Endocrine Pharm

• glucose
• Sulfonylureas
• M-agonists
• B2-agonists

alpha2 agonists

• Drugs: acarbose, mitigol
• Mechanism: inhibits intestinal brush boarder alpha-glucosidases, dealyed sugar hydrolysis & glu absorption (decreasing CHO absorption in gut)
• Clinical Use: monotherapy in type II or in combo
• Contraindications: malabsorption
• Side effects: GI disturbances, no hypoglycemia, recently hepatotoxicity
• Best option for: mild post-prandial hyperglycemia

• 1st gen drugs: tolbtamine, chloropromide
• 2nd gen drugs: glybunide, glipizide, glemipride; 2nd gen are more commonly used
• Mechanism: closes K channels on the beta-cell mb = causes cell depolarization = insulin release via Ca channel influx
• Clinical use: release of endogenous insulin, for type 2 DM, need some beta-cell function, not useful for type 1, tolbtamine can be used in renal dysfn
• Contraindications: severe renal/hepatic dz bc it causes longer hypoglycemia
• Side effects: 1st gen = disulfiram-like reaction), hypoglycemia, weight gain
• Best option for: monotherapy or in combo with biguanides/TZD
• Drug interactions: mostly 1st gen = hypoglycemia with cimetidine, insulin, salicylates, sulfonamides

• Drug: metformin
• Mechanism: decreases gluconeogenesis, decreases serum glucose, overal insulin sensitizer
• Clinical use: oral hypoglycemia, can be used in pts with no beta-cell function
• Contraindications: creatinine >1.5, CHF, liver dz
• Side effects: lactic acidosis, GI upset, weight loss, no hypoglycemia
• Best option for: mono or combo therapy, synergistic with sulfonylureas

• Drug: pioglitazone, rosiglitazone
• Mechanism: Peroxisome Proliferator-Activated Receptor (PPAR) agonist, receptor is expressed on adipose cells, muscle cells, vascular ep = promotes fat storage/redistribution, makes large insulin resistant cells --> smaller insulin sensitive cells causing a flux of FFA to subcutaneous tissue away from viscera = increased insulin sensitivity, increases peripheral BG tissue uptake
• Contraindications: CHF severe liver dz
• Side effects: fluid retention, weight gain, edema, CV/hepatoxocity
• Best option for: mono or combo therapy

• Drug: Exenatide
• Mechanism: gut detects BG, incretin hormones, increase secretion of insulin, decrease glucagon release
• Contraindications: ESRD, gastric dz
• Side effects: hypoglycemia (when used with sulfonylureas), GI disturbances, pancreatitis, weight loss
• Best option for: combo w/ metformin, TZD, sulfonylureas, injectable

• Drug: Sitagliptin
• Mechanism: DPP-4 enzyme degrades GLP-1 = increases incretin hormone level = increased pancreatic secretion of insulin and decreases liver glucose production
• Side effects: no weight gain, nasal congestion, rhinorrhea
• Clinical use: DM in kidney dz

• Drugs: Pramlintide
• Mechanism: decreases post-prandial glucose, and slows GI transit
• Side effects: hypoglycemia, nausea, diarrhea, weight loss
• Contradindications: gastroparesis, hypoglycemia, unawareness
• Clinical use: subQ injection, not used alone, but in combo therapy w/ insulin, for type I and II

Glucose enters beta cell = increases intracellular ATP = closes K channels = membrane depolarization = increases Ca influx = insulin release

Insulin = less glucagon released from pancreatic alpha cells

• Drugs: Lispro, Aspart, Regular
• Mechanism: bind insulin receptor (tyrosine receptor kinase activity). Liver: increased glu storage as glycogen. Muscle: increased glycogen and protein synthesis, K uptake. Fat: aids in TG storage
• Clinical use: type I & II DM, life-threatening hyperkalemia and stress-induced hyperglycemia
• Toxicity: hypoglycemia, hypersensitivity rxn (rare)

• Drugs: NPH (intermediate), Glargine, Detemir
• Mechanism: binds insulin receptor (tyrosine kinase activity). Liver: increased glu storage as glycogen. Muscle: increased glycogen and protein synthesis, K uptake. Fat: aids in TG storage, "peakless" insulin
• Clinical use: type I & II DM, life-threatening hyperkalemia and stress-induced hyperglycemia
• Toxicity: hypoglycemia, hypersensitivity rxn (rare)

Symptoms: lip/tongue tingling, lethargy, confusion, sweats, tremors, tachycardia, coma, seizures

