ReproEndo Drugs - Sheet1 Flashcards
(102 cards)
1
Q
amiloride
A
blocks Na channels -> decr MC effects in hyperaldosteronism *weaker effect than spirolactone
2
Q
spironolactone: action, use and dosage (3 doses for 6 diseases)
A
antagonist at MC receptors (also androgen and progesterone receptors); 25-50 mg daily as K sparing diuretic for HTN and edematous states (CHF, cirrhosis, nephoris); 400 mg daily in primary hyperaldosteronism; 200 mg daily in PCOS (used off label for anti-androgen effects)
3
Q
spironolactone side effects (4)
A
hyperkalemia, volume depletion, men: gynecomastia, impaired libido, impotence; women: mest. irregularities
4
Q
eplerenone
A
highly selective (and expensive) MC antagonist (not androgens nor progesterone)
5
Q
contraindications for spironolactone (3)
A
renal impairment, hyperkalemia, pregnancy
6
Q
metyrapone
A
blocks 11-beta enzyme that converts 11-DOC -> cortisol; doesn’t interfere with aldosterone or androgen production (dx adrenal insufficiency as primary or central by seeing relative ACTH/11-DOC levels)
7
Q
hydrocortisone dosing
A
physiological: 20-30 mg/day in the am; stress: 50 mg every 6-8 hrs; acute: 100 mg IV/IM every 6-8 hrs (don’t need MC replacement b/c hydrocortisone works as MC above 100 mg)
8
Q
dex dosing
A
physiological: .5 mg daily; stress: 2 mg every 12 hrs; acute: 4 mg IV/IM
9
Q
ketoconazole
A
non-specific inhibitor of cortisol synthesis (inhibits at 3 steps)
10
Q
cabergoline
A
DA agonist used to tx somatotroph adenoma -> paradoxical effect
11
Q
octreotide
A
STT analog used to tx somatotroph or thyrotroph adenoma
12
Q
pegvisomant
A
GH anatagonist used to tx somatotroph adenoma -> binds only 1/2 receptor and thus blocks it
13
Q
metformin: action, MOA
A
prevents gluconeogenesis (and poss glycogenolysis); phosphorylation (activation) of AMPK; improves fasting glucose (little effect on postprandial); not metabolized, renally excreted unchanged (can accum. if renal insuff); adverse: anorexia, nausea, diarrhea, lactic acidosis; benefits: immed onset (altho need to titrate slowly to avoid GI effects), no hypoglycemia, weight neutral (poss loss) -> first drug of choice; contraindications: prone to acidosis, hypoxic states, renal failure, cardiac ischemia, T1DM; need insulin to work!
14
Q
Metformin effect
A
improves fasting glucose (little effect on postprandial)
15
Q
metformin metabolism
A
not metabolized, renally excreted
16
Q
metformin adverse effects (4)
A
anorexia, nausea, diarrhea, lactic acidosis
17
Q
metformin benefits (3)
A
immediate onsent, no hypoglycemia, weight neutral
18
Q
metformin contraind (5)
A
prone to acidosis, hypoxic states, renal failure, cardiac ischemia, T1DM (need insulin to work)
19
Q
TZDs: action, MOA
A
incr. periph tissue sensitivity to insulin; binds to nuclear PPAR-gamma receptor (incr. GLUT4 transcription)
20
Q
TZD effect
A
decreases fasting and post-meal glucose
21
Q
TZD duration/onset
A
slow onset of action (fasting gluc begins to decrease within 5-7 days but doesn’t completely decline until 2-3 months)
22
Q
TZD contraind (3)
A
liver disease, heart failure, renal insufficiency
23
Q
TZD adverse effects (3)
A
weight gain (increased water due to Na reabsorption), hepatocellular injury, increased LDL
24
Q
TZD benefits (3)
A
reduces TGs, raises HDL, no hypoglycemia
25
secretagogues: types (2), differences
sulfonylurea and meglitinides; both bind the beta cell ATP-dep K channel but meglitinide binds more quickly and dissociates more quickly (shorter duration -> 3-4 hrs vs 12-24)
26
sulfonylurea: action, MOA, duration
secretagogue; binds to sulfonyl receptor in beta cell causing depolarization of ATP-dependent K channels; 12-24 hrs duration
27
sulfonylurea effect
effect on fasting glucose
28
sulfonylurea metabolism
excreted via kidney with active metabolites (careful w/ renal problems)
29
sulfonylurea contraind (3)
T1DM, DKA (need fxning beta cells!), sulfa allergy
30
sulfonyl adverse effects (3)
hypoglycemia, weight gain, hunger
31
meglitinides: action, MOA, duration and onset, metab, contraindications (4), adverse effects (2), aka
