Acts on target tissues (esp liver) through JAK(a TK)/STAT signaling pathway;

Results in production of IGF-1(&2) to exert effects;

↓ insulin sensitivity, ↑ lipolysis, ↑ protein synthesis, ↑ epiphyseal growth;

Secretion stimulated by hypoglycemia, insulin;

Physiologic release is pulsatile

hGH;

Replacement therapy in children;

Tx: In kids: pituitary dwarfism (dc when growth stops); In adults: to ↓ CV dz mortality, tx AIDS-associated wasting;

SE: In kids = CNS: ↑ ICP, N/V, HA, visual disturbances; In adults = Peripheral: carpal tunnel, peripheral edema, arthralgia, myalgia;

CI: Use within 2 years of cancer tx (leukemia has been reported)

hGH + methionine;

Replacement therapy in kids;

Tx: In kids: pituitary dwarfism (dc when growth stops); In adults: to ↓ CV dz mortality, tx AIDS-associated wasting;

SE: In kids = CNS: ↑ ICP, N/V, HA, visual disturbances; In adults = Peripheral: carpal tunnel, peripheral edema, arthralgia, myalgia;

CI: Use within 2 years of cancer tx (leukemia has been reported)

GHRH, short form; First 29 AA;

Uses are primarily diagnostic but has been approved to tx GH deficiency.

GH receptor antagonist;

Covalently bound to Polyethylene glycol (PEG) to ↓ renal clearence and to ↑ half life;

↓ IGF-1;

Tx: Acromegly

IGF-1 + IGFBP-3 (IGF binding protein; both recombinant humaniod);

Binding protein added to ↑ t1/2 of IGF-1;

Tx IGF-deficiency

(a subset of cases where pt are not deficient in GH but in IGF and often also in IGFBP and do not respond to hGH)

Rises during pregnancy til birth;

Levels maintained for breast feeding, drop if no feeding;

Know symptoms of hyperprolactemia: anovulatory infertility, decreased menstruation, galactorrhea, decreased libido, vaginal dryness etc...

Release of Prolactin is promoted by PRH and TRH* and inhibited by Dopamine.

D2 receptor agonist;

↓ prolactin production at the anterior pituitary;

Cheaper drug;

Tx: hyperprolactinemia from pituitary adenoma, Parkinson's (primary use)

D2 receptor agonist;

↓ prolactin production at the anterior pituitary;

Has a higher affinity for D2 and therefore an ↑ t1/2 relative ot Pergolide;

Tx: hyperprolactinemia from pituitary adenoma

Somatostatin analog;

↓ secretion of GH and TSH;

Short t1/2;

Frequently used drug;

Tx: Gigantism/acromegaly;

SE - diarrhea, nausea, abdominal pain

Somatostatin analog;

↓ secretion of GH and TSH;

Long-acting;

Tx: Gigantism/acromegaly;

SE - diarrhea, nausea, abdominal pain

Thyroid Stimulating Hormone (TSH);

Glycoprotein hormone released in anterior pituitary;

Stimulated by TRH and by ↓ iodine;

Inhibited by somatostatin;

↑ release of T4,T3 secretion, THEN synthesis;

Causes thyroid hypertrohpy, hyperplasia;

High levels of TSH/phospholipase C - ↑ cystolic Ca;

Used as a dx tool to distinguish 1* from 2* hypothyroid

Glycoprotein hormone released from the anterior pituitary;

In Men: acts at the Leydig cells to stimulate androgen production, spermatogenesis;

In women Women, a spike will induce ovulation;

Release is stimulated by GnRH

Glycoprotein hormone released from the anterior pituitary;

Release stimulated by GnRH;

Female - gametogenesis and follicle development, used in replacement;

Male - initiation and maintenance of spermatogenesis

FSH + LH;

Extracted from post-menopausal urine;

IM admin;

Tx female infertility

SC admin;

Tx female infertility

rFSH;

SC admin;

Tx female infertility

Secreted by placenta in early pregnancy;

Detected in urine to dx pregnancy;

Extracted from the urine of pregnant women and used to Tx female infertility

Corticotropin (ACTH),

alpha-MSH/beta-MSH (melanocyte stimulating hormone),

CLIP

POMC-derived from anterior pituitary;

↑ production concurrent w/ ↑ ACTH production leads to hyperpigmentation in cases of excess ACTH (as in primary hypocortism).

Hypothalamic stimulatory hormone;

↑ GH release;

Negative feedback by rising GH levels;

Used to determine the cause of GH deficiency

Hypothalamic stimulatory hormone;

Stimulates FSH, LH production;

Synthetic GnRH;

SHORT t_1/2;

Diagnostic testing to diff pituitary and hypothalamic lesions in pts w/ hypogonadotropism

GnRH analog;

↑ t_1/2, ↑ receptor binding - induces receptor downregulation;

Tx: prostate cancer, uterine fibroids

Diagnostic testing of thyroid function;

Stimulates TSH and prolactin

Used in diagnostic testing to distinguish

Cushings Dz from ectopic ACTH syndrome

(ACTH)

POMC-derived peptide (39AA) from the anterior pituitary;

Works at G-protein coupled receptor to stimulate AC to produce cAMP;

Used to test integrity of HPA axis

Circadian rhythms;

(+) stress (can override neg feedback of cortisol);

(-) cortisol @ pituitary and hypothalamus;

(-) ACTH

"Natural" ACTH;

From animal sources,

POMC peptide;

Used to test integrity of HPA axis;

Synthetic form (cosyntropin is prefered over Acthar gel as the animal products are often contaminated with ADH).

Synthetic ACTH (24 AA);

Preferred to natural product b/c it has no vasopressin activity;

Used to test the integrity of the HPA axis

Produced in adrenal cortex;

Stimulates gluconeogenesis, glycogenolysis, ↑ lipolysis (permissive);

Anti-inflammatory, acts by ↓ Phospholipase A2, ↓ cytokines, ↓ histamine;

In the Periphery cortisol opposes insulin: ↓ glucose use, ↑ proteolysis, ↑ lipolysis;

Mostly effects are delayed due to primary action being through nuclear receptors and alterations in gene transcription;

Suppression of ACTH and TSH production;

↑ lipolysis, fat redistribution;

↑ DM risk (opposes insulin);

Peptic ulcers;

CNS - arousal, euphoria, insomnia, ↑ motor activity; Blood - ↑ Hgb RBCs PMNs, ↓ lymphocytes eosinophils monocytes basophils;

Men - hypogonadism, ↓ testosterone production;

Women - stops ovulation, dysmenorrhea, osteoporosis (post-men);

Children - ↓ GH/inhibits IGF-1;

Loss of Ca++ and osteoporosis (especially in children and postmenopausal women)

Produced in adrenal cortex (10mg/day);

Stimulates gluconeogenesis and glycogenolysis;

Anti-inflammatory, acts by ↓ Phospholipase A2, ↓ cytokines, ↓ histamine;

Periphery - [opposes insulin] ↓ glu use, ↑ proteolysis, lipolysis;

