BEP - Endocrine and Hyperlipidemia
MOA of statins
inhibit HMG-CoA reductase, which is the enzyme responsible for a key step in cholesterol formation
MOA of ezetimibe (Zetia)
inhibits absorption of cholesterol from the small intestine
The DPP-4 inhibitors and their brands (4)
"The Gliptins" saxogliptin (Onglyza) alogliptin (Nesina) linagliptin (Trajenta) sitagliptin (Januvia)
Expected decrease in lipid levels wtih PCSK9 inhibitors?
*Decrease LDL: ~60 %*
Which diabetic classes should be avoided in heart failure?
*metformin* in symptomatic heart failure *TZDs (like pioglitazone)*: CI in DHF and can cause/worse edema There is conflicting data with regards to the *DPP-4 inhibitors*, but they should be avoided in severe/symptomatic HF
results when tissues are exposed to excessive levels of thyroid hormone(s)
*thyrotoxicosis* Hyperthyroidism, which is one cause of thyrotoxicosis, refers specifically to overproduction of thyroid hormone by the thyroid gland.
The statin benefit groups
1) anyone 21 and up with ASCVD 2) anyone 21 and up with LDL >/= 190 3) patients 40-75 years old (diabetes or not) with LDL 70 - 189 mg/dl AND *ASCVD risk >/= 7.5%*
A1c range for pre-diabetes
5.6-6.4%
Define hypertensive crises
A SBP > 180 *or* DBP > 120 Assess for end-organ damage to determine whether HTN urgency (no organ damage) or emergency (organ damage)
Patient with HTN and CKD with albuminuria (> 300 mg/d) may benefit from which medication class
ACE Inhibitors (or ARBs when ACEs are not tolerated) may slow kidney disease progression in these patients
MOA of the fibrates
Activate PPARα (a *gene*) ultimately leading to increased catabolism of VLDL particles, decreasing TG significantly
Avoiding DDIs with bile acid sequestrants
Administer other medications one hour before or 4 hours after BAS Use particular care/further seperate: digoxin, levothyroxine, tetracyclines, warfarin, and vitamins
What are the two PCSK9 inhibitors? How are they dosed?
Alirocumab (Praluent): 75-150mg SC once every two weeks OR 300 mg SC monthly Evolocumab (Repatha): 140 mg SC once every 2 weeks or 420 mg once monthly (for HoFH)
All statins are approved in children beginning at what age? What is the exception?
All are approved for 10 year olds and up pravastatin and (I think) simvastatin are approved ages 8 and up
D-PP4 Inhibitor dosing and adjustments Most common ADR Contraindication (1)
All gliptins except linagliptin (Trajenta) require renal dose adjusting sitagliptin (Januvia): normally 100 mg once daily eGFR ≥30 to <45: 50 mg once daily. eGFR <30: 25 mg once daily most common class ADR: upper resp infections including the flu CI: pancreatitis
Who should be screened for diabetes and when?
At a minimum, everyone 45 years or older should be screened every 3 years (annually for higher risk pts)
Two brand names for glucagon emergency kit and their formulations
Baqsimi - nasal dispenser (does not have to be inhaled) GlucaGen - IM injection with generic
Plan for Stage 2 HTN per guidelines
Begin first line agent immediately with management of lifestyle Reassess in one month If patient still has not met goal, you can optimize therapy and/or start a second agent Two agents are indicated when BP is >20/10mmHg over target (150/90)
Blood pressure =
Blood pressure = cardiac output x total peripheral resistance
Plan for Stage 1 HTN per guidelines
Calculate their ASCVD risk. If it is greater than 10%, they have diabetes, or they have CKD, begin them on a first-line antihypertensive and reassess them in one month. If their ASCVD risk is under 10%, try lifestyle modifications and reassess in 3 - 6 months
Candidates for thrombolytic therapy should have their BP lowered SLOWLY (not defined) to *_____________* before rTPA and maintained under *______________* for 24 hrs thereafter Restart appropriate maintenance HTN therapy once patients are neurologically stable
Candidates for thrombolytic therapy should have their BP lowered SLOWLY (not defined) to *< 185/110 mmHg* before rTPA and maintained under *180/105 mmHg* for 24 hrs thereafter Restart appropriate maintenance HTN therapy once patients are neurologically stable
Name the bile acid sequestrants
Colesevelam (Welchol) Cholestyramine Colestipol
renal adjustment for rosuvastatin
CrCl < 30 ml/min: use 5-10mg daily
When should you withdraw medications for a low LDL?
Current evidence says go as low as you can. No recommendations to stop lipid therapy, even if calculated LDL level is negative. Reduce dose when two LDL levels are < 40
Which two diabetic classes are contraindicated in patients with pancreatitis?
