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Marylou V. Robinson PhD FNP

Reproductive System Drugs OB will cover cover uterine relaxants, drugs to induce labor & fertility drugs. Marylou V. Robinson PhD FNP. Drugs Affecting the Female Reproductive System. Contraceptives Estrogen ( Premarin ) Estrogen-progestin combos (EPT) HRT

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Marylou V. Robinson PhD FNP

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  1. Reproductive System DrugsOB will cover cover uterine relaxants, drugs to induce labor & fertility drugs Marylou V. Robinson PhD FNP

  2. Drugs Affecting the Female Reproductive System Contraceptives Estrogen (Premarin) Estrogen-progestin combos (EPT) HRT Medroxyprogesterone (Depro-Provera) SERMs IUDs

  3. Cycle Overview (pg. 768) • Estrogen • Negative-feedback on ant. Pituitary hormones luteinizing hormone (LH) & follicle-stimulating hormone (FSH) • Rapid peak in LH causes ovulation in middle of cycle (between follicular & luteal phases)  quick LH  to nl post-ovulation • Makes ruptured follicle (corpus luteum) make progesterone • FSH makes follicles produce estrogen in follicular phase  estrogen  causes FSH  Progesterone • Increases mostly during luteal phase while being made by corpeus luteum • fertilized ovum implant doesn’t occur  corpeus luteum atrophy   progesterone & estrogen production • menses (approx. days 1-5 of 28-day cycle) •  secretions but makes them more viscous and difficult for sperm to travel thru 

  4. Estrogens (pg. 769), KNOW • Premenopausal women: most estrogen (also progesterone) production occurs in ovaries (post-menopausal, decline then production cessation in ovaries) • Small amounts made in peripheral tissues: liver, fat, bone (also placenta w/ progesterone during pregnancy) • Also affects bone, blood vessels, liver, heart & CNS • Main endogenous estrogen = estradiol (others include estrone & estriol) • Synthetic estrogens identical to endogenous ones • Function: female maturation, female reproductive organs, metabolic actions • Action:  synthesis of DNA, RNA & protein in estrogen-sensitive tissues • Na and water retention,  cholesterol 

  5. Approved Estrogen Uses (pg. 776) • OCPs: estrogen thickens cervical mucus barrier &  vaginal acidity to block fertilization, also exerts negative feedback on LH & FSH (prevents follicular maturation & ovulation) • Menopause HRT (estrogen deficiency, Turner’s): manage vasomotor symptoms (hot flush, night-sweat) that don’t go away w/in first few months • most common non-contraceptive use • Short-term safe, long-term use discouraged D/T risks • Urogenital atrophy: urethra/vagina have highest concentration of estrogen receptors • Degenerate post-menopause when estrogen  • Urethra: incontinence, urinary frequency • Vagina: dryness, pain w/ intercourse topicals preferred (lower estrogen blood concentrations • Osteoporosis (secondary) PPX:  risk after ovarian removal or menopause, when estrogen  accelerates bone reabsorption  12% bone loss shortly after menopause  • Estrogen can moderately slow bone reabsorption & osteoporosis, doesn’t really reverse bone loss & stopping estrogen HT will just cause the 12% bone loss to happen anyway • Osteoporosis drugs work better and are generally safer • NEVER GIVE THESE FOR BONE HEALTH ALONE (TOO MANY SE) 

  6. Estrogen SE • Stomach cramps or gas • HA, n/v (less with non-PO routes and/or taken w/ food or HS) • Some women: migraines somewhat during ovulation D/T estrogen  • decreased libido • Fluid retention: edema of LE (lower extremity), breast pain & enlargement  also WEIGHT GAIN (5 lbs)  • Estrogens activate RAAS  possible bloating, weight gain, HTN 