Mostly delayed effects due to actions being nuclear;

90% bound to CBP or albumin;

Converted (kidney, colon, salivary glands) to cortisone - won't bind MC receptors, allowing the aldosterone (present in much lower concentrations) to exert its effects;

Glucocorticoid ~ Cortisol;

Short t_1/2;

IM, IV, oral admin;

Tx: replacement therapy for adrenal insufficiency and CAH, ALL, lymphoma, skin dz, IBD;

SE: See corticosteroid side effects

Glucocorticoid;

Short t_1/2;

IM, IV, oral admin;

Tx: replacement therapy for adrenal insufficiency and CAH, ALL, lymphoma

Glucocorticoid;

Intermediate t_1/2;

Oral admin;

Tx: replacement therapy for adrenal insufficiency and CAH, ALL, lymphoma, RHEUMATIC dz, RENAL dz, IBD, HEPATIC dz

Glucocorticoid;

Intermediate t_1/2;

IM, IV admin;

Tx: replacement therapy for adrenal insuff. and CAH, ALL, lymphoma, HEPATIC dz

Glucocorticoid;

Intermediate t_1/2;

IM, IV, Oral admin;

Tx: replacement therapy for adrenal insufficiency and CAH, ALL, lymphoma;

General immunosuppression*

Glucocorticoid;

Long t_1/2;

IM, IV, topical, oral admin;

Tx: replacement therapy for adrenal insuff. and CAH, ALL, lymphoma, OCULAR DZ

Glucocorticoid;

Long t_1/2;

Oral (inhalation suspension), topical admin;

Tx: asthma

Glucocorticoid;

Long t_1/2;

Oral, topical admin;

Tx: asthma

(Pulmicort)

Glucocorticoid;

↓ mucus secretion, ↓ bronchial hyperactivity;

Tx: asthma, COPD, IBD;

Has a very high first pass effect and must be formulated in extended release capsules for local effects inthe SI and colon (to tx chrons and UC)

Mineralocorticoid (0.125 mg/day [much less than cortisol]);

Promotes Na/water retention, K+ and H+ secretion by action @DCT;

↑ ExCell fluid, hypoK (muscle weakness), alkalosis;

↑ synthesis of adrenergic receptors;

Release of aldosterone is stimulated by angiotensin II, high plasma [K+], and ACTH (secondary to other two);

SE: Edema, HTN, cardiomyopathy, CHF, hemorrhage (all basically due to volume overload);

Mineralocorticoid - synthetic Aldosterone;

Promotes Na/water retention, K+ and H+ secretion @DCT;

↑ ECF, hypoK (muscle weakness) and causes alkalosis;

SE: Edema, HTN, cardiomyopathy, CHF, hemorrhage;

Aldoesterone antagonist - K-sparing diuretic;

Also competes for testosterone receptor binding;

Prevents water retention/acts as a diuretic and prevents hypokalemia (which causes muscle weakness with many other diuretics.).

Tx: Primary or Secondary hyperaldosteronism, anti-Hypertensive agent, Hirsutism in women;

SE: Hyperkalemia, hypoT, gynecomastia in men

Adrenocortical "inhibitor";

Inhibits CYP450 (scc, the side chain cleavage enzyme which carries out the first step in cortisol synthesis from cholesterol);

↓ cortisol production;

Tx: cortisol overproduction in Cushing's

Antifungal - secondary Adrenocortical "inhibitor";

Inhibits CYP450-17α hydroxylase (cat. the 1st step in synth of bile acids and P450scc (side chain cleavage, 1st step in steroid synthesis): ↓  cortisol production; Inhibits testosterone production (by inhbiting CYP enzymes ness for its synthesis, important for SE but not useful as a direct therapy);

Tx: Cushings and systemic fungal infections;

SE: Gynecomastia

Estradiol (most potent)> estrone> estriol (least);

70% bound to SHBG;

Reproductive: birth control, ↑ libido;

Musculoskeletal: closes epiphysis, ↓ osteoclasts, ↑ bone maturation/ muscle content;

Hepatic: ↑ clotting factors, binding proteins;

Lipids: ↑ HDL, ↓ LDL;

High first pass metabolism, low p.o. efficacy;

Tx: Osteoporosis, prostate cancer, HRT;

SE - endomerial cancer risk, thromboembolism, HTN, GI, CHD;

One of the two types of nuclear estrogen receptors;

Located in the female reproductive tract (uterus, vagina, ovaries);

One of the two types of nuclear estrogen receptors;

Located in the prostate and ovaries;

Estrogen - synthetic 17alpha;

Lowered first pass metabolism due to ethinyl group;

Tx: CONTRACEPTION (one of the two most common Rx);

Estrogen - synthetic 17alpha;

Lower first pass metabolism;

Tx: Birth control (one of the two most common Rx)

Found in the urine of pregnant mares;

IM injection - ↓ first pass metabolism;

Dissolved in oil - absorbed over several weeks;

Tx: sypmtoms of menopause (HRT)

An Este of estradiol;

IM injection - ↓ first pass metabolism;

Dissolved in oil - absorbed over several weeks;

Tx: sypmtoms of menopause, HRT

Crystalline estrone sulfate;

Estrogen formulation for standard tx's

(DES)

Non-steroidal estrogen;

Lower first pass metabolism;

Can be admin transdermally;

Tx: Prostate cancer, used as birth control;

SE: Teratogenic***

Non-steroidal estrogen;

Lower first pass metabolism;

Transdermal admin;

Tx: Prostate cancer, used as birth control;

↑ after ovulation to maintain pregnancy;

Bound to Transcortin for transport;

Reproductive: ↓ uterine contraction & oviduct motility, thicken cervical mucus, promote alveolobular duct development (breast);

Lipids: ↓ HDL, ↑ LDL (bad);

Metabolic: ↑ insulin, ↑ lipoprotein lipase (more cholesterol in the tissues);

SE - CAD, CNS depressant, acne, weight gain

Synthetic progesterone;

Tx: endometrial cancer, component of birth control

Synthetic progesterone;

Tx: endometrial cancer, component of birth control

Synthetic progesterone;

Morning-after pill, first 72 hours post-intercourse;

Tx: endometrial cancer, component of birth control

SERM;

Tissue-selective effects: Agonist in bone, brain, liver;

Antagonist in breast, endometrium;

Tx: breast & endometrial cancers

SERM;

Tissue-specific effects: Agonist in bone, brain, liver;

Antagonist in breast, endometrium;

Tx: breast & endometrial cancers

SERM;

Tissue-specific effects: Agonist in bone, brain, liver;

Antagonist in breast, endometrium;

Tx: breast & endometrial cancers

True Anti-estrogen;

Antagonist in all tissues (ER-alpha & -beta);

Used to induce Ovulation via reflex ↑ GnRH that comes with blockage of estrogen;

Tx: infertility

Ture Anti-estrogen;

Antagonist in all tissues (ER-alpha & -beta);

Induces Ovulation via reflex inc GnRH;

Tx: infertility

Anti-progestin;

Blocks the Progesterone receptor to terminate gestation in first 7 weeks/49 days;

Abortificant

Anti-progestin - pure antagonist;

Blocks Progesterone receptor for the termination of gestation;

Used to terminate pregnancy

(potentially useful as a contraceptive, a labor inducer or a treatment for breast cancer).