secretagogue; binds to sulfonyl receptor in beta cell causing depolarization of ATP-dependent K channels; 3-4 hrs duration w/ fast onset (give w/ every meal -> hard for compliance); metab: hepatic (P450) w/ most metabs excreted GI; contraind: T1DM, liver failure, DKA, sulfa allergy; adverse effects: low glucose 2-4 hrs after meal, weight gain; aka glinides
32
meglitinides duration and onset
3-4 hour duration wtih fast onset (different from sulfonylureas)
33
meglitinides metabolism
hepatic (P450) with most metabolites secreted via GI
34
meglitinides contraind (4)
T1DM, DKA (need fxning beta cells!), sulfa allergy, liver failure
35
meglitinides adverse effects (2)
low glucose 2-4 hours after meal, weight gain
36
alpha-glucoside inhibitors: MOA
delay carbohydrate absorption (inhibits intestinal enzymes ability to break down sugars) and thus incr GLP-1; effects postprandial glucose only; side effects: flatulence, bloating -> titrate slowly to minimize; contraindications: GI disorders (esp IBD); metab: renally excreted unchanged
37
alpha-glucosidase inhibitors effects
decreases post-prandial glucose
38
alpha-glucosidase side effects
flatulence, bloating
39
alpha-glucosidase contraindications
GI disorders
40
alpha-glucosidase metabolism
renally excreted unchanged
41
GLP-1 mimetic: names (2), comparison, contraindications (2), effect, metab, benefits (2), side effects (1)
exenatide (from Gila monster) and liraglutide; liraglutide is once daily injection b/c binds albumin vs. exenatide is twice daily (60 mins before each meal); avoid in pts with severe GI disease or on drugs that need rapid GI abs; effect on postprandial glucose; metab: renal after DPP-4 breakdown; benefit: weight loss, no hypoglycemia; side effects: GI
42
GLP-1 mimetic contraindications (2)
GI disease or drugs that need rapid GI absorption
43
GLP-1 mimetic effect
decrease post-prandial glucose
44
GLP-1 mimetic metabolism
broken down by DPP-4 then renal
45
GLP-1 mimetic benefits (2)
weight loss, no hypoglycemia (glucose dependent)
46
GLP-1 mimetic side effects
GI
47
biguanides: names (1)
metformin
48
incretin enhancers: MOA, duration, effect, metab, contraind, adverse effects, benefits (2)
DPP-4 inhibitors; 80% inhib at 24 hrs (take 1 daily); immed effect on postprandial glucose; metab: renally excreted unchanged (dose adj for renal probs); contraindications: none; adverse effects: GI; benefits: weight neutral, no hypoglycemia
49
incretin enhancer effect
decrease post-prandial glucose
50
incretin enhancer metabolism
renally excreted unchanged
51
incretin enhancer contraindiaction
none
52
incretin enhancer adverse effects
GI
53
incretin enhancer benefits (2)
weight neutral, no hypoglycemia
54
glimeperide: what is it, brand name
aka Amaryl, a sulfonyurea
55
bolus insulin types (3) and peak times
rapid: Aspart, Lipro (1 hr to peak); short-acting: regular (2-4 hrs to peak -> complexed w/ zinc)
56
basal insulin types (3) and dosing
intermediate: NPH (once or twice/day); long acting: glargine (once/day), detemir (once or twice/day)
57
rapid-acting insulin: names (3), kinetics (peak, onset, duration), vs. regular (2)
Aspart, Lispro, Glulisine; 1 hr peak (base substitutions disrupt monomer-monomer interactions and decr hexamer formation), 10-20 mins onset, 3-5 hr duration; 2x faster absorption and 2x higher peak concentration
58
NPH: what is it, duration, dosage, onset, peak
suspension of zinc insulin w/ protamine (positively charged peptide); 10-20 hrs duration; dosed once/twice daily; 1-2 hr onset, 4-8 hrs peak
59
glargine: what is it, dosage, onset
human analog insulin w/ base substitutions that cause it to exist at pH 4.0 -> when injected it forms microprecipate below skin that takes time to absorb (long lasting); dosed once daily; 1-2 hr onset (flat course)
60
detemir: what is it, dosage, duration, onset
insulin analog that is acylated w/ myristic acid (remains in solution after injection -> binds to albumin and slowly releases); dosed once or twice daily; duration is dose dependent (up to 24 hrs); .8-2 hr onset (flat course)
61
regular insulin kinetics (onset, peak, duration)
30-60 mins (complexed w/ zinc) onset, 2-4 hr peak, 6-10 hr duration
62
PARP inhibitors (olaparib)
used in BRCA1/2 mutation carriers to prevent ss break repair -> "two hit" hypothesis; tumors may restore BRCA1/2 function and thus become resistant to PARP inhibitors and cisplatin (but not taxane now!)
