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drugs that cause hypothyroidism
- amiodarone interferes w/ conversion of T4 to T3
- Li+ blocks release of thyroid hormones & I- incorporation to thyroglobulin
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More potent than levothroxine, but not recommended due to its multiple dosing schedule (up to 4x/daily)
Higher potency not advised in Cardiovascular (CV) patients. Stimulates SANS
May have some benefit for short term TSH suppression
Liothyronine
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Medication should be taken on empty stomach
Levothyroxine & biphosphonate
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Levothyroxine drug interactions
- Reduction of T4 absorption
- Induction of drug metabolism
- Increase catabolism of vitamin K dependent clotting factors, enhancing effect of anticoagulants Increase insulin
- increases digoxin clearance
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drugs whose actions are further induced by Levothyroxine
Nifedipine, protease inhibitors, carbamazepine, glucocorticoids, phenytoin, phenobarbital, and rifampin
-
Should give sugar to pts on Levothyroxine because...
Levothyroxine incr insulin and raises metabolism
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inhibits thyroid-peroxidase catalyzed rxn --> inhibits T3, T4 synthesis.
Block iodine organification
Block iodotyrosine couplings
Inhibit deiodination of T4 and T3
Require 3-4 weeks to take effect
Thiomides, Propylthiouracil (PTU), Methimazole
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Action of radiocontrast agents, beta blockers, amiodarone, proprylthiouracil, and methimazole
blocks T4 --> T3 peripherally
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Rapid but incomplete absorption, large first pass effect
T1/2 1.5hr, is preferred over methimazole due to its high protein binding --> doesnt cross placenta
Inhibits T4 to T3 conversion –brings thyroid level down quicker than methimazole
AE: rash, nausea, hepatitis
proprylthiouracil
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Drugs in pregnancy
- Category A: levothyroxine (safe)
- Category B: amoxicillin and some types of insulin (safe)
- Category C: sertraline (risk vs benefit)
- Category D: chemotherapeutics, proprylthiouracil (risk vs benefit)
- Category X: misoprostol, isotretinoin (contraindicated—NEVER used)
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Agranulocytosis
rare side effect of antithyroids (PTU, methimazole, thiomides), risk in elderly & high dose pts.
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stimulate insulin release
sulfonylureas and Meglitinides
-
increase glucose uptake
Pioglitazone
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suppresses glucagon release
Pramlintide
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binds to liver receptors to induce IGF production
recombinant hGH
-
Blocks GH receptors
Pegvisomant
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GHRH antagonists at Anterior Pituitary
- Octreotide (analog of Somatostatin)
- Bromocriptine (DA agonist)
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Recombinant human IGF-1 (rhIGF-1)
Mecasermin
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side effects of mecasermin
Hypoglycemia, Intracranial hypertension, joint and muscle pain, convulsions, tonsilar hypertrophy, snoring, apnea
-
Octreotide
somatostatin formulation. sc, 1/2 90 min
-
Lanreotide
somatostatin formulation. sc, 1/2 90 mins
-
side effect of Pegvisomant
Block of negative feedback may double GH levels. Opposes Pegvisomant action.
-
Susceptible to proteolytic cleavage, only given parenterally (by injection). Short t1/2
posterior pituitary hormones
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side effects of oxytocin
Toxicities uncommon, but can cause hypertension, water retention (similar to ADH structurally), uterine rupture & fetal death.
-
Releases von Willebrand Factor; Used for von Willebrand Disease & Hemophilia A
Desmopressin. V2 agonist, not much activity at V1
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medication that replaces T3
Liothyronine
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Lispro, Aspart, Glulisine
rapid acting insulin for diabetes type 1. Onset for all three is 5-15 min and all claim an advantage over regular insulin of no delay (30 min)
-
shorting acting insulin
- exact structure as human insulin (hexamer). Advantage: cost effective and available IV for diabetic crisis situations.
- Disadvantage: Slow, inconvenient onset and coverage (hyperglycemia early in meal) extended duration (hypoglycemia later)
-
Neutral Protamine Hagedorn (NPH)
intermediate acting insulin. complexing protamine with insulin to create stable, slowly degraded product. Onset 2-5 h, duration 4-12 h. Can cover the day w/ 2-4 injections/day. Used w/ rapid or regular insulin to cover day plus meals
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Glargine and Determir
Long acting insulin. onset 1-2 h, duration 12-24 h, no peak. Rapid or regular insulin may be added at meals to stop spikes in sugar. These formulas result in less hypoglycemia
-
Glargine action
formulated to precipitate upon injection, forming a crystalline depot for slow and continuous release
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Determir action
formulated to bind albumin. A slow dissociation from the protein results in a prolonged, constant rate of availability
-
Sulfonylureas 1st generation
- increase insulin release from pancreatic β cells; reduces glucagon levels long term
- Tolbutamide (safest in avoiding hypoglycemia)
- Chlorpropamide (t1/2 32 hrs, flush w/ alcohol)
- Tolazemide (t1/2 7 hrs)
-
Both are contraindicated in the elderly and in patients with renal or hepatic impairment
Risk of hypoglycemia especially with drugs that inhibit metabolism
Chlorpropamide and Tolazemide. 1st gen sulfonylureas. incr insulin release from beta cells
-
2nd generation sulfonylureas
- Glyburide – daily, AM. Give lower dose in renal or hepatic impairmt
- Glipizide – give 30 min or more before food. Lower dose in renal or hepatic impairmt Glimepiride – daily, AM. No concern in renal. Completely metabolized by liver****
- High protein bound; may be displaced from albumin binding sites by NSAIDs --> temporary hypoglycemia
- Watch DI (CYP2C9) with any drug that induces or inhibits its metabolism
-
MOA is same as sulfonylureas. However, absence of sulfur in structure means they are an alternative to patients with drug sensitivity
- Meglitinides: Repaglinide.