DPP-4s and GLP-1 agonists (due to similar MOA involving slowed gastric motility)
Level of lowering expected with niacin
Decrease LDL: 5 to 25% Increase HDL: 15 to 35% Decrease TG: 20-50%
Expected LDL lowering with Zetia
Decrease LDL: ~20 % best case scenario (but lowering is only 6% when a statin dose is doubled)
Expected decrease in LDL on statins
Decrease LDL: ~20 to 55%
MOA of niacin in lipid lowering
Decreases the rate of hepatic synthesis of VLDL and LDL and increases the rate of TG removal from plasma
Diagnostic Criteria for Diabetes: A1c: Fasting BG: 2-hr PP glucose:
Diagnostic Criteria for Diabetes: A1c: *> 6.5%* Fasting BG: > 126 2-hr PP glucose: > 200 + symptoms
Plan for elevated BP per guidelines
Elevated BP: give more specific and stringent lifestyle modifications FIRST Reassess in 3 - 6 months (giving the patient time to make these changes) If still high in 6 months, may consider starting a low-dose ACE or ARB
How does fish oil lower TGs? How much can they lower TG?
Exact mechanism is not completely understood. May reduce hepatic synthesis of triglycerides. TG reduction: ~10-30% LDL inc: Up to 44% (lovaza)
Ezetimibe Brand: Dosing: Interactions:
Ezetimibe Brand: Zetia Dosing: 10mg once daily without regard to food Interactions: - statins increase risk of myopathy - combination with a fibrate increases risk of gallbladder disease - bile acid resins decrease absorption
Fibrates: fenofibrate, fenofibric acid, and gemfibrozil Brands: primary benefit: ADR and monitoring: absolute contraindication (1)
Fibrates: fenofibrate, fenofibric acid, and gemfibrozil Brands: *fenofibrate: Tricor* dosed once daily fenofibric acid: *gemfibrozil: Lopid* dosed twice daily with food primary benefit: triglyceride lowering through reduction of apolipoproteins ADR and monitoring: - increased risk of myopathy with statins - gallstones can happen (avoid in history of gallbladder disease) - CYP 3A4 interactions and renally dose adjusted absolute contraindication: severe renal or hepatic disease
Contraindications to GLP-1 agonist use
GLP-1 = injectable non-insulin medications CIs: pancreatitis, gastroporesis (as MOA slows gastric emptying), and medulary thyroid cancer
Goals for diabetic patients: A1c: Fasting BG: 2-hr PP glucose:
Goals for diabetic patients: A1c: < 7% (with more and less stringent goals for certain populations) Fasting BG: 80 - 130 2-hr PP glucose: < 180
the autoimmune condition resulting from cell and antibody-mediated thyroid injury
Hashimotos (hypothyroid)
Bempedoic acid dosing and adjustments
HeteroFH and ASCVD: 180 mg orally once daily with or without food Renal Dose: Limited data in eGFR < 30 but no dose adjustments provided
HeFH and HoFH
Heterozygous Familial Hypercholesterolemia and Homozygous Familial Hypercholesterolemia
What do high and low serum TSH levels indicate?
In GENERAL: Low TSH levels indicate *hyperthyroidism* as the stimulating hormone is negatively downregulated by high free thyroid hormone concs. In hypothyroidism, you are more likely to see elevated TSH levels as the hormone tries to correct the deficiency.
In black adults with hypertension but without HF or CKD, including those with DM, initial antihypertensive treatment should include:
In black adults with hypertension but without HF or CKD, including those with DM, initial antihypertensive treatment should include: a thiazide-type diuretic or CCB If they have diabetes, must have an ACE on boards
What is lomitapide?
Juxtapid Binds and inhibits microsomal triglyceride transfer protein (MTP) which prevents the assembly of apoB containing lipoproteins Approved for use in HomoFH
Formula for LDL calculation
LDL = TC - (HDL + TG/5) where TG/5 is estimating VLDL *do not use Friedewald equation when TG are > 400*
LDL lowering effects of Nexletol
LDL reduction ~18%
Lipid effects of fibrates
Lipid Effects Decrease TG: 20 to 50% Increase HDL: ~15% Decrease LDL: ~5 to 20% (can increase LDL when TG are high) No conclusive data to reduce ASCVD risk
brand names of lovastatin
Mevacor, Altoprev
The non-dihydropyridine CCBs and how they're different
NON-DHPs: verapamil and diltiazem These REDUCE cardiac contractility (negative inotropic effect)
Niacin (nicotinic acid, vitamin B3) Brands: primary benefit: ADR and monitoring: (4/5) absolute contraindication (1)
Niacin (nicotinic acid, vitamin B3) Brands: Niaspan is ER, Slo-Niacin is SR, Niacor is IR primary benefit: lowers triglycerides and LDL ADR and monitoring: - GI upset: take with food and titrate up slowly - flushing: avoid alcohol, hot drinks, and spicy food. pre-treat with first dose of the day using ASA 325 or 200mg ibuprofen - hepatotoxicity (regular LFT monitoring reqd) - elevation in uric acid and serum glucose (diabetes, gout, and peptic ulcer disease are relative contraindications: absolute contraindication: severe liver disease
Do patients need to go to the hospital if they have hypertensive urgency without signs of organ damage?