Treatment: Oral glucose, IV dextrose if unconscious, or glucagom (IM/inhalation)

• low-sugar diet
• insulin replacement

• dietary modification
• exercise for weight loss
• oral hypoglycemics
• insulin replacement

• Mechanism: stimulates insulin release from pancreatic beta cells
• Use: adjunctive use in type II DM - administer right before meals due to short half-life

• Mechanism: alters fat metabolism by inhibiting pancreatic lipases
• Clinical use: long-term obesity management (in conjunction w/ modified diet)
• Toxicity: steatorrhea, GI discomfort, reduced absorption of fat-sol viatmins (A, D , E, K), headache

OrliSTAT gets rid of FAT

• Mechanism: sympathomimetic serotinin and NEp reuptake inhibitor
• Clinical use: ST & LT obesity management
• Toxicity: htn, tachycardia

• Mechanism: inhibits organification of iodide and coupling of thyroid hormone synthesis, propylthriouracil also decreases the peripheral conversion of T4 --> T3, slow onset
• Clinical use: hyperthyroidism,
• Toxicity: skin rash, agranulocytosis (rare), aplastic anemia
• Pregnancy: both drugs cross placenta, but propylthiouracil is safter bc it is extensive protein bound

• Mechanism: thyroxine replacement
• Clinical use: hypothyroidsm, myxedema
• Toxicity: tachycardia, heat intolerance, tremors, arrhythmias

• Drug: K-I + Iodine (Lugol's solution)
• clinical use: thyrotoxicosis, pre-operatively, decreases gland size, fragility, vascularity, no LT use bc thyroid gland 'escapes' from effects after 10 - 14 days

• Drug: somatrem, somatropin
• Clinical use: GH deficiency, Turner's syndrome, osteoporosis

• Drug: octreotide
• Clinical use: Acromegaly, carcinoid, gastrinoma, glucagonoma

release of vasoactive substances like 5HT (5-HIAA is a marker), histamine and PG

Tx: octreotide, plus maybe serotinin receptor blocker (cyprohepatidine or methyseride)

Clinical use: stimulation of labour, uterine contractions, milk let-down; controls uterine hemorrhage

• Drugs: leuprolide, nafarelin
• Clinical use: endometriosis, prostat carcinoma (repository form)

• Drugs: Urofollitropin (FSH), Placental HCG (LH), menotropins (FSH, LH)
• Clinical use: hypogonadal states

• Drug: Bromocriptine
• Clinical use: hyperPRLemia

• Drug: cosyntropin
• Clinical use: infanitle spasms

• drug: desmopressin
• Mechanism: V2 selective
• clinical use: pituitary (central NOT nephrogenic) DI, hemophilia A (increases Factor 8 release from liver), vW dz (increases vW factor from endothelium), primary nocturnal enuresis

• Mechanism: ADH antagonist (member of the tetracycline family)
• Clinical use: SAIDH
• Toxicity: nephrogenic DI, photosensitivity, abnormalities in bone and teeth

• Drugs: hydrocortisone, prednisone, tramcinolone, dexamethasone, beclomethasone
• Mechanism: decrease the production of leukotrienes & PGs by inhibiting phospholipase A2 & expression of COX-2
• Clinical use: Addisons, inflammation, immune suppression, astham
• Toxicity: Iatrogenic Cushing's syndrome: buffalo hump, moon facies, truncal obesity, muslce wasting, thin skin, easy bruisability, osteoporosis, adrenaocortical atrophy, peptic ulcers, diabetes (if chronic)

• Endocrine uses: glucocorticoids (ie prednisone, dexamethasone), mineralocortoids (fludrocortisone)
• Uses:
• Addison disease: replacement
• Adrenal insufficiency states: trauma, infection, shock, supplementation
• Premature delivery: to prevent respiratory distress syndrome, supplementation
• Adrenal hyperplasia: feedback inhibition of ACTH

• Spironolactone
• blocks aldosterone and androgen receptors

• Mechanism: competitive inhibitor of progestins at progesterone receptors, blocks glucocorticoid receptors too!
• Clinical use: termination of pregnancy, administered with misoprostol (PGE1)
• Toxicity: heavy bleeding, GI effects (nausea/vomiting/anorexia), abdominal pain

