S2 Pharm Master

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Dopamine agonist treatment for prolactinoma

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Bromocriptine (D2/D1) and Cabergoline (D2)

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Side effects of Cabergoline

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Headache, nausea, orthostatis HTN; discontinue for psychosis

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Treatment for Acromegaly: Octreotide

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Somatostatin analogue (cholesterol gallstones common)

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Treatment for Acromegaly: Bromocriptine

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Dopamine agonist (20% see improvement)

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Treatment for Acromegaly: Pegvisomant

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Competitive GH-receptor antagonist

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Dexamethasone testing for HPA differentiation on cortisol

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Adrenal/ectopic ACTH-production cortisol levels NOT suppressed by negative feedback

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Metyrapone testing

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If ACTH rises, but cortisol precursors don't, signals adrenal insufficency. If neither ACTH or precursors rise, impaired HPA axis. (MOA: blocks conversion of precursors to cortisol)

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Vasopressin receptors

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V1- vasoconstrictor (IP3,Low affinity); V2- antidiuretic (cAMP, high); V3- ACTH stimulation from pituitary

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Desmopressin receptor selectivity

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V2- antidiuretic

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Desmopressin in DI treatment

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Central (eliminates thirst/fluid intake), Dipsogenic (eliminates urination, not thirst/intake)

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Water deprivation test

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Central/polydipsia respond as normal. Central responds with Desmopressin. Nephrogenic never responds.

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Treatment for SIADH

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Cautious infusion of hypertonic saline / furosemide (diuretic) (not too quickly, avoid demyelination); fluid restriction if not severe, V2 receptor antagonists (Aquaretics)

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Somatropin MOA

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Recombinant human GH

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Mecasermin MOA

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Agonist directly at IGF-1 receptor in target tissues if somatropin fails

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Desmopressin MOA

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Selective V2 receptor agonist in kidney (antidiuretic)

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Cellular response to Desmopressin

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Activates G protein in V2 receptor; activation of kinases to receptor coupled aquaporin; increases transport of H2O to reverse hyperosmolality; dilutes concentration of sodium

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Vasopressin

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Non-selective V1/V2 receptor; corrects low bp; may lead to HTN / CNS toxicity

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Octreocide MOA

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Somatostatin receptor to inhibit GH release; injection; gallstones, GI, hyperglycemia, hypoinsulinemia

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Pegvisomant MOA

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Liver GH receptor antagonist; blocks IGF-1 production

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Conivaptan MOA

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Non-seletive vasopressin V1/V2 receptor antagonist (SIADH), reduces hyponatremia

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Tolvaptan MOA

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Oral V2 antagonist (SIADH)

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Common side-effects of dopamine receptor agonists

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Bromocriptine/Cabergoline- orthostatic HTN, ergot-related (burning), CV risk (arrythmia), CNS (delusions, hallucinations, psychosis)

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Mineralocorticoid MOA

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Alters transcription to increase Na+/K+ ATPase expression (inc. blood vol.)

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Glucocorticoid MOA

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Dislodged heat shock protein (HSP), activates receptor, activates glucocorticoid response element (GRE)

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Anti-inflammatory MOA of glucocorticoids

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Cortisol binds GRE, prevents transcription of cytokines and increases anti-inflammatory transcription (PLA2 inhibitor)

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Adrenal steroid agonist with 1:1 ratio

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Hydrocortisone (gluco:mineralo)

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Short-acting, low selectivity corticosteroids

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Prednisone (oral), prednisolone, methyprednisolone

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Intermediate-acting low selectivity corticosteroids

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Triamcinolone

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Long-acting, highly selective corticosteroids

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Betamethasone, dexamethasone, beclomethasone (antiinflammatory effect)

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MOA for corticosteroids

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Increase transcription of lipocortin-1 (inhibits PLA2)

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Long-term effects of corticosteroids

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Catabolic (growth suppression, muscle loss), osteoporosis, cataracts/glaucoma, neurological (hypomania, psychosis, insomnia, anxiety)

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Why must pt ween off of corticosteroids?

