GI+Repro Pharm Flashcards
androgens
testosterone, methyltestosterone
HRT in hypogonadism, secondary sex characteristics in trans men, reverse protein loss (+anabolic steroids)
MOA: testosterone converted to dihydrotestosterone by 5-alpha-reductase; testosterone and dihydrotestosterone bind to cell receptors and regulate protein expression
androgen AEs
in females: masculinization (hirsutism, clitoral enlargement, deepening voice); amenorrhea
in males: azoospermia, decreased testicular size, gynecomastia
both: acne, sleep apnea, erythrocytosis, decreased HDL, increased LDL, aggressiveness, psychosis, premature closing of epiphyseal plate (short stature), hepatic dysfunction
antiandrogens (drugs and MOAs)
abiraterone: 17-alpha-hydroxylase/17,20-lyase inhibitor => decreased steroid synthesis
finasteride: type II 5-alpha-reductase inhibitor => blocks testosterone action in prostate
flutamide, bicalutamide: non-steroidal antiandrogen
spironolactone: aldosterone antagonist that also antagonizes testosterone receptor (may also inhibit synthesis)
ketoconazole: antifungal that also inhibits 17-alpha-hydroxylase/17,20-lyase
antiandrogen indications
abiraterone: metastatic prostate cancer, hypertension, hypokalemia
finasteride: benign prostatic hyperplasia, male pattern baldness
flutamide, bicalutamide: prostate cancer; to treat flare response when GnRH analogues are used; hirsutism
spironolactone: PCOS, hirsutism (off-label)
ketoconazole: prostate cancer (not first line)
selective estrogen receptor modulators (SERMs)
tamoxifen: antagonist in breast, partial agonist in endometrium
raloxifene: antagonist in breast and endometrium, agonist at bone
clomiphene: antagonist in hypothalamus and pituitary, agonist in ovary => induces ovulation
tamoxifen, raloxifene for osteoporosis; clomiphene to stimulate ovulation
selective estrogen receptor modulators (SERMs): AEs
tamoxifen: venous thrombosis, hot flashes, weight gain due to fluid retention, mild nausea, endometrial carcinoma
raloxifene: same as tamoxifen but WITHOUT endometrial carcinoma
clomiphene: ovarian enlargement, hot flashes
aromatase inhibitors
anastrozole, letrozole
MOA: block synthesis of estrogen
indication: ER+ breast cancer in post-menopausal women; ovulation induction (letrozole)
danazole
MOA: weak partial agonist activity at progestin, androgen, and glucocorticoid receptors; also inhibits steroid synthesis
indication: endometriosis, fibrocystic disease of breast
AE: weight gain, edema, decreased breast size, acne, oily skin, increased hair growth
fulvestrant
MOA: selective estrogen receptor downregulator (SERD) and potent antiestrogen; immobilizes ERa in nuclear matrix => polyubiquitination and degradation via 26S proteosome
indication: ER+ breast cancer when other treatments have failed
mifepristone
MOA: competitive progesterone antagonist => causes blastocyst to die => eliminates source of hCG required to maintain corpus luteum
indication: induces abortion; administered with misoprostol (stimulates uterine contractions)
AE: excessive vaginal bleeding
estrogen preparations
premarin, prempro (conjugated equine estrogens)
ethinyl estradiol, mestranol (synthetic estrogen)
transdermal estradiol
estradiol cypionate, estradiol valerate (slowly absorbed IM injections)
progestin preparations
medroxyprogesterone acetate (progesterone esters)
norgestrel, levonorgestrel (earlier synthetic analogues that have some androgenic activity)
northindrone (intermediate androgenic activity)
drospirenone (spironolactone derivative with anti-aldosterone and anti-androgenic effects)
combination oral contraceptives
yasmin (ethinyl estradiol + drospirenone); ethinyl estradiol + levonorgestrel
MOA: prevent midcycle LH surge at hypothalamus and pituitary; also cause glandular atrophy of uterine endometrium and formation of thick cervical mucus
AE (estrogen): nausea, breast tenderness, edema, skin hyperpigmentation, migraine, headache, hypertension, small increased risk of gallstones or gallbladder disease, endometrial hyperplasia/ cancer, increased blood coagulation, DVT, MI, strike
AE (progesterone): hirsutism, acne, weight gain, glucose intolerance, increased LDL, decreased HDL, breakthrough bleeding, depression, vaginitis, UTI
progestin-only contraception
norethindrone
MOA: prevents ovulation in 70-80% of cycles by slowing frequency of GnRH pulse generation and blunting LH surge; thickens cervical mucus; endometrial atrophy
indication: breastfeeding women and those with estrogen contraindications
AE: more irregular spotting
morning-after contraception
levonorgestrel (Plan B): may prevent ovulation, transport of fertilized egg, or implantation
ulipristal: progesterone receptor modulator
