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Flashcards in Pharmacology Deck (42)
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What do sufonylureas do in the treatment of Type II diabetes?

close K+ channel in beta-cell membrane so cell depolarizes, leading to Ca2+ influx and insulin release


Name the sulfonylureas. What are they used to treat? Side effects?

Used for Type II diabetes only (useless in Type I due to necessity for islet function)

1st generation:
- tolbutamide
- chlorpropamide
Side effects are disulfiram-like effects

2nd generation:
- glyburide
- glimepiride
- glipizide
Side effects are hypoglycemia


What do sulfonylureas do to insulin, C-peptide, and pro-insulin levels? Mechanism?

increase in insulin, C-peptide, pro-insulin! due to release of endogenous insulin

close K+ channel in beta-cell membrane so cell depolarizes
Ca2+ influx triggers insulin release


What is the mechanism of DDAVP administered to pt with prolonged bleeding after a tooth extraction?

increase in vWF release from endothelial cells

vWF augments platelet binding to the endothelial cells at the initial injury, helping in formation of the initial platelet plug.


What are the major side effects of metformin? What is the mechanism?

GI upset and lactic acidosis (contraindicated in renal failure; or in any situation that could precipitate lactic acidosis like liver dysfunction, CHF, alcoholism, sepsis)

exact mechanism unknown, but:
- increases glycolysis
- decreases gluconeogenesis
- decreasing GI glucose absorption
- increasing peripheral glucose uptake/insulin sensitivity


What is flutamide and what is it used for? Side effects?

nonsteroidal competitive inhibitor of androgens at the testosterone receptor
(competes with testosterone and DHT for their receptors in target cells)

used for prostate carcinoma (alone with continuous leuprolide/GnRH analog)
prevention of androgen-receptor binding blocks stimulatory effect of androgens on the primary tumor and metastases, reducing size.
Flutamide alone causes a gradual increase in blood testosterone levels due to negative feedback - the effect is reduced by simultaneous administration of GnRH agonists.

side effects: androgen depletion (gynecomastia, impotence, hot flashes)


Name some GnRH analogs - what are they used to treat?

goserelin, nafarelin, histrelin

pulsatile = GnRH agonist
used to treat infertility

continuous = GnRH antagonist
prostate cancer (with flutamide), uterine fibroids, precocious puberty


What is anastrozole and what is it used for? Mechanism?

nonsteroidal aromatase inhibitor used in postmenopausal women with breast cancer

effective treatment in postmenopausal women with breast cancer in whom the greatest source of estrogen is the conversion of androstenedione (produced in adrenals) to ESTRONE in the liver, muscle, and fat (through aromatization).


What drugs prevent hirsutism in the context of polycystic ovarian syndrome? Side effects?

Ketoconazole and spironolactone

- inhibits steroid synthesis (inhibits 17,20-desmolase)

- inhibits steroid binding (androgen-receptor complex on target)
- inhibits 17a-hydroxylase and 17,20-desmolase

Side effects include gynecomastia and amenorrhea


What is finasteride? What is it used for?

a 5alpha-reductase inhibitor (antiandrogen that decreases conversion of testosterone to DHT)

Used in benign prostatic hyperplasia; also promotes hair growth and is thus used to treat male-pattern baldness


Acute effects of prednisone on cell counts?

increase neutrophil count (due to "demargination" of neutrophils previously attached to vessel wall coming into the circulation)

decrease in lymphocyte, monocyte, basophil, and eosinophil counts


Name the glucocorticoids. Used for?

Fludrocortisone (mineralocorticoid and glucocorticoid activity)

Used for Addison disease, inflammation, immune suppression, asthma


What is the mechanism of methimazole and propylthiouracil? What are they used for?

Both block thyroid peroxidase.
PTU also blocks 5'-deiodinase, which decreases Peripheral conversion of T4 to T3.

Used for Hyperthyroidism
PTU also used in Pregnancy (methimazole is a potential teratogen).