  7. Cautions with Estrogen • Risk of endometrial CA with prolonged use: estrogens cause endometrial proliferation/hyperplasia when used alone (in women w/ uterus) may become CA (esp. post-menopausal women) • Hormone combos greatly  risk: progesterone opposes estrogen-caused hyperplasia & decreases endometrial proliferation • Admin: assess for endometrial carcinoma if “benign” bleeding persists pasts first 6 months of TX or begins after prolonged use • Somewhat-similar to breast cancer: they’re both estrogen-sensitive tissues • Should not be given to lactating women ( milk production) • Could also feminize male babies or cause severe acne & development of secondary sex characteristics in female babies • Preg Cat X: not dangerous but useless during pregnancy • Baseline liver labs before therapy: benign hepatic adenoma risk w/ OCPs (can still rupture & cause fatal bleeding) • Also drug use or Hepatitis concerns • Increases lipid levels: LDL • Increases heartburn/GERD: relaxes cardiac sphincter • Increases gallbladder stones: risk of cholecystitis D/T chronic gallstones greatest in postmenopausal women on HRT > 5 years • Estrogen & OCPs precipitate gallstones & gallbladder disease already present 

  8. Estrogen & CV Risk •  CV risk: R/T MI, CVA, DVT & pulmonary embolism • Not PPX: doesn’t slow atherosclerosis or prevent recurrent CVA • Pt Edu: avoid smoking, exercise regularly, avoid saturated fats, follow treatments for maintenance of HTN/DM/hypercholesterolemia • Coagulation tendencies: estrogen  coagulation-suppressing factor antithrombin &  levels of clotting factors II, VII, IX, X & XII • Only somewhat  levels of factors that break down fibrin in clots • Combos  venous thromboembolism (VTE) risk in pre/post-menopausal women • Estrogen alone  risk of MI or CHD in women > age 60 • Tobacco: smoking  risk of serious cardiac events (CVA, TIAs, thromboembolism, pulmonary embolism) • Absolute contraindication: risk is higher in women > 35 years of age • Estrogen is #1 cause of strokes in women < age 35 

  9. Estrogen Contraindications • Known or suspected BCA: estrogen hasn’t been shown to cause BCA but promotes estrogen-receptor BCA cancer growth • more dose-dependent & R/T older age • R/O ER-BCA before RX, annual breast exam, annual mammogram > age 40 • Abnormal vaginal bleeding, endometriosis, uterine fibroids • Hypercalcemia (estrogens may  mineral deposits) • Thrombophlebitis or hx of VTE or pulmonary embolism  

  10. Estrogen Preparations • Estradiol and estrone are natural occurring steroidal estrogens • Conjugated estrogen (Premarin): natural formulation but processed (most common) • Diethylstilbesterol (DES): synthetic estrogen • Preg Cat X: causes clear cell carcinoma (rare vaginal cancer) in women who had fetal exposure, off-market • Male children have risk of testicular cancer • Transdermal estrogen (Estraderm) • Vaginal creams • Compounded mixtures: made by hand into individualized estrogen mixture (typically topical, also PO)  not standardized tho • Synthetic estrogens typically identical, but natural estrogen may have fewer SE (recent research) 

  11. Progesterone and Progestin • Prototype: progestin • Action • Pro-gestational: produce biochemical changes in the endometrium to prepare for implantation of embryo (also maintain uterus during pregnancy) • Opposes estrogen-mediated endometrium stimulation • Suppresses ovulation during pregnancy • Can increase appetite 

  12. Progestin • Indication • Female hormonal imbalance • Amenorrhea, dysmenorrhea, endometriosis • Combined with estrogen to lower risk of endometrial Ca • Prevent pregnancy in lactating women (can’t give them estrogen) 

  13. Oral Contraceptives • Newer, low-dose OCPs have: • Lower risk for adverse CV effects (stroke, thromboembolus) • Decreased risk for ectopic pregnancy • Low dose formulations are for the thin teenager. • Most older and heavier folks they are not as effective (possibly D/T  blood levels, sequestration in adipose, altered metabolism) 

  14. OCPs • Estrogens and progestins (various manufacturers) • Action • Inhibit secretion of FSH and LH • Changes in endometrium that impair ova implantation • Increased vaginal mucus to impede passage of sperm 

  15. OCPs • SE • Wt Gain, • Stomach cramps, Swelling of Face and LE • HA (esp. aural migraines) • Mood alteration • Gall stones • Increased clotting • Amenorrhea, • Breakthrough Bleeding, • Menorrhagia, • Acne (androgens) • Insomnia, • Breast Pain, • Increased risk STD (behavior & more viscosity can trap STDs • Hyperglycemia 

  16. Benefits • protection against pregnancy • 98% best use • 70% in many women • Less than 50% in teens • ovarian cysts suppression (PCOS): very painful condition • iron deficiency anemia resolution ( OCs  heavy menstrual bleeding   blood loss) • reduced rheumatoid arthritis (D/T  immune system?): women feel better w/ RA when pregnant (same as OCPs) • higher bone density ? 

