Exam 2 Flashcards
starting age and interval at which patients should be screened for elevated cholesterol, which components should be tested?
all adults 20 years or older should be screened every 5 years using a fasting blood sample, total cholesterol, non-HDL cholesterol, LDL cholesterol, HDL cholesterol, triglycerides
which lipid component is primary diagnostic and therapeutic target?
LDL
chronic kidney disease, hypothyroidism, obstructive liver disease/biliary cirrhosis
secondary causes of hyperlipidemia
- established clinical ASCVD (secondary prevention)
- Elevation of LDL cholesterol levels 190 or higher (primary)
- Diabetes age 40-75 regardless of LDL cholesterol levels
- Without diabetes, age 40-75, with an estimated 10-year risk of 7.5% or greater and LDL cholesterol 70-189
4 risk groups for statin treatment
patients between the ages of 40-75 who have cholesterol between 70-189, should be used to evaluate primary prevention not secondary prevention
group that require ASCVD risk calculation
family history of premature ASCVD (male < 55, female < 65), primary hypercholesterolemia, metabolic syndrome, chronic kidney disease, chronic inflammatory conditions like psoriasis/RA/HIV/AIDS, history of premature menopause (before 40 years) and history of pregnancy associated conditions that increase later ASCVD risk (preeclampsia), high risk race/ethnicities (South Asian ancestry), lipid/biomarkers associated with increased ASCVD risk
risk enhancing factors for hyperlipidemia
coronary heart disease (MI, angina), cerebrovascular disease (stroke, TIA), peripheral artery disease
examples of clinical ASCVD
acute coronary syndrome, MI, ischemic stroke, peripheral arterial disease
major ASCVD events
- dietary cholesterol < 200 mg/day
- saturated fats < 7% of total calories and reduce intake of trans fatty acids
- therapeutic options for LDL-lowering plant stanols/sterols 2 g/day
- increase viscous (soluble) fiber 10-25 g/day
- total calories - adjust caloric intake to maintain desirable body weight and prevent weight gain
- physical activity 150 min/week of moderate intensity or 75 min/week of vigorous intensity
examples of lifestyle changes that are recommended to reduce cardiovascular risk
- inhibitor of HMG-CoA reductase
- 10-80 mg daily at any time of day, dose adjustment in renal dysfunction patients is not necessary
- adverse effects: constipation, abdominal pain, diarrhea, nausea, myopathy (change therapy)
- contraindications: acute liver failure, decompensated cirrhosis
- monitoring: lipid panel, AST, ALT
atorvastatin
- inhibitor of HMG-CoA reductase
- 20-40 mg as a single dose in the evening or 40 mg twice daily, 80 mg ER once daily, dose adjustment for mild to moderate renal impairment not necessary
- adverse effects: constipation, abdominal pain, diarrhea, nausea, myopathy (change therapy)
- contraindications: acute liver failure, decompensated cirrhosis
- monitoring: lipid panel, AST, ALT
fluvastatin
- inhibitor of HMG-CoA reductase
- 10-80 mg as a single dose with evening meal or divided twice daily with food, patients with severe renal insufficiency (CrCl above 30) dosages above 20 mg/day should be carefully considered and used cautiously
- adverse effects: constipation, abdominal pain, diarrhea, nausea, myopathy (change therapy)
- contraindications: active liver failure or decompensated cirrhosis, concomitant use of strong CYP3A4 inhibitors and erythromycin
- monitoring: lipid panel, AST, ALT
lovastatin
- inhibitor of HMG-CoA reductase
- 1-4 mg/day as a single dose that can be taken with or without food at any time of day, moderate renal impairment and end stage renal disease on hemodialysis should have starting dose of 1 mg daily (max 2 mg daily)
- adverse effects: constipation, abdominal pain, diarrhea, nausea, myopathy (change therapy)
- contraindications: active liver disease, decompensated cirrhosis, coadministration with cyclosporine, significant drug interactions
- monitoring: lipid panel, AST, ALT
pitavastatin
- inhibitor of HMG-CoA reductase
- 10-80 mg.day as a single dose at bedtime, significant renal or hepatic dysfunction starting dose of 10 mg daily recommended
- adverse effects: constipation, abdominal pain, diarrhea, nausea, myopathy (change therapy)
- contraindications: active liver disease, decompensated cirrhosis
- monitoring: lipid panel, AST, ALT
pravastatin
- inhibitor of HMG-CoA reductase
- 5-40 mg/day at any time of day, 40 mg reserved for those who do not achieve LDL cholesterol goal on 20 mg, renal dysfunction or Asian descent starting dose of 5 mg recommended
- adverse effects: constipation, abdominal pain, diarrhea, nausea, myopathy (change therapy)
- contraindications: active liver failure, decompensated cirrhosis
- monitoring: lipid panel, AST, ALT
rosuvastatin
- inhibitor of HMG-CoA reductase
- 5-40 mg/day as a single dose in the evening or divided, mild to moderate renal insufficiency dosage adjustment not necessary but caution should be used in patients with severe renal insufficiency (start at 5 mg daily and closely monitor), due to increased risk of myopathy use of 80 mg dose should be reserved for patients who have been taking it for greater than 12 months without muscle toxicity
- adverse effects: constipation, abdominal pain, diarrhea, nausea, myopathy (change therapy)
- contraindications: acute liver disease, decompensated cirrhosis, concomitant use of CYP3A4 inhibitors (select azole antifungals, select macrolide antibiotics, select HIV protease inhibitors, select hep C virus protease inhibitors), cyclosporine, gemfibrozil
- monitoring: lipid panel, AST, ALT
simvastatin
- inhibits absorption of cholesterol at the brush border of small intestine, decreased delivery of cholesterol to the liver
- 10 mg daily, no dosage adjustment necessary in patients with renal or mild hepatic insufficiency
- adverse effects: increased serum transaminases and hepatotoxicity, myopathy
- contraindications: significant drug interactions
- monitoring: lipid panel, AST, ALT
ezetimibe
- forms nonabsorbable compex with bile acids in intestine releasing chloride ions in the process, inhibits enterohepatic reuptake of intestinal bile salts increasing fecal loss of LDLs
- 4-24 g/day in two or more divided doses
