Exam II- DM, Hormones, Thyroid Flashcards
Raloxifene/ Evista
Class: SERM
MOA: modulates estrogen receptors, inc BD, dec cholesterol without increased risk of E2 cancers
Significantly reduces BCa incidence
PO once daily dosing
SE: hot flashes, arthralgias, myalgias, edema, pruritis, increased risk of DVT
***CI: pregnancy, lactation, Hx of DVT, PE, stroke, retinal vein thrombosis
Calcitonin/ Miacalcin
Produced by parafollicular C cells in thyroid
decreases osteoclasts can activity
Decreases risk spinal fx, possibly hip fx too
Class: synthetic hormone
MOA: increases serum Ca
Indic: osteoporosis Tx
SE: nose bleeds, sinusitis, HA, dizziness, edema, anorexia, diarrhea, rashes
IV and nasal spray routes available
Teriparatide/ Forteo
Class: synthetic PTH analog Indic: females with osteoporosis MOA: activates bone turnover with osteoblasts activation Char: SQ, once daily, up to 24 months SE: nausea, leg cramps, dizziness
Benefits continue after discontinuation
chronic high PTH–> inc risk fx; but daily low dose PTH –> dec risk fx
Denosumab/ Prolia
Monoclonal antibodies, anti-TNF agent
Indic: osteoporosis tx, bone metastasis, RA, MMyeloma, giant cell bone carcinoma
MOA: targets RANK Ligand (usu primary signal for bone remodeling)
Char: SQ q6months
SE: increased susceptibility of infx
Sitagliptin/ Januvia
Class: dipeptidyl peptidase-4 inhibitor (DDP-4)
MOA: prevents DDP-4 breakdown of GLP-1/GIP–> increased insulin, decreased glucagon postparandially
Tends to normalize insulin without risk of hypoglycemia
Approved as monotx or with Met/Sulfonly/TZDs but not with insulin
25/50/100 mg tabs available
100mg once daily
$200-400/ month
T2DM medications and their MOAs
Biguinides (metformin): inhibits liver glucose production
Sulfonylureas: increase insulin secretion
Meglitinides: increased insulin secretion
Alpha- glucoidase inhibitors: delays intestinal glucose absorption
TZDs: decreased insulin resistance
DPP-4 inhibitors: increased postparandial insulin release
Metformin/ glucophage / fortamet
Class: biguanide
MOA: decreases hepatic glucose production, increases skeletal musc insulin sensitivity
when used alone, generally won’t cause hypoglycemia
Similar effects on hba1c as sulfonlureas with modest weight loss
SE: wt loss, abd cramping, nausea (decreased in ExR form), metallic taste, increased risk of B12 deficiency (supplementation recommended), LACTIC ACIDOSIS
CI in pts with renal impairment (creative >1.4/1.5)
500/800/1000mg BID or QD if ExR; $55-100/ month
Alendronate/ Fosamax
Class: bisphosphates
MOA: inhibits osteoclasts
Indic: primary drug to treat osteoporosis (postmenopausal and post corticosteroid tx)
SE: upset stomach, esophageal irritation/erosion, esophagitis, atypical femur fractures, osteonecrosis of jaw, myalgia,
low bioavailability
**Take away from meals! Prevent esophageal Sxs by standing upright for 30-60mins after taking PO. D/c after 5yrs increases risk vertebral fx **
Glipizide/ glyburide/ glimepiride (chlorpropamide, tolbutamide 1st generations)
Class: sulfonlureas
MOA: stimulate beta cells to inc insulin production (partially blocks ATP sensitive K channels, increasing the insulin release stage)
Second generations preferred
SE: hypoglycemia, weight gain
Generally ineffective after 5-10 years of use
Avoid in pts with sulfa allergy**