  17. Estrogen-progestin Combos • Monophasics: fixed ratio of estrogen and progestin that is taken for 21 days • Alesse-28, Ortho-Cyclen, Lo-Ovral • Biphasic: supplies 2 different amounts of progestin during the first (follicular) and second (luteal) phases of the menstrual cycle • Ortho-Novum • Triphasic: dose of estrogen is constant while progestin is progressively increased (three times) for 21 days • Ortho-Novum 777, Triphasil, Ortho-Tri-Cyclen 

  18. Extended Cycle (Seasonale meds) • Take for 3 months/withdraw for period (only 3 days off meds) • Lots of break through bleeding  most don’t get to 3 months without sudden onset menses • Best suggestion is when have bleeding, do withdraw and then start on own schedule. 

  19. Something about those pills • What is different about YAZ (pg. 788)? • What diuretic drug is it similar to? • Yaz = drosperinone + ethinyl estradiol • Drosperinone: 4th gen progestine & structural analog of spirolactone (blocks aldosterone), added to  OC fluid retention • What are the risks? • Drosperinone also K-sparing (hyerkalemia)  caution using w/ other hyperkalemia-associated drugs (ARBs, ACE inhibitors) • Greater risk of VTE than other progestins • What is the link between OCP and glaucoma? • Raise blood pressure, sodium & water retention (greater risk for life, along with cataracts) 

  20. Rings and Things • Rings (NuvaRing) • Insert for 3 weeks  remove for menses • Clear to the eye • If fall out, rinse and re-insert (need back-up contraception for 7 days if ring is out > 3 hours during weeks 1-3) • Better for “discrete” birth control over OCPs • Patches • Changed weekly. Three in a box • Can’t place on breasts (adipose tissue or breast tissue stimulation): higher BCA risk • Need back-up contraception for 7 days if patch is off > 24 hours during weeks 1-3) • Both have higher risk for clotting than pills ( higher estrogen exposure needed for other routes) 

  21. Other Contraceptives • Low-dose progestogens (mini-pill): do not contain estrogen • less effective/forgiving (don’t inhibit ovulation as well), most when just starting these • Breastfeeding AOK (progestin don’t  milk production) • Long-acting: progestin-only • Implanon (capsule implanted in arm) • Depo-Provera (IM injection q 3 mo) • IUD (with and without med), pg. 796 • SE: vag bleeding, muscle pain, GI distress, wt gain, vaginitis, breast discharge 

  22. Medroxyprogesterone (Depro-Provera), pg. 796 • Long-acting OC (progestin-only): protects against pregnancy for ≥ 3 months • Admin: IM (also SQ) q 3 months • Discontinuing TX delays fertility by ≈ 9 months (up to 2-3 years) • Starting TX: give during first 5 days nl menses or w/in first 5 days post-partum (if not breastfeeding)/ w/in first 6 weeks post-partum if breastfeeding • Mechanism: inhibits gonadotropin secretion • Inhibits follicular maturation & ovulation • Thickens cervical mucus • Thins endometrium  egg implantation less likely • SE: similar to other progestin-only TX (bloating, HA, depression,  libido) • No significant cervical/breast/ovarian CA risk • Highly bone-bleaching: may cause reversible bone loss, but regular bone marrow density scans (BMDs) aren’t recommended  need more dairy & calcium supplements (this is less mitigated as age increases) 

  23. Education • Compliance is important: choosing the right birth control depends on effectiveness, safety & personal preference • Patient: life may begin at conception instead of implantation • Take tablets at the same time every day • Miss 1 dose: take ASAP • Miss 2 doses: take 2 tabs/day for the next 2 days • Miss 3 doses: stop taking, use another form until menses occurs or pregnancy R/O • Last 7 tablets are placebo in traditional packs • Newer branded are only 3-4 days placebo 