- adverse effects: nausea, constipation, bloating, flatulence, impairs absorption of fat-soluble vitamins
- contraindications: complete biliary obstruction
- monitoring: lipid profile
cholestyramine
- binds with bile acids in intestine to form insoluble complex that is eliminated in the feces, results in increased oxidation of cholesterol to bile acid lowering serum cholesterol
- 3.75 g/day as single dose or divided twice daily with meals
- adverse effects: nausea, constipation, bloating, flatulence, impairs absorption of fat soluble vitamins
- contraindications: history of bowel obstruction, serum TG concentrations of more than 500 mg/dL, history of hypertriglyceridemia induced pancreatitis
- monitoring: lipid profile
colesevelam
- binds with bile acids in intestine to form insoluble complex that is eliminated in feces, results in increased oxidation of cholesterol to bile acid lowering serum cholesterol
- 5-30 g/day as single or divided dose
- adverse effects: nausea, constipation, bloating, flatulence, impairs absorption of fat soluble vitamins
- no contraindications
- monitoring: lipid profile
colestipol
- may involve several actions including partial inhibition of release of free fatty acids from adipose tissue and increased lipoprotein lipase activity which may increase the rate of chylomicron triglyceride removal from plasma
- ER is 1000-2000 mg daily at bedtime (use with caution in patients with renal impairment), IR is 1-6 g/day in two to three divided doses (do not exceed 6 g daily)
- adverse effects: flushing, itching, gastric distress, headache, hepatotoxicity, hyperglycemia, hyperuricemia
- contraindications: active hepatic disease or significant/unexplained persistent elevations in hepatic transaminases, active peptic ulcer, arterial hemorrhage
- monitoring: blood glucose in patients with diabetes, if on concurrent statin then may periodically check CPK and serum potassium, liver function tests pretreatment, lipid profile, platelets, PT, uric acid, phosphorous
niacin ER and IR
- agonist for PPAR-alpha, increase in VLDL catabolism, fatty acid oxidation, elimination of triglyceride rich particles
- 54-160 mg/day, dosage should be minimized in severe renal impairment
- adverse effects: nausea, diarrhea, abdominal pain, rash, increased risk of rhabdomyolysis when given with statin, gallstones, myositis, hepatitis
- contraindications: acute liver disease, biliary cirrhosis, persistent liver function abnormality, severe kidney impairment or end stage kidney disease, preexisting gallbladder disease, breastfeeding
- monitoring: periodic blood counts during first year, lipid profile, LFTs, kidney function, S/S of myopathy
fenofibrate
- can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL, together these actions decrease serum VLDL levels and increase HDL
- 1200 mg/day in two doses 30 minutes before meals, should be avoided in hepatic or severe renal impairment
- adverse effects: nausea, diarrhea, abdominal pain, rash, increased risk of rhabdomyolysis when given with statin, gallstones, myositis, hepatitis
- contraindications: hepatic or severe renal dysfunction, primary biliary cirrhosis, preexisting gallbladder disease, concurrent use with dasabuvir, repaglinide, simvastatin, significant drug interactions exist
- monitoring: serum cholesterol, LFTs, CBC
gemfibrozil
- reduction in the hepatic production of triglyceride-rich very VLDLs
- 4 g/day taken as a single dose or two 2 g doses daily
- adverse effects: should be used in caution in patients with known hypersensitivity to fish/shellfish, dysgeusia (loss of taste), dyspepsia, eructation (burping)
- no contraindications
- monitoring: triglycerides and other lipids (LDL) should be monitored at baseline and periodically, ALT/AST
omega-3-ethyl esters
- reduction in the hepatic production of triglyceride rich VLDLs
- 2 g twice daily with meals
- adverse effects: should be used in caution in patients with known hypersensitivity to fish/shellfish, arthralgia
- no contraindications
- triglycerides and LDL monitored at baseline and periodically, hepatic impairment need to monitor ALT/AST, S/S of bleeding
icosapent ethyl
- human monoclonal antibody that binds to and inhibits PCSK9 which binds to LDL receptors on hepatocyte surfaces to promote downregulation of the receptors within the liver, this inhibition increases the number of LDL receptors available to clear LDL which lowers LDL levels
- 75-150 mg once every 2 weeks SubQ injection or 300 mg once every month
- adverse reactions: injection site reactions, nasopharyngitis, influenza, upper respiratory tract infections, urinary tract infections, elevation in liver enzymes
- contraindications: hypersensitivity to the drug
- monitoring: lipid profile, hypersensitivity reactions
alirocumab
- human monoclonal antibody that binds to and inhibits PCSK9 which binds to LDL receptors on hepatocyte surfaces to promote downregulation of the receptors within the liver, this inhibition increases the number of LDL receptors available to clear LDL which lowers LDL levels
- 140 mg every 2 weeks or 420 mg once monthly subQ injection
- adverse effects: injection site reactions, nasopharyngitis, influenza, upper respiratory tract infections, urinary tract infections, back pain
- contraindications: hypersensitivity to drug
- monitoring: lipid profile, monitor for hypersensitivity reactions
evolocumab
- adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers LDL cholesterol by inhibiting cholesterol synthesis in the liver
- 180 mg once daily, no dosage adjustments for patients with renal or hepatic insufficiency
- adverse effects: hyperuricemia
- contraindications: hypersensitivity to drug
- monitoring: lipid levels, S/S of hyperuricemia, assess uric acid levels as clinically indicated, S/S of tendinopathy or tendon rupture
bempedoic acid
atorvastatin 40-80
rosuvastatin 20-40
high intensity statins (greater than or equal 50% reduction)
atorvastatin 10-20
rosuvastatin 5-10
simvastatin 20-40
pravastatin 40-80
lovastatin 40-80
fluvastatin XL 80
fluvastatin 40 BID
Pitavastatin 1-4
moderate intensity statins (30-49% reduction)
simvastatin 10
pravastatin 10-20
lovastatin 20
fluvastatin 20-40
low intensity statin (less than 30% reduction)
what intensity statin in recommended for secondary prevention with history of multiple ASCVD events?
