other alternatives: Exluton 500 mcg & Cerazette 75 mcg ● Use of progestin implants or Depo medroxyprogesterone acetate (DMPA) injectables instead of peroral pills. ● Utilizing intrauterine devices (IUD) to deliver the progestin levonorgestrel. Lesson 3: Pregnancy and Lactation Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] 11 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder M3.L 3. While Task Pregnancy & Lactation Selective Serotonin Reuptake Inhibitor (SSRI) at 20 mg per day. The group assigned will Create a power point or AVP presentation on the 4 cases for pregnancy and lactation use FARM/SOAP format in presenting the case. Answer the questions found after each case make sure all group members present and participate during case presentation. Assessme nt Question 1 Case 1: Plan A 2 day old full term infant has excessive shrill crying , jittery and feeding poorly. The medical team cannot find any cause for these effects. The mother, Maria, is worried that they maybe due to paroxetine exposure via breast milk and wonders whether St. Johns Wort would be as safer alternative. Maria has been taking 20 mg paroxetine daily throughout her pregnancy and this has been continued after delivery. 1. What is the most likely drug related explanation? ● Paroxetine is an antidepressant in the Selective Serotonin Reuptake Inhibitor class, under pregnancy category D. Paroxetine exposure can explain the symptoms experienced by the 2-day-old infant since the mother has been taking the medication through her pregnancy. Infants exposed to Paroxetine, especially during the first trimester of pregnancy, have an increased risk of congenital malformations, particularly cardiovascular malformations. 2. Is it safe for the mother to continue to take paroxetine while breastfeeding? ● Generally, it is safe to take Paroxetine because it is one of the most preferred antidepressants for breastfeeding mothers. But with exposure to Paroxetine during pregnancy, the infant has a higher risk of experiencing occasional mild side effects like insomnia, restlessness, and increased crying. 3. Is St John's Wort a reasonable alternative? ● St. John’s Wort is also effective in managing depression however, it is not recommended to be taken by pregnant or breastfeeding women. Hypericin and hyperforin are detected in the breastmilk. Toxicity is also observed in infants with long-term exposure to St. John’s Wort. References: https://www.ncbi.nlm.nih.gov/books/NBK501190/ Subjective The patient has been taking 20mg of Paroxetine daily throughout her pregnancy and it was continued after delivery. Her 2 day old infant has been experiencing excessive crying, jittering and poor feeding behavior which the mother suspects was due to Paroxetine exposure during her breastfeeding. Objective The patient is currently taking Paroxetine, a Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] During pregnancy, women are at higher risk of being depressed. Paroxetine is taken by the mother to address her depression. After birth, symptoms of Paroxetine withdrawal syndrome are observed in the infant. ● ● ● ● The pharmacotherapeutic goal for Maria is to manage her condition without jeopardizing the safety of her newborn and herself. The patient should be advised to consult with her physician to address the withdrawal symptoms being experienced by her 2-day-old newborn. The withdrawal symptoms, specifically the poor eating habit must be monitored and addressed because it could lead to poor nutrition which is not good for the baby. The mother is advised to take intervals between feeding and taking Paroxetine. Question 2 Case 2: A 30 year old epileptic woman is currently taking 1500mg valproic acid daily. She wishes to conceive but is concerned about the possibility of birth defects due to valproate exposure in pregnancy. Her Seizure has been difficult to control with alternative anticonvulsants. 1. What are the risks associated with valproate treatment during pregnancy? ● Children born from mothers who have taken valproic acid during pregnancy have an increased risk of developing decreased communication, social and cognitive skills, developmental delay, and memory impairment. Taking valproic acid during pregnancy increases the risk of birth defects – congenital malformations (neural tube defects and malformations in the body). Hypoglycemia is also observed in neonates, while some infants have hepatic failure. Women taking valproic acid during pregnancy are also at risk of developing hepatic failure and clotting abnormalities which can cause hemorrhagic complications to the neonate, leading to death. 2. How can these risk be minimized? ● The risks associated with Valproate treatment during pregnancy may be minimized by taking folic acid supplementation during the first trimester and tapering off the dose of the Valproic acid since it is not safe to abruptly stop taking this medication once started. Polytherapy of antiepileptic drugs should also be considered. Increased congenital malformations were 12 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder observed in the monotherapy of antiepileptic drugs than with antiepileptic drugs polytherapy. neonatal fluconazole dosage. It means that the dose to the breastfed infant is estimated to be less than the dose that would be given directly to the infant to treat an infection. Subjective Objective Assessme nt Plan The patient is a 30-year-old woman who was diagnosed with epilepsy she is planning to conceive but is concerned about the risks associated with the drug she is taking during pregnancy. She is having difficulty controlling her seizures with alternative anticonvulsants. Therefore, the infant would not be exposed to this amount with The patient is currently taking 1500mg of Valproic acid daily. fluconazole is often used. The patient is currently taking Valproic acid for her epilepsy and she is planning to conceive a baby. Valproate is not recommended during pregnancy because it increases the risk of the child developing birth defects and developmental delays. The patient is having a hard time controlling her seizures using alternative anticonvulsants. concern for a breastfeeding mother since only small amounts ● ● ● ● The pharmacotherapeutic goal for the patient is to effectively manage her seizures and find a way to safely conceive a child while undergoing epilepsy treatment. In order to reduce the risks of taking Valproate during pregnancy, the patient may be prescribed with folic acid and the dosage of the Valproic acid should be gradually reduced if possible because stopping it abruptly is not safe The patient will still continue on taking the prescribed Valproic acid for her seizures since there are no other suitable alternatives for her condition. Continuous monitoring and follow-up check-ups must be conducted regularly. each feeding. In addition, a study has found that fluconazole is often prescribed for breastfeeding mothers to treat breast candidiasis, especially with recurrent or persistent infections. It was also stated that when other treatments fail, treatment with Similarly, miconazole cream 2% should not be a of the product pass into the breastmilk.However, the mother must be advised to remove all topical products before feeding. Reference https://www.ncbi.nlm.nih.gov/books/NBK582846/#:~:text=Ther e%20are%20currently%20no%20studies,expected%20to%20b e%20a%20concern. 