• Mechanism: binds estrogen receptors, estridiol is the major natural estrogen, increases oral bioavailability, halflife, and feedback inhibtion of LH, FSH
• Clinical use: hypogonadism, ovarian failure, menstrual abnormalities, HRT in post menopausal women; use in men with androgen-dep prostate cancer (palliative), contraception (FD of low gonadotropins), acne
• Toxicity: increasd risk of endometrial cancer (hyperplasia), bleeding in post menopausal women, clear cell adenocarcinoma in vagina in females exposed to DES in utero, increased thrombi
• Side effects: nausea, breast tenderness, endometrial hyperplasia, increased gall bladder disease, migrain, blood coagulation, cancer risk
• Contraindications: ER-positive breast cancer, hx of DVT
• Note: conjugated equine estrogens (premarin) - natural, ethinyl estradiol and mestranol (steroidal), DES (nonsteroidal)

• Mechanism: aromatase inhibitor = decreases estrogen synthesis
• Clinical use: estrogen-dependent, post menopausal breast cancer

• Mechanism: partial agonist at estrogen receptors in hypothalamus, prevents nl feedback inhibition and increases release of LH and FSH from pit = stimulates ovulation
• Clinical use: treat infertility and PCOS
• Side effects: hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances

• Mechansim: antagonist on breast tissue, actions vary depending on 'target' tissue
• Tissue effects: E-receptor agonist (bone), antagonist (breast), partial agonist (endometrium)
• Clinical use: treat and prevent recurrence of ER-positive breast cancer
• Toxicity: increased endometrial cancer

• Mechanism: agonist on bone, antagonist on breast and uterus
• Clinical use: reduces resorption of bone, tx of osteoporosis
• Toxicity: if used in menopause - no increased cancer risk

• Mechanism: B2 agonists = uterine relaxation
• Clinical use: reduces premature uterine contractions

Ritodrine, allows the fetus to retrun to dreams; by preventing early delivery

• Drugs: medroxyprogesterone, norethindrone, desogestrel (synthetic lacking androgenic & antiestrogenic activity)
• Mechanism: progestin is a synthetic version of progesterone to increase oral bioavailability, increase feedback inhibition of gonadotorpins (especially LH)
• Clinical use: contraception (w/ oral estrogens), depot contraception (mthoxyprogesterone q 3mo), HRT w/ estrogens to decrease endometrial cencer
• Side effects: decreased HDL increased LDL, glu intolerance, breakthrough bleeding, androgenic (hirsuitism, acne), antiestrogenic (block lipid changes)
• Antagonist: mifepristone - abortifacient (used w/ PGs)

Mechanism: prevent the estrogen surge, LH surge does not occur = ovulation does not occur

Advantages: reliable, decreased risk of endometrial/ovarian cancer, decreases ectopic pregnancy, decreased pelvic infections, regulation of menses

Disadvantages: taken daily, no protection against STDs, increased TG, depression, weight gain, nausea, htn, hypercoagulability

• Drug: finasteride (propecia)
• Mechanism: 5-alpha-reducatse inhibitor (decreases conversion of testosterone into DHT)
• Clinical use: BPH, promotes hair growth (male-pattern baldness tx)
• Toxicity: teratogenicity

• Mechanism: nonsteroidal competitive inhibitor of androgens at the testosterone receptor
• Clinical use: prostate carcinoma

• Mechanism: inhibits steroid synthesis (inhibits desmolase)
• Clinical use: tx of PCOS to prevent hirsuitism
• Side effects: gynecomastia and amenorrhea

note: to prevent male pattern hair loss give a drug that will encourage female breast growth

• Mechanism: inhibits steroid binding
• clinical use: tx of PCOS to prevent hirsuitism
• Side effects: gynecomastia and amenorrhea

note: to prevent male pattern hair loss give a drug that will encourage female breast growth

• Mechanism: inhibits cGMP phosphodiesterase = increased cGMP = smooth muscle relaxation in corpus cavernosum = increased BF = penile erection
• Sildenafil and vardenafil fill the penis

Clincal use: tx of ED

Toxicity: headache, flushing, impaired green-blue colour vision, life-threatening hypotension if pt is taking nitrates

Hot and sweaty, but then Headache, Heartburn, Hypertension

• Drugs: etidronate, pamidronate, alendronate, risedronae
• Mechanism: inhibits osteoclastic activity; reduces both formation resorption of hydroxyapetite
• Clinical use: malignancy-associated hypercalemia, Paget's disease of bone, postmenopausal osteoporosis
• Toxicity: Corrosive esophagitis, nausea, diarrhea

• Mechanism: recombinant DNA PTH analogue
• Clinical use: once daily to stimulate the osteoblasts & new bone formation
• Continuous infusion would stimulate osteoclast activity
• has to be used for less than 2 years = bc of increased risk of osteosarcoma