AE: cramping, nausea
drugs used in HRT for osteoporosis
raloxifene (SERM), allendronate (bisphosphae derivative)
drugs to treat gonorrhea (name, MOA, AE)
ceftriaxone
-MOA: third generation cephalosporin; inhibits cell wall synthesis by binding to transpeptidase
-AE: hypersensitivity reactions, seizures
doxycycline
-MOA: tetracycline; inhibits protein synthesis by binding to 30S subunit and blocking amino acid-linked tRNA from binding
-AE: esophageal irritation, discoloration of teeth (contraindicated in pregnancy and children)
drugs to treat syphilis (drug, MOA, AE)
penicillin G
MOA: inhibits biosynthesis of cell wall peptidoglycan => makes organism osmotically unstable
AE: Jarisch-Herxheimer reaction (acute febrile reaction with headache and myalgia that occurs within 24 hours of syphilis treatment - not a penicillin AE)
drugs to treat trichomoniasis (drugs, MOA, AE)
metronidazole (preferred), tinidazole
MOA: nitroimidazole family; nitro group is reduced in anaerobic bacteria and sensitive protozoans, reactive products are responsible for antimicrobial activity
AE: nausea, headache, anorexia, metallic taste; patients should abstain from alcohol for 24 hours
drugs to treat pelvic inflammatory disease (regimens, MOA, AE)
1) ceftriaxone + doxycycline + metronidazole
2) cefotetan OR cefoxitin + doxycycline
cefoxitin/cefotetan:
-MOA: second generation cephalosporins
-AE: thrombophlebitis, disulfiram-like reaction with ethanol, inhibit vitamin K production (prolong bleeding time)
drugs to treat herpes (drugs, MOA, AE)
acyclovir, famciclovir, valacyclovir
MOA: nucleoside analogues; phosphorylated by viral thymidine kinase => compound acts as a substrate and inhibitor of viral DNA polymerase and is incorporated into DNA (terminates chain elongation)
AE: crystalluria if not well-hydrated
[?] has a lower degree of placental metabolism, so it crosses the placenta; it is used to promote fetal lung maturation
betamethasone (a corticosteroid)
[?] overdose is the most common poisoning in pregnancy
acetaminophen
fetal hepatocytes cannot conjugate the highly reactive metabolic intermediate
[?] have been associated with fetal renal failure, and are contraindicated in pregnancy
angiotensin-converting enzyme (ACE) inhibitors
[?] may produce fetal hypothyroidism when exposure occurs beyond 12-14 weeks
propylthiouracil, methimazole
[?] chelate calcium ions that are deposited in developing teeth, producing discoloration
tetracyclines (doxycycline)
fetal exposure to [?] causes vaginal carcinoma in young women
diethylstilbestrol
injectable drugs for ED
aprostadil (PGE1 analogue => increases cAMP)
trimix (phentolamine [blocks a-adrenergic receptor vasoconstriction] + papaverine [vasorelaxation] + PGE1 [increases cAMP])
AE: pain at injection site
phosphodiesterase-5 inhibitors for ED
sildenafil, vardenafil, tadalafil
MOA: inhibition of PDE-5 prevents the degradation of cGMP => potentiates relaxation of corporeal arterial and sinusoidal smooth muscle
AE: headache, flushing, dyspepsia, nasal congestion, altered vision (blue aura), diarrhea
centrally acting agent for ED
apomorphine
MOA: dopamine D1/D2 agonist; works at level of hypothalamus
AE: nausea, headache, yawning, dizziness
proton pump inhibitors
lansoprazole, omeprazole, esomeprazole, pantoprazole, dexlansoprazole
use: peptic ulcer disease, NSAID-associated ulcers, GERD, laryngopharyngeal reflux, Zollinger-Ellison syndrome, stress-related gastritis
MOA: forms covalent disulfide link with cysteinyl residue in proton pump on luminal side of parietal cells => irreversible inhibition of acid secretion
AE: increased hip fractures, B12 deficiency, increased C. difficile, possible pneumonia link, chronic use can => fundic gland polyposis of stomach and chronic kidney disease
omeprazole/ esomeprazole drug interactions
inhibits metabolism of warfarin, diazepam, phenytoin, carbamazepine
inhibits conversion of clopidogrel to active form
gastric antacids
aluminum and magnesium hydroxides, calcium carbonate, sodium bicarbonate
use: acid indigestion, peptic ulcer disease
MOA: neutralizes acid
AE: constipation (aluminum alone), diarrhea (magnesium alone), calcium carbonate and sodium bicarbonate => flatulence
mucosal protective agents
sucralfate: adheres to ulcer craters and epithelial cells, allows ulcer to heal
-use: peptic ulcer disease
-DDI: inhibits absorption of digoxin
bismuth subsalicylate: antisecretory, anti-inflammatory, antimicrobial effects
-use: nausea, abdominal cramps
-AE: dark stool, black staining of tongue
antihistamines for nausea/vomiting
dimenhydrinate, meclizine, diphenhydramine: motion sickness
promethazine: nausea/vomiting induced by medications, anesthetics, etc.
