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104 Cards in this Set
- Front
- Back
Specifically cytotoxic to the adrenal cortex.
Generally restricted to use in adrenal carcinoma Selective for mets |
Mitotane
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This enzyme inhibitor shuts down 11-beta hydroxylase.
Has some function to diagnose primary and secondary adrenal dysfunction |
Metyrapone-adrenal enzyme inhibitor
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This enzyme inhibitor blocks cholesterol side chain cleavage--the rate limiting step in the synthesis of ALL steroid hormones
Not selective for adrenal gland Has been used as an adjunct in the treatment of breast cancer |
Aminoglutethimide
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Nonspecific inhibition of all steroidogenic CYP450s--as well as hepatic 450s.
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Ketoconazole
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Inhibits 11-beta hydroxlase and aldosterone synthase at high doses
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Spironolactone
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This corticosteroid receptor antagonist may have utility in the management of neoplasms that are glucocorticoid receptor positive.
Good for glucocorticoid-excessive situations Can block progestrone receptor at much lower concentrations |
RU 486 (Mifepristone)
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Aldosterone receptor antagonist that can also be used as a potassium sparring diuretic
At high doses, can block the androgen receptor |
Spironolactone
Eplerenone |
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Testosterone propionate
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Androgenic ester
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Testosterone cypionate
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Androgenic ester
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testosterone enanthate
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androgenic ester
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fluoxymesterone
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androgenic alkyl
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methyltestosterone
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androgenic alkyl
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oxymetholon
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anabolic steroid
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oxandrolone
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anabolic steroid
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nadrolone
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anabolic steroid
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stanozolol
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anabolic steroid
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calusterone
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anabolic steroid
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Testosterone converted into..
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17 Beta-estradiol
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Androstenedione converted into...
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estrone
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Nine Therapeutic Applications of Androgens/anabolic steroids
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1) hypogonadism
2) infertility 3) osteoporosis 4) mild anemia 5) breast carcinoma in women 6) anabolic disorders/debilitating disorders 7) promotion of athletic performance 8) treatment of short stature 9) heriditary angioedema |
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Adverse effects of special consideration in HRT in older men (6)
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1) fluid retention
2) gynecomastia 3) sleep apnea 4) increased erythropoiesis 5) C/V disease 6) prostate |
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Aminoglutethimide actions
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inhibits testosterone synthesis
nonselective works thru cholesterol side chain cleavage |
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Cyanoketone
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inhibitor of testosterone synthesis
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Trilostane
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inhibitor of testosterone synthesis
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Ketoconazole
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non-selective inhibitor of cytochrome P450
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Finasteride actions and mechs
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-inhibitor of activation
-androgen antagonist -5-alpha reductase inhibitor -offers the selectivity of treating DHT dependent abnormalities such as prostatic carcinoma, acne, hirsutism, baldness, without affecting testosterone driven functions (sex differntiation, sex drive, skeletal muscle growth) |
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Name the two Androgen Receptor Antagonist
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1. flutamide
2. bicalutamide |
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Flutamide actions and mechs
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-non steroidal
-devoid of any intrinsic androgenic activity -limited usefulness in men due to compensatory increases in LH and testosterone -useful in inhibiting adrenal androgens in men on GnRH therapy (prostate cancer), women, and castrate men. -Blocks initial disease flare. |
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Bicalutamide
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-non steroidal
-devoid of any intrinsic androgenic activity -limited usefulness in men due to compensatory increases in LH and testosterone -useful in inhibiting adrenal androgens in men on GnRH therapy (prostate cancer), women, and castrate men. -Blocks initial disease flare. |
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Cyproterone acetate
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-Androgen receptor antagonist
-actually a progestin that inhibits gonadotropin secretion -a MALE CONTRACEPTIVE holy shit -limited clinical use to sex offenders -orphan drug status for hirsutism that is really, really nasty |
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Name the "mixed inhibitor" of androgen antagonism
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spironolactone. It inhibits steroidogenic P450, and it is a weak androgen receptor antagonist
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When do you give glucocorticoids?
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1) hypercalcemia of sarcoidosis
2) To increase renal calcium excretion 3) To decrease the expression of renal vitamin D 1-alpha hydroxylase |
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When do you NOT give glucocorticoids?
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1) primary hypercalcemia/hyperparathyroidism
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Ergocalciferol
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Pure vitamin D2.
give when PTH and 1-a-hydroxylase are intact |
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Cholecalciferol
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Pure Vitamin D3
Calderol Give when PTH and 1-a-hydroxylase are intact |
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Calcitrol
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pure 1, 25 dihydroxyvitamin D3.
Use if patient has 1a-hydroxylase deficiency OR rapid fluctuations |
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Dihydrotachysterol
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Reduced Vitamin D2.
Use if 1a-hydroxylase deficient Only needs -OH added at C25 for activation |
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Doxercalciferol
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1a-hydroxyvitamin D2.