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Adrenal suppression

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Tx for Addison's

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Hydrocortisone, androgens, fludrocortisone (selective mineralocorticoid receptor agonist)

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Reason for iatrogenic Cushing's in pt on Ritonavir

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Ritonavir is a CYP3A4 inhibitor, required for corticosteroid metabolism

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Ketoconazole MOA

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Inhibits 17a-hydroxylase and 11B-hydroxylase

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Aminoglutethimide MOA

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Inhibits Cholesterol desmolase and aromatase; nausea, dizziness (decreased T4 -> T3 conversion)

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Major ketoconazole effect

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CYP3A4 inhibitor (drug interactions), hepatotoxicity

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Metyrapone MOA in Cushing's Tx

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11B-hydroxylase inhibitor, causes HTN (precursor build-up), androgenic

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Drug interaction if given Metyrapone and Aminoglutethimide together

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Iatrogenic adrenal insufficiency

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Major side effect in males of spironolactone

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Gynecomastia; competitive antagonist at androgen receptors (inhibits CYP450 too)

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Eplerenone MOA

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Selective aldosterone antagonist (no andorgen receptor antagonism)

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Alternative use for spironolactone (not hypoeraldosteronism)

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Treatment for female hirsutism due to androgen receptor antagonism)

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Phenoxybenzamine MOA

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Irreversible non-competitive alpha adrenergic receptor inhibitor (blocks catecholamines, reduces HTN in pheochromocytoma)

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Propranolol MOA

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Non-selective competitive beta adrenergic antagonist (block catecholamines, reduces tachycardia)

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Sequence for pheochromocytoma Tx prior to surgery

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Alpha-adrenergic (phenoxybenzamine) prior to beta-adrenergic (propranolol) antagonist to avoid B2-mediated vasodilation inhibition leading to hypertensive crisis.

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Test for adrenal insufficiency (not Metyrapone)

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Cosyntropin; ACTH analogue

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MIBG

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Iobenguane (mIGB), radiolabeled molecule like noradrenaline (iodine-123) (specific for pheochromocytoma)

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Tx for Hypervitaminosis D

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Decrease Ca2+ / Vit D intake; loop diuretic (furosemide)

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Effect on thyroid of amiodarone

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Both hypo and hyperthyroidism

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1st line Tx- hypothyroidism

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Levothyroxine (Levo)- T4

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Drugs reducing conversion T4 -> T3

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Inhibit 5' deiodinase: propranolol (beta blockers), corticosteroids, aminoglutethemide (comp. selective mineralo), antiarrhythmic amiodarone

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Liotrix MOA

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Mix T3/T4 if pt can't convert T4 -> T3

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Emergency hypothyroid Tx

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Ex) myxedema coma. Liothyronine- T3, rapid onset, short duration, highly potent (not for long-term use)

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AE of Liothyronine

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Cardiotoxicity, increased risk of arrhythmia, insomnia, anxiety

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Iodine Salt MOA

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Hyperthyroid- inhibits TH synthesis/release, decreased vascularity of thyroid

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Thiomide MOA

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Inhibit peroxidase (organification), inhibit iodotyrosine coupling, inhibit 5'-deiodinase (propylthiouracil/PTU, methimazole)

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PTU vs. Methimazole

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PTU (short acting, less potent, rapid acting) vs. Methimazole (10x potent, long duration)

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Contraindication of PTU in children

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Hepatotoxicity (hepatocellular necrosis), prefer lower risk Methimazole

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AE of Thioamides

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GI, macropapular rash, hypothyroid symptoms, hepatitis (children), lupus-like syndrome, agranulocytosis

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Tx of Thyroid Storm

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Propranolol (beta blocker- CV, anxiety, T4->T3 conversion), IV PTU (rapid), hydrocortisone (reduce T4->T3), supportive therapy for fever

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Postoperative radioablation for thyroid tumor is indicated when:

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1. distant mets; 2. gross extrathyroidal extension; 3. >4cm tumors

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DM2 treatment if A1c over 10?