How do ions like perchlorate and thiocyanate work to treat hyperthyroidism?

compete against iodide for entry into the thyroid gland (via the energy-dependent Na-I symporter), resulting in decreased iodide uptake by the thyroid follicular cells

TSH on the other hand positively upregulates iodide uptake.


What drugs are used to treat the acute sympathetic symptoms of thyrotoxicosis (tachycardia, hypertension, tremor)?

Beta-adrenergic antagonists like propranolol (used to treat acute symptoms in preparation for thyroid surgery)


What are the glitazones/thiazolidinediones (TZDs)? What is it used for? Side effects?


increase insulin sensitivity in peripheral tissue
binds to PPAR-gamma nuclear transcription regulator (of genes involved in glucose and lipid metabolism)

used for Type 2 DM as a monotherapy or in combination with other agents

Side effects: weight gain, edema; hepatotoxicity, heart failure


What does the PPAR-gamma transcription factor regulate? What drugs act on this TF? Outcomes?

Fatty acid storage and glucose metabolism.

TZDs like pioglitazone and rosiglitazone bind to/activate PPAR-gamma to increase insulin sensitivty.

Increases levels of adiponectin - a cytokine secreted by fate tissue that is low in Type 2 DM and is one of the ways that PPAR decreases insulin resistance.


Side effects of TZDs?

hepatotoxicity - periodic liver function tests recommended
fluid retention - can exacerbate CHF in pts with cardiac dysfunction


What synthesizes dihydrotestosterone?

5-alpha-reductase (from testosterone)


Difference between hirsutism and virilization?

Hirsutism - terminal hair growth in a male-like pattern in a female

Virilization - hirsutism in association with clitoromegaly, increased muscle mass, acne, increased libido, and voice deepening


What is idiopathic hirsutism? What is use to treat this?

Idiopathic hirsutism develops due to increased conversion of testosterone into DHT by 5-a-reductase or due to higher sensitivity of hair follicles to DHT
(vs. the other cause of hirsutism = increased testosterone production seen in syndromes and tumors)

Treatment is antiandrogens like spironolactone, flutamide, and finasteride.


What is mifrepristone (RU-486)? What is it used for? Side effects?

competitive inhibitor of progestins at progesterone receptors

used for termination of pregnancy and administered with misoprostol (PGE1)

Heavy bleeding, GI effects, abdominal pain


What is clomiphene? Used for?

antagonist of estrogen receptors in hypothalamus - blocks negative feedback to increase GnRH, FSH, LH levels

used for treatment of fertility, especially due to anovulation (e.g., PCOS)


What is danazol? Uses and side effects?

Synthetic androgen that acts as a partial agonist at androgen receptors

Used for endometriosis and hereditary angioedema

Side effects: hirsutism, masculinization, fluid retention, weight gain


Treatment for prostate cancer? What changes in testosterone and DHT occur?

Leuprolide (continuous) - GnRH analog with antagonist properties when used continuous (use along with flutamide/competitive testosterone receptor inhibitor)

Initial increase in testosterone and DHT levels, then a decrease!
brief period of initial stimulation = "start up flare"


What type of insulin is used for postprandial glucose control? Name them.

Rapid acting insulin used for postprandial control:
- lispro
- aspart
- glulisine

Given 3x a day with meals - rapid onset of action with peak effects (45-75min) coinciding with peak postprandial hyperglycemia


What are the best basal long-acting insulins?

Glargine and Detemir
administered as once-a-day shots


What is the medication of choice for the treatment of gestational diabetes mellitus?

for those pts in whom diet and light exercise have failed to control blood glucose levels


Mechanism of tamoxifen? Side effects and use?

selective estrogen receptor modulator (SERM)
Antagonist at breast tissue
Agonist at uterus and bone

Side effects: endometrial hyperplasia/cancer, thromboembolic events

Used to treat and prevent recurrence of ER+ breast cancer


Mechanism of raloxifene? Side effects and use?

selective estrogen receptor modulator (SERM)
Agonist on bone
Antagonist on uterus

Side effects: increased risk of thromboembolic events

Used for osteoporosis (decreases resorption of bone)