Aromatase inhibitor;

Blocks the production of estrogens from androgens (catalyzed by aromatase);

Tx: breast cancer after Tamoxifen fails

Aromatase inhibitor;

Blocks the production of estrogens from androgens (catalyzed by aromatase);

 Tx breast cancer after Tamoxifen fails

Androgen;

[1] Binds androgen receptor - transcriptional regulation w/ tissue-specific co-activators/repressors;

[2] Is converted to DHT (higher potency, converted by 5α-reductase) in the prostate (not muscle or kidney);

[3] Converted to estradiol - closes epiphyseal plates;

IM injection;

Tx: replacement therapy elderly men (↑ muscle mass), also for endometriosis, PMS, anabolic steroids;

SE: masculinization, virilization, CAD, hepatic carcinoma, suppression of LH & FSH

Testosterone derivative;

Efficacious because it avoids first pass metabolism, "better" than oral or IM routes;

[1] Binds androgen receptors - tissue-specific transcriptional regulation;

[2] Is converted to DHT - ↑ potency;

[3] Converted to estradiol - closes epiphyseal plates;

Tx: elderly men (inc muscle mass), IM injection for HRT, endometriosis, anabolic steroids;

Testosterone derivatve;

Oral, short acting;

[1] Bind androgen receptor - transcriptional regulation; [2] Conv to DHT - inc potency;

[3] Converts to estradiol - closes epiphyseal plates;

Tx: elderly men (inc muscle mass), IM injection for HRT, endometriosis, anabolic steroids;

Testosterone derivatve;

IM, short acting;

[1] Binds androgen receptor - transcriptional regulation; [2] Converted to DHT - inc potency;

[3] Conv to estradiol - closes epiphyseal plates;

Tx: elderly men (inc muscle mass), IM injection for HRT, endometriosis, anabolic steroids;

(Depo-testosterone);

Testosterone derivatve;

IM, long acting;

[1] Binds androgen receptor - transcriptional regulation;

[2] Converted to DHT in the prostate by 5-alpha-reductase - inc potency;

[3] Converted to estradiol - closes epiphyseal plates;

Tx: elderly men (inc muscle mass), IM injection for HRT, endometriosis, anabolic steroids;

Testosterone derivatve;

IM, long acting;

[1] Binds androgen receptor - tissue-specific transcriptional regulation;

[2] Conv to DHT in the prostate by 5-alpha reductase - inc potency;

[3] Converted to estradiol - closes epiphyseal plates;

Tx: elderly men (inc muscle mass), IM injection for HRT, endometriosis, anabolic steroids;

Testosterone derivatve;

Oral, short acting;

[1] Binds androgen receptor - transcriptional regulation; [2] Converts to DHT - inc potency;

[3] Converts to estradiol - closes epiphyseal plates;

Tx: elderly men (inc muscle mass), IM injection for HRT, endometriosis, anabolic steroids;

Testosterone derivatve;

IM, long acting;

[1] Binds androgen receptor - transcriptional regulation; [2] Converts to DHT - inc potency;

[3] Converts to estradiol - closes epiphyseal plates;

Tx: ENDOMETRIOSIS/PMS,* HRT in elderly men (inc muscle mass), IM injection for HRT, endometriosis, PMS, anabolic steroids;

Androgen receptor antagonist;

Competes with DHT;

Tx: Acne, baldness, virilizing syndrome, sexual deviants (↓ their libido)

Androgen receptor antagonist;

Tx: Prostate cancer;

SE: Hepatotoxicity (no longer the primary choice due to this serious SE)

Androgen receptor antagonist;

Tx: Prostate cancer;

SE: Hepatotoxic

Androgen receptor antagonist;

Tx: Prostate cancer;

Less hepatotoxic*

Is being used over other androgen receptor antagonists for this reason.

(Propecia);

Inhibits 5-alpha reductase blocking the conversion of Testosterone to DHT;

Tx: BPH, male-pattern baldness;

CI: Teratogenic* (pregnant women should not even touch it!), users should not donate blood

Insulin-dependent glucose transporter;

Found in adipose tissue and striated muscle (skeletal and cardiac);

Responsible for insulin-mediated transportation of glucose into these cells;

Animal insulin used in insulin replacement therapy;

Differs from human insulin at 3 AAs;

↓ use due to the equally affordable human insulin;

Antibodies to drug can develop

Animal insulin used for replacement therapy; Differs from human insulin at 1 AA;

↓ use due to the equally affordable human insulin;

Antibodies to drug can develop

Animal (from Sheep) insulin used in insulin replacement therapy;

Differs from human insulin at 3 AA;

↓ use due to the equally affordable human insulin;

Antibodies to drug can develop

NPH = Neutral, Protamide, Hagedorn;

Compound with insulin activity;

Intermed duration of action;

Injected 2x daily;

Glucose levels before dinner represent NPH injection at breakfast and glucose before breakfast represents evening NPH dose.

Intermediate-duration insulin (NPH) combined w/ short-acting (Regular Insulin) injected before meals;

Decreases the post-prandial spike and provides longer maintainence of insulin levels and longer blood sugar control.

Long acting insulin crystals included in 'Lente' preparation;

Long acting due to the presence of large crystals which slow absorption and prolong half life of this drug and other long-acting insulins.

Humulin = Regular Insulin;

Recombinant "regular" human insulin, Made in bacteria/yeast;

Limited anti-insulin Ab formation;

Short duration of action;

The only insulin preparation that is injected IV (all others are SC or IM)

Recombinant "regular" human insulin;

Synthesized beginning with porcine insulin and replacing the 1 different AA;

Limited anti-insulin Ab's

Short acting insulin preparation;

Synthesized beginning w/ Humulin, 1 AA replaced (via rDNA) to prevent hexamer formation w/ zinc;

End product - faster onset (circulates as a monomer);

Short t_1/2

Short acting insulin preparation;

Synthesized beginning w/ Humulin, 1 AA replaced (via rDNA) to prevent hexamer formation w/ zinc;

End product - faster onset (circulates as a monomer);

Short t_1/2

Long acting insulin preparation;

1 AA substituted, + Arg at C-term;

Prepared in acidic solution - Crystals precipitate upon injection - SLOW ABSORPTION;

PK - Slow release - long plateau w/ no peaks;

Long acting insulin preparation;

1 AA substituted;

Prepared in acidic solution - Crystals precipitate upon injection - SLOW ABSORPTION;

PK - Slow release - long plateau w/ no peaks (decreases chances of nocturnal hypoglycemic episodes);

Short acting insulin preparation;

Synthesized beginning w/ Humulin, 2 AAs replaced (via rDNA) to prevent hexamer formation w/ zinc;

End product - faster onset (circulates as a monomer);

Short t_1/2

1st Gen. Sulfonylurea;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

1st Gen. Sulfonylurea;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

1st Gen. Sulfonylurea;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

1st Gen. Sulfonylurea;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

2nd Gen Sulfonylurea - 10-100X more potent;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

2nd Gen Sulfonylurea - 10-100X more potent;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

2nd Gen Sulfonylurea - 10-100X more potent;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

2nd Gen Sulfonylurea - 10-100X more potent;

Acts @K+ channel;

Initially ↑ insulin release (effect does not hold long-term), ↓ insulin metabolism by the liver, ↑  insulin sensitivity = ↑ glucose uptake;

Oral admin, rapidly absorbed, extensive protein binding;

Tx: DM, promote hypoglycemia;

NSAIDs enhance the hypoglycemic action of this drug class.

