Thyroid hormone that is converted to T3 in the periphery (pituitary, liver, kidney, heart, muscle, lung, and intestine)

Effects: tissue development, calorigenesis, metabolic effects, increases beta receptors, increases HR, cardiac work. Has a direct positive chronotropic effect on Ca ATPase in the SR

Uses: Hypothyroidism (adult and infant), endemic goiter (iodine deficiency)

Adverse Effects: Cardiac sx, angina, and palpitations

Drug interactions: Rifampin increases clearance, cholestyramine decreases GI absorption

DRUG OF CHOICE FOR HYPOTHYROIDISM

Given once daily

Thyroid hormone that is the physiologically active hormone.

Effects: tissue development, calorigenesis, metabolic effects, increases beta receptors, increases HR, cardiac work. Has a direct positive chronotropic effect on Ca ATPase in the SR

Uses: short term suppression of TSH

Adverse Effects: greater risk of cardiotoxicity than T4 (avoid in pts with heart disease)

Has a shorter half life than T4

Has greater biological potency than T4

More expensive and harder to monitor

Thioamide drug that prevents thyroid hormone synthesis by inhibiting Thyroidal Perioxidase catalyzed reactions to block iodide organification

Effects: inhibits TPO and blocks peripheral conversion of T4 to T3

Uses: Hyperthyroidism and thyrotoxicosis

Adverse Effects: skin rash, joint pain, agranulocytosis

Suppression of gland can occur after 2 years of therapy

Chance of relapse in 60-70%

Preferred over Methimazole in pregnancy

Thioamide drug that prevents thyroid hormone synthesis by inhibiting Thyroidal Peroxidase catalyzed reactions to block iodide organification

Uses: hyperthyroidism and thyrotoxicosis

Adverse Effects: skin rash, joint pain, agranulocytosis, congenital scalp defects

Suppression of gland can occur in 2 years

Chance of relapse 60-70%

Element that can be given in hyperthyroidism, in combination with PTU and Beta blocker

Mechanism of action is via autoregulation

Effects: inhibition of organification, hormone release, and decreased size of hyperplastic gland

Adverse Effects: acniform rash, swollen salivary glands, mucous membrane ulcerations

Side effects are uncommon and reversible

DO NOT USE IN PREGNANCY

Rarely used therapeutically since the introduction of thioamides

Radioactive element that gets concentrated in thyroid follicle cells

Effects: Selectively destroys gland without injury to adjacent cells

Uses: thyrotoxicosis

Adverse Effects: hypothyroid in 50%

Contraindicated in children and pregnancy

Can be taken orally

Can become euthyroid in 6-8 weeks

Bovine, porcine, or human hormone that can be used therapeutically to increase glucose uptake from the blood

Comes in ultra-short acting, rapid acting, intermediate acting, and long acting forms

Effects: energy storage - biochemical reactions that cause increase storage of energy (liver, adipocytes, and muscle)

Uses: Type 1 diabetes and Type 2 diabetes in later stages

Adverse Effects: hypersensitivity causes lipoatrophy, hypoglycemia (can be reversed by glucagon or glucose), which is exacerbated by alcohol, Beta blockers, and salicylates

Can be injected SC, IM, of IV

Available in depot preps, portable pen, aerosols

A second generation sulfonylurea drug that binds to and inhibits ATP sensitive K channels

Effects: depolarization and Ca++ influx, enhanced realease of insulin from Beta cells

Uses: T2DM

Adverse Effects: hypoglycemia, esp in the elderly, weight gain, GI effects, jaundice, leukopenia

Drug Interactions: MANY - NSAIDs, salicylates, dicumarol, Ethanol, MAOIs

Cross allergy with sulfonamides

With chronic treatment, insulin levels can return to normal, but blood glucose levels can remain elevated

This is a second line drug for Type 2 diabetes

Do not give in pregnancy

A metiglinide drug that acts like a sulfonylurea but has a different chemical composition

Effects: enhances insulin secretion

Uses: T2DM, with metformin or TZDs

Can cause hypoglycemia

Drug interactions with CYP3A4 inducers

Shorter acting than sulfonylureas

Given orally 3x per day

An alpha glucoside inhibitor that inhibits a brush border enzyme to interfere with starch hydrolysis and carbohydrate absorption

Effects: blunts post-prandial rise in blood glucose

Uses: T2DM, alone or with sulfonylureas

Adverse Effects: GI bloating, diarrhea

Decreases the bioavailability of metformin

A biguanide that activates the liver enzyme AMPK to inhibits TORC2 to inhibit gluconeogenesis

Uses: T2DM, with sulfonylureas, TZDs, or sitagliptin

Adverse Effects: ab pain, diarrhea, metallic taste

Avoid ethanol and conditions that cause lactic acidosis

Avoid in renal failure, cardiac failure, and EtOH abuse

Contraindicated in acute heart failure

This is a first line drug - does not cause hypoglycemia, does not cause weight gain, and inhibits microvascular complications

