1. 1 Practice Questions Diuretics

2. Pharmacology Practice Questions 1 - An 80-yr old woman with a history of acute MI & CHF presents to the ER Dept with a chief complaint of fever and lethargy. After a full workup a urinalysis is performed, yielding a specimen with a pH 5.5 & increased NaCl, K, & Ca concentrations. Which of the following drugs would cause results consistent with the urinalysis findings? 2

3. Pharmacology Practice Questions A – Acetazolamide B – Furosemide C – Spironolactone D – Thiazides E - Triamterene 3

4. 2. 2. A 72 yr-old male is treated for CHF, HTN and diabetes mellitus. He experienced a MI 2 yrs ago. He presents to your office saying that he has developed “cancer” in his right breast because it has become enlarged. Which of the following drugs could be responsible for this patient’s problem ? Pharmacology Practice Questions

5. A. Hydrochlorothiazide B. Torsemide C. Aldosterone antagonist D. Triamterene E. Acetazolamide F. Amiloride G. Na channel blocker Pharmacology Practice Questions

6. 3. 3. A 65-year-old female is hospitalized with a hip fracture. Her bone density, measured by quantitative X-ray densitometry, corresponds to the lowest 10%. Her comorbidities include hypertension; diabetes mellitus, type 2; and congestive heart failure (CHE). The attending physician suggests that if this patient had received long-term treatment with a drug affecting calcium metabolism her fracture could have been avoided.

7. Which drug is most likely mentioned by the physician ? A. Furosemide B. Hydrochlorothiazide C. Spironolactone D. Digoxin E. Enalapril F. Glyburide G. Acarbose

8. 8 ESTROGENS & ANDROGENS.

9. Quick Review: Reproductive Physiology 9 During normal female reproductive years,   ovulates once per month.   Before the egg is released, it develops within a small swelling or follicle or tiny cyst.   Egg release heavily regulated by Gonadotropins: LH & FSH and then E & P.   E & P - assist in breast development and are the main controllers of the menstrual cycle.

10. 10 The Menstrual Cycle

11. Reproductive Loop 11

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14. 14 Estrogens Natural: Estradiol, estrone & estriol Conjugated: premarin (estrone and equillin) Steroidal synthetic: Mestranol & Ethinyl estradiol Non-steroidal synthetic: Diethylstilbesterol Rationale for synthetic: to ↑ oral- bioavailability, half-life and ↑ feedback inhibition on FSH & LH.

15. 15 Estradiol – Transdermal patch, IM Oral – Premarin ( Estrone + Equilin), Estinyl estradiol, Mestranol Excretion - Renal.

16. 16 Estrogens: Clinical Uses Contraception: ↓ feedback release of gonadotropins Female Hypogonadism (estrogen + progestin) or ovarian failure Estrogens for HRT - in menopausal women to ↓ bone resorption Uterine bleeding Dysmenorrhea Men with androgen dependent prostate cancer to slow the growth of the cancer cell.

17. SIDE EFFECT : Nausea Breast tenderness Endometrial hyperplasia Increased skin pigmentation Increased blood coagulation at high doses (V, VII, X, I) Increased risk of endometrial cancer unless progestin is added Breakthrough bleeding DES in utero - Clear cell adenocarcinoma of vagina 17

18. 18 Contraindicated Patients: With estrogen-dependent neoplasm (e.g. endometrial carcinoma) At higher risk for or with breast carcinoma that are estrogen dependent Predisposed to thromboembolic disease (why ???).

19. SELECTIVE ESTROGEN RECEPTOR MODULATOR (SERMS) Are non-steroidal compounds that bind to estrogen receptors. They can act as either agonist, partial agonists and antagonists depending on the tissue 19.

20. Tamoxifene Tamoxifene: Has various actions depending on the tissue Bone: agonist to prevent bone resorption Breast: antagonist Endometrium: a partial agonist with the risk of increasing endometrial cancer USES: estrogen dependent breast cancer SE : Hot flushes, nausea and vomiting 20.

21. Raloxifene Bone: agonist Uterus and breast: antagonist USES: prophylaxis of postmenopausal osteoporosis. SE : increased risk of DVT, pulmonary embolism 21.

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23. Clomiphene MOA: ↓ feedback inhibition→ ↑FSH and LH USE: for infertility caused by anovulatory cycle such as those seen in patients with PCOS Side effect: multiple pregnancies, ovarian enlargement 23.

24. ANTI ESTROGENS Anastrozole: MOA: is an aromatase inhibitor, resulting in decreased estrogen synthesis USE: estrogen-dependent postmenopausal breast cancer. 24.

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26. 26 Progestin's Progestins can be androgenic and antiestrogenic in action Progesterone: major natural progesterone Medroxyprogesterone Norethindrone 17α-Hydroxyprogesterone Norgestrel Desogestrel: devoid of androgenic and antiestrogenic actions.