No But they must follow up with their provider within two weeks to modify HTN regimen.
Can you use statins in pregnant or breastfeeding women?
No (only Welchol/colesevelam is used in pregnancy for hyperlipidemia)
Low Na+ dietary recommendation for HTN
No more than 2,400mg of sodium a day and ideally less than 1,500mg/day
Does Zetia require dose adj? What are the most common ADR with Zetia?
No renal dose adjustment Myalgias and arthralgias can happen, but these are typically very well tolerated with little-no side effects
Bile Acid Sequestrants MOA
Non-absorbed, lipid-lowering polymers that bind bile acids in the intestines and impede their reabsorption to ↓ LDL-C levels: As monotherapy or in combination with statin.
Normal blood pressure definition: Elevated classification:
Normal blood pressure definition: <120 and < 80 mmHg Elevated classification: SBP 120-129 *and* DBP < 80
Omga-3 fatty acid dosing for prescription forms What would be the equivalent of OTC caps?
Omga-3 fatty acid dosing for prescription forms: 4g daily or 2g BID What would be the equivalent of OTC caps? Up to 11 capsules may be needed for equivalent effect
Optimal/desirable lipid levels: TC: LDL: HDL: TG:
Optimal/desirable lipid levels: TC: < 200 LDL: < 100 HDL: > 40 TG: < 150
Per the *AHA* guidelines, everyone receiving HTN therapy has a BP goal of:
Per the *AHA* guidelines, everyone receiving HTN therapy has a BP goal of: 130/80 mmHg The ADA and KDIGO guidelines have more lenient disease-specific recommendations (AHA is more strict)
Indications for PCSK9 inhibitors
Praluent and Repatha are indicated in HETERO-FH and in patients with ASCVD on optimal statins (or who cannot tolerate them) who require additional LDL lowering Repatha (evolocumab) is also used in HoFH
MOA of PCKS9 Inhibitors
Proprotein convertase subtilisin klexin type 9 (PCSK9) is an enzyme that degrades the LDL receptor. These MABs block PCSK9's ability to bind to the LDL receptor to dramatically reduce LDL cholesterol.
ADR/Monitoring with Juxtapid (lomitapide)
REMS program for hepatotoxicity ADR: NVD Dyspepsia, abd pain, constipation, flatulence Increased LFTs Chest/back pain and fatigue Monitoring LFTS and lipids
Dose reduction with fibrates
Reduce fibrate dose if CrCl:31-80 mL/min. (may use lowest available dose) *Do not use gemfibrozil with statins or Zetia
brand for oral semaglutide how should it be taken?
Rybelsus taken with 4 oz plain water only and kept in original blister card until time for dose
What should you do if a patient with ICH (intracerebral hemorrhage) presents to the hospital with: SBP > 220mmHg? < 220 mmHg?
SBP > 220mmHg: lower BP with continuous antihypertensive infusion with close monitoring < 220 mmHg: Do not seek to lower BP using continuous infusion, as this may lead to poor outcomes in ICH
SGLT2 Renal Cutoffs Class-wide ADR Invokana (cana) specific risk
SGLT2 Renal Cutoffs (These differ from APhA book and Lexicomp) canagliflozin (Invokana) and empagliflozin (Jardiance) should not be used with eGFR < 30 No renal cutoff for dapagliflozin (Farxiga) on Lexicomp Class-wide ADR: *euglycemic DKA* Invokana (cana) specific risk: lower limp amputation
For HTN emergency, what are some signs of end-organ damage where you should refer someone to the ER?
Signs of target organ damage: severe headache, confusion, vision changes, chest pain. These may be indicative or encephalopathy, stroke, MI, liver failure, unstable angina aneurysm, acute renal failure, etc.
Stage 1 HTN definition: Stage 2 HTN definition:
Stage 1 HTN definition: SBP 130-139 *or* DBP 80-89 Stage 2 HTN definition: SBP > 140 *or* DBP > 90 mmHg
Hwo quickly does statin-related muscle weakness develop?