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Insulin

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Essure ®

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Tubal occlusion device placed into fallopian tubes via hysteroscopy

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Copper T IUD

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Polyethylene w/ copper causes immune response and hostile environment preventing fertilization

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Risks of Copper IUD

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Perforation, expulsion, increased risk of infection during 1st month

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Levonorgestrel Intrauterine System MOA

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Thickens cervical mucus (inhibits sperm motility/function), endometrial atrophy prevents fertilization

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Risks of Levonorgestrel IUS

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Perforation, expulsion, infection (1st month), unpredictable bleeding, progestin-mediated (breast tenderness, mood, acne, headache), follicular ovarian cysts

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IUD/IUS Contraindications

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Pelvic infection, purulent cervicitis, UAB, malignancy, uterine distortion, pelvic TB

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Implant (Nexplanon) MOA

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Etonorgestrel, 3 years, bleeding/amenorrhea common

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Treatment for Premenstrual dysphoric disorder

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Drospirenone (spironolactone derived), anti-androgenic, exerts progestational and antimineralocorticoid effects by inhibiting and binding androgens to its receptors

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Progesterone OC MOA

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Alters fallopian tube peristalsis, cervical mucus thickens, atrophic endometrium

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OrthoEvra patch MOA

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Avoids 1st pass, VTE risk

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NuvaRing MOA

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Flexible, AE= coital problems, expulsion, vaginal discharge

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Progestin-Only OC

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"mini-pill", norethindrone or norgestrel, suppresses ovulation/thickens mucus; CONSISTENT use critical (miss by 3 hrs, use back-up protection)

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Depo-Provera shot

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Depot medroxprogesterone acetate (DMPA); convenient; AE= weight gain, irregular bleeding, bone mineral density

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Risk of frequent spermicide use

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increased HIV risk

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Plan B / Ulipristal MOA

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Inhibit or delay ovulation (causes a lot of nausea)

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Methotrexate MOA

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Antifolate antimetabolite, single dose, cytotoxic during S-phase, inhibits DNA synthesis

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Mifepristone MOA

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Abortifactent: Anti-progesterone, softens/dilates cervix, decidual necrosis, prostaglandin release/contraction. Day 1.

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Misoprostol MOA

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Abortifactent: Prostaglandin binds to myometrial cells to cause contractions, cervical softening/dilation. Effects: diarrhea, longer induction times.

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Misoprostol route reduces infection risk and shortens time of termination

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Buccal

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Rhogam MOA

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Anti-D gamma globulin mops up fetal RBC in maternal circulation/ prevents B cell activation and memory cell formation.

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Tx for Invasive moles

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Methotrexate followed by hCG monitoring

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Prevent HSV outbreak during pregnancy

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Prophylactic Acyclovir

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Oral contraceptive used for PCOS treatment

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Ethinyl-estradiol; Drospirenone (Yasmin) a progresterone with spironolactone-like properties

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OC to avoid in PCOS treatment

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Levonorgestrel (a progestin) can be androgenic

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Rx to treat insulin resistance

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Metformin- decreases hepatic gluconeogenesis, intestinal absorption of glucose, peripheral glucose uptake, fasting insulin levels, LH, free testosterone

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Antiandrogens for PCOS treatment and major side effect

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Spironolactone, flutamide, finasteride. All are teratogenic.

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Treatment of acanthosis nigricans

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Correct hyperinsulinemia. Lac Hydrin lotion (ammonium lactate 12%) and Retin A cream (Retin A 0.05%)

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NSAID treatment for Endometriosis

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Ibuprofen / Mefenamic acid (prostaglandin receptor antagonist and COX inhibitor) - Decrease intra-uterine pressure and lowers PGF2α; GI upset common

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Contraindications to NSAID Tx for Endometriosis

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Renal insufficiency, PUD, gastritis, bleeding disorder, aspirin hypersensitivity

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OCP treatment for Endometriosis

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COC's- ethinyl estradiol and progestin (norgestimate, norethindrone, desogestrel); reduce menstrual flow, inhibit ovulation / prostaglandin production in luteal phase.

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GnRH Analog treatment of Endometriosis

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Leuprolide, Nafarelin, Goserelin- GnRH analogs are continuous, not pulsatile, causing initial LH/FSH burst and pituitary desensitization and loss of LH/FSH production. Causes profound hypoestrogenic state.

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Progestin treatment of Endometriosis

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Norethindrone acetate, Medroxyprogesterone acetate (MPA) - Negative feedback on hypothalamus, antagonizes estrogen at endometrium

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Androgen treatment of Endometriosis

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Danazol - suppresses FSH through HPO axis and endometriosis locally, weak androgen, may cause virilization.