A thiazolidinedione (TZD) that binds and activates PPARy to alter gene expression at target tissues (adipocytes) to enhance insulin sensitivity

Effects: increases glucose uptake and utilization, increases FFA uptake and utilization, increases lipid enzymes, and decreases resistin. Overall, it decreases insulin resistance, and improves glucose metabolism

Uses: T2DM, alone or with sulfonylureas or metformin

Adverse Effects: edema, mild anemia, weight gain, decreased bone density, hepatotoxicity, and increased risk of CHF

Usually a second line drug due to severe adverse effects

An incretin mimetic that inhibits DDP-4 to enhance endogenous GLP-1 to enhance glucose mediated insulin release, decrease glucagon release, and increased beta cell number and function. Also lowers appetite and enhances gastric emptying

Uses: T2DM, with metformin

Adverse Effects: runny nose, sore throat, UTI, HA, nausea, constipation, hypoglycemia, and hypersensitivity

Avail in combination drug with metformin

An anti-tuberculosis dug that is metabolized by N-acetylaion

You can measure plasma concentration of the drug after 6 hours to determine how quickly the drug is metabolized.

Fast acetylation means fast metabolism

Slow acetylation means slow metabolism and patient is more subject to neurotoxicity

An anti-hypertensive drug that is metabolized by CYP2D6 that interferes with the release of NE

Ultra-rapid metabolizers have a duplicate gene

Extensive metabolizers show variation in therapeutic levels

Poor metabolizers have no functional enzyme and are subject to exaggerated hypotensive effects

Supplement given as a salt

Can also be given in active form to rapid acting (24-48 hours)

Effects: promotes bone formation

Uses: IV to treat severe hypocalcemia, osteoporosis, osteomalacia, Rickets, Pagets

IV: chloride, gluconate

Oral: carbonate, lactate, phosphate, citrate, gluconte

Carbonate has best bioavailabilty

Vit D is necessary for oral absorption

Synthetic form of PTH

Effects: unsure, but thought to preferentially active osteoblasts and increase serum Ca++

Uses: osteoporosis

Adverse Effects: increased risk of osteosarcoma

Cholecalciferol found in diet and synthesized from sunlight

Gets converted to active Vitamin D in the kidney

Effects: induces new proteins in intestine, modulates Ca++ flux across the brush border, induces osteoclast differentiation, and regulates PTH secretion

Uses: increase intestinal absorption of Ca++, prophylaxis of Vitamin D deficient states, hypoparathyroidism, and chronic renal failure (as Calcitriol)

Adverse effects: toxicity can result from overdose, hypercalcemia

Stored in adipose

Alendronate

Ibandronate

Nitrogen containing bisphosphonates, analogues of pyrophosphate that concentrates in the bone

Effects: inactivates osteoclasts, interferes with cholesterol synthesis, inhibiting activation of clasts, and protein prenylation of clasts

Uses: osteoporosis, Pagets

Adverse Effects: severe bone, joint, and muscle pain

Absorption is poor and it must be taken on an empty stomach

Ibandronate - monthly (Boniva)

Alendronate - weekly (Fosamax)

Hormone secreted by parafollicular cells of the mammalian thyroid

Effects: decrease serum Ca++ and P via actions on the bone and kidney, inhibits osteoclastic bone resoprtion, decreased new bone formation, and decreases Ca and P reabsorption in the kidney

Uses: Pagets, osteoporosis, and hypercalcemia

From salmon

Nasal spray or parenteral injection

Hormone used to prevent accelerated bone loss during postmenopausal period

Effects: Decreases bone resorption action of PTH

Increases calcitriol levels in the blood, and inhibits osteoclasts

Uses: osteoporosis

Adverse effects: increased risk of breast cancer, endometrial cancer, increased risk CV events, and persistence of menstrual bleeding, endometrial hyperplasia

Should take with progestins to be safer

Hormone that is produced by ovaries

Can be steroidal, non-steroidal, and conjugated

Effects: normal sexual maturation, development of primary and secondary female sex characteristics, long bone growth, epiphyseal closure, body fat distribution, skin pigmentations, endometrial proliferation, maintenance of BV, decreased bone resorption, increases in HDL and TG, decreases in LDL, increases in coagulation of blood and progesterone receptor, and behavioral changes

Uses: oophorectomy, during menopause (for vasomotor instability), contraception, dysfunctional uterine bleeding, and dysmenorrhea

Adverse Effects: uterine bleeding, CV events, gallbladder disease, cholestasis, HTN, migraine, nausea, endometrial and breast cancer

Contraindicated in estrogen dependent cancers, liver disease, hx of thrombosis, and heavy smoker