Glyburide has an increased risk of hypoglycemic events
Char: one AM dose, $4-50/month
Nateglinide (Starlix)
Repaglinide (Prandin)
Class: Meglitinide (non-sulfonylurea secretagogue)
MOA: increased insulin secretion, binds ATP dependent K channels
Prandin better than Starlix, Prandin is equal to sulfonlureas in activity
SE: hypoglycemia, weight gain
Approved for use with metformin, Sulfonylurea
Rapid,y absorbed in GI
TID-QID dosing before each meal, do not take if meals are skipped
No generic available $150-300/month
Rosiglitazone (Avandia)
Pioglitazone (ACTOS)
Class: thiazolidinediones (TZDs)/ glitazones
MOA: increase insulin sensitivity in skeletal muscle, decrease liver glucose production
Dosed once daily, may take 6-14 wks to have effect. Approved as mono therapy or with Sulfonylurea/ metformin
Only ACTOS is approved with insulin
SE: inc risk CHF, MI, dec BMD, inc risk fx, weight gain
*monitor lv fxn tests at 1 month and q3months
$125-200/month
Acarbose (precose)
Miglitol (Glyset)
Class: alpha-glucosidase inhibitors
MOA: inhibits brunch border alpha glucosidase in SI –> inhibited carbohydrate hydrolysis–> delayed glucose abs
Must be taken with each meal
No hypoglycemic risk alone, but inc risk with sulfonylurea/ insulin use
TID-QID $90-125/month
SE: abd pain, diarrhea, flatulence, inc transaminases, hepatic failure (acarbose)
CI: chronic intestinal dz, IBD, colonic ulceration, intestinal obstruction
*incase of hypoglycemia, give GLUCOSE, not sucrose
Pramlintide/ Symlin
Class: synthetic amylin (usu produced with insulin in beta cells)
Indic: Type 1 and 2 diabetics who use insulin
Allows put to use less insulin
Cannot be injected in same vial/syringe as insulin
1st drug for type 1 diabetics since insulin!
Inject at meal times
SE: modest weight loss, nausea (improves with optimal dose)
Exenatide/ Byetta
Class: incretin mimetics, synthetic exedin-4 hormone
Isolated from the Gila monster
Increases insulin secretion
Does not inc risk of hypoglycemia on its own, but can if taken with sulfonylureas
Sildenafil citrate / viagra
Tadalafil/ Cialis
Vardenafil/ Levitra
Class: phosphodiesterase type 5 inhibitor
MOA: increases cyclic GMP in smooth muscle–> inc blood in c.cavernosum
Indic: ED, pulmonary hypertension
SE: cyanopsia, photophobia, HA, flushing, hypotension, glaucoma, stroke, priapism
No erection without stimulation
25/50/100mg tabs available
Take 30mins to 4hrs prior to intercourse, no more than 1 tab qd
CI: nitrites, nitrates, NO, nitroglycerin…. Liver/renal impairment, hypotension, degenerative retinal disorders
Doxazosin (Cardura)
Terazosin (Hytrin)
Tamsulosin (Flomax/Urimax)
Silodosin (Urief)
Alpha blockers
Indic: BPH
All equally effective
SE: weakness, orthostatic hypotension, nasal congestion
Finasteride/ Proscar
Class: type 2 5-a-reductive inhibitor
MOA: decs DHT conversion, anti-androgen if
Indic: BPH, male pattern baldness, prostate CA
SE: dec libido, ED, impotency, depression, breast tenderness, breast swelling
PREGNANT FEMALES SHOULD NOT HANDLE
Leuprolide/ Lupron
Anti- androgenic, anti-estrogen if
Indic: prostate ca, precocious puberty, endometriosis, uterine fibroids, some IVF protocols
GnRH synthetic analog, interrupts T and E2 production
SE: dec libido, impotence, N/V, hot flashes, night sweats, arthralgias, myalgias, osteoporosis