Statins have to accumulate before peripheral HMG-CoA are affected; typically seen day 3-4 to 14 days after dose change or initiation.
triiodothyronine hormone
T3 the more potent thyroid hormone
thyroxine hormone
T4 secreted from thyroid and converted to T3 in the periphery
The SGLT-2 inhibitors and their brands (3)
The Flozins empagliflozin (Jardiance) canagliflozin (Invokana) dapagliflozin (Farxiga)
What is the primary use for omga-3 fatty acids? What is one lipid-related drawback?
They reduce triglycerides but may also increase LDL
Monitoring for levothyroxine
Thyroid function tests (TSH and T4)- 6-8 weeks after initiating therapy or dose adjustment and then annually once euthyroid
When do patients qualify for two anti-hypertensives as initial therapy?
Two agents are indicated when BP is >20/10mmHg over target (Typically > 150/90)
Which fish oil product has shown ASCVD risk benefit in clinical trials?
Vascepa (icosapent ethyl)
ingredients of: Vascepa Lovaza
Vascepa: icosapent ethyl Lovaza: Omega-3 ethyl esters
Definition of resistant hypertension
When a patient is prescribed three antihypertensive meds at optimal doses, including a diuretic, and their BP is still elevated. OR When a patient has a BP at goal but is requiring four or more medications to do so.
a-glucoside inhibitors and their brands why aren't these used much?
acarbose (Precose) miglitol (Glyset) These delay carb digestion so they have significant GI upset They are also does frequently and aren't highly efficacious in lowering A1c
Tx for Cushing's Disease: 4 drugs and their brands
all of these decrease synthesis of cortisol ketoconazole (Nizoral) aminoglutethimide (Cytadren) mitotane (Lysodren) metyrapone (Metopirone)
The dihydropyridine CCBs and what makes them so
amlodipine and nifedipine negligible effect on cardiac contractility
What is ticlodipine?
antiplatelet no longer available in the US due to significant risk of blood dyscrasias and use replaced by clopidogrel (brand names include ticlodipine)
What are the high intensity statin options?
atorvastatin 40mg and 80mg rosuvastatin 20mg and 40mg
What is Nexletol?
bempedoic acid This is an adenosine triphosphate-citrate lyase (ACL) inhibitor which inhibits cholesterol synthesis in the liver Typically going to be reserved for maximally dosed statins and Zetia as third option to help reach lipid goals.
This class of anti-hyperlipid medications can be used in hepatic failure
bile acid sequestrants
Which two SGLT-2 inhibitors provide CV benefit? (brand and generic) Which ones (may) improve renal function and hypertension?
canagliflozin (Invokana) and empagliflozin (Jardiance) improve CV outcomes the entire class may improve renal function and lower BP (esp in patients with DMT2)
brand names of the bile acid resins and their dosage forms
cholestyramine (Questran) - powder only colestipol (Colestid) - powder and tablets colesevelam (Welchol) - tablets only (large size)
Which antihyperlipidemic agent is safest in pregnany?
colesevelam (Welchol) - category B other BAS are category C statins are category X
3 absolute contraindications for bile acid sequestrants and 1 relative contraindication
contraindications: history of bowel obstruction hypertriglyceride-associated pancreatitis triglycerides > 500 Use caution when TG are > 200 (may exacerbate hypertriglyceridemia)
two agents used for diagnosis of adrenal insufficiency/Addison's Disease
corticotropic/ACTH (Acthar) - endogenous hormone cosyntropin (Cortrosyn) - synthetic ACTH
Contraindications for metformin (5)
eGFR < 30 ml/min (and max 1g daily for < 45) hepatic impairment of any degree increases risk of lactic acidosis (relative CI) unstable, symptomatic heart failure with iodinated contrast in acute or chronic acidosis
GLP-1 agonists The 5 most commonly used ones and their brands, plus how often they are dosed
exenatide (Byetta) - TWICE daily exenatide ER (Bydureon) - weekly liraglutide (Victoza) - *daily* dulaglutide (Trulicity) - weekly semaglutide (Ozempic) - weekly
ingredients in Vytorin
ezetimibe + simvastatin *all doses are still 10mg of Zetia
Which anti-lipid class is most likely to cause myopathy when given with a statin?
fibrates!
which statin can be safely used with gemfibrozil with no dose adjustment?