high intensity
what intensity statin is recommended for secondary prevention with history of 1 major ASCVD event + multiple high risk conditions?
high intensity
what intensity statin is recommended for primary prevention with LDL greater than or equal to 190?
high intensity
what intensity statin is recommended for primary prevention with LDL 70-189 without diabetes (2 categories)?
ASCVD risk 7.5-20% and risk factors, moderate intensity
ASCVD risk greater than 20%, high intensity
what intensity statin is recommended for primary prevention with LDL 70-189 with diabetes?
moderate intensity
when is ezetimibe used?
used primarily in combination with a statin when adequate reductions in cholesterol are not achieved or in patients who are statin intolerant
when are PCSK9 inhibitors used?
recommended to be added to maximum tolerated statin therapy in very high risk ASCVD patients
at what level are triglycerides addressed? what drug therapy options are recommended to treat elevated triglycerides?
above 500 mg/dL, niacin, fibrates, long chain omega-3 fatty acids
when should a repeat lipid panel be drawn?
4-12 weeks after initiation/titration and then every 3-12 months after that
when would it be recommended to reduce the dose of a statin?
muscle pain, liver enzyme abnormalities, kidney dysfunction
what components are used in the assessment of an overweight or obese patient?
body mass index (BMI), waist circumference (WC), body fat percentage, comorbidities, readiness to lose weight
BMI less than 18.5
underweight BMI classification
BMI 18.5-24.9
normal weight BMI classification
BMI 25-29.9
overweight BMI classification
BMI 30-34.9
obesity class 1 BMI classification
BMI 35-39.9
obesity class 2 BMI classification
BMI greater than or equal to 40
extreme obesity class 3 BMI classification
high risk waist circumference for men and women?
greater than 40 inches in men and greater than 35 inches in women
CVD, type 2 diabetes, sleep apnea, cardiovascular risk factors (smoking, elevated LDL, decreased HDL, impaired fasting glucose)
comorbidities and risk factors that heighten the need for treatment of an overweight patient
what is the recommended initial weight loss goal and in what time frame should this occur?
5-10% weight loss, 1-2 lb per week meeting the initial weight loss goal within the first 6 months of therapy
who is weight loss indicated for?
BMI of 25-29.9 with one or more indicators of increased CVD risk (elevated waist circumference, prediabetes or type 2 diabetes, HTN, dyslipidemia, current cigarette smoker) or for any patient with BMI greater than 30
anticonvulsants/mood stabilizers (carbamazepine, gabapentin, pregabalin, lithium), antidepressants (phenelzine, mirtazapine, citalopram, escitalopram, duloxetine), antidiabetics (insulin, glipizide, glyburide)
drug therapies that could contribute to weight gain
how many calories reduced equals one pound of weight loss?
500 calories
when should pharmacotherapy be initiated in addition to lifestyle modifications for weight loss?
BMI 27-29.9 with comorbidity or any BMI above 30
when should weight loss pharmacotherapy be discontinued?
weight will likely be regained if lifestyle changes/therapeutic interventions are not continued indefinitely
in which patients is bariatric surgery an option?
when other treatment attempts have failed in severely obese patients (BMI greater than 40 or greater than 35 with obesity related comorbidities)
what medication adjustments need to be considered after bariatric surgery?