  24. IUDs (pg. 796) • Long-term OC • Copper T380A (Paraguard): doesn’t release meds • Levonorgestrel-releasing (Mirena): used esp. for menorrhagia (heavy menstrual bleeding) • Potentially good option for at-risk teens (less issues of compliance) • Mechanism: harmless local inflammatory response (spermicidal), does not prevent ovulation • Paraguard copper may also prevent implantation (also EC when placed w/in 5 days unprotected sex) • Mirena endometrial involution & thickening of mucus • Placed w/in 7 days menses onset: lidocaine & ibuprofen can prevent cramping • SE: abd cramping, altered menses (more local, less systemic [lower bone loss?]) • Paraguard:  monthly bleeding • Mirena: commonly amenorrhea or light spotting • PID secondary to STD: only use in women at low risk of STIs (monogamous couples) • Greater risk ectopic pregnancy 

  25. Mifepristone (RU-486) [Mifeprex] pg. 799 • Progesterone Antagonist (abortifacient): given with misoprostol to stimulate uterine contraction and aid in expulsion of the tissue dislodged (fetus or excessive lining) • Used w/in first 7 weeks of conception • Safe alternative to surgical abortion • Also the most effective known emergency contraceptive EC when taken w/in 5 days after sex, but not approved for EC • MD giving Mifeprex has to be able to perform surgical abortion or curettage (surgical tissue removal from uterus) if abortion fails • Abortion requires 3 visits to MD: • Day 1: get pill • Day 3: ultrasound to determine if abortion occurred (re-admin Mifeprex if it didn’t) • Day 14: ultrasound to confirm pregnancy’s termination (surgical abortion if it didn’t) • Bleeding can be severe and require transfusions • Cannot be used in patients w/ tubal (ectopic) pregnancy, hemorrhagic disorders or anticoagulant drugs • Bleeding caused by Mifeprex could mask symptoms of these serious conditions 

  26. Levonorgestrel (Plan B), pg. 797most commonly used ECP • Levonorgestrel: progestin • Separate RX or use of pills on hand (formula by pharmacist) • Large dose impairs implantation of fertilized egg • Must be taken w/in 5 days after unprotected sex • Successful if menstrual bleeding occurs w/in 21 days • “large dose” still for “avg woman” ≤ 120 lbs • Doesn’t abort implanted eggs • Pregnancy = implantation of fertilized egg • Spike in clotting risks: not recommended for routine use • No Rx in most states for women ≥ age 17 

  27. Why don’t we use indomethacin (Indocin) in later pregnancy? • Closes ductus arteriosis in fetus (inhibits prostaglandin synthesis) • Normally blood goes around fetus’ lungs during pregnancy • Infants with patent ductus arteriosus (PDA) didn’t have valve close between aorta & pulmonary artery  indomethacin is used on them to fix PDA • NL use: NSAID & antirheumatic • NSAIDS BAD 4 PREGNANCY 

  28. Post-Menopause (pg. 771) • Estrogen can be used for hot flashes & bone health • MUST have progestin if have uterus • SSRI & SNRI have hot flash indication (paroxetine or venlafaxine):  vasomotor S/S in post-menopause by  CNS serotonin • Herbals have no evidence of helping • Selective estrogen receptor modulator (SERM) [covered with MSK]: can help with bones (activates estrogen receptors) & lipids • Tamoxifen (Nolvadex): can inhibit (cancerous) breast growth by blocking estrogen receptors • Blocking estrogen receptors leads to  hot flashes  • Also has  risk of endometrial cancer & VTE 

  29. Clomiphene (Clomid) • Ovulation Inducer: Preg Cat X • Use: Induces ovulation in anovulatory women who desire pregnancy. Requires intact anterior pituitary, thyroid, and adrenal function. • Mechanism: Stimulates release of pituitary gonadotropins, follicle-stimulating hormone, and luteinizing hormone, resulting in ovulation and the development of the corpus luteum.

  30. ospemifene (Osphena) • SERM-like medication (not actually SERM): hormone, estrogen agonist/antagonist • Same estrogen issues: • potential uterine cancer • Cannot take with hx of blood clots, CA •  risk HD: cigarette smoking, high BP, high cholesterol, diabetes, and being overweight during estrogen therapy • DM patients esp. as risk for clots! 

