Diabetes, thyroid not covered in sketchy Flashcards
When are sulfanyl ureas contraindicated?
Pregnancy *Renal/Liver disease* Sulfa allergies Type-1 diabetes Elderly
When are meglitinides contraindicated?
Pregnancy
*Liver disease
What is the difference b/w the indications for sulfanyl ureas and meglitinides?
Sulfas: Slow onset
Long duration
Lowers fasting glucose
Meglitinides: Fast acting
Short duration
Lowers postprandial glucose
Can use when allergic to sulfas
When is metformin contraindicated?
Elderly >80 yrs Pregnancy *Renal failure, MI, CHF* Liver disease/alcohol abuse Hypoxia/Shock/septicemia Iodinated contrast agent Serious acute illness (eg viral infection) Hypoxic/ischemic states (eg COPD, lung dz)
Besides lactic acidosis and GI side effects, what is the 3rd minor SE of metformin?
v B12 absorption
When are the thiazolidinediones contraindicated?
Liver disease
CHF (stage III, stage IV; due to edema)
CVD
Pregnancy
How is pramlintide administered?
Requires injections (SQ)
When are alpha-glucosidase inhibitors contraindicated?
Chronic intestinal disease
IBD
Colonic ulceration
Besides being contraindicated in renal impairment, when else are SGLT2 inhibitors contraindicated?
T1DM
Besides UTIs and hypotension, what are some other adverse effects of SGLT2 inhibitors?
Thirst/dehydration
^ LDL
Hyperkalemi
What is the MoA of bromocriptine in treating DM?
Dopamine D2 agonist acts on the CNS to normalize hypothalamic DA levels, thereby decreasing sympathetic tone, resulting in: v Hepatic GNG v Lipolysis/FFA v Lipogenesis/TG ^ Glucose tolerance ^ Insulin sensitivity
~0.5% decrease in HbA1C
What is the MoA of colvelesalam in treating DM?
Prevents bile acid reabsorption. Allows bile acids to enter the colon.
Bile acids bind TGR5 GPCR expressed on intestinal cells and induce GLP-1 secretion.
~0.5% decrease in HbA1C
When is radioactive iodine contraindicated?
Pregnancy
Breast feeding
Severe ophthalmopathy
What are some adverse affects a/w using beta-blockers to treat hyperthyroidism sx?
Exacerbation of HF
^ Airway resistance
Exacerbation of peripheral artery disease
When are beta-blockers contraindicated?
Asthma, COPD, HF
What is an alternative drug choice to beta-blockers when treating hyperthyroid sx?
Which beta-blockers are cardioselective?
Diltiazem (Ca2+ blocker)
Metropolol/atenolol (cardiac-selective beta blocker)
What is the name of synthetic T3? T4?
Which is more useful and why?
T3: liothyronine/triiodothyronine
T4: levothyroxine/tetraiodothyronine
Levothyroxine (has smoother dosing, less peaks and troughs)
What is the MoA for liothyronine and levothyroxine?
- Liothyronine: Active hormone acts as an agonists of the TR transcription factor
- Levothyroxine: Pro-hormone converted in vivo to the active T3 form, which acts as an agonists of the TR transcription factor
What are the indications for T3 vs T4?
- Liothyronine (T3): Hypothyroidism when rapid onset of action is required, e.g.
1. Myxedema coma
2. Preparation of thyroid cancer pt for radioiodine therapy to avoid extended period of thyroid hormone withdrawal - Levothyroxine (T4): Hypothyroidism
Adverse affects of liothyronine vs. levothyroxine?
Risk of thyrotoxicosis w/OD
Hyperthyroidism w/OD
^ risk a-fib
^ Bone loss in postmenopausal women
Name 2 formulations of iodide.
- Saturated potassium iodide [SSKI]
- Potassium iodide-iodine [Lugol’s solution]
What is the MoA for iodide?
Acutely and rapidly inhibits thyroid hormone secretion
Inhibits hormone synthesis via
Wolff-Chaikoff effect (Transient- 10 days)
Decreases thyroid organ vascularity
What are the indications for iodide therapy?
a) Severe hyperthyroidism, e.g. thyroid storm
b) Preoperative prep of pts for thyroidectomy (decreases vascularity)
c) Adjunct therapy following radioiodide or antithyroid drugs
d) After major nuclear accidents to prevent radioiodine uptake
What adverse effect is a/w iodide therapy?