crush tablets, open capsules, use liquids until appropriate to restart solid foods, avoid NSAIDs, diuretics, oral bisphosphonates, extended/delayed release products
- sympathomimetic amine, stimulation of the hypothalamus to release NE
- 8-37.5 mg daily given in 1-3 divided doses
- adverse effects: restlessness, tremor, palpitations/tachycardia, HTN, pulmonary HTN
- contraindications: history of cardiovascular disease, hyperthyroidism, glaucoma, agitated states, history of drug abuse, MAO inhibitor within 14 days, pregnancy, breastfeeding
- monitoring: weight and waist circumference every month for first 3 months, then at 3-month intervals
phentermine
- first drug is a sympathomimetic amine, stimulation of the hypothalamus to release NE, other drug blocks neuronal voltage-dependent sodium channels, enhances GABAA activity
- 3.75/23 mg daily x 14 days, 7.5/46 mg daily x 12 weeks, titrate up to 11.25/69 mg daily x 14 days then 15/92 mg daily if first 12 weeks successful
- adverse effects: constipation, paresthesia, xerostomia, blurred vision, impaired cognition, headache, kidney stones, increased upper respiratory tract infections, tachycardiac, metabolic acidosis
- contraindications: hyperthyroidism, MAO inhibitor within 14 days, pregnancy, glaucoma
- monitoring: weight, resting HR, serum potassium, glucose, creatinine, BP, mood disorders, glaucoma, dermatologic reactions
phentermine/topiramate
- reducing appetite appears to be secondary to CNS effects including stimulation of the hypothalamus to release NE
- SHORT TERM THERAPY: IR 25 mg 3 times daily 1 hour before meals, CR 75 mg once daily midmorning
- adverse effects: cardiac arrhythmias, ECG changes, HTN, palpitations, tachycardia, anxiety, depression, dizziness
- contraindications: arteriosclerosis, severe HTN, hyperthyroidism, glaucoma, agitated states, history of drug abuse, MAO inhibitor within 14 days
- monitoring: baseline cardiac evaluation, weight, waist circumference, BP, HR
diethylpropion
- sympathomimetic amine, reducing appetite appears to be secondary to CNS effects, including stimulation of the hypothalamus to release NE
- SHORT TERM THERAPY: ER 105 mg once daily 30-60 minutes before morning meal, IR 17.5-35 mg 2-3 times daily 1 hour before meals
- adverse effects: flushing, HTN, palpitations, tachycardia, agitation, dizziness, headache, insomnia
- contraindications: glaucoma, pregnancy, highly nervous or agitated patients, history of drug abuse, hyperthyroidism, MAO inhibitor within 14 days
- monitoring: baseline cardiac evaluation, weight, waist circumference, BP, HR
phendimetrazine
first drug is a pure opioid antagonist, second drug is a relatively weak inhibitor of the neuronal reuptake of dopamine and NE, may result from action on areas of the brain involved in regulation of food intake
- LONG TERM THERAPY: tablets come as 8/90 mg daily x 1 week, increase as tolerated in weekly intervals, maximum dose 4 tabs/day
- adverse effects: constipation, nausea, vomiting, headache, insomnia, sleep disturbances
- contraindications: concomitant use of other products containing the drugs, chronic opioid, opiate agonist/partial agonist, acute opioid withdrawal, HTN, seizures, abrupt discontinuation of other drugs, MAO inhibitor within 14 days
- monitoring: BP, HR, blood glucose, weight, BMI, renal and liver function, mental status for depression, suicidal ideation, anxiety
naltrexone/bupropion
- reversible inhibitor of gastric and pancreatic lipases thus inhibiting absorption of dietary fats by 30%
- Rx is 120 mg TID with each main meal during or up to 1 hour after the meal, OTC is 60 mg 3 times daily with each main meal containing fat
- adverse effects: vitamin deficiency, abdominal distress, abdominal pain, bowel urgency, frequent bowel movements, headache, back pain, infections
- contraindications: pregnancy, chronic malabsorption syndrome, cholestasis
- monitoring: BMI, weight, diet, serum glucose in patients with diabetes, LFTs in patients with hepatic impairment, renal function in patients at risk of renal impairment
orlistat
- long acting analog of human glucagon-like peptide-1 (GLP-1) which increases glucose dependent insulin secretion, decreases inappropriate glucagon secretion, increases B-cell growth and replication, slows gastric emptying, decreases food intake
- LONG TERM, SC 0.6 mg once daily for 1 week, increase by 0.6 mg/day at weekly intervals to a target dose of 3 mg once daily
- adverse effects: acute kidney injury, gallbladder disease, GI symptoms, medullary thyroid carcinoma, pancreatitis
- contraindications: history/family history of medullary thyroid carcinoma, pregnancy
- monitoring: plasma glucose, renal function, pancreatitis, triglycerides, gallbladder disease, suicidal thoughts/behaviors, HR, body weight
liraglutide
- selective glucagon-like peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, slows gastric emptying; also acts in the areas of the brain involved in regulation of appetite and caloric intake
- SC injection - 0.25 mg weekly for weeks 1-4 and titrate up every 4 weeks to maintenance dose of 2.4 mg weekly
- adverse effects: acute kidney injury, gallbladder disease, GI symptoms, medullary thyroid carcinoma, pancreatitis
- contraindications: history/family history of medullary thyroid carcinoma, patients with multiple endocrine neoplasia syndrome type 2
- monitoring: plasma glucose, heart rate, body weight, renal function, S/S of pancreatitis or gallbladder disease
semaglutide
- glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, slows gastric emptying, and decreases food intake (likely due to appetite mediation)
- SC injection - 2.5 mg weekly for 4 weeks and titrate up every 4 weeks to a maximum weekly dose of 15 mg/week
- adverse effects: acute kidney injury, gallbladder disease, GI symptoms, hypoglycemia, medullary thyroid carcinoma, pancreatitis
- contraindications: history/family history of medullary thyroid carcinoma, patients with multiple endocrine neoplasia syndrome type 2
- monitoring: plasma glucose, GI adverse reactions, S/S of pancreatitis or gallbladder disease, emergence of worsening depression/suicidal thoughts or behaviors, changes in behavior, HR, body weight
tirzepatide
- production and release of thyroid hormones are regulated by this
- TRH is synthesized in the neurons within the hypothalamus and is then carried to the pituitary
- TRH activates the pituitary to synthesize and release TSH
- TSH activates thyroid to stimulate the synthesis and secretion of thyroxine (T4) and triiodothyronine (T3)
- T4 and T3 inhibit secretion of TSH which closes the feedback loop
hypothalamic-pituitary-thyroid axis
what is the preferred lab when monitoring patients with thyroid problems? target range?
