GI Pharmacology-A Flashcards
Glyburide: Drug Class
Sulfonylurea
Sulfonylureas: Mechanism of action
They bind to specific receptors on the insulin producing pancreatic beta cells and close a certain K+ channel. This causes depolarization and triggers an increase of intracellular calcium which, in turn, augments the release of granules of insulin
Name the three Sulfonylureas
Glipizide, Glyburide, and Glimepiride
Glipizide: Drug Class
Sulfonylurea
Sulfonylureas: Side Effects
Dominant adverse effect is hypoglycemia (risk factors are age, poor nutrition, and renal failure). It also causes weight gain and elevation of triglycerides & LDL cholesterol (further aggravating coronary risk factors of DM II)
Glimepiride: Drug Class
Sulfonylurea
Repaglinide: Drug Class
Glinide
Glinides: Side Effects
Dominant adverse effect is hypoglycemia
Glinides: Mechanism of action
They bind to specific receptors on the insulin producing pancreatic beta cells and close a certain K+ channel. This causes depolarization and triggers an increase of intracellular calcium which, in turn, augments the release of granules of insulin
Nateglinide: Drug Class
Glinide
Name the two Glinides
Repaglinide and Nateglinide
Metformin: Drug Class
Biguanide
Metformin: Mechanism of action
It enhances insulin’s suppression of gluconeogenesis by the liver (thus decreasing hepatic glucose output), and it enhances glucose uptake and utilization primarily in skeletal muscle
Which Diabetes drug(s) reduce(s) triglycerides and LDL cholesterol levels
Metformin
Metformin: Side Effects
Early (Transient): Nausea, abdominal discomfort, and diarrhea. Late: Lactic acidosis (rare but increased in renal failure, liver failure, CHF or shock and has 50% mortality rate)
Metformin is contraindicated in what condition(s)
Renal failure, liver failure, CHF or shock
Pioglitazone: Drug Class
Thiazolidinedione
This drug class acts by activating PPARs (especially PPAR?) which, when activated, increases transcription of a number of specific genes (and decreases transcription of others). This all results in increased peripheral (muscle) sensitivity to glucose
Thiazolidinediones
Pioglitazone is the only remaining Thiazolidinedione on the market because
It does not cause hepatic and cardiac toxicity like troglitazone and rosiglitazone do respectively
This diabetes drug class takes 4-6 weeks to exert its affects on the patient
Thiazolidinediones
Which Diabetes drug(s) reduce(s) triglycerides and raise HDL cholesterol levels
Pioglitazone
Which diabetes drug(s) can cause fluid retention and thus are contraindicated in CHF
Pioglitazone
Acarbose: Drug Class
Alpha-Glucosidase Inhibitor
Name the two Alpha-Glucosidase Inhibitors
Acarbose and Miglitol
Which diabetes drug class will reduce post-prandial hyperglycemia
Alpha-Glucosidase Inhibitors
Miglitol: Drug Class
Alpha-Glucosidase Inhibitor
Alpha-Glucosidase Inhibitors: Mechanism of action
They inhibit Alpha-Glucosidase at the jejunal brush border, preventing it from cleaving oligosaccharides for rapid carbohydrate absorption. As a result, carbohydrates are absorbed more slowly
Alpha-Glucosidase Inhibitors: Side Effects
Abdominal discomfort, diarrhea, and flatulence (symptoms ameliorate or subside after 4-8 weeks). It can cause liver toxicity
Sitagliptin: Drug Class
Dipeptidyl-peptidase 4 (DPP4) Inhibitor
Dipeptidyl-peptidase 4 (DPP4) Inhibitors: Mechanism of action
They inhibit DPP4, an enzyme that breaks down GLP-1 and GIP. GLP-1 increases insulin secretion, decreases glucagon secretion, and delays gastric emptying (in a glucose dependent manner). Thus by inhibiting DPP4, GLP-1 levels increase and their function is enhanced
Saxagliptin: Drug Class
Dipeptidyl-peptidase 4 (DPP4) Inhibitor
Name the two Dipeptidyl-peptidase 4 (DPP4) Inhibitors
Sitagliptin, Saxagliptin
Methimazole: Drug Class and function
Anti-thyroid agent used to treat hyperthyroidism
Anti-thyroid agents: Mechanism of action
Inhibit thyroid peroxidase-mediated iodination of thyroglobulin to form T4 and T3 in thyroid gland. Propylthiouracil also partially inhibits the peripheral deiodination of T4 and T3
Anti-thyroid agents: Uses
Used to shrink the thyroid, decrease friability (ability to be broken into bits), and control until thyroidectomy. Rarely used chronically. Also used in Pts in whom iodine 131 is planned (methimazole is prefered)
Propylthiouracil: Drug Class and function
Anti-thyroid agent used to treat hyperthyroidism
Name the two Anti-thyroid agents
Methimazole and Propylthiouracil
Anti-thyroid agents: Side Effects
Agranulocytosis (manifests as sore throat and fever), hepatotoxicity, jaundice, and angioneurotic edema
Calcitriol: Drug Class and function
Bone mineral hormone that increases the level of calcium and phosphate in the blood
Calcitriol: Mechanism of action
It decreases kdney excretion of calcium and phosphate, increases calcium and phosphate absorption in GI tract, and increases calcium and phosphate resorption in bone
PTH: Drug Class and function