Use if 1a-hydroxylase deficient Only needs -OH added at C25 to be active |
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Name the analogs of Vit D that suppress PTH (2)
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1) 22-oxacalcitriol
2) paricalcitol |
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22-oxacalcitriol
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1, 25 dihydroxy-22-O-Vit D3.
Reduces PTH levels while having little activity in the GI tract and bone No hypercalcemia, no hyperphosphatemia For use in Primary Hyperparathyroidism ( cancer) and Secondary Hyperparathyroidism associated with chronic renal failure |
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Paricalcitol
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19-nor dihydroxyvitamin D2
Reduces PTH levels while having little activity in the GI tract and bone No hypercalcemia, no hyperphosphatemia For use in Primary Hyperparathyroidism ( cancer) and Secondary Hyperparathyroidism associated with chronic renal failure |
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Cinacalcet
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Calcium sensor mimetic
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Cinacalcet uses
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1) hypercalcemia of parathyroid cancer
2) hyperparathyroidism of renal failure does not effect bone density more effective in primary than secondary HPT. start low and titrate upwards to lower risk of hypocalcemia |
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Bisphosphonates all end with...
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-dronate
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Bisphosphonates mech and actions
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1)Potency AND selectivity for osteoclasts increase
2) bone toxicity decreases, for each consecutive generation 3) increases bone density correlated to decreased risk of atraumatic fractures only with 2nd and 3rd generations 4) decreases the recruitment of osteoclasts |
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Hypocalcemic agents and calcitonin are used in combination with what else?
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1. dietary restriction of calcium
2. volume expansion 3. + or - diuretic |
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Most likely cause of hypophosphatemia?
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Aluminum or carbonate containing antiacid
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Hyperphospatemia treatment?
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sevelamer--a phosphate binding polymer gel
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Antiresorptive agents in Post-Menopausal Osteoporosis (7)
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1. calcium
2. thiazide 3. estrogen 4. SERM (raloxifene) 5. Vit D 6. Calcitonin 7. Biphosphonate |
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Bone-Forming Agents (6)
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1. fluoride
2. androgens 3. PTH cyclic administration 4. Statins 5. GH 6 IGF-1 |
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Thyroid Peroxidase functions
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1. activates Iodide
2. Catalyzes iodination of tyrosyl residues of thyroglobulin 3. Condensation of monoiodinated and diiodinated tyrosine to T3 and T4. |
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T4 is activated by what enzyme and where?
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Type 1 iodothyronine 5' deiodinase ( 5'D-I) in liver
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Sodium levothyroxine preparation
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synthetic T4
Relative dosage: 4 (100 micrograms) |
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Sodium liothyronine
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synthetic T3.
Faster onset shorter duration of action Relative dose: 1 (25 micrograms) Used when faster onset is required, ie myxedema coma. |
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Thyroid drug with increased risk of cardiotoxicity?
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Liothyronine
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Liotrix
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4:1 mix of T4:T3.
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Antithyroid drugs (2)
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Methimazole
PTU (prototype) |
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Can cause fatal aplastic anemia
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Perchlorate
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Lithium mechanism
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inhibits thyroid secretion, but thyroid generally escapes.
Risk of interfering with calcium metabolism |
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Primary action of iodide
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Inhibits T4 and T3 release.
simple dose causes an acute, transient inhibition of hormone secretion. |
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Indications for iodide
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1. preop for thyroidectomy
2. In conjunction with PTU or methimazole |
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Untoward rxns of iodide
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1. hypersensitivity
2. iodism |
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131 I (radioactive iodide)
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emits beta and gamma rays. Provides definitive treatment. Beta particles are absorbed, leading to necrosis.
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123 I (radioactive iodide)
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used for thyroid scans
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CI of radioactive iodide
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1. pregnancy
2. less than 25 of 30 y/o due to risk of inducing cancer 3. coexisting, severe opthalmopathy |
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High doses of this drug can inhibit hepatic 5'-D I
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Propranolol
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Glucocorticoid effects on hyperthyroidism.
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Decrease peripheral conversion of T4 to T3.
Increase conversion of T4 to rT3. Inhibits TSH secretion Inhibits iodide uptake and T4/T3 release. |
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Cholestyramine
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Bile acid resin that will bind thyroid hormone conjugates secreted in bile and prevent their enterohepatic recycling
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Uses of iodinated radiocontrast media
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1. reduction of T4
2. Inhibits 5'-DI, thus limiting peripheral conversion of T4 to T3. |
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PTU mechanism of action
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accumlates in the thyroid gland and IRREVERSIBLY inhibits the peroxidase enzyme.