TSH - highly sensitive biomarker of thyroid axis so changes in TSH are more easily seen, 0.5-4.5 mU/L
presence of these means that there is an autoimmune disorder in the patient and is often present in patients with hypothyroidism
anti-TPOAb
in what disease state is TSHR-SAb found?
Graves’ disease
why are total T4 and total T3 not useful for assessing thyroid function?
high degree of protein binding of these hormones so the free fraction can be changed by the levels of binding proteins or degree of protein binding
chronic autoimmune thyroiditis (Hashimoto’s disease), iatrogenic causes (irradiation, surgery), drugs (amiodarone, radiocontrast media, lithium, interferon alpha tyrosine kinase inhibitors, immune checkpoint inhibitors), transient thyroiditis (viral, postpartum), iodine deficiency/excess, thyroid gland infiltration (infection, malignancies, autoimmune, inflammatory)
primary causes of hypothyroidism
pituitary or hypothalamic disease are examples of…
secondary causes of hypothyroidism
- fatigue, lethargy, sleepiness, mental impairment, depression, weight gain, menstrual disturbances, paresthesia, cold intolerance, change in voice, dry skin, decreased perspiration, decreased appetite, constipation, arthralgia, myalgia, infertility
- slow movements, goiter, slow speech, hoarseness, bradycardia, anemia, dry skin, weight gain, non-pitting edema, hyporeflexia, delayed relaxation of reflexes
hypothyroidism signs and symptoms
replace the missing thyroid hormones, relieve signs/symptoms, achieve a stable biochemical euthyroid (normal thyroid) state
three major goals in treatment of hypothyroidism
why is LT4 the treatment of choice for almost all hypothyroid patients?
LT4 mimics the normal physiology of the thyroid gland which secretes mostly T4 as a prohormone and peripheral tissues convert T4 to T3 as they need it based on metabolic demands
- content: synthetic LT4
- gold standard for treating hypothyroidism
levothyroxine
- content: synthetic T3
- rarely needed in treatment of hypothyroidism, no outcome benefit to combining with LT4
liothyronine
- content: dessicated pork thyroid glands, contains T3 and T4
- non-physiologic T4:T3 ratio, no advantage over LT4 monotherapy
dessicated thyroid (Armour)
how do the pharmacokinetics differ in LT4 and T3?
LT4 has pharmacokinetic advantages over T3, LT4 has a 7-10 day half-life so little peak and trough effect on dose-response curve making LT4 the preferred choice over T3 UNLESS patient has impairment of conversion of T4 to T3 then addition of T3 may be necessary
TRUE/FALSE: patients should be maintained on the same LT4 product which can be done by prescribing name brand without allowing substitution
TRUE
patients with long term ________ (over/under) treatment of hypothyroidism are at risk for atrial fibrillation and other cardiovascular morbidities, anxiety, depression, osteoporosis
over
patients with long term ______ (over/under) treatment of hypothyroidism are at risk for hypercholesterolemia and other cardiovascular problems, depression, obstetric complications
under
how might the coadministration of calcium and iron change the way you counsel a patient on their use of LT4?
LT4 has greatest and most consistent bioavailability when taken in evening on empty stomach, patients should take LT4 dose at least 2 hours before or 6 hours after calcium or iron dose
what factors may alter LT4 dose requirements?
aging, weight loss, drugs/dietary factors, increased TBG (thyroxine-binding globulin) due to cirrhosis, estrogen therapy, increased clearance, critical illness
what is the recommended interval for general monitoring of TSH for hypothyroidism? Following a dose change?
monitor serum TSH every 6-12 months or if change in clinical status, 6-8 weeks after any dose of product change, as soon as possible in pregnancy then monthly
any syndrome resulting from excess thyroid hormone
thyrotoxicosis
related to excess thyroid hormone production and secretion by the thyroid gland
hyperthyroidism
most common cause of hyperthyroidism in non-elderly adults
Graves’ disease
Graves’ disease, toxic multinodular goiter, toxic adenoma, thyroid cancer, struma ovarii, iodine excess (including radiocontrast, amiodarone)
causes of primary hyperthyroidism
TSH-secreting pituitary tumors, trophoblastic (hCG-secreting) tumors, gestational thyrotoxicosis
causes of secondary hyperthyroidism
subacute thyroiditis, silent (painless) thyroiditis, postpartum thyroiditis, excess thyroid hormone intake, drug induced (amiodarone, iodine, lithium, interferons, tyrosine kinase inhibitors, immune checkpoint inhibitors)
thyrotoxicosis without hyperthyroidism
- nervousness, fatigue, weakness, increased perspiration, heat intolerance, tremor, hyperactivity, irritability, palpitations, appetite changes (usually increased), weight change (usually weight loss), menstrual disturbances, frequent bowel movements or diarrhea
- hyperactivity, tachycardia, atrial fibrillation (especially in elderly adults), hyperreflexia, warm/moist skin, ophthalmopathy or dermopathy (Graves’ disease), goiter, muscle weakness
signs/symptoms of hyperthyroidism
_____ (high/low) TSH level signifies thyrotoxicosis, FT4 is _______ (high/low) in overt hyperthyroidism, almost all patients with Graves’ disease will have positive TSHR-SAb and positive anti-TPOAb
low, high
ophthalmologic changes, eyelid retraction, vague eye discomfort or excess tearing, thyroid dermopathy over the lateral aspects of the shins, thyroid clubbing or acropathy
unique clinical features of Graves’ disease as compared to other causes of thyrotoxicosis
many manifestations of hyperthyroidism appear to be mediated by beta adrenergic system so these drugs are used to rapidly relieve palpitations, tremors, anxiety, and heat intolerance, these can only be used until more specific antithyroid therapy is effective because these drugs do not reduce the synthesis of thyroid hormones
beta blockers
which type of beta blockers are used in hyperthyroidism? Why?