63
medical tx of impotence: what is it, how does it work, examples (3)
PDE5 inhibitors: sildenafil (Viagra) is prototype -> also vardenafil (Levitra) and tadalafil (Cialis); works by inhibiting breakdown of cGMP by PDE 5, thus incr cGMP and relaxing arteries/trabeculae smooth muscles; works to maintain vasodilatory response (cannot cause it)
64
PDE5 inhibitors pharmacokinetics: onset, metabolism, distribution, changes in metabolism due to... (4)
work quickly (peak plasma 30-90 mins after oral dose); metabolized by CYP3A4 to active metabolite (accounts for 20% activity); widely distributed throughout body tissues; incr. plasma levels (-> hypotension) in elderly (40% incr), liver disease (80%), severe renal disease (100%), w/ CYP3A4 inhibitors (100% incr -> macrolide antibiotics, antifungals, protease inhibitors, cimetidine - OOC for heartburn)
65
PDE5 inhibitors indications (4)
current: impotence, primary pulmonary hypertension; future: CF, BPH
66
PDE5 inhibitors side effects
PDE5 inhibitors prevent breakdown of cGMP, and cGMP is in several other pathways: sperm motility, test synthesis, vaginal smooth muscle, esophageal motility, retinal color vision, inhibition of platelet aggregation; side effects can be divided into four groups: vasodilation (headahce, flushing, rhinitis), CV (hypotension, tachycardia, platelet inhibition), GI (reflux), visual changes (blue green tinged vision, incr. light perception, blurred vision)
67
tx of female sexual dysfn (6)
educational: behavioral/sex therapy, anatomy arousal and response; HRT (estrogen, sometimes testosterone); vascular tx: PDE5 inhibitors (for SSRI induced dysfn only), Eros therapy (handheld device to incr clitoral blood flow), L-arginine tropical tx (Vigael, Sensua -> substrate for NO synthesis)
68
mifepristone
used for abortion up to 63 days (approved for 49 days); anti-progestin; take 4-6 hrs to complete abortion (needs 2 visits)
69
misoprostol
prostaglandin E1 analog (stimulates uterine contractions, softens/primes cervix); FDA approved for prevention and tx of gastric/duodenal ulcers; benefits: heat stable (no refrig), inexpensive, widely available; side effects: flu-like sx (diarrhea, nausea, vomiting, headaches); given vaginally or buccally
70
methotrexate
anti-folate (used off label for abortion - given IV); takes 3-45 days to complete abortion; slightly less effective than mifepristone (90-95% vs 93-98%); used where mifepristone isn't approved and to end ectopic pregnancies (vs mifepristone, which only ends uterine pregnancies)
71
dosing of LT4
start: if under age 60 w/o cardiac disease -> 50-100 mcg, if over 60 or w/ cardiac disease -> 25 mcg; avg final dose (for pts w/o thyroid) = 1.6 mcg/kg PO qd (lower in elderly); give 75% of oral dose if given IV
72
methimazole: half life, dosing, protein bound? how long to see effects? side effects
half life 4-6 hrs (need 1x daily); starting does 10-30 mg QD; 2-4 weeks for improvement w/ 6-12 weeks to euthyroid; freq of side effects is dose related and there are fewer side effects than PTU; rare teratogenic effects -> use instead of PTU unless in pregnancy or thyroid storm
73
PTU: half life, dosing, protein bound? how long to see effects? side effects
half life 1 hr (need 3x daily); starting dose 100 mg TID; 2-4 weeks for improvement w/ 6-12 weeks to euthyroid; worse side effects than methimazole (i.e. severe hepatitis only seen w/ PTU) and no dose relationship of side effects; not teratogenic -> use only in pregnancy