Bone mineral hormone that increases the level of calcium and decreases the level of phosphate in the blood
PTH: Mechanism of action
It decreases calcium excretion by the kidney, increases phosphate excretion by the kidney, increases calcium and phosphate resorption in bone, and increases the production of Vitamin D (Calcitriol) which increases calcium and phosphate absorption in GI tract
Calcitonin: Drug Class and function
Bone mineral hormone that decreases the level of calcium and phosphate in the blood
Calcitonin: Mechanism of action
It decreases calcium and phosphate resorption in the kidney, and inhibits bone osteoclasts thus reducing bone resorption of calcium and phosphate
Which tissue/organ produces Calcitonin
The thyroid
Calcium Chloride: Drug Class
Calcium mineral supplement
Calcium Chloride: Side Effects
It can act as an irritant by desiccating moist skin. Solid calcium chloride dissolves exothermically, and burns can result in the mouth and esophagus if it is ingested. Ingestion of concentrated solutions or solid products may cause gastrointestinal irritation or ulceration
Calcium gluconate: Side Effects
Nausea, constipation, upset stomach. Rapid intravenous injections of calcium gluconate may cause hypercalcaemia, which can result in vasodilation, cardiac arrhythmias, decreased blood pressure, and bradycardia. Extravasation of calcium gluconate can lead to cellulitis. Intramuscular injections may lead to local necrosis and abscess formation
Calcium Gluconate: Drug Class
Calcium mineral supplement
Calcium Gluconate: Uses
Used in the treatment of hypocalcemia and to counteract an overdose of magnesium sulfate
Alendronate: Drug Class
Bisphosphonate
Alendronate: Uses
Tx for Paget Dx (excessive breakdown and formation of bone). Most potent Bisphosphonate and used for osteoporosis in post-menopausal women
Ibandronate: Drug Class
Bisphosphonate
Pamindronate: Drug Class
Bisphosphonate
Pamindronate: Uses
Tx for Paget Dx (excessive breakdown and formation of bone).
Resendronate: Drug Class
Bisphosphonate
Which Bisphosphonates are available for weekly oral dosing regimens
Alendronate and Resendronate
Which Bisphosphonates are available for monthly oral dosing regimens
Ibandronate and Resendronate
Bisphosphonates: Mechanism of action
Inhibit the activity of osteoclasts
Bisphosphates: Side Effects
Significant esophageal and gastric irritation. Risk of bone fractures with chronic use.
Name the four Bisphosphates
Alendronate, Ibandronate, Pamindronate, Resendronate
Food interferes with absorption of which drug class
Bisphosphonates
Which Bisphosphonate is available for IV dosing every 3 months
Ibandronate
Raloxifene: Drug Class [and mechanism of action]
Selective Estrogen Receptor Modulator (SERM) [Inhibits nuclear binding of the estrogen receptor, decreasing secretion of stimulatory growth factor TGF-alpha and increasing inhibitory growth factor TGF-Beta, thus blocking estrogen stimulation of breast cancer cells. It has a static effect on Tumor cell growth]
Name the two Selective Estrogen Receptor Modulators (SERMs)
Raloxifene and Tamoxifen
How does Raloxifene differ from Tamoxifen
It has a better adverse event profile (lower risk of uterine cancer) but tamoxifen is superior in breast cancer risk reduction. I also can only be used in post-menpausal women
Tamoxifen: Drug Class [and mechanism of action]
Selective Estrogen Receptor Modulator (SERM) [Inhibits nuclear binding of the estrogen receptor, decreasing secretion of stimulatory growth factor TGF-alpha and increasing inhibitory growth factor TGF-Beta, thus blocking estrogen stimulation of breast cancer cells. It has a static effect on Tumor cell growth]
In what tissues does Tamoxifen act as an estrogen agonist and an estrogen antagonist
Agonist: Endometrium. Antagonist: Breast cancer cells and vaginal mucosa
Tamoxifen: Uses
Adjuvant Tx of breast cancer alone or following chemo in pre & post menopausal women (only hormonal therapy for premenopausal women), Tx of metastatic breast cancer, and prophylaxis in high risk women/women with ductal carcinoma in situ
Tamoxifen: Side Effects
Improves bone density, improves lipid profile, Hot flashes, nausea/vomiting, edema, thromboembolism, endometrial cancer (3x incidence), cataracts, vaginal discharge and bleeding
Tamoxifen should not be given concurrently with what
CYP2D6 converts Tamoxifen to the much more potent metabolite endoxifen. Tamoxifen should not be given concurrently with a potent CYP2D6 inhibitor
Anastrozole: Drug Class
Aromatase Inhibitor
Aromatase Inhibitor: Mechanism of action
Selectively Inhibits aromatase which converts androstenedione and testosterone to estrone and estradiol respectively
Name the three Aromatase Inhibitors
Anastrozole, Exemestane, and Letrozole
Exemestane: Drug Class
Aromatase Inhibitor
Aromatase Inhibitors: Uses
Tx of locally advanced or metastatic breast cancer (hormone receptor positive or unknown) in post menopausal women, Tx of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy, adjuvant Tx of early hormone receptor positive breast cancer in post menopausal women.