nonselective (propranolol or nadolol) because they can impair the conversion of T4 to T3
large doses of iodide inhibit the synthesis and release of thyroid hormones, most commonly used in Graves’ disease patients before surgery and to quickly reduce hormone release in patients with thyroid storm, frequent toxic effects are hypersensitivity reactions and iodism (palpitations, depression, weight loss, pustular skin eruptions, gynecomastia)
iodide (saturated solution of potassium iodide SSKI or Lugol’s solution)
these drugs inhibit thyroid hormone synthesis by interfering with the thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin, used as primary therapy for Graves’ disease or as preparative therapy before surgery or radioactive iodine administration, overall low rate of adverse effects but serious adverse effects can occur (skin rash, arthralgias, GI upset, hepatotoxicity, agranulocytosis)
PTU (can also inhibit conversion of T4 to T3), methimazole
this drug produces thyroid ablation without surgery, iodine is concentrated in the thyroid gland, thyroid cells that have taken up iodine begin to develop abnormalities and necrosis, eventually thyroid cells are destroyed and hormone production is reduced, slow onset of action so most patients are treated with a beta blocker initially to avoid thyroid storm, may cause painful thyroiditis
radioactive iodine
subtotal thyroidectomy indicated in patients with very large goiters or thyroid malignancies or cannot tolerate other therapies/did not respond to other therapies
surgery
- S/S: high fever, tachycardia, tachypnea, dehydration, delirium, coma, GI disturbances
- precipitated in a previously hyperthyroid patient by infection, trauma, surgery, radioactive iodine treatment, sudden withdrawal from antithyroid drugs
- treated with short acting beta blocker like IV esmolol, IV or oral iodide, large doses of PTU or methimazole, supportive care with acetaminophen to suppress fever, fluid and electrolyte management, antiarrhythmic agents, IV hydrocortisone because of potential presence of adrenal insufficiency
thyroid storm
growth and dissemination of ___________ are stimulated by TSH so LT4 is important component of management because it suppresses TSH secretion
thyroid carcinomas
contains two iodine atoms, blocks conversion of T4 to T3, inhibits entry of T3 into cells and decreases T3 receptor binding, rapid reduction in serum T3 levels, increases free and total T4 levels, increases TSH, patients receiving this must receive monitoring (baseline serum TSH, FT4, FT3, anti-TPOAb, TSHR-SAb, should be checked 3 months after initiation and then every 3-6 months
amiodarone
associated with hypothyroidism and may occur after years of therapy, inhibits thyroid hormone synthesis and secretion, may require LT4 replacement even if this drug is discontinued
lithium
causes hypothyroidism in some patients being treated for hepatitis C infection, mechanism not known
interferon alpha
hormone that helps to promote growth of the follicle in preparation for ovulation by causing granulosa cells lining the follicle to grow and produce estrogen, peak levels just prior to ovulation
follicle stimulating hormone (FSH)
hormone that promotes androgen production by theca cells in the follicle, promotes ovulation and oocyte maturation, converts granulosa cells to cells that secrete progesterone just after ovulation, peak levels just prior to ovulation
luteinizing hormone (LH)
spotting or bleeding during which week is caused by insufficient estrogen so the adjustment to be made is increased estrogen or triphasic with lower early progestin?
week 1
spotting or bleeding during which week has a difficult to determine cause so the adjustment to be made is to increase both estrogen and progestin?
week 2
spotting or bleeding during which week is caused by insufficient progestin and the adjustment that can be made is a monophasic OC with increased progestin or triphasic with increasing progestin?
week 3
patients who have been diagnosed with dyslipidemia should be switched to progestin with _______ (lower/higher) androgenicity and some examples of this are…..
lower, norgestimate, norethindrone, drospirenone
a patient consistently experiences headaches during the placebo week of her OC, which formulations could you switch her to?
24 combination hormone tabs, 2 estrogen only, 2 placebos (shorter hormone free interval and may allow for shorter periods and menstrual related symptoms), monophasic combination that is 91 day treatment cycle with 84 active tabs and 7 placebos (allows for one menstrual cycle per season/4 per year)
which combined OCs are FDA approved for acne and are also considered to have low androgenicity?