fluvastatin
sulfonylureas and their brands (3) and which has the greatest risk of hypoglycemia
glipizide (Glucotrol) glimiperide (Amaryl) glyburide (Micronase, Diabeta) - highest rate of hypoglycemia (limit use in the elderly)
drug of choice for acute adrenal crisis/Addisonian crisis
hydrocortisone 100mg IV q8h
levothyroxine brand names
levothyroxine is T4 Brands: Unithyroid, Synthroid, Levoxyl
synthetic T3 cons to T4
liothyronine shorter half life, more monitoring, and greater CV effects than levothyroxine
Baseline testing for statins and when to repeat
lipid panel liver function tests thyroid function tests serum creatinine A1c (statins may increase rate of T2DM) CPK in patients with personal or family hx of statin muscle sx only need to repeat LFTs and CPK when symptoms arise
GLP-1 agonists with CV benefit (3)
liraglutide (Victoza), semaglutide (Ozempic), and dulaglutide (Trulicity) These also help patients lose weight
Microsomal Triglyceride Transfer Protein (MTP) Inhibitor which reduces LDL and VLDL orphan drug designation for HoFH
lomitapide (Juxtapid) 5 - 60 mg orally once daily
Which statins are renal dose adjusted?
lovastatin simvastatin rosuvastatin pitavastatin
max fose of atorvastatin with clarithromycin, itraconazole, and ritonzvir-boosted regimens
max 20mg atorvastatin
max doses of simvastatin with interacting medications
max of 20 mg: amiodarone, amlodipine, ranolazone max of 10mg: diltiazem, verapamil, dronedarone *completely contraindicated* with strong 3A4 inhibitors like ketoconazole and avoid grapefruit juice
drug-drug interactions with levothyroxine
may decrease effect of anti-diabetic medications decreases digoxin effect increases warfarin levels and risk of bleeding *must seperate all bile acid resins, antacids, and oral supplements by 4 hours*
HTN meds safe in pregnancy
methyldopa labetolol nifedipine
oligonicleotide inhibitor of apo-B synthesis which lowers VLDL and LDL and is indicated in adults with *homozygous* familial hypercholesterol
mipomersen (Kynamro, brand no longer available) once weekly injection
rosuvastatin dose adjustments
must start at 5mg in all Asian patients Dose adjust if CrCl is < 30 ml/min to 5-10 mg daily max
end-stage hypothyroidism
myexedema coma
meglitinides and their brands (2) class requirements and ADR
nateglinide (Starlix) repaglinide (Prandin) These have to be dosed before all meals and must have 30g of carbs ADR: weight gain and hypoglycemia (secretagogues)
which anti-lipid medication has the greatest potential to raise HDL?
niacin/nicotinic acid may increase up to 35%!
New fibrate now in clinical trials that will more selectively target PPARa, reducing side effects.
pemafibrate
TZDs and their brands MOA: Contraindications (3)
pioglitazone (Actos) rosiglitazone (Avandia) MOA: bind PPAR to improve insulin sensitivity (delayed benefit) CIs: bladder cancer, bone fractures, and *symptomatic heart failure* (can cause/worsen edema)
pramlintide brand, MOA, use
pramlintide Brand: Symlin MOA: andogenous amylin mimetic (injection) Pramlintide acetate is used as an adjunct to preprandial insulin therapy for the management of type 1 diabetes mellitus in patients who have not achieved adequate glycemic control with insulin therapy (may also be used as a last resort in T2 DM)
elevated TSH but low T4 indicates what?
primary hypothyroidism with the problem located at the thyroid level
anti-thyroid thioamines: 2 brands and generics MOA: dosing: preference:
propylthiouracil (PTU) methimazole (Topazole) MOA: inhibit iodine incorporation preventing thyroid hormone production dosing: can both be given once daily or divided preference: methimazole is preferred first because PTU carries a BBW for hepatotoxicity (both can cause agranulocytosis)
When should patients at increased risk of heart disease be tested for hyperlipidemia?
starting at age 20, test lipid panel every 4 - 6 years for hyperlipidemia screening
the glycoprotein within the thyroid cell in which thyroid hormones are produced
thyroglobulin (TG) iodinated tyrosine residues in TG bind together to form active thyroid hormonse
TSH what is it? where does it come from?
thyroid stimulating hormone or *thyrotropin* MOA; stimulates the thyrotropin receptor which is a G-protein coupled receptor secreted from the pituitary gland Germline mutations may exist which over-stimulate this receptor or block TSH from binding
vasopressin Brand: Dosing: Use: ADR and monitoring:
vasopressin/ADH Brand: Pitressin Dosing: 10 - 20 units daily IV, IM, or SQ Use: primarily for diabetes insipidues ADR and monitoring: angina/MI/gangrene can result from vasoconstriction tissue necrosis if extravasation occurs hyponatremia from flluid retention increases BP