Meglitinide - benzoic acid derivative oral hypoglycemic;

↑  insulin secretion;

Very rapid GI absorption, Short t1/2;

Taken before meals for post-prandial control of glucose levels;

Tx: DM;

SE: hypoglycemia

SE - severe hypoglycemia;

Meglitinide - benzoic acid derivative oral hypoglycemic;

↑  insulin secretion;

Very rapid GI absorption, Short t1/2;

Taken before meals for post-prandial control of glucose levels;

Tx: DM;

SE: hypoglycemia

Biguanide hypoglycemic agent - First Line in Type II DM and many pre-diabetic patients;

↓ hepatic glucose production, inhibits hepatic and renal gluconeogeneisis, stimulates peripheral glucose uptake, slows gulcose absorption form the GI and ↓ glucagon release;

No hypoglycemia, NO INSULIN AXN, does not cause weight gain;

SE - BLACK BOX lactic acidosis

Thiazolidindione oral hypoglycemic;

Regulates gene expression by binding the PPAR-gamma receptor, ↑ insulin sensitivity;

Tx: Type II DM;

SE: edema, anemia, weight gain, bone fractures, may worsen heart dz;

BLACK BOX MI risk

Thiazolidindione oral hypoglycemic;

Regulates gene expression by binding the PPAR-gamma receptor, ↑ insulin sensitivity;

Tx: Type II DM;

Alpha-glucosidase (brush border enzyme) inhibitor;

↓ carbohydrate (starch) absorption; ↓ post-prandial glucose spike;

Oral admin (typically in combo with other agents);

Tx: DM (Type II);

SE: GI disturbances

Inhibitor of brush boarder Alpha-glucosidase;

↓ carbohydrate (starch) absorption; ↓ post-prandial glucose spike;

Oral admin (typically in combo with other agents);

Tx: DM (Type II);

SE: GI disturbances

Incretin mimetic - GLP-1 analog, acts on the GLP-1 receptor:

↑ glucose-dependant insulin secretion, ↓ glycogenolysis, slows gastric emptying, ↓ appetite, ↓ glucagon. Overall: reduces post-prandial blood glucose, may also preserve pancreatic beta cells;

Parenteral admin (not an oral drug!);

Tx: Type II DM;

SE: GI disturbances, HA, Pancreatitis

'Incretin' drug;

Inhibits dipeptidyl peptidase-4, inhibiting inactivation of Incretins (GIP/GLP-1);

↑ glucose-dependant insulin secretion, ↓ glycogenolysis, slows gastric emptying, ↓ appetite, ↓ glucagon.

Overall: reduces post-prandial blood glucose, may also preserve pancreatic beta cells;

Oral admin;

Tx: Type II DM;

SE: Rhinitis, URI, allergic rxns (rare)

Amylin (peptide hornome released from beta cells with insulin after meals) analog;

Slows gastric emptying, ↑ satiety (@hypothalamus), inhibits inappropriate secreation of glucagon; 

Parenteral admin;

Tx: Type I and Type II (who use insulin) DM pts;

SE: hypoglycemia, GI disturbances, HA

Diazoxide

(ASMT 10-relevant information is in CAPS)

Direct vasodilator, HYPERGLYCEMIC AXN;

Tx: HTN crisis, HYPOGLYCEMIA, INOPERABLE INSULINOMAS (INHIBITS INSULIN SECRETION);

SE: tachycardia, fluid retention, palpitations, HYPERGLYCEMIA

Somastatin analog - long acting;

Inhibits insulin, glucagon, GH, and TSH release;

Tx: insulinomas, glucagonomas, acromegaly

Synthesized by the parathyroid glands in response to detection of low plasma Ca2+ and acts to increase plasma Ca2+;

Activates Adenylate Cyclase to ↑ cAMP; 

*Testing urinary cAMP is a test for PTH function*

↑ plasma Ca by [1] ↑ bone resorption to free Ca2+,

[2] ↑ renal Ca2+ reabsorption (distal tubules),

[3] ↑ active VitD/calcitriol;

hPTH[1-34] (human PTH);

Activates AC to ↑ cAMP; 

↑ plasma Ca by [1] ↑ bone resorption,

[2] ↑ kidney reabsorption,

[3] ↑ active VitD/calcitriol;

Tx: Hypoparathyroidism;

Full length (84 aa) human PTH;

Activates AC to ↑ cAMP; 

↑ plasma Ca by [1] ↑ bone resorption,

[2] ↑ kidney reabsorption,

[3] ↑ active VitD/calcitriol;

Tx: Hypoparathyroidism;

Has a short half life. More often, hypoparathyroidism is tx with Vit D +/- Ca2+ supplements.

↓ plasma Ca by

[1] ↓ bone resorption,

[2] ↓ kidney reabsorption,

[3] ↓ active VitD/calcitriol;

↓ osteoclast surface area;

"Calcitonin tones down plasma Ca levels";

Injection or nasal spray;

Tx: hypercalcemia, Paget's dz, osteoporosis;

Very effective for short term treatment.

SE: Abs can develop if used for long periods of time (prednisone can be used to counter this)

Natural calcitonin from salmon;

↓ plasma Ca by [1] ↓ bone resorption,

[2] ↓ kidney reabsorption,

[3] ↓ active VitD/calcitriol;

↓ osteoclast surface area;

"Calcitonin tones down plasma Ca levels";

Tx: hypercalcemia, Paget's dz, osteoporosis

Natural calcitonin from salmon;

↓ plasma Ca by [1] ↓ bone resorption,

[2] ↓ kidney reabsorption,

[3] ↓ active VitD/calcitriol;

↓ osteoclast surface area;

"Calcitonin tones down plasma Ca levels";

Tx: hypercalcemia, Paget's dz, osteoporosis

Calcitriol is the active form of Vitamin D = 1,25-(OH)₂D₃;

Choecalciferaol (Vitamin D₃) synthesized in the skin and transported to the blood, binds to specific receptors in perhipheral cells → first OH added in the liver (25-OH-D₃);

In the kidney, 25-OH-D₃ can be converted to either the active form Calcitriol (1,25) or the inactive form (24,25); The diols are converted to 1,24,25 for excretion;

↑ plasma Ca by...