norgestimate, norethindrone, drospirenone
contain a synthetic estrogen and one of several steroids with progestational activity, primary mechanism of preventing pregnancy is through inhibition of ovulation, other mechanisms include reduced penetration of the egg by the sperm, reduced implantation of fertilized eggs, thickening of cervical mucus to prevent sperm penetration into the upper genital tract, slowed tubal motility which may delay transport of sperm
combined hormonal contraceptives (CHCs)/combined oral contraceptives (OCs)
reduction in risk of endometrial cancer, reduction in risk of ovarian cancer, improved regulation of menstruation and reduction in risk of anemia, reduction in the risk of fetal neural tube defects, relief from symptoms associated with premenstrual dysphoric disorder, prevention of benign breast disease, prevention of ovarian cysts, decrease in symptoms related to endometriosis, improvement of acne control
benefits of oral contraceptives
sexually transmitted infections, cardiovascular events and hypertension, venous thromboembolism, gallbladder disease, hepatic tumors, cervical cancer, breast cancer
risks of oral contraceptives
history of thromboembolic disease, history of stroke or current cerebrovascular disease, history of or current cardiovascular disease/ischemic heart disease/peripheral vascular disease, history of carcinoma of the breast (known or suspected), history of any estrogen-dependent neoplasms (known or suspected), undiagnosed abnormal uterine/vaginal bleeding, pregnancy (known or suspected), breastfeeding less than 21 days postpartum, heavy smoking (15 or more cigarettes daily) by women who are 35 years old or older, history of hepatic tumors (benign or malignant), acute liver disease, migraine headaches with aura
absolute contraindications for combined oral contraceptive use
smoking (less than 15 cigarettes a day) at any age, migraine headaches without aura, hypertension (unacceptable when systolic over 160 or diastolic over 90), fibroid tumors of the uterus, breastfeeding greater than 21 days postpartum, superficial venous thrombosis (acute or history), multiple sclerosis with prolonged immobility, diabetes, family history of dyslipidemia, sickle cell disease, active gallbladder disease, age over 50, elective major surgery requiring immobilization
relative contraindications for combined oral contraceptive use
this type of contraceptive is preferred/recommended for women who are at increased risk of cardiovascular or thromboembolic complications because it is believed that estrogen component of CHCs stimulates enhanced hepatic production of clotting factors
progestin only contraceptives
a patient is taking a chronic medication that increases the metabolism of CHCs by induction of CYP3A4 and is being prescribed a combined oral contraceptive, what do you recommend?
recommend using an alternative non-hormonal method of contraception (backup) during treatment with the CYP3A4 inducer
marked by the final menstrual period resulting from loss of follicular activity and confirmed by 12 months of amenorrhea, FSH is greater than 40 IU/L and a fivefold increase in LH can be seen but the increase in LH is not required to make a diagnosis
menopause
transitional period prior to menopause when hormonal and biologic changes begin, begins with onset of menstrual cycle irregularities/other menopausal symptoms, may still ovulate intermittently during this time
perimenopause
vasomotor symptoms like hot flashes or night sweats, sleep disturbances, mood changes, genitourinary syndrome of menopause (GSM, genital symptoms like dryness/burning/irritation, urinary symptoms like dysuria/urgency/retention/recurrent urinary tract symptoms, sexual symptoms like dryness/dyspareunia), new onset depression, problems with concentration/memory
clinical presentation of menopause
when is use of a progestin required?
women who have an intact uterus should be prescribed a progestin in addition to estrogen due to the increased risk of endometrial hyperplasia and endometrial cancer with estrogen monotherapy/unopposed estrogen
type of HRT administration, estrogen is administered daily, progestin is administered for 12-14 days of the month, menses returns in about 90% of women 1-2 days following the last progestin dose, women may view this scheduled bleeding as an advantage as it limits spotting
continuous estrogen and cyclic progestin
type of HRT administration, estrogen and progestin are administered daily and can result in endometrial atrophy, women do not experience withdrawal bleeding but may experience unanticipated breakthrough bleeding or spotting, this type of HRT administration offers the best protection against endometrial hyperplasia and cancer, if bleeding persists beyond 6-12 months women should seek medical attention to rule out endometrial hyperplasia or cancer
continuous combined estrogen and progestin
first line dosage form for vulvovaginal atrophy? is a progestin used with this dosage form?
topical vaginal preparations for women with moderate to severe GSM who do not respond to lubricants and moisturizers, vaginal estrogen does not require supplementation with progestin in women using low doses but women with an increased risk of endometrial cancer may warrant endometrial surveillance
which has systemic absorption - Femring or Estring?
Femring
this refers to exogenous hormones that are identical to those produced in a woman’s body (estradiol, estrone, estriol, progesterone) that are either commercially manufactured or custom compounded into formulations like topical creams/gels or suppositories
bioidentical hormones
nausea, headache, bloating, breast tenderness, breakthrough uterine bleeding, coronary heart disease, stroke, venous thromboembolism, breast cancer, gallbladder disease are adverse of effects of ________ (estrogen/progestins)
estrogen
nausea, headache, weight gain, bleeding, irritability, depression, decreased bone mineral density are adverse effects of _______ (estrogen/progestins)
progestins
- relief from vasomotor symptoms, pharmacotherapy individualized and reassessed every 6-12 months, extended treatment duration may be warranted for relief of persistent VMS and prevention of bone loss
- relief from GSM, topical vaginal preparations or systemic if VMS are also present
benefits of HRT
what is the recommended duration for hormone replacement therapy?
4-5 years, should be tapered at discontinuation to limit the recurrence of hot flashes, slowly discontinuing HRT over 3-6 months after 4-5 years of therapy is considered reasonable and associated with less risk of recurrent symptoms while mitigating the increase in breast cancer risk that occurs at this time
both arms of this study were terminated early due to significant increase in risk of stroke, VTE, and breast cancer in estrogen plus progestin and stroke in estrogen monotherapy
Women’s Health Initiative (WHI)
type of bone that comprises approximately 80% of the skeleton and its density and compactness account for much of bone strength, generally found on the surfaces of long and flat bones
cortical bone
type of bone that has a sponge-like appearance and is found along the inner surfaces of long bones and throughout the vertebrae, pelvis, ribs, more susceptible to osteoporotic fractures
trabecular bone
type of cells that are involved with resorption or breakdown of bone and continuously create microscopic cavities in bone tissue
osteoclasts
type of cells that are involved in bone formation and continuously mineralize new bone in the cavities created by the other type of cells
osteoblasts
at what age to patients attain their peak bone mass? what does before this age look like in terms of bone formation?