doxylamine, pyridoxine (B6): nausea/vomiting related to pregnancy
MOA: block H1 receptors, significant antimuscarinic activity
AE: sedation, confusion, dizziness, tinnitus, incoordination, tremors, antimuscarinic effects
anticholinergics for nausea/vomiting
scopolamine
uses: motion sickness, postoperative nausea/vomiting
AE: dry mouth, urinary retention, blurred vision, exacerbation of narrow angle glaucoma
dopamine receptor antagonists for nausea/vomiting
prochlorperazine: post-chemotherapy/radiation nausea/vomiting, pre/postoperative
metoclopramide: nausea/vomiting in GI dysmotility syndromes, GERD, intractable hiccups
MOA: blocks D2 (both) and 5HT3 (metoclopramide) receptors in chemo trigger zone
AE: sedation, dystonia, EPS, impaired thermoregulation, tardive dyskinesia
serotonin receptor antagonists for nausea/vomiting
ondansetron, granisetron, palonosetron
use: chemotherapy/ irradiation-induced nausea/vomiting, postoperative
MOA: 5HT3 antagonist that acts at solitary tract nucleus and area postrema
substance P antagonists for nausea/vomiting
aprepitant, fosaprepitant
MOA: substance P is present in vagal afferents innervating solitary tract nucleus
uses: combined with other treatments, delayed nausea
agents to treat chronic hepatitis B
entecavir: nucleoside analogue that inhibits all 3 functions of BHV polymerase
tenofovir: nucleotide analogue
INF-alpha/pegylated interferon: binds to cell surface receptors => suppression of cell proliferation, increased phagocytosis, augmentation of lymphocytic cytotoxicity, inhibits viral replication
INF-alpha/pegylated interferon AE
severe flare of disease (prelude to HBeAg clearance, can lead to liver failure in patients with cirrhosis)
headache, fever, chills, myalgia, malaise in 30% during first week of therapy
agents to treat chronic hepatitis C
glecaprevir: NS3/4A protease inhibitor
velpatasvir, ledipasavir, pibrentasvir: NS5A inhibitor
sofosbuvir: NS5B polymerase inhibitor
agents to treat IBD
dicyclomine: antimuscarinic; blocks muscarinic receptors on enteric plexus and smooth muscle
sulfasalazine/ mesalamine: 5-aminosalicylic acid may inhibit prostaglandin synthesis, block neutrophil migration, or act as free radical scavengers
azathioprine, 6-mercaptopurine, methotrexate: immunosppressants
infliximab, adalimumab: anti-TNF
vedolizumab: integrin receptor antagonist (prevent T cell migration)
agents to treat non-infectious diarrhea
diphenoxylate, loperamide: opioid agonists => sustained segmental contraction of smooth muscle, which prevents rhythmic waves of smooth muscle
bismuth subsalicylate: inhibits intestinal secretions
bulk-forming laxatives
bran, psyllium, methylcellulose
MOA: indigestable hydrophilic substances that swell upon contact with water, forming a bulky gel that distends colon and promotes peristalsis
AE: abdominal pain; flatulence and bloating (bran)
stool softeners
docusate sodium
MOA: emulsify stool by permitting water and lipids to penetrate; may also cause water secretion into intestine and colon
short-term setting only
lubricants
mineral oil, glycerin suppositories
MOA: coat the bowel and decrease colonic absorption of water => easier passage of stool
AE: long-term use can impair absorption of fat-soluble vitamins
stimulant laxatives
senna, bisacodyl
MOA: thought to stimulate intestinal motility
AE: abdominal cramps, diarrhea
short-term treatments only; bowel prep for colonoscopy (biscodyl)
osmotic laxatives
magnesium hydroxide, lactulose, low dose polyethylene glycol
MOA: poorly absorbed in intestine and colon => net water movement into GI tract => distends bowel, increasing intestinal motility
magnesium hydroxide can cause hypermagnesium in patients with renal insufficiency
purgatives
balanced polyethylene glycol, magnesium citrate, sodium phosphate
MOA: rapid movement of water into distal small bowel => high volume liquid stool
AE: magnesium citrate and sodium phosphate can cause electrolyte disorders
chloride channel activators (laxatives)
lubiprostone: directly stimulates chloride channel in small intestine => chloride-rich secretion in intestine => stimulates intestinal motility
linaclatode: stimulates guanylate cyclase on luminal side of epithelium => increase chloride and bicarb secretion => increased fluid retention and motility
anti-nematodes
albendazole, mebendazole: binds B-tubulin => inhibits production of tubulin dimers and formation of cytoplasmic tubules => decrease glucose uptake, depletes, glycogen/ATP
pyrantel pamoate: activate cholinergic receptors => depolarization blockade
ivermectin: may activate glutamate-gated chloride channel => hyperpolarize cell membrane
moxidectin: binds chloride channels and GABA receptors to increase permeability => paralysis of pharyngeal muscles
anti-trematodes/ cestodes
praziquantel
MOA: increased permeability of outer segment (tegument) of schistosomes to Ca++ => depolarization; also causes tegument breakdown
anti-ectoparasides
permethrin: blocks sodium channels => paralysis
malathion: inhibits acetylcholinesterase => increase ACh => activate and desensitize nicotinic receptors
spinosad: activates nicotinic receptors => paralysis