Clomiphene/ Clomid
Class: SERM
Indic: infertility, amenorrhea
MOA: binds estrogen receptor sites –> inc GnRH –> inc LH, FSH –> ovulation stimulation
SE: multiple gestations, vaginal dryness, anxiety, hot flashes
Usual etiology for primary vs secondary vs tertiary hypothyroidism
Primary: autoimmune thyroiditis, iodine deficiency, malnutrition, surgery/ ablation
Secondary: pituitary dysfunction
Tertiary: hypothalamic dysfunction
1 grain equivalent doses for
Armor thyroid
Synthroid
Cytomel
1g= 60mg Armour Thyroid= 100mcg of T4 (Synthroid)= 25mcg of T3 (Cytomel)
Mifepristone/ Mifeprex
synthetic steroid, abortifacient within first 2 mo of Pgx
MOA: progestin antagonist, decreases hCG
85% effective in abortion within the first trimester
often used with Cytotec (prostaglandin E1 analog)
SE: abd pain, cramping, vag bleeding for 9-16 days, N/V, diarrhea, dizziness, fatigue, fever, excessive uterine bleeding
CI: IUD, ectopic pregnancy, Prednisone Tx, hemorrhagic d/o, anticoagulation Tx
Morning after pill
1 dose 1.5mg Levonorgestrel (progestin)
or 2 doses 750microgm q12hrs
Prevents implantation, can obtain same effect by taking multiple OCPs
OR
Ulipristal acetate (Ella)
Class: SPRM
given within 5 days of unprotected sex, inhibits ovulation
Skyla
IUD with 13.5mg Levonorgestrel at implantation
14 mcg/day released
FDA approves 3yrs continued use
Liletta
IUD with 52mg Levonorgestrel
20mcg/day released
5yrs continued use approved
Mirena
IUD with 52mg Levonorgestrel
20mcg/day released
5yrs continued use approved
Paragard
copper, non-hormonal IUD
MOA: impairs sperm mobility, ongoing inflammation decreases implantation
approved for 10 years
Nuvaring
Low dose progestin and E2 release
inserted for 3wks, then removed for 2wk for withdrawal bleed.
decreased efficacy if removed for 3 hours. If removed for 3+ hours, use back-up contraception for 7 days.
SE: vaginitis, HA, leucorrhea, nausea, weight gain
CI in Hx of blood clots or in pt at inc risk of clotting
Ortho Evra
transdermal contraceptive patch
inner adhesive layer, norelgestromin and ethanol estradiol middle layer, outer protective layer
applied week for 3 weeks
if patch detaches, replace w/in 48 hours with no effect on contraceptive efficacy.
2x risk of blood clots compared to oral contraception dt higher E2 exposure!
Implantable Contraceptives
Levonorgestrel (Norplant) no longer available
Implanon (also a progestin implant) approved for up to 3 years, then must be removed
Medroxyprogesterone acetate/ Depro-provera IM
150mg aqueous suspension
required 4x per year to maintain contraceptive efficacy
high dose progesterone inhibits follicular development, decs GnRH —> dec FSH, LH
decreased risk of endometrial Ca
SE: irregular menses, abd discomfort, weight changes, HA2yrs due to osteoporosis risk**
Drospirenone
Synthetic progestin (Yaz/Yasmin) closest pharmacology to natural progesterone, non-androgenic, a-mineralocorticoid properties
6-7x the risk of thromboembolism to placebo
2x the risk of thromboembolism to levonorgestrel
What drugs can interact with BCPs/ Oral contraceptives?
Penicillin, amoxicillin, tetracycline, cephalosporins, sulfa drugs, seizure drugs,
St Johns wort!
What is the most commonly used oral contraceptive formulation?
What is the efficacy?