27. 27 Clinical Uses: Progestins Major uses: hormone contraception : ↑ feedback inhibition esp LH → no ovulation hormone replacement treatment along with estrogen to decrease endometrial cancer dysmenorrhea.

28. 28 Adverse Effects: Progestins reduce plasma HDL ↑LDL = ↑↑ atherosclerosis Breakthrough bleeding - (mid-cycle bleed) Acne, weight gain and hirsutism (androgenic effect).

29. ANTIPROGESTIN Mifepristone (RU-486) : Used as an abortifacient, administered with misoprostol (PGE ₁) Also an antiglucocorticoid SIDE EFFECT: bleeding, GI effects(nausea, vomiting) and abdominal pain 29.

30. 30 Hormonal Contraception Progestins (Mini pill) only (norethindrone or norgestrel) Estrogens and progestins (combination pills) Progestin implants Post-coital contraception uses estrogen (mestranol or etinyl estradiol) Mechanism of Action: contraception ovulation-inhibition by suppressing gonadotropins change in cervical mucus(progesterone).

31. Drug interaction: p450 inducers ↓ contraceptive effectiveness Can result in unwanted pregnancies Be careful of anti-epileptics Is there anti-epileptic drug that does not induce p450 ? 31.

32. P450 Inhibitors Don't join this group it will make your spirit go down... SICKFACES.COM Group S odium valproate I soniazid C imetidine K etoconazole F luconazole A lcohol..binge drinking C hloramphenicol E rythromycin S ulfonamides C iprofloxacin O meprazole M etronidazole G rapefruit juice SICKFACES.COM 32 P450 Inducers CRAP GPS induce me to madness!! Carbemazepines Rifampicin Alcohol (chronic) Phenytoin Griseofulvin Phenobarbitone Sulphonylureas.

33. Combined oral contraceptive pill ADVANTAGEDISADVANTAGE Reliable (<1% failure)Taken daily ↓ risk of endometrial and ovarian cancerNo protection against STDs ↓ pelvic infections↑ triglycerides ↓ risk of osteoporosisDepression, weight gain, nausea, hypertension No dysmenorrheaHypercoagulable state 33

34. SIDE EFFECTS ESTROGENS: Nausea Bloating Headache Mastalgia Increase skin pigmentation Weight gain Breakthrough bleeding Withdrawal bleeding 34.

35. PROGESTIN: Weight gain Hirsutism Acne Increase LDL 35.

36. 36 Adverse Effects of combined ocps Venous Thromboembolic Disease breakthrough bleeding Withdrawal bleeding RISK FACTORS: Smoking, Increased age.

37. 37 ANDROGENS Testosterone - Cypionate, Enanthate,Propionate dihydrotestosterone Fluoxymesterone Danazol Androstenedione Nandrolone.

38. USES: Male hypogonadism (e.g. 47 XXY) For anabolic actions to increase muscle mass Illicit use in athletes 38.

39. 39 Replacement therapy in men Acne excessive libido & erections, increased muscle & bone mass, aggravation of pre existing prostate cancer. Reduce plasma HDL and increase LDL.

40. 40 Gynecological Disorders: Androgens Danazol used in the treatment of endometriosis which is the growth of endometrial tissue outside the uterus, especially in the pelvis..

41. SIDE EFFECTS OF ANDROGENS SE: Excessive masculinization Premature closure of epiphysis Aggression Dependence and abuse Depression of menses and hirsutism in women 41.

42. She is Gorgeous … Yes !!! 42

43. 43 Contraindications: Androgenic Steroids Pregnant women: its teratogenic Children Androgens - Not used in children, why??? Men with prostatic carcinoma.

44. 44 Anti-Androgen Cyproterone acetate Flutamide Finasteride Leuprolide.

45. 45 Androgen Suppression & Antiandrogens Androgen Suppression: Symptomatic Management of prostatic carcinoma Management of BPH.

46. 46 Antiandrogens Conversion Inhibitors Finasteride: Inhibits 5 alpha reductase decreases dihydrotestosterone levels in the prostate Uses – BPH to reduce the size of the prostate and male pattern baldness Has been replaced by α1 blockers in the symptomatic treatment of BPH e.g. prazosin.

47. 47 Antiandrogens Competitive androgenic Receptor Inhibitors: Cyproterone & Cyproterone acetate Clinical use: Women - hirsutism Men - reduction of sexual drive.

48. 48 Antiandrogens Flutamide Competitive inhibitor of androgens Used in androgen receptor positive Prostatic Carcinoma.

49. Bicalutamide Effective orally for the treatment of metastatic prostatic cancer. 49.