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Aromatase Inhibitor (AI) treatment of Endometriosis

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Letrozole- Decrease body supply of estrogen and local production in implant

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Definitive surgery for Endometriosis treatment

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Hysterectomy with bilateral salpingo-oophorectomy (surgical menopause)

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Treatment of adenomyosis

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NSAID / progesterone for symptoms, but hysterectomy is only definitive treatment.

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Treatment for Lichen Sclerosus

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Topical corticosteroids (Clobetasol)- ultrapotent topical steroid; ointment preferred

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Side effects of Clobetasol treatment

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Pituitary-adrenal axis suppression, atrophy, hypopigmentation, allergic contact dermatitis

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Treatment of Lichen Simplex Chronicus

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Topical medium-strength steroids and prophylactic fluconazole (for history or current Candida)

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Treatment of Hidradenitis Suppurativa

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Stage I - Antiandrogenics, antibiotics, zinc gluconate, intralesional steroids. Stage II- early local unroofing. Stage III- Wide excision.

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Treatment of BV

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Oral / vaginal therapy with metronidazole or clindamycin, or single dose therapy with tinidazole for everyone except pregnant patients.

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OTC Treatment for Uncomplicated VVC

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Azole intravaginal prep w/ topical creams (Butoconazole, Clotrimazole, Miconazole, Tioconazole)

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Rx Treatment for Uncomplicated VVC

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Vaginal agents (Butoconazole, Nystatin, Terconazole) or Oral Fluconazole

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Treatment for Complicated VVC

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Topical therapy or oral fluconazole with weekly maintenance fluconazole.

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Treatment for non-albicans VVC

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Non-fluconazole azole drug, boric acid capsule vaginally

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Treatment of Condyloma

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Medical imiquimod- topical immunoresponse modifier. Surgical ablative or cryotherapy approach. Chemical cautery: tri-chloro or bichloro acetic acid. Podophyllin resin (Condylox) home Tx.

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Treatment for Chlamydia

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Azythromycin (oral, once) or Doxycycline (7 days)

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Treatment for Lymphogranuloma venereum

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21 day course of doxycycline

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Treatment for Gonorrheal cervicitis / urethritis

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Ceftriaxone or cefixime

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Treatment of PID

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Ceftiraxone + Doxycycline +/- Metronidazole

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Treatment for Tuboovarian Abscess

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(A) Cefotetan or Cefoxitin + Doxycycline (B) Clindamycin + Gentamicin

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Management of PTL

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Hospitalization, tocolytic drugs, antenatal glucocorticoids, antibiotic prophylaxis

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How does magnesium sulfate work as a tocolytic?

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Uncouples excitation-contraction in myometrial cells and decreases calcium uptake while activating intracellular adenylyl cyclase

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When is magnesium sulfate contraindicated for use as a tocolytic?

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Being phased out, but absolute contraindication in myasthenia gravis and renal impairment.

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What is the use of 17-OH Progesterone in preventing preterm labor?

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Prevention only. Progesterone receptor modulator decreases estrogen-mediated enhancement of oxytocin-induced contractions. Prophylaxis in women with history of PTL. Intramuscular / vaginal delivery.

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To avoid 1st pass effect in hormone replacement therapy, other admin options include:

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transdermal patch (less gallstones/VTE), creams (local only), rings (systemic)

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Types of progesterone used in HRT:

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MPA (medroxyprogesterone acetate), drospirenone (aldosterone antagonist), micro-ionized progesterone

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Types of progestin used in HRT:

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Androgenic progesterone: norethindrone, levonorgestrel

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Common side effects of progesterone HRT

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Hirsutism, "spotting", abnormal bleeding, weight gain, HTN

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Treatment for irregular menses and anovulation due to obesity.

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Oral contraceptives (likely has PCOS); no DepoProvera due to hirsutism (probably already bad)

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Treatment for 40 y/o w/ irregular menses, DM, HTN, normal TSH/FSH/pap/us/endometrial biopsy.