- Fast acting, 1 h peak, 5-8 h duration. Take with meals. Hypoglycemia if doesn't eat.
-
same MOA as Repaglinide but is Phenylalanine derivative (also a Meglitinide)
Nateglinide. Hypoglycemia (Safest of all oral diabetic agents). shorter duration than Repaglinide
-
Biguanides
Phenformin (discontinued due to fatal lactic acidosis) and Metformin (1st line for diabetics)
-
risk for lactic acidosis, decr B12 levels.
Other treatments: polycystic ovary syndrome (reduces insulin resistance in these patients)
Lowers LDL/TG
Metformin
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Thiazolidinediones (TZD)
- Pioglitazone, Rosiglitazone. agonist at PPAR-γ (Peroxisome Proliferator-Activated Receptor-Gamma)
- incr glucose uptake into adipose tissues
- decr insulin resistance, improved TG/HDL values
-
TZD w/ incr risk of cardiovascular dz
rosiglitazone
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side effects of TZDs (pioglitazone and rosiglitazone)
- Edema, weight gain, mild anemia, fractures in women, CI in pregnancy, CHF, hepatotoxicity
- CV risks w/ rosiglitazone
-
induces metabolism of oral contraceptives
Pioglitazone
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Suppresses glucagon release, delays gastric emptying, and produces appetite suppression due to CNS effect. Synthetic amylin analog (amylin released like insulin from β cells)
Pramlintide
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Synthetic amylin analog (amylin released like insulin from β cells)Injected sq before each meal; never mix with insulin. Peak in 20 min. Duration 150 min.
For type I and II diabetics
Pramlintide
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Side effects of pramlintide
GI upset and possible hypoglycemia
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Incretin based drugs
- exenatide: GLP-1 analog, binds to GLP- receptors, incr beta cell mass
- sitagliptin, and saxagliptin: DPP-4 inhibitor, blocks GLP-1 degradation, raises GLP-1 levels
-
Injected 60 min before meal. Dosed twice daily. Weight loss potential makes it attractive
AE: GI upset, hypoglycemia possible
Fatal: necrotizing, hemorrhagic pancreatitis
Exenatide
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Glucagon-like peptide-1 (GLP-1) receptor agonist; antagonist to glucagon release. Helps pancreas make insulin after meals. New drug of 2010
Liraglutide
-
behaves like beta agonists, incr cAMP --> gluconeogenesis
glucagon injection. for hypoglycemic pts who are unconscious
-
Reversible and drug-related causes of osteoporosis
- Glucocorticoids, long-term therapy
- Post-menopausal estrogen deficiency
- Thyrotoxicosis
- Hyperparathyroidism
- Alcoholism
- Cigarette smoking
-
MOA of biphosphonates
inhibition of osteoclast bone resorption
-
Action of prednisone in Ca balance
- rapid reduction of hypercalcemia
- may enhance PTH mediated bone resorption
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Imitates Parathyroid Hormone. low dose PTH or intermittent PTH causes bone formation as the osteoblastic/osteoclastic ratio has not reached a bone resorption outcome
Teriparatide
-
admin routes for salmon calcitonin
subcapsular, intramuscular, and nasal inhalation
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SERM (Selective Estrogen Receptor Modulator). less potent than estrogen on bone density, offers less breast and endometrial cancer, and improves outcome against vertebral fractures. Has same risk of thrombophlebitis as estrogen
Raloxifene
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Agonist at the Calcium Sensing Receptor (CaR)
Blocks release of PTH by the Parathyroid Gland
Cinacalcet
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Managemt of hypercalcemia of malignancy.
Inhibits bone resorption.
Possible nephrotoxicity.
Gallium nitrate
-
Cortisol withdrawal
- Acute adrenal insufficiency. Fever, myalgia, arthralgia, and malaise
- Rarely pseudo tumor cerebri
-
Inhibits 11β-hydroxylation
Interferes w/ cortisol and corticosterone synthesis
Treatment of Cushings
Testing the integrity of the feedback loop
Metyrapone
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Inhibits 3β dehydrogenase. Treatment of Cushings
Trilostane
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