↑ absorption/uptake of P and Ca from the SI (primary);

↑ synthesis of calbindin (a Ca2+ binding protein);

↑ kidney reabsorption of Ca2+;

↑ bone resorption of Ca2+;

Synthesis is ↑ by ↑ levels of PTH;

Thereputic Uses:

Prophylaxis and cure for nutritional rickets, treatment of metabolic rickets, osteomalacia, hypoparathyroidism. Prevention and treatemetn of osteoporosis.

Calcitriol mimetic;

Vitamin D3 from fish liver oils;

Takes effect in ~12 hours but remains in lipid stores for months;

Tx: rickets, osteomalacia, hypoparathyroidism, osteoporosis

Calcitriol mimetic; similar to cholesterol;

Tx: rickets, osteomalacia, hypoparathyroidism, osteoporosis

Calcitriol mimetic;

After irradiation = Vitamin D2;

Tx: rickets, osteomalacia, hypoparathyroidism, osteoporosis

Calcitriol mimetic;

Converted to calcitriol in the body;

Tx: rickets, osteomalacia, hypoparathyroidism, osteoporosis

Calcitriol analog;

Tx: PSORIASIS (better than GCs*), rickets, osteomalacia, hypoparathyroid, osteoporosis

Calcitriol analog (DHT) - Reduced Vitamin D2;

Injection, nasal spray;

Less active than calcitriol but effective in high doses;

Tx: Osteoprosis*

Calcitriol analog;

MOA: ↓ PTH secretion;

Tx: rickets, osteomalacia, hypoparathyroidism, osteoporosis

Calcitriol analog;

MOA: ↓ PTH synthesis via suppression of PTH gene expression;

Tx: rickets, osteomalacia, hypoparathyroidism, osteoporosis

1,25-(OH)₂D₃;

↑ plasma Ca by... ↑ absorption/uptake of P and Ca (primary);

↑ calbindin;

↑ kidney reabsorption;

↑ bone resorption;

Tx: rickets, osteomalacia, hypoparathyroidism, osteoporosis

1st Gen. Bisphosphonate (non-hydrolyzable analogs of inorganic pyrophosphate);

Less effective orally;

Take in am after overnight fast with a full glass of water, wait 30 mins before eating;

Inhibits bone resorption;

Tx: Pagets, osteoporosis, hypercalcemia;

SE: osteonecrosis of jaw (less common in 1st gen)

(Fosamax)

2nd Gen. Bisphosphonate - more potent;

Analog of inorganic pyrophosphate;

Take in morning, without food;

Inhibits bone resorption;

Tx: Pagets, osteoporosis;

Most common Rx for post-meno Tx;

SE - via IV admin, osteonecrosis of jaw (less common in 2nd gen), irritation of esophagus

2nd Gen. Bisphosphonate - more potent;

Analog of inorganic pyrophosphate;

Take in morning, without food;

Inhibits bone resorption;

Tx: Pagets, osteoporosis;

Most common Rx for post-meno Tx;

SE - via IV admin, osteonecrosis of jaw (less common in 2nd gen), irritation of esophagus

(Boniva)

2nd Gen. Bisphosphonate - more potent;

Analog of inorganic pyrophosphate;

Take in morning, without food;

Inhibits bone resorption;

Tx: Pagets, osteoporosis;

Most common Rx for post-meno Tx;

SE - via IV admin, osteonecrosis of jaw (less common in 2nd gen), irritation of esophagus

3rd Gen. Bisphosphonate - HIGH POTENCY;

Analog of inorganic pyrophosphate;

Take in morning, without food;

Inhibits bone resorption;

Tx: Pagets, osteoporosis, BONE CANCER;

SE - via IV admin, osteonecrosis of jaw* (MC with 3rd generation drugs in this group)

3rd Gen. Bisphosphonate - HIGH POTENCY;

Analog of inorganic pyrophosphate;

Take in morning, without food;

Inhibits bone resorption;

Tx: Pagets, osteoporosis, BONE CANCER;

SE: via IV admin, osteonecrosis of jaw!

Calcimimetic - Ca sensing receptor mimetic;

Binds allosterically to the receptor and allows PTH suppression at lower [Ca2+];

Tx: hyperparathyroid w/ Parathyroid-carcinoma

Binds Ca;

Cavity prophylaxis - benefits only if present during tooth development;

Prevents blood clotting;

Prevents osteoporosis;

SE: osteosclerosis (elevated bone density), mottled enamel; NO cancer risk

(Cytomel tablets, Triostat injectable)

Thyroid replacement theraputic agent - L-T3;

Note oral or injectable;

Calorigenic, inc HR, cardiac contraction force

T3 replacement is short term, T4 replacement is typically used on a chronic basis.

Thioureylene - anti-thyroid drug;

Inhibits Iodine organification (via peroxidases), which interferes with the binding of Iodine to thyroglobulin;

Tx hyperthyroidism

A radiocontrast agent used off label as an anti-thyroid drug;

Inhibits peripheral (liver, kidney, pituitary, brain) conversion of T4->T3;

Tx hyperthyroidism (off-label)

Anti-Protozoal agent;

Requires metabolic activation via enzymatic reduction; Blocks pyruvate:ferrodoxone oxidoreductase;

90% bioavail, BBB penetration, low protein binding;

Tx: Protazoan infx (DOC for trichomonas, entamoeba histolytica, giardia), Anaerobic infx (DOC for both B. fragilis, C. diff infections);

SE: GI, HA, metallic taste, dizziness, disulfriam-like rxns with alcohol, anorexia, neuro tox;

CI: In neuro dz (vertigo, numbness, etc), Pregnancy, with Coumadin (will increase the PT further (bleeding risk)

Anti-Protozoal agent;

Inhibits electron transport, ↓ pyrimidine synthesis;

99% protein bound (enterohepatic recirculation), lipophillic, hydrophobic (lipidy);

Tx: pneumocystic pneumonia (cidal effects, effects on others are static), toxoplasma, entamoeba, trichomonas, P. falciparum (combined atovaquonone products used here);

SE: Mild, rash and nausea possible

Anti-Protozoal agent;

Poor absorption - IV, inhaled admin;

Tx: [2nd line due to SE]- pneumocystis, leishmania, trypanosoma;

SE [50%, many are serious]: hypoT, hypoGly, blood dyscrasias, cardiotoxicity, nephrotoxicity

Anti-Protozoal agent;

Oral (50% bioavail) or IV admin;

Inhibits ornithine decarboxylase (an essential enzyme in paracites) to block polyamine synthesis;

Tx: W. trypanosoma (not effective against E. African);

SE: anemia, leucopenia, diarrhea, convulsions, GI upset, alopecia;

Thereputic doses are large and require concurrent IV fluids.