containing both estrogen (prevents ovulation) and progestin (prevents implantation)
MC estrogen: ethanol estradiol
MC progestin: norgestrel
~97-98% effective
Medroxyprogesterone/ Provera
Class: synthetic progesteron variant
Indic: contraceptive, HRT
Progestins were added to Premarin/HRT in order to:
prevent endometrial hyperplasia
Premarin
Conjugated estrogen (estrone, equillon)
Indic: P/Tx osteoporosis, post-menopause Sxs
MOA: alters gene expression
PO/topical creams available
progesterone should be added in any female without a Hx of hysterectomy
SE: vaginal bleeding, breast tenderness, increased DVT risk, inc atherosclerosis, CVD, increased risk of uterine, breast Ca, palpitations, fever, hives, SOB, weight gain
CI: Hx of DVT, thromboembolism, Breast/Uterine/Ovarian Ca
BiEst/ TriEst
Bioidentical Hormones, PO and topical applications
BiEst: 80:20 Estriol: Estradiol
TriEst: 80:10:10 Estriol:Estradiol:Estrone
Some Pros/Cons of HRT (estrogen only)
PROS: reduced vasoconstrictive events (hot flashes, night sweats, etc). Prevention/Tx of postmenopausal vaginal atrophy, increased sleep quality, dec bone resorption, osteoporosis prevention
CONS: increased stroke risk, blood clot risk, ovarian Ca, endometrial Ca, breast Ca
[Note: Estrogen and progesterone formulations have an increased risk of DVT/PE/Stroke/Breast Ca but a decreased risk of Fx, colorectal Ca relative to estrogen only formulations]
Hypoglycemia Tx
Glucagon
stimulates glucagon receptors –> breakdown of hepatic glycogen
made from recombinant DNA
IV/IM/SQ 1mg doses
Insulin Side Effects
weight gain, hypoglycemia, seizures, coma, death, hypokalemia, fibrotic injection sites, musc/fat atrophy at injection site
Long Acting Insulin Therapy onset/peak/duration
Glargine (Lantus)
Onset: 4-6 hours
Peak: none
Duration: 24 hours
intermediate acting insulin therapy onset/peak/duration timing
NPH (humulin N)
Onset: 1-3 hours
Peak: 6-10 hours
Duration: 10-18 hours
Short acting insulin therapy onset/peak/duration timing
Regular/ Humulin R
Onset: 0.5-1 hour
Peak: 2-4 hour
Duration 4-12 hours
Rapid acting insulin therapy onset/peak/duration timing
SQ/IM/IV only
Lispro/Aspart
Humulog/Novalog
Onset:
Exubera
nasal insulin
withdrawn in 2007 dt lack of acceptance by the market
Insulin MOA overview
anabolic hormone that promotes energy storage, stimulates glucose movement into cells, activates gene transcription
–> increased cell growth and differentiation
Promotes: glycogen productions, FA synthesis, Triglyceride storage
Inhibits: hepatic ketogenesis, gluconeogenesis, glycogenesis
Dr. Miller preferences for DM treatment
newer drugs are no more effective, no safer, are more expensive than older Rxs
Stick to metformin and sulfonylureas
metformin alone is 1st choice
Troglitazone (Rezulin)
Class: TZD/ Glitazone
succesful in DB-RCT studies, but found lethal SEs later.
removed from market in 2000
DM Diagnostic Criteria
Fasting glucose >126mg/dl OR Non-fasting glucose >200mg/dl in patient with Sxs of DM OR OGTT >200mg/dl at 2 hours postprandial
Ipriflavone
synthetic isoflavone
may conserve bone loss but evidence is conflicting
Types of phytoestrogens and food sources
Isoflavones (genistein, diadzein, glyceitein, equol, eg): from soy beans, chickpeas, legumes
Lignans (enterolactone, enterodiol, eg): oilseeds, flaxseeds, cereal bran, legumes, alcohol
Coumestrans (coumestrol, eg): alfalfa, clover
Lovastatin (Mevacor)
Simvastatin (Zocor)
HMG-CoA reductase inhibitors (statins)
may decrease risk of hip fracture, increase BMD but not confirmed
Estrogen/ HRT for osteoporosis
reduces bone loss, incs BMD, dec risk fx
Indic: prevention of osteoporosis in females
PO/patch 0.625 mg/day
E2+P decreases risk of endometrial Ca (Prempro)
SE: vaginal bleeding, breast tenderness, venous blog clots, inc risk gall bladder dz
Premarin: inc risk stroke
Prempro: inc risk stroke, MI, Breast Ca
*Transdermal E2 does not affect clotting!
Risk Factors for osteoporosis
Gender Age Size Ethnicity Family Hx Diet low in Ca, Vit D Sex hormones (estrogen) inactive lifestyle smoking, alcohol use glucocorticoid, anticonvulsant meds
Magnesium supplementation
300-1000 mg/day
to help minimize bone loss with concurrent Ca/D supplementation
SE: diarrhea at high doses
Vitamin D for osteoporosis
increases absorption of Ca in GI
70yo: 800 IU or higher
Calcitriol/Rocaltrol: Rx D Derivative to inc bone mass, dec fx
SE: elevated serum Ca- requires frequent monitoring
Calcium supplementation
50yo: 1200-1500 mg qd
Breastfeeding: 2000 mg qd
Ca citrate better absorbed that other salts
Ca from oyster shells may have lead contamination
effects of dietary Ca unclear (may increase risk?)
may not provide benefit in patients with Hx of osteoporosis related fx already
Strontium supplementation
absorbed as Ca, increases osteoblastic activity
Protos/ Strontium Ranelate is available in Europe
may dec risk vertebral fx in postmenopausal females
500mg-1000mg qd in existing osteoporosis
SE: generally well tolerated, mild diarrhea/GI upset
> 2gm may increase risk of fx- use caution!!