Alpha receptors: female repro tract, hypothalamus, and vascular smooth muscle

Beta receptors: prostate, lung, and brain

Endogenous progestin that is produced in the ovary by the corpus luteum

Physiologic doses: supports luteal phase, generates secretory endometrium, feedback inhibition of LH

Pharmacologic doses: endometrial atrophy, thick cervical mucous, and feedback inhibition of GnRH and LH

Uses: contraception, HRT, test of estrogen secretion

Long term suppression can create prolonged anovulation and amenorrhea

19-Nor progesterone that has more androgenic activity

Physiologic doses: supports luteal phase, generates secretory endometrium, feedback inhibition of LH

Pharmacologic doses: endometrial atrophy, thick cervical mucous, and feedback inhibition of GnRH and LH

Uses: contraception, HRT, test of estrogen secretion

Long term suppression can create prolonged anovulation and amenorrhea

Adverse Effects: Increases in BP and decreases in HDL

13-Ethyl progesterone that has less androgenic activity

Physiologic doses: supports luteal phase, generates secretory endometrium, feedback inhibition of LH

Pharmacologic doses: endometrial atrophy, thick cervical mucous, and feedback inhibition of GnRH and LH

Uses: contraception, HRT, test of estrogen secretion

Long term suppression can create prolonged anovulation and amenorrhea

Adverse Effects: Increases in BP and decreases in HDL (though not as much as 19-Nors)

Estrogen and Progestins block the ovulation process by

Progestins: suppresses LH surge, creates thick cervical mucous, causes endometrial atrophy

Estrogens: suppresses FSH and changes the tubular transport of the egg

Uses: contraception, endometriosis, hirsutism, acne

Adverse Effects: N/V, breast enlargement, alterations in libido, breakthrough bleeding, melasma

Androgenic effects: acne, hirsutism, oily skin

Estrogenic effects: thromboembolism, MI, migraine, gallbladder disease

Anti-carcinogenic effects on ovary and endometrium

Decreases risk of colorectal cancer

Decreases HDL and increases LDL

Benign liver tumors, mild HTN, and delay in return to fertility

Undergoes enterohepatic cycling

Contraindicated in CV disorders, HTN, heart failure, vaginal bleeding, breast cancer, liver disease, asthma, migraine, DM, and fibroids

Conventional pill: fixed E+P

Triphasic pill: increasing amounts of P

Blocks ovulation in 60-80% of cycles by suppressing LH surge, creating thick cervical mucous, endometrial atrophy, and decreasing GnRH pulses

Uses: contraception, endometriosis, hirsutism, acne

Adverse Effects: Same as combination OCP, though exhibits more androgenic effects and less cardiovascular effects

SERM that is a partial estrogen agonist and estrogen antagonist

Agonist effects on: bone, endometrium, coagulation, and lipids

Antagonist effects on: breast

Uses: breast cancer tx and prophylaxis

Adverse Effects: hot flashes, increased risk of DVT and PE, increased endometrial cancer, cataracts, and nausea

SERM

Agonist effects on: bone, lipids

Antagonist effects on: breast, endometrium

Uses: osteoporosis, breast cancer

Adverse effects: hot flashes, leg cramps, and increased risk of DVT, PE

SERM that is a weak agonist and strong antagonist

Effect: increases GnRH secretion and increases FSH and LH secretion, causing ovulation

Uses: anovulatory of oligovulatory women with a functional HPO axis

Adverse effects: increased risk of multiple births

Cis: agonist

Trans: antagonist

An aromatase inhibitor that prevents the conversion of testosterone to estrogen

Uses: advance breast cancer

Can cause extended remission longer than Tamoxifen

An anti-progestin that binds to the progesteron receptor and inhibits its activity

Effects: Inhibits P receptor activity and inhibits glucocorticoid activity

Uses: termination of early pregnancy (< 49 days), endometriosis, and Cushing's syndrome

Adverse Effects: bleeding

An endogenous hormone that affect uterine activity by altering ion currents in the myometrial muscle

Secreted from posterior pituitary

Effects: sustained uterine contraction and contraction of mammary alveoli

Uses: IV stimulation of labor, contracting the uterus after delivery, and inducing lactation (nasal spray)

Adverse Effects: maternal death due to HTN episode, uterine rupture, water intoxication, fetal death

Serious toxicity is very rare

Can be inhibited by Beta 2 agonits, Mg sulfate, inhalational anesthetics

Endogenous compound that is inhibited by estrogen and progesterone in pregnancy

Causes uterine contractions by increasing intracellular Ca++ of uterine smooth muscle

Uses: ripen cervix before oxytocin, induction of therapeutic abortion in combination with mifepristone

Adverse Effects: N/V, diarrhea

Interferes with Ca++ actions in contraction

Slows neuromuscular transmission to decrease contractions

Uses: preeclampsia and eclampsia as seizure prophylaxis

Adverse Effects: chest pain, flushing, and N/V