Can cross the placenta inhibits the peripheral conversion of T4 to T3. |
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Methimazole mechanism of action
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accumlates in the thyroid gland and IRREVERSIBLY inhibits the peroxidase enzyme.
works faster than PTU Can cross the placenta, this one more so than PTU |
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Side effects of PTU and Methimazole
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1. Mild rash
2. Nausea, headache, pain/stiffness in joints 3. mild, transient leukopenia is common in children 4. agranulocytosis/leukopenia |
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Name the Rapid Acting Insulins (3)
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1. Lispro
2. Aspart 3. Glulisine LAG |
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Name the short-acting insulin
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Regular Insulin (Zinc)
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Name the intermediate acting Insulin
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Isophane Insulin (NPH)
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Name the 2 long acting insulins
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1. insulin Glargine
2. Insulin Detemir |
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Other forms of insulin
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Inhaled insulin
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Rapid acting insulin characteristics
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1. rapid onset, short duration
2. used to control prandial glucose 3. taken immediately before mealtime 4. Risk of hypoglycemia 5. Requires a prescription |
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Short acting insulin (regular zinc) characteristics.
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1. complex, concentration dependent injection kinetics
2. taken 30-45 minutes before meal |
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Intermediate acting insulins (Isophane/NPH) characteristics
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1. protamine causes delayed absorption
2. 6 insulin molecules, 1 protamine |
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Long acting insulins- Insulin glargine characterisitcs
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1. Two Arg residues makes this insoluable at neutral pH.
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Long acting insulins-Insulin detemir
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1. myrisitic acid moiety increases self-aggregation and binding to albumin
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Inhaled Insulin (exubera) characteristics
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Not used for background coverage
can cause pulmonary fibrosis |
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Name the insulin secretagogues, First Generation, sulfonylureas
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1. Tolbutamide
2. Cholorproamide 3. Tolazamide |
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Name the insulin secretagogues, Second Gen, Sulfonyureas
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1. Glyburide
2. Glipizide 3. Glimperidide |
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Name the insulin secretagogues, Meglitinides
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1. Repaglinide
2. nateglinide |
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Mechanism of sulfonyureas
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Increase insulin release from the pancreas by binding to a high affinity receptor on B-cells that is associated wtih an ATP-sensitive K+ channel. Inhibits K+ efflux leading to depolarization. Ca++ influx occurs and insulin is released
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Tolbutamide
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1st gen sulfonyureas. Inhibits K+ efflux, leading to Ca++ influx and insulin release
-well absorbed, short mech of action, rapidly metabolized by liver Treats DMII |
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Chlorpropamide
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1st gen sulfonyureas. Inhibits K+ efflux, leading to Ca++ influx and insulin release
-long half-life, slow metabolism |
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Tolazamide
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1st gen sulfonyureas. Inhibits K+ efflux, leading to Ca++ influx and insulin release
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Glimepiride
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2nd gen sulfonyureas. Much better at reducing glucose than first gen, but cause problems with hypoglycemia.
Not recommended in the elderly, those with hepatic or C/V disease Most potent and longest duration of action |
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Glyburide
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2nd gen sulfonyureas. Much better at reducing glucose than first gen, but cause problems with hypoglycemia.
Not recommended in the elderly, those with hepatic or C/V disease Less potent with fewer side effects |
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Glipizide
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2nd gen sulfonyureas. Much better at reducing glucose than first gen, but cause problems with hypoglycemia.
Not recommended in the elderly, those with hepatic or C/V disease Short half life, more potent |
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Repaglinide
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2nd gen sulfonyurea.
Fast onset of action |
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Nateglinide
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2nd gen sulfonyurea
D-phenylalanine derivative Amplifies insulin secretion in response to glucose but has little effect in the prescence of normal glycemic levels. Lowest incidence of hypoglycemia. Safe in individuals with renal dysfunction. |
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Metformin (biguanide)
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Euglycemic agent
Works for Type 1 and Type 2 DM No hypoglycemia Insulin-sensitizer No weight gain May prevent onset of DMII |
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4 mechanisms of action of Metformin
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1. Reduces hepatic gluconeogenesis
2. Slows glucose absorption from GI 3. Stimulates glycolysis in tissues 4. Reduces plasma glucagon levels |
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Adverse effects of metformin
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1. GI
2. Inhibits Vit B12 absorption |
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Thiazolidinediones (2)
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Pioglitazone
Rosiglitazone |
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Thiazolidinedione mech of action
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1. Decrease insulin resistance by altering genes controlling glucose and lipid metabolism and adipocyte differentiation.
2. Ligands of PPAR gamma |
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Pioglitazone
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PPAR alpha and PPAR-gamma.
Greater trigylceride lowering capacity than its counterpart can alter other drugs metabolism |
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Rosiglitazone
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Does not alter metabolism of other drugs.
Increased risk of C/V disease |
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Alpha-Glucosidase Inhibitors (2)
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Acarbose
Miglitol |
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Alph-Glucosidas Inhbitors mechanisms
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Disrupt transport of monosaccharides out of the intestine by competitively inhibiting the breakdown of starches, oligosaccharides, and disaccharides in the intestine.
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