2. What other therapeutic measures must be taken? Since the mother is complaining of bilateral nipple pain during and after breastfeeding, this is a sign of thrush or yeast infection in the breast. In this case, the infant might develop thrush in the mouth. Although the mother was given fluconazole, the amount of fluconazole transferred through breast milk is not enough to treat the breastfed infant. If the infant does have an infection, medical treatment will be needed. Subjective 4 weeks after delivery, a breastfeeding mother complains about bilateral nipple pain before and after feeding, which she has been feeding for the past 4 days. She was prescribed with miconazole cream 2% to be applied to the nipple after feeding. Alongside, she was given fluconazole 200 mg for a presumed candidal infection. She expressed concern that the medication might affect the infant. Objective The patient was given miconazole cream 2% to be applied to her nipples. She was also asked to take fluconazole 200 mg dailly for 14 days. Assessme nt The mother expressed her concern that the medication might have effects on the infant. Although both prescribed medications do not have significant effects on the baby. Plan The mother should continue taking the prescribed medications. Although her symptoms suggest a sign of thrush or yeast infection, the mother is advised to temporarily stop breastfeeding the infant in order to prevent the transfer of infection to the infant’s mouth. The patient is also advised to monitor Question 3 Case 3: A breastfeeding mother returned to see her midwife 4 weeks after delivery of a full term healthy infant. She is complaining of bilateral nipple pain during and after breast feeding, a problem that was constant for the past 4 days. She was advised to use miconazole cream 2% to the nipples after each feed. This provided initial relief but symptoms returned after a few days. She was given a course of fluconazole 200 mg daily for 14 days for a presumed candidal infection but expressed concern that the medication affect the infant. 1. Is the regimen safe to use during lactation? Fluconazole 200 mg daily for 14 days in breastfeeding mothers is considered acceptable. Even though fluconazole can enter breast milk, it is still acceptable because the amount of fluconazole excreted into the breast milk is less than the Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] 13 M3. Pharmacotherapy for Obstetrics & Gynecologic Disorder the child for signs of infection or even signs of reactions. Assessment Smoking causes damage to the fetus in the lungs and brain, and increased the risk of developing a cleft lip. Nicotine from smoke can also be transferred to the baby causing an increased risk of sudden infant death syndrome (SIDS). Abrupt quitting of smoking can cause withdrawal, especially for the smoker. The mother should consider NRT. Plan The mother should consider NRT. Nicotine replacement therapy is available in patches, gum, inhalator, nasal spray, mouth spray, oral spray, lozenges (except licorice flavor), and micro tabs. This is safer than smoking because it is believed to produce lesser chemicals. The mother is advised to take oral forms of NRT first and when pregnancy-related nausea and vomiting are experienced, patches can be used. Although, the effects of NRTs differ for every patient. It is important to choose to use only licensed NRT. Question 4 Case 4: A mother who wishes to give up smoking seeks advice on the safety of nicotine replacement therapy while breastfeeding. She is currently in the latter stages of pregnancy but does not wish to use these products until after delivery and has not been successful in significantly reducing her smoking without aids? 1. What are the likely effect of smoking in breastfeeding? Smoking while breastfeeding can allow harmful chemicals to pass from the mother to the infant through breast milk. According to the Centers for Disease Control and Prevention, “maternal smoking is a risk factor for sudden infant death syndrome (SIDS), as well as lower respiratory illnesses, ear infections, and impaired lung function in infants.” The presence of nicotine also lowers the serum prolactin level, decreasing the maternal milk supply. 2. Can NRT be used safely while breastfeeding? Nicotine replacement therapy is safe while breastfeeding. It increases chances of quitting smoking. Although there has not been much research on NRT, it is said that the amount of nicotine excreted into the breast milk from nicotine therapy is less dangerous for the baby than smoke inhalation from smoking tobacco products. Studies have mentioned that: ● ● Reference https://www.nhs.uk/pregnancy/keeping-well/stop-smoking/#:~:t ext=Nicotine%20replacement%20therapy,Champix%20or%20 Zyban%20during%20pregnancy. https://www.publichealth.hscni.net/sites/default/files/Smoking% 20Pregnancy%20A5_Leaflet_02_16.pdf Nicotine absorption from NRT is SLOWER than from smoking. Increase in blood level of nicotine from NRT is also SLOWER. In addition to this, nicotine replacement therapy prevents or lessens withdrawal symptoms because it only supplies enough blood nicotine levels (Mohrbacher, 2020). 3. If Yes, which products are preferred? There are numerous nicotine replacement therapies that the patient can use. However, it is more preferred that the patient first use a short-acting oral form of NRT like gum, lozenge or inhaler. In addition, the patient is advised not to use nicotine patches first as they provide a constant delivery of nicotine into the body. Subjective A pregnant mother smokes and now wants to quit smoking so she is looking into nicotine replacement therapy. Objective NA Group 1 BSP3B [Angeles, Bagsit, Ballena, Bambalan, Bautista, Cabal] 14