  31. Male Hormonal Meds 5-Alpha reductase inhibitors (Proscar) Phosphodiesterase inhibitors (Viagra) Testosterone (Ch. 65) 

  32. Androgens • Male sex hormones necessary for development of male sex characteristics • Primarily testosterone • Can be given to women with low levels to help with libido issues • Bad acne 

  33. Testosterone • Naturally occurring, produced in testes • Synthetic testosterone in various forms • Action • Stimulates synthesis and activity of RNA • Potent anabolic agents that increase muscular and skeletal proteins • Enhanced storage of phosphorus, sulfate, sodium and potassium 

  34. Testosterone • Indication • Main: Androgen deficiency, hypogonadism • Androgen deficiency: S/S & testosterone blood levels < 220 ng/dL adjust to mid-normal range (300-450 ng/dL) • Might reverse ED • Delayed male puberty • Treatment of anemia (stimulates erythropoiesis), no strong impact • NOT used for infertility, prostate cancer or nodules, HF • Abuse potential: illegal use for wt gain, muscle development and strength • Most androgens Schedule III 

  35. Testosterone • Administration: PO, IM, patches • SE: Abd pain, insomnia, dizziness, red skin, HA, N/V/D, depression, pruritus, jaundice (hepatotoxic), libido  • Females • Acne, deepening of the voice, increase hair growth or alopecia, enlarged clitoris, irregular menses • Androgens can injure female fetus (masculinization) • Males • Urinary urgency, gynecomastia, frequent erections • Salt & water retention may lead to edema • Children: premature epiphyseal closure (radiograph hands/wrists biannually) 

  36. Testosterone Therapy • Caution • Causes fluid retention and hypercholesterolemia  use carefully w/ cardiac issues or renal disease •  HDL &  LDL • DDI: anticoagulants ( warfarin levels) • May cause prostate enlargement and worsen BPH • Makes hypercalcemia secondary to metastatic Ca worse • Testosterone can promote PCA growth that’s started 

  37. Testosterone Therapy • Baseline ht, wt, and sexual develop. in children, bone age determination q6mo • Monitor serum calcium, cholesterol levels, LFTs, H & H for polycythemia • Monitor tumor growth • Older men, monitor for signs of BPH 

  38. BPH (pg. 839) • Prototype: finasteride (Proscar), a 5-Alpha-Reductase Inhibitor • Action: blocks enzyme that converts testosterone into potent androgen (DHT) by 70%  causes shrinkage of prostate epithelial tissue  mechanical obstruction of urethra (results in 6-12 months) • Doesn’t  blood testosterone levels • Goal:  urinary symptoms & slow disease progression • Taken for life • Use: preferred for men w/ very large BPH (mechanical obstruction, more epithelial tissue) • alpha blockers (antihypertensives) for smaller BPH, relax bladder smooth muscle to  dynamic obstruction (no effect on BPH size) • Saw palmetto ineffective for BPH • Finasteride also made as Propecia, used for male-pattern baldness 

  39. Finasteride (Proscar) SE • SE:  libido, impotency, decreased amount of ejaculate, gynecomastia • Proscar  PSA (prostate-specific androgen) levels, get baseline test • Consider possible prostate cancer if PSA doesn’t  after 6 months of therapy • Preg Cat X: alters fetal development of male genitalia (hypospadias), smaller prostate & seminal vesicles • Women pregnant with male fetus should not handle the drug • Manufacturer recommends women who might get pregnant not handle drug without gloves (can be absorbed thru the skin) 

  40. Drugs That Impair Libido and Sexual Gratification • Antihistamines • Anticholinergics • Antihypertensives (BB, CCB, diltiazem) • Antianxiety and psychotropic drugs • Antidepressants • Antifungals • Opioids • Thiazide diuretics • ETOH • Barbiturates • H2 receptor antagonists (cimetidine, ranitidine) • Hormones 

  41. Drugs That Enhance Libido & Sexual Gratification • None specifically approved but there are substances that temporarily modify physiologic responses and perception of enjoyment • Numerous aphrodisiacs have been tried: • Cantharis (Spanish fly) • Yohimbine (from West African tree) • Opioids: morphine, heroin, cocaine, marijuana, LSD • Amyl nitrite • Alprostadil (prostaglandin): injectable into corpus cavernosus 