between the ages of 25 and 35, before this time bone formation exceeds bone resorption for an overall increase in bone mass
low bone mineral density, female sex, age 65 and older, race/ethnicity, history of previous low trauma/fragility fracture after age 50, osteoporotic fracture in a first degree relative, low BMI or body weight, premature menopause, secondary osteoporosis, rheumatoid arthritis, oral glucocorticoid therapy, current cigarette smoking, excessive alcohol intake, loss of height
risk factors for osteoporosis
- conditions: alcoholism, chronic kidney disease, COPD, Cushing syndrome, cystic fibrosis, diabetes, eating disorders, GI disorders, hematologic disorders (hemophilia), hyperparathyroidism, hyperthyroidism, hypogonadal states, immunologic diseases (HIV/AIDS, rheumatoid arthritis), organ transplantation, renal failure, skeletal cancer (myeloma), vitamin D deficiency
- drugs: anticoagulants (heparin, warfarin), anticonvulsants (phenytoin, phenobarbital, primidone, valproic acid), aromatase inhibitors (anastrozole, exemestane, letrozole), cytotoxic agents (methotrexate, cisplatin), glucocorticoids (5 mg of prednisone equivalent for at least 3 months), gonadotropin releasing hormone analogs, immunosuppressants, lithium, medroxyprogesterone acetate, PPIs, SSRIs, SGLT2 inhibitors, thyroid supplements, TPN
causes of secondary osteoporosis or bone mass
many patients with osteoporosis are _______ (symptomatic/asymptomatic), when is this true?
asymptomatic UNLESS they experience a low trauma fracture
the number of standard deviations from the mean bone mineral density (BMD) in healthy young white women
T-score
number of standard deviations from the mean bone mineral density (BMD) of age and sex matched controls, corrected for both age and sex of the patient, used more often clinically in premenopausal women, men younger than 50, patients who may have secondary causes for low BMD
Z-score
what is the recommended standardized approach to bone mineral density measurement?
central measurement of BMD by DXA scan at total hip, femoral neck, lumbar spine
women 65 and older, men 70 and older, perimenopausal women and men aged 50-69 with risk factors, anyone with a fracture after age 50, adults with secondary cause for this
recommended groups for BMD measurement for osteoporosis
what is the recommendation for calcium intake? vitamin D intake?
daily calcium intake of 1000 mg for men between 51-70 and 1200 mg for women older than 51 and men older than 71
what is the maximum amount of calcium that can be taken at one time? What amount of calcium can lead to toxicity?
500-600 mg at once, intakes over 1200-1500 mg/day may increase risk of developing kidney stones, supplementation over 2500 mg/day can lead to hypercalcemia, hypercalciuria, and increased risk of cardiovascular events
which patients may prefer calcium carbonate? calcium citrate?
calcium carbonate needs to be taken with food to maximize absorption, older adults or patients taking PPIs or H2 receptor antagonists may have difficulty absorbing calcium supplements due to reduced stomach acidity so calcium citrate may be a better option in these patients because it doesn’t need an acidic environment for absorption and can be taken with or without food
history of hip or vertebral fracture, T score -2.5 or less at femoral neck or spine, osteopenia and at least a 3% 10 year probability of hip fracture or at least a 20% 10 year probability of major osteoporosis related fracture as determined by FRAX
patients recommended for treatment of osteoporosis
an additional tool developed by WHO to evaluate an individual’s 10 year probability of developing hip and major osteoporotic fractures based on femoral neck T-score, age, and other risk factors
FRAX
- inhibit bone resorption via actions on osteoclasts or on osteoclast precursors, decreases the rate of bone resorption leading to an indirect increase in bone mineral density, decreases bone resorption by rapidly binding to the bone matrix and inhibiting osteoclast activity
- take after an overnight fast with plain water while sitting upright for at least 30/60 minutes prior to morning meal, do not crush or chew
- osteonecrosis of the jaw
- prevention and treatment
bisphosphonates
- selective estrogen receptor modulator (SERM), selective binding activates estrogenic pathways in some tissues and antagonizes estrogenic pathways in other tissues, acts as an estrogen agonist in the bone to prevent bone loss (decreases bone resorption increasing bone mineral density and decreasing fracture incidence), overall reduces bone resorption and decreases overall bone turnover
- may be taken with or without food
- treatment
raloxifene
- peptide sequence similar to the human version of this, functionally antagonizes the effects of parathyroid hormone, directly inhibits osteoclastic bone resorption, inhibits bone resorption by binding to osteoclast receptors
- alternate nostrils on a daily basis (nasal spray)
- treatment
calcitonin
- recombinant formulation of endogenous parathyroid hormone containing amino acid sequence, similar activity as parathyroid hormone, stimulates osteoblast function increasing bone mineral density, bone mass, strength
- inject into thigh or abdomen, keep pen refrigerated
- treatment (men and women)
teriparatide
- analog of human parathyroid hormone related peptide which acts as agonist at PTH1 receptor, stimulation of osteoblast function and increased bone mass
- inject into abdomen, keep refrigerated
- treatment (PM)
abaloparatide
- monoclonal antibody that binds to RANKL and blocks the interaction between RANKL and RANK (receptor located on osteoclast surfaces), prevents osteoclast formation leading to decreased bone resorption and increased bone mass
- inject into upper arm, upper thigh, or abdomen, keep refrigerated
- treatment (PM and men)
denosumab
- inhibits sclerostin (regulatory factor in bone metabolism that inhibits the signaling pathway that regulates bone growth) increasing bone formation and to a lesser extent decreases bone resorption, increases production of mature osteoblasts
romosozumab
what is maximum duration of use for Forteo and Tymlos (teriparatide and abaloparatide)?
treatment not recommended beyond 2 years due to unestablished safety and efficacy with long term treatment