Anti-Protozoal agent;

Aminoglycoside Abx (protein synthesis inhibition);

Tx: Entamoeba DOC when there is intestinal colonization, add metronidazole if there is ametic colitis or liver abscess), Tapeworms, Anti-protozoal (leishmanias, giardia (DOC in pregnancy), Crypto in AIDS);

SE: diarrhea/GI upset;

CI: Renal dz*

Anti-Protozoal agent;

IV, IM admin;

Interferes with the trypanothine redox system - rapid efflux of trypanothione and glutathione from cells + inhibition of trypanothione reductase;

Tx: Leishmaniasis;

SE: Pancreatitis, myelosuppression, muscle/joint pain

Anti-Protozoal agent;

Poor absorption;

MOA unknown but contains Iodine;

Tx: Tapeworms, luminal (not intenstinal wall or extraintestinal) trophozoites;

SE: diarrhea, iodine toxicity, GI upset (take w/ meals);

CI - optic neuropathy, renal dz, thyroid dz and in pt who are iodine intolorant;

Preferred alternative is Paramomycin;

Anti-Protozoal agent;

Rapid exretion, IV admin, significant passage into CNS;

Arsenic-containing, inhibits trypanothione reductase;

Tx: trypanosoma brucei (E. african meningoencephalic stage);

SE: [prevent w/ prednisone prophylaxis] - fever, reactive encephalopathy (serious, 50% mortality), peripheral neuropathy

Anti-malarial agent - Blood schizontocide;

MOA is unclear;

Wide distribution, slow clearance (months), a loading dose is required initially;

Resistance - efflux at P-gp;

Tx: Plasmodium, non-GI amebiasis; Prophylactic use;

SE (related to strong melanin binding): blurred vision (melanin binding, corneal deposits), retinal pigmentation, hemolysis (if G6PD deficient);

Anti-malarial agent - Blood schizontocide;

Blocks DNA synthesis;

Tx: P. falci, gametes of P. vivax and P. malariae;

Not used as a prophylactic agent;

Poor therapeutic index;

SE: ↓ cardiac contractility, dilates vessels, contracts uterus, causes vertigo, hemolysis (if G6PD deficient), Cinchonism - tinnitus, blurred vision, HA, ↓ hearing [Strong effects on CN VIII];

Interactions: Rifampin ↑ clearence of Quinine

aka Quinidine gluconate;

Blood schizontocide and antiarrhythmic;

Blocks DNA synthesis;

Tx: severe/life threatening P. falciparum, gametes of P. vivax and P. malariae, is also an antiarrhythmic;

SE: Anticholinergic;

CI - AV heart block;

Interactions: May interfere with anti-HTN drugs and acidification of the urine will ↑ excretion of quinidine

Blood schizontocide;

Oral admin, 98% protein bound, concentrates in erythrocytes, excreted in bile;

Acts only @ asexual erythrocytic stages;

Blocks DNA synthesis;

Tx: P. falciparum (more mature = more succeptible), gametes of P. vivax and P. malariae;

SE: GI, vertigo, convulsions;

CI: BBs, chloroquine, quinine, quinidine, hx of seizures

Anti-malarial agent - Blood schizontocide;

Acts only @ asexual erythrocytic stages;

HIGH absorption when admin w/ [fatty] food (CI!);

Tx: multi-resistant P. falciparum (used as an alternative to quninine and mefloquine);

SE: prolonged QT interval, arrhythmias;

Variable absorption, time to peak [plasma], and elimination (do not take with fatty foods, excessive absorption = toxicity)

Blood schizontocide;

Variable oral absorption;

Tx: P. falciparum;

Lower cardiotox but is expensive;

Often used in combination with Artemisinin (ACT)

Blood schizontocide - from Chinese herb;

Free radicals damage macromolecules in Plasmodium, endoperoxide interaction with FE forms ROS and carbon radicals also alkylate and damage macromolecules;

Tx: Severe chloroquine-resistant P. falciparum (has lots of Fe), leishmania, toxoplasma, schistosomiasis

Anti-malarial agent - Blood schizontocide;

Tetracycline Abx;

Attacks plasmodia in red blood cells preventing or terminating the clinical attack;

Acts only @ asexual erythrocytic stages;

Anti-malarial - Blood schizontocide;

Attacks plasmodia in red blood cells preventing or terminating the clinical attack;

Acts @ asexual erythrocytic stages and primary liver stages;

Anti-malarial agent - Tissue schizontocide;

Gametocidal, Hypnozoitocidal;

Rapidly absorbed and converted to Carboxyprim.;

Tx: Prophylaxis, P. vivax and P. ovale @ hepatic and gamete stages;

KILLS P. FALCI GAMETES;

CI: G6PD deficient (X-linked) leads to hemolytic anemia

Anti-malarial agent - Blood and Tissue schizontocide;

High absorption;

Inhibits (paracite) DHFR;

SE: ↓ hematopoeisis, megaloblastic anemia;

Never used alone, often w/ Sulfadoxine

(Sulfadoxine/Pyrimethamine)

Anti-Malarial agent - Tissue schizontocide axn;

Tx: chloroquine-resistant P. falci, Toxoplasma;

SE: fatal cutaneous rxns (incl erythema multiforme, Steven Johnson Syndrome, and epidermal necrolysis);

Benzimidazole - Anti-helmintic;

Rapid metabolism to albendazole sulfoxide;

Inhibits carbohydreate transport and microtubule assembly - immobilization and death;

Blocks larval development;

Tx: helmintics - ascariasis, enterobius, hookworm;

SE: Teratogen*

Benzimidazole - Anti-helmintic;

Poor absorption, highly bound;

Inhibits carbohydrate transport and microtubule assembly - immobilization and death;

Blocks larval development;

Tx: helmintics - ascariasis, enterobius (pin), Trichuris (whip), hookworm;

SE: Teratogen*

Anti-helmintic;

↑ Ca++ permiability of the worms causing spastic paralysis;

High first pass metabolism makes it ok for use in humans;

Tx: tapeworms, schistosomiasis, 3 forms of fluke;

SE: GI, HA;

CI: Ocular schistosomiasis;

Interactions: Carbamazepine & Phenobarbital induce P450 and therefore ↓ bioavail;

Cimetidine blocks P450 and ↑ bioavail of drug.

Anti-helmintic;

Oral admin, no met, long t1/2 (slow cl);

↑ Cl permiability inhibiting glutamate and GABA-ergic channels = paralysis;

Tx: strongyloidiasis, onchocerca (River blindness);

SE: GI, itch, dizzy, inflamm rxn to dying bugs

Anti-helmintic;

Rapid GI abs;

MOA unclear, induction of apoptosis (?);

Tx: lymphatic filariasis;

SE: anorexia, nausea, HA

Anti-helmintic;

Binds Nicotinic receptors causing a depolarizing blockade - spastic paralysis (bug falls off GI wall);

Tx: MONILIFORMIS, Intestinal nematodes;

↓ SE due to localization of drug in GI - HA, dizziness, rash

Antilipemic - Bile acid sequesterant;

Powder, take w/ OJ;

Anionic (+) molecules bind bile acids (+) in GI - interupt enterohepatic recycling of cholesterol by bile acids - liver ends up getting rid of more cholesterol;

Safe for children and pt with hepatic dz;

↓  LDL by up to 25%;

SE: Gritty texture, flatulence, bloating, hypertriglyceridemia, constipation, fecal impaction;