Radioactive iodine (131 I)
Radioactive Iodine Ablation (CATEGORY X)
Indic: definitive hyperthyroid Tx, Thyroid Ca
PO, radioactivity gone in 3-5 days (but postpone pregnancy 6-12 months)
thyroid cell destruction goes on the wks
SE: minimal systemic SEs, tenderness, swelling, N/V, bone marrow depression, acute leukemia possible, decreased sperm count (consider sperm banking)
patient needs to be euthyroid prior to Tx
no evidence of increased risk of malignancy
lifelong T3/T4 supplementation required after procedure
Iodine/ SSKI
Class: elemental Iodine
Indications: hyperthyroidism, thyroid storm
MOA: large 1 dose inhibits thyroxine release
PO/IV
SE: rash, fever, 2-3 wks of benefit
Propranolol/ Inderal
Class: Non-selective B-blocker
Indic: adrenergic block, hyperthyroidism, tachycardia, anxiety, thyroid storm
MOA: B1/B2 block
PO/IV
SE: fatigue, sedation, impotency, depression
Propylthiouracil (PTU)
Class: Thionamide
CATEGORY D (safer than methimazole)
Indic: hyperthyroidism (Graves), used to control Sxs before surgery/ablation
MOA: inhibits conversion of inorganic to organic
Blocks peripheral T3-T4 conversion
PO, qd
NOT used for thyroid storm
SE: hypothyroidism, rash, edema, arthralgia, agranulocytosis
Methimazole/ Tapazole
Class: Thionamide
Indic: hyperthyroidism, Graves, may control Sxs until thyroid ablation
MOA: inhibits transformation to organic iodine –> blocked thyroxine, dec T3/T4 formation
PO qd dosing, NOT for thyroid storm
CI IN PREGNANCY AND LONG-TERM USE
SE: hypothyroidism, rash, edema, arthralgia, agranulocytosis
Hyperthyroidism common causes and Sxs:
autoimmune (Graves), thyroiditis, thyroiditis factitia
Sis: nervousness, tachycardia, weight loss, heat intolerance, sweating, diarrhea, generalized weakness, increased risk of osteoporosis, CVD, goiter, exophthalmos, pretrial myxedema
Liothyronine/ Cytomel
synthetic T3
Indications: hypothyroidism not improving with T4, myxedema coma, Wilsons syndrome
PO- 100% absorption, rapid absorption, half life of several hours
SE: higher peaks/troughs and high CVD/Osteoporosis risk
Thyroid USP/ Armour
Porcine desiccated thyroid gland
0.2% Iodine standardized, PO
60mg= 1 grain= 38mcg T4/ 9mcg T3
SE: angina, palpitations, tachycardia, heat intolerance, anxiety, may accelerate CVD/osteoporosis
Levothyroxine/ Synthroid
Synthetic T4
Indic: hypothyroidism, TSH suppression with thyroid nodules and thyroid cancer
PO/IV, once daily dosing, ramp up dose slowly, reduce if pt complains of angina
SE: palpitations, tachycardia, heat intolerance, anxiety, may accelerate CVD/osteoporosis in the long term
replace cortisol first in Addisons before replacing thyroid
Clinical Findings in Hypothyroidism
fatigue, generalized weakness, cold intolerance, constipation, thinning hair, bradycardia, poor concentration
respiratory depression, hypothermia, coma (myxedema coma), death
Thyroid Storm Sxs and Tx
Sxs: high fever, irritability, delirium, vomiting, diarrhea, dehydration, hypotension, vascular collapse, coma, death
Tx: Beta blockers, IV-Iodine to “stun” thyroid
*(can occur in septic hyperthyroid pts)