Why are Aromatase Inhibitors not used in premenopausal women
Because in premenopausal women, 95% of estrogen is produced by the ovary not by aromatase conversion
Letrozole: Drug Class
Aromatase Inhibitor
Which drug class is never given concurrently with chemotherapy (always given sequentially)
Aromatase Inhibitors
Aromatase Inhibitors: Side Effects
Fatigue, arthralgias/myalgias, osteoporosis/osteopenia, hot flashes, vaginal dryness.
Which Aromatase Inhibitor does not have a lower incidence of endometrial cancer and thromboembolic events compared with tamoxifen.
Letrozole
Which Aromatase Inhibitor may cause less bone turnover than the others
Exemsestane
Goserelin: Drug Class
Gonadotropin Releasing Hormone Agonist (synonymous with LHRH agonist)
Gonadotropin Releasing Hormone Agonists: Mechanism of Action
Inhibit the synthesis of sex steroids in both men and women: after initial surge, supresses LH, FSH, and subsequently testosterone (males & females) and estrogen (premenopausal females)
Which Gonadotropin Releasing Hormone Agonist can cause headache, vaginitis, and diaphoresis
Goserelin
Histrelin: Drug Class
Gonadotropin Releasing Hormone Agonist (synonymous with LHRH agonist)
Name the four Gonadotropin Releasing Hormone Agonists
Goserelin, Histrelin, Leuprolide, Triptorelin
Which Gonadotropin Releasing Hormone Agonist can cause urinary retention
Histrelin
Leuprolide: Drug Class
Gonadotropin Releasing Hormone Agonist (synonymous with LHRH agonist)
Gonadotropin Releasing Hormone Agonists: Side Effects
Initial tumor flare (lasts a week), Gynecomastia/breast tenderness, hot flashes, and longterm use can lead to osteoporosis (bisphosphonates can be used to help)
Gonadotropin Releasing Hormone Agonists are started with what in order to avoid tumor flare
An antiandrogenic agent
Triptorelin: Drug Class
Gonadotropin Releasing Hormone Agonist (synonymous with LHRH agonist)
Bicalutamide: Drug Class
Anti-androgenic Agent
Name the three traditional (Non-steroidal) Anti-androgenic Agents
Bicalutamide, Flutamide, and Nilutamide
What are the Uses of the traditional Anti-androgenic Agents (Bicalutamide, Flutamide, and Nilutamide)
Inferior to LHRH agonists and so are not used alone. Used in combination with LHRH agonists for prostate cancer and to prevent tumor flare, used to prevent hot flashes associated with castration, all agents are equally efficacious but differ in toxicity
Flutamide: Drug Class
Anti-androgenic Agent
Name the two new Anti-androgenic Agents
Abiraterone and Enzalutamide
What are the side effects of the traditional Anti-androgenic Agents (Bicalutamide, Flutamide, and Nilutamide)
Gynecomastia, hot flashes, increase in liver enzymes, nausea/vomiting, diarrhea (most severe with flutamide), disulfuram type reaction with nilutamide
Nilutamide: Drug Class
Anti-androgenic Agent
What is the mechanism of action of the traditional Anti-androgenic Agents (Bicalutamide, Flutamide, and Nilutamide)
Bind to androgen receptors and competitively inhibit the binding of dihydrotestosterone and testosterone