Drug interactions: prevents the absroption of digoxin, beta blockers, thyroxine and coumadin (take all other meds 1 hr bf or 3-4 hrs after Colestopol);

CI: Hypertriglyceridemia or in pt on complex drug regiments with critical medications

Antilipemic - Bile acid sequesterant;

Powder form;

Anionic (+) molecules bind bile acids (+) in GI - interupt enterohepatic recycling of cholesterol by bile acids - liver ends up getting rid of more cholesterol;

Safe for children and pt with hepatic dz;

↓  LDL by up to 25%;

SE: Gritty texture, flatulence, bloating, hypertriglyceridemia, constipation, fecal impaction;

Drug interactions: prevents the absroption of digoxin, beta blockers, thyroxine and coumadin (take all other meds 1 hr bf or 3-4 hrs after Colestopol);

CI: Hypertriglyceridemia or in pt on complex drug regiments with critical medications

Antilipemic - Bile acid sequesterant;

Tablet (Potent) that forms a gel, take with lots of water;

Anionic (+) molecules bind bile acids (+) in GI - interupt enterohepatic recycling of cholesterol by bile acids - liver ends up getting rid of more cholesterol;

Safe for children and pt with hepatic dz;

↓  LDL by up to 25%;

SE: Gritty texture, flatulence, bloating, hypertriglyceridemia, constipation, fecal impaction;

Drug interactions: prevents the absroption of digoxin, beta blockers, thyroxine and coumadin (take all other meds 1 hr bf or 3-4 hrs after Colestopol);

CI: Hypertriglyceridemia or in pt on complex drug regiments with critical medications

Antilipetic - Statin;

Inhibits HMG-CoA Reductase (the rate-limiting step in cholesterol synthesis);

Prodrug, converted by CYP3A4, intestinal reabsorption by P-gp, CYP3A4 hepatic metabolism;

↓ lipoprotein secretion by the liver, promotes cleavage of SREBP-2 by ↓ hepatic cholesterol content which results in upregulation of LDL-receptors in the liver which ↑ clearance of plasma VLDL and LDL;

↓ LDL by 60%, moderate ↓ in TG, and ↑ in HDL, effectively ↓ MI//CHD death;

SE: GI, sleep disruption, teratogenic, rhabdomyolysis, myositis, myalgia, inc aminotransferases;

CI: Renal dz

(Zocor)

Antilipetic - Statin;

Inhibits HMG-CoA Reductase (the rate-limiting step in cholesterol synthesis);

Prodrug, converted by CYP3A4, intestinal reabsorption by P-gp, CYP3A4 (ineractions***) hepatic metabolism;

↓ lipoprotein secretion by the liver, promotes cleavage of SREBP-2 by ↓ hepatic cholesterol content which results in upregulation of LDL-receptors in the liver which ↑ clearance of plasma VLDL and LDL;

↓ LDL by 60%, moderate ↓ in TG, and ↑ in HDL, effectively ↓ MI//CHD death;

SE: GI, sleep disruption, teratogenic, rhabdomyolysis, myositis, myalgia, ↑ aminotransferases;

CI: Renal dz, with CYP3A4 inhbitiors, Gemfibrozil, and Cyclosporine, ↓ dose in Renal dz pts.

Antilipetic - Statin;

Inhibits HMG-CoA Reductase (the rate-limiting step in cholesterol synthesis);

Prodrug, converted by CYP3A4, intestinal reabsorption by P-gp, hepatic metabolism is not by CYP;

↓ lipoprotein secretion by the liver, promotes cleavage of SREBP-2 by ↓ hepatic cholesterol content which results in upregulation of LDL-receptors in the liver which ↑ clearance of plasma VLDL and LDL;

↓ LDL by 60%, moderate ↓ in TG, and ↑ in HDL, effectively ↓ MI//CHD death;

Inc safety, low potency;

SE: GI, sleep disruption, teratogenic, rhabdomyolysis, myositis, myalgia, inc aminotransferases;

CI: Renal dz

Antilipetic - Statin;

Inhibits HMG-CoA Reductase (the rate-limiting step in cholesterol synthesis);

Prodrug, converted by CYP3A4, intestinal reabsorption by P-gp, hepatic metabolism is not by CYP3A4 but by CYP 2C9;

↓ lipoprotein secretion by the liver, promotes cleavage of SREBP-2 by ↓ hepatic cholesterol content which results in upregulation of LDL-receptors in the liver which ↑ clearance of plasma VLDL and LDL;

↓ LDL by 60%, moderate ↓ in TG, and ↑ in HDL, effectively ↓ MI//CHD death;

Inc safety, low potency;

SE: GI, sleep disruption, teratogenic, rhabdomyolysis, myositis, myalgia, inc aminotransferases;

CI: Renal dz

Is the sole exception to the interaction that exists between most statins and fibrinates*

Antilipetic - Statin;

Inhibits HMG-CoA Reductase (the rate-limiting step in cholesterol synthesis);

Prodrug, converted by CYP3A4, intestinal reabsorption by P-gp, hepatic metabolism by CYP3A4 (interactions*);

↓ lipoprotein secretion by the liver, promotes cleavage of SREBP-2 by ↓ hepatic cholesterol content which results in upregulation of LDL-receptors in the liver which ↑ clearance of plasma VLDL and LDL;

↓ LDL by 60%, moderate ↓ in TG, and ↑ in HDL, effectively ↓ MI//CHD death;

Inc safety, low potency;

SE: GI, sleep disruption, teratogenic, rhabdomyolysis, myositis, myalgia, inc aminotransferases;

CI: Renal dz

(Crestor)

Antilipetic - Statin (most potent statin);

Inhibits HMG-CoA Reductase (the rate-limiting step in cholesterol synthesis);

Prodrug, converted by CYP3A4, intestinal reabsorption by P-gp, hepatic metabolism is not by CYP3A4;

↓ lipoprotein secretion by the liver, promotes cleavage of SREBP-2 by ↓ hepatic cholesterol content which results in upregulation of LDL-receptors in the liver which ↑ clearance of plasma VLDL and LDL;

↓ LDL by 60%, moderate ↓ in TG, and ↑ in HDL, effectively ↓ MI//CHD death;

Inc safety, low potency;

SE: GI, sleep disruption, teratogenic, rhabdomyolysis, myositis, myalgia, inc aminotransferases;

CI: Renal dz

Antilipetic - Cholesterol absorption inhibitor;

Blocks internalization of NPC1L1/prevents intestinal uptake of cholesterol itself - ↓ cholesterol absorption by 50% - ↓ hepatic cholesterol - upregulation of LDL receptors - ↓ LDL and TG, slight ↑ in HDL;

Dosing: 10 mg tablets, activated by conjugation to a phelolic glucuronide in the liver and SI, absorption ↑ by a high fat meal;

 Does not reduce CHD risk (?);

SE: GI, fatiuge, gallstones (especially when given with fibrinates, DC if gallstones are dx*), Category C in Pregnancy, ↑ liver enzymes;

Use caution whe giving with Cyclosporine;

CI: < 10 yrs, hepatic or renal insufficiency, breast feeding, discontinue if LFTs elevate to > 3x ULN