Can exacerbate hyperthyroid sx if given alone. Prevent by using as an adjunct therapy following either radioiodide or antithyroid drugs.
What disease of the thyroid can bile acid sequesterants such as cholestyramine be used to treat?
Thyroid storm (prevents the absorption of thyroid hormone)
When are bisphosphonates indicated for use, besides osteoporosis, hypercalcemia, Paget’s?
Metastatic bone disease
Osteogenesis imperfecta
What are the adverse effects of bisphosphonates besides esophageal irritation, osteonecrosis of the jaw, and hypocalcemia?
When are they contraindicated?
Renal impairment
Ocular side effects
Contra:
Esophageal disease
CKD
What are the adverse effects of denosumab, and when is it contraindicated?
Hypocalcemia
Osteonecrosis of the jaw
Contra: hypocalcemia
When is calcitonin indicated for use, besides severe hypercalcemia, 2nd-line osteoporosis, and 2nd-line Paget’s?
Bone pain a/w osteoporotic fx
What are the adverse effects of calcitonin, besides hypocalcemia?
Concern regarding ↑ rates of cancer
Rhinitis/epistaxis
What are the adverse effects of teriparatide, besides (transient) hypercalcemia?
When is it contraindicated?
Hyperuricemia
↑ Risk of osteosarcoma
H/o gout Hypercalcemia Regarding risk of osteosarcoma: - Active malignancy of the bone - Radiation therapy of the bone - Paget’s Disease of the bone - Children /adolescents
When is cincalcet indicated, besides primary hyperparathyroidism and secondary hyperparathyroidism (due to CKD, on dialysis)?
Hypercalcemia a/w parathyroid carcinoma
What are the adverse effects of cincalcet?
When is it contraindicated?
Hypocalcemia: ↑ Seizure risk
If serum Ca2+ is < 8.4 mg/dL
What drug is not to be administered in presence of hyperphosphatemia due to risk of metastatic calcification?
Vitamin D (calcitriol, doxercalciferol, ergocholecalciferol, cholecalciferol)
What drug is useful for protecting against metastatic calcification when vit D is administered in the presence of hyperphosphatemia?
Sevelamer
What corticosteroids are best for hormone replacement therapy? (acute/chronic adrenal insufficiency, CAH)
Hydrocortisone (cortisol replacement)
or
Fludrocortisone (aldosterone replacement)
What corticosteroids are best for non-endocrine therapy? (auto-immune diseases, asthma, anti-inflammatory, cancer, cerebral edema)
Prednisone/dexamethasone
List 5 adrenal corticosteroid synthesis inhibitors.
Ketaconazole Etomidate (IV) Metyrapone Mitotane Mifepristone
What other drug has the same MoA as ketaconzaole?
What is said MoA?
Etomidate
Inhibits CYP11A1/CYP11B1
Decreases cortisol synthesis
What is the MoA for metyrapone?
Inhibits CYP11A1/CYP11B2
Decreases cortisol synthesis
What is the MoA for mifepristone?
Glucocorticoid receptor antagonists (@ high dose)
Decreases cortisol response
When are the 5 adrenal corticosteroid synthesis inhibitor drugs indicated for use?
Tx of Cushing’s disease when surgery is not an option, delayed, or refused.
What adverse effect is a/w all 5 of the adrenal corticosteroid synthesis inhibitors?
Which of the 5 have other adverse effects?
All: increased risk of adrenal insufficiency
Ketaconazole: Hepatotoxicity, impotency, gynecomastia Etomidate (IV): Metyrapone: Mitotane: GI/Rash/ataxia Mifepristone: Abortifascent
*Which of the 5 adrenal corticosteroid synthesis inhibitors is safe during pregnancy?
Metyrapone
Which glucocorticoid is indicated in neonatal respiratory distress syndrome, and why?
Dexamethasone (crosses blood-placenta barrier without being inactivated by enzymes)
Name the short-acting, intermediate-acting, and long-acting glucocorticoids.
Short: Hydrocortisone AKA cortisol; cortisone (inactive)
Intermediate: Fludrocortisone (mineralocorticoid) prednisone (inactive pro-drug); prednisolone; triamcinolone
Long: Dexamethasone; beclamethasone
What is the name of the channel that sulfas and meglitinides close?
Kir6.2/Sur1
beta-cell K+ channel
What is the MoA for mitotane?
Ablation of adrenocortical cells
Decrease cortisol synthesis
What’s another name for hydrocortisone?
Cortisol (NOT cortisone!)