74
when to use PTU
use methimazole in all Grave's except: first trimester pregnancy, thyroid storm, adverse rxn to methimazole
75
side effects of antithyroid drugs (5)
most important side effect = agranulocytosis -> rare (.1-.5%) but severe -> can kill and can appear at any dose; severe hepatitis (PTU only at .1%, hence we don't use it); cholestasis (not as severe as PTU hepatitis, seen w/ methimazole rarely); vasculitis (rare), severe polyarthritis (rare)
76
special instructions with antithyroid drugs
agranulocytosis is dangerous side effect, so tell pts to stop drug and check WBC for fever or sore throat; if granulocytes <500, hospitalize and give broad spectrum antibiotics, if not, resume drug
77
amiodarone
anti-arrhytmia drug w/ 37% weight iodine -> can cause hypothyroidism due to Wolf-Chakoff effect, or hyperthryoidism: type 1 due to Jod-Basedow phenomenon in pts w/ underlying thyroid nodular or Graves' disease, type 2 due to toxic effect of amiodarone causing destructive thyroiditis in normal thyroids causing T3/4 release
78
raloxifene
type III SERM; competes with E2; acts as estrogen in bone and CVS but anti-estrogen in breast and uterus
79
type III SERM
raloxifene; competes with E2; acts as estrogen in bone and CVS but anti-estrogen in breast and uterus
80
tamoxifen
type IV SERM; competes with E2; acts as estrogen in bone, CVS, uterus, but anti-estrogen in breast
81
type IV SERM
tamoxifen; competes with E2; acts as estrogen in bone, CVS, uterus, but anti-estrogen in breast
82
RU-486 is what antagonist type?
type II antagonist
83
Equilin
ERT
84
Mestranol
estrogen -> inhibit lactation
85
letrozole
aromatase inhibitors -> use in breast cancer
86
Norethindrone
progestin -> use in endometriosis
87
finasteride
type II 5-alpha reductase inhibitor; used in BPH and baldness to prevent DHT from exerting its effects in the prostate and hair follicles (more dramatic effect on BPH then on baldness, however)
88
flutamide
non-steroidal androgen receptor antagonist
89
cyproterone acetate
steroidal androgen receptor antagonist
90
Medroxyprogesterone acetate
aka MPA, progesterone-derived progestin in Depo-Provera -> only prog-derived on market
91
Drosperinone
derived from 17-alpha spirolactone, used in Yaz/Yasmin b/c more mineralocorticoid activity
92
bromocriptine
dopamine agonist; can be used to inhibit lactogenesis, treat lactotroph/somatotroph adenoma
93
Herceptin
monoclonal antibody effective for breast cancer with HER-2/neu overexpression/amplification
94
pegvisomat
gh receptor antagonist - GH adenomas
95
eplereone
like spiralactone, exept only acts on MC -- more expensive
96
fludrocortisine
synthetic MC - side effect: hyperaldosteronism
97
mitotane
adrenal cytotoxic (sometimes used for cushings)
98
mifeprostone
GC receptor antagonist (also progesterone antagonist ) -s ometimes used for cushings
99
metyrapone, ketoocnazole
inhibit steroidognesis enzymes - hypercortisolism ** hepatotoxic
100
somatostatin analogue: pasireotide (anything ending in reotide)
inhibit ACTH secretion - used for hypercortisolism, doesnt work for acth-indepnedent adrenal adenomas
101
methimazole/PTU
antithryoid - try these before iodone' 60% remissoin * do not use during pregnancy
102
thyroid surgery
when thyroid is compresion OR pregnancy