Antilipolic - Fibrate;

Safe for renal, liver dz;

Ligand for/activates the PPAR-alpha receptor (lier, muscle, kidney, heart) causing FA oxidation, ↑ biliary cholesterol excretion (Dec TG by 50%);

↑ HDL (Apo-A1), no effect on LDL*;

↓ MI/CHD morbidity;

SE: gallstones (especially w Ezetimibe), reflux, diarrhea, myopathy (if w/ statin);

Blocks hepatic metabolism of all statins (except fluvastatin) - ↑ metabolites;

(Tricor) Fibrate - anti-lipid;

Active metabolite is - fenofibric acid - glucaronidation;

Microionized capsule, hepatic activation, renal excretion (accumulates in renal failure pt);

Ligand for/activates the PPAR-alpha receptor (liver, muscle, kidney, heart) causing FA oxidation, ↑ biliary cholesterol excretion (Dec TG by 50%);

↑ HDL (Apo-A1), no effect on LDL*;

SE: gallstones (when w Ezetimibe), ↑ transaminases, ↓ GFR, azotemia;

CI: Renal dz, paradoxical reduction in HDL when given with Thiazolindione (PPAR-gamma);

Does not effect statin metabolism.

aka Nicotininc Acid - Antilipolic;

↓ FFA mobilization - ↓ TG & ApoB synthesis (which ↓ VLDL), ↑ HDL transport and ↑ Apo1a (which also ↑ HDL), enhanced LPL;

↓ LDL and TG, ↓ Lp(a);

↓ CHD/MI incidence by 60%*;

SE - hepatotox (inc enzymes), flushing (common), conjunctivitis, retinal detachment, ↑ insulin resistance (a. nigricans)*, gout, dry skin, Pregnancy Category C, pruritis

Omega-3 FAs - ALA, EPA, DHA;

↓ TGs (35%), antiplatelet, hypotensive, antiarrhythmic effects, little/no effect on LDL and HDL;

↓ CHD;

↓ hepatic TG synthesis by ↓ SREBP-1, activates PPAR-alpha which increases FA oxidation (like fibrates);

Useful adjunct to niacin/fibrinates in extreme HTG;

Myositis: Muscle symptoms with high CPK elevations.

Rhabdomyolysis: Muscle symptoms, marked CPK elevations, dark colored urine (myogobinuria) and acute renal failure*

Caused by statin inhibition of cholesterol synthesis in the muscles.

Risk factors include: advanced age (>75 years), renal or hepatic dz, diabeteis, high doses of statins.

Made worse by taking statins with Gemfibrozil.

1) Macrolide Abx (erythromycin and clarithromycin, not azithro),

2) Oral Azole Antifungals,

3) Selected SSRIs (nefazodone),

4) CCBs (verapamil and diltizem > DHPs),

5) Grapefruit juice,

6) HIV Protease inhbitors,

7) Selected Immunosuppressants (Cyclosporine*)

Key because it inhbitis pathways involved in statin metabolism*

CI with simvastatin and dose reductions are required with Pravastatin.

Also increases the occurence of rhabdomyositis with other statins,

Increases the risk of gallstone formation when admin with Ezetimibe.

Class C in pregnancy.

Synthroid - L-T4;

Thyroid replacement therapy for hypothyroid pt;

High doses required in children;

Takes several weeks for a steady state to be reached, monitor levels to acheive max control.

Mixture of T3 and T4 from desiccated animal thyroid preparations;

Used in thyroid replacement therapy;

Animal preparations are less desirable as they are often unpredictable.

(PTU) - Antithyroid drug;

Inhbitis iodine organification (iodination and coupling in teh thyroid) and also inhibits peripheral conversion of T4 to the more active T3 form by deiodinases;

Readily abosrbed, shorter t1/2 than methimazole;

Prefered drug in pregnancy (less placental transfer, ltd excretion in milk);

SE: minimal, rash, agranulocytosis

Antithyroid Drug;

10x more potent than PTU;

Inhbitis iodine organification (peroxidase catalyzed reactions of iodination and couping);

Avoid in pregnancy (crosses the placenta and becomes concentrated in the fetal thyroid).

Radioactive Iodine;

Oral admin;

Concentrates in the thyroid gland where it emits beta-radiation which destroys part or all of the thyroid parenchyma;

Used to tx hyperthyroidism in pt who are 35 years or older (not used in women of childbearing age);

No evidence has been found of radiation damage to other tissues.

Contrast agent;

Used in treatemetn of hyperthyroidism (off-label) as they inhbit conversion of T4 to T3 peripherally.

G Protein-Coupled Receptor;

Found in the parathyroid glands as well as in the C-cells of the thyroid. Is also expressed in the kidney, on osteoblasts, some cells of the GI, and in some hematopoietic cells;

Activation of the GPCR → Phospholipase C activation → generation of IP3 and DAG → inhibition of cAMP

Synthesized as a preprohormone by the parafollicular/C -cells of the Thyroid gland;

Act on Osteoclasts and osteoblasts by binding to a membrane receptor;

Binding to membrane receptors on osteoclasts → ↓ ruffled border SA on clasts*

Note that Calcitonin, though it generally opposes the effects of PTH, is not a global inhbitor of PTH*

GnRH antagonist;

↓ release of FSH and LH from the AP;

Tx: some hormone-sensitive cancer, uterine conditions (fibrosis, endometriosis), and in IVF;

CI: Renal Failure or in women 65 or older

GnRH antagonist;

Blocks the release of FSH/LH from the AP;

Used in fertility clinics to control ovulation

GnRH agonist;

Promotes release of FSH and LH from the AP;

 Non-pulsitile/constant stimulation of FSH/LH suppresses the release of sex hormones;

Tx: prostate and breast cancers, also in benign disorders of  the endometrium, assissted reproduction and precocious puberty;

SE: Bone pain, GI upset, decreased erections/libido, memory loss.

GnRH agonist;

Promotes release of FSH and LH from the AP;

 Non-pulsitile/constant stimulation of FSH/LH suppresses the release of sex hormones;

Tx: prostate and breast cancers, also in benign disorders of  the endometrium, assissted reproduction and precocious puberty;

Shows an initial surge of Testosterone followed by reduced levels of T.

GnRH analog;

Constant stimulation of FSH/LH reduces sex hormone release;

Daily IM injection or long-lasting SubQ implant;

Tx: Prostate cancer, uterine fibroids and precocious puberty;

GnRH agonist;

Constant stimulation of gonadotropes of the AP leads to desensitization and decreased sex hormone release;

Tx: endometriosis, uterine fibroids, in IVF and precocious puberty;

SE: (due to reduced estrogen levels) hot flashes, vaginal dryness, decreased libido, HA

Thyrotropin-releasing hormone;

Increases TSH which increases Thyroid hormone release.

Synthetic vasopressin;

Binds the V2 receptors on the collecting ducts inducing resorption of water;

Tx: Diabetes insipidus, nocturia (bedwetting);

SE: HA, flushing, hyponatremia, seizures*