  42. ED Drugs (pg. 834) • Prototype: sildenafil (Viagra) • Phosphodiesterase Type 5 (PDE5) inhibitor • 1st approved PO drug for ED, 1st-line ED TX • Not an aphrodisiac • NL: arousal  PNS  local nitric oxide  nitric oxide activates cyclic guanosine monophosphate (cGMP)  relaxed arterial/trabecular smooth muscle  arterial dilation  local blood flow &  BP  expanded corpus cavernosum  venous occlusion &  venous outflow  erection • Goes away when cGMP is removed by PDE5 (enzyme converts cGMP  guanosine monophosphate) • Action:  levels of cGMP, a smooth muscle relaxant  inflow of blood & erection • Indication: impotence (ED) • Also pulmonary arterial HTN (PAH) • Administration: 1 hr before sexual activity (t ½ 4 hours) 

  43. Viagra • SE: HA, nausea, facial flushing, nasal congestion, back pain, flu syndrome, arthralgia, allergic rxn, priaprism • Cardiovascular sx (angina, tachycardia, hypotension): could be Viagra (huge vascular shifting) or sex activity • Visual changes at higher doses (blurring, blue tint, photosensitivity), nonarteritic Ischemia Optic Neuropathy (NAION) also possible when blood flow to optic nerve’s blocked (esp. in men w/ anatomic or vascular risk factors) • Contraindication: concomitant use of organic nitrates, alpha blockers, CYP3A4 inhibitors • Nitrates (NTG, nitroprusside): also promote vasodilation via cGMP (nitrates  synthesis & Viagra slows breakdown), could cause fatal hypotension  must wait 24 hours between Viagra & nitrate, more if Viagra was taken w/ a CYP3A4 inhibitor that slows elimination • α-andrenergic blockers: dilate arterioles &  BP combined effect causes significant postural hypotension • CYP3A4 inhibitors (also hepatic/renal impairment): ketoconazole, erythromycin, cimetidine, grapefruit suppress metabolism &  levels • Education • Delayed response if taken with high-fat meal (slows liver metabolism, absorption) • Increase fluids to 2000 mL per day can prevent UTI • Seek immediate TX for chest pain, palpitations, sudden sharp HA • Report visual changes “blue” • Seek immediate TX if erection > 4 hours 

  44. Other ED meds • Varendafil (Levitra), pg. 837: similar to Viagra • Also requires no alpha blocker meds • DDIs w/ CYP3A4 meds (grapefruit) • Taldalafil (Cialis), pg. 838: lasts much longer than Viagra or Levitra • Provides coverage for 36 hours, therapeutic levels in 2 hours • Most men use it within 4 hours • Now available in daily dosing for more spontaneous lifestyle (only if “get lucky” ≥ 2x/week 

  45. Drugs Used in Renal Diseasekidneys = major organ for drug elimination Renal dose adjustments: made w/ CCr (creatinine clearance) or measuring certain drugs’ blood levels 

  46. Multiple Drugs • Epogen (ethrythropioetin): anemia reversal • Bind excess phosphates (PO43-) that accumulate in renal disease • Aluminum hydroxide (also antiulcer, antacid): binds to phosphate in GI tract, but has aluminum absorption over time • Calcium Acetate: binds to excess phosphate & excreted • Vitamin D supplementation: Calcitriol (Rocaltrol), CKD patients can’t convert Vitamin D to active form • Helps body absorb phosphates & calcium from blood instead of dissolving it from bone or over-compensating PTH • Diuretics (loop & osmotic): help with fluid balance • Sodium bicarbonate for acid-base imbalance (metabolic acidosis): will make basically all drugs inert cement (not work) • Given IV: binds most other drugs and cannot be mingled in the line • Encourages severe salt and water retention • sodium overload (CV workload), gastric acid hypersecretion 

  47. Hyperkalemia Issues* • Serious cardiac risks of rhythm issues • Spiked T waves on EKGs, possible cardiac arrest • Confusion, anxiety, paresthesias 

  48. Cation-Exchange Resin • Prototype: sodium polystyrene (Kayexalate) • Proven to not work!!!!!! • Indication: elevated serum potassium levels • Action: given as enema • Exchanges sodium ions for potassium ions • K+ binds to the substrate  eliminated via feces • What can happen to the VS of a patient with vagal issues (enema)? HR will drop. • Vagus nerve innervates PNS below neck, i.e., lung, heart, abd viscera • Stimulation: bradycardia & arrhythmia 

  49. Hyperkalemia Interventions • Stop K sources of any drugs: K-sparing diuretics & KCL supplements • Infuse insulin + glucose to promote uptake into cells • If acidotic might use NaHCO3 (sodium bicarb.) • Dialysis • New drug just approved 11/2014 

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