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Loevonorgestrel (not estrogen, may have vascular disease and endothelial damage- Virchow's Triad)

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1st line SERM for ER+ breast cancer

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Tamoxifen

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MOA for Tamoxifen

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Metabolized by cyp2D6 to more bioactive metabolite with high affinity for ERα & Erβ receptors. Binds co-repressor in breast/hypothalamus and co-activator in blood/uterus.

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Agonist/Antagonist effects of Tamoxifen

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Antagonist at breast / hypothalamus (hot flashes). Agonist at blood (VTE, clot) / uterus (endometrial hyperplasia). Partial agonist in bone (blocks resorption).

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Use for Toremifene

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Acts like Tamoxifen (ER receptor agonist/antagonist) more active than its metabolites (does not need cyp activation.) - Used in Tamoxifen resistant cancer.

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Raloxifene Use

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Breast cancer prevention (primary or reoccurence) (1st line in osteoporosis for agonist action in bone)

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Raloxifene vs. Tamoxifen

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Raloxifene is antagonist in uterus- no endometrial hyperplasia (no longterm risk of endometrial cancer) and more potent bone agonist (increases bone mass)

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Action of Aromatase Inhibitors

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Block action of aromatase enzyme in converting androstenedione to estrogen.

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Aromatase Inhibitors indicated in what type of patient

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Postmenopausal women (1st line for Stage III)

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MOA for Anastrazole

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Reversible Aromatase Inhibitor

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MOA for Exemestane

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Irreversible Aromatase Inhibitor

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Major side effects of Exemestane

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Androgenic effects: build-up of substrate (androstenedione) unable to out-compete drug due to "suicide" mechanism

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MOA for Fulvestrant

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Competitive antagonist @ ER receptors

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Indication for Fulvestrant Use

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Alternative for postmenopausal women if SERM or aromatase inhibitors fail.

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Progestins in order of most to least androgenic

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Levonorgestrel > Norgestrel > Etonogestrel > Norethindrone > Desogestrel > Norgestimate/Norelgestromin > Drospirenone

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Least androgenic progestin

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Dropsirenone (Yasmin) (Spironolactone derivative)

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Tx for menorrhagia if estrogen contraindicated

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Oral MPA (medroxyprogesterone acetate), Norethindrone minipill, Levonorgestrel IUS

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Fertility Tx for male hypothalamic hypogonadism

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Clomiphene citrate, hCG injections, IVF

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MOA for infertility drugs: Clomiphene citrate, Anastrozole/Letrozole

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Estrogen receptor antagonist, aromtase inhibitor. Block estrogen action on hypothalamus, increasing FSH production in HPO axis.

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MOA for infertility drugs: Gonadotropins

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FSH/LH increases, skipping HPO axis, leads to multiple gestations

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MOA for infertility drugs: hCG

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Triggers ovulation

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Prostate therapies

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GnRH antagonist (degarelix), GnRH agonist (leuprolide), androgen synthesis inhibitors (aminoglutethimide, ketoconazole), aromatase inhibitor, 5-alpha reductase inhibitor (finasteride), androgen receptor antagonist (flutamide)

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Doxazosin MOA (Terazosin, alfuzosin)

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α1-adrenergic receptor antagonist, relax prostate smooth muscle (symptomatic relief)

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Tamsulosin MOA

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Selective alpha-1A antagonist, less hypotension, nasal congestion

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Finasteride MOA

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5alpha-reductase inhibitor (Finasteride- selective, Dutasteride- nonselective); decrease serum PSA, impotence/libido, rare inc. of male breast cancer

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AE of Aminoglutethimide

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Hypothyroidism, hyperlipidemia

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Flutamide MOA

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DHT receptor antagonist in prostate; gynecomastia, libido drop, hepatix dysfunction

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Degarelix MOA

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GnRH antagonist, shuts down LH/FSH w/o testosterone spike (better for adv. Stage)

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Nitric oxide MOA

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Goes into smooth muscle cells of penis and stimulates production of cGMP: erection

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PDE5 MOA

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causes breakdown of cGMP leading to contraction of smooth muscle: decreased blood flow in / increased blood flow out.

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Viagra MOA

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PDE5 inhibitor; inc. cGMP levels, delays tumesences (Cialis, Levitra)

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Direct vasodilators MOA

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PGE1 (Caverject, Edex) or Papavarine, direct injectables into penis