PHAR 190 - Therapeutics I Exam 1 (Thyroid, Hyperlipidemia/Obesity, Women's Health)

What is the starting age and interval at which patients should be screened for elevated cholesterol and which components are recommended to test?

20+ every 5 years; TC, non HDL, LDL, HDL, TG

Which lipid component is the primary diagnostic and therapeutic target?

LDL

Provide 4 examples of secondary causes of hyperlipidemia

hypothyroidism, renal disease, anorexia, corticosteroids

What are the 3 risk groups under primary ASCVD prevent?

LDL over 190 mg/dL, patients with DM/40-75/LDL 70-189, patients without DM/40-75/10 yr risk of 7.5% or higher/LDL 70-189

Which groups require ASCVD risk calculation?

patients 40-75 with LDL between 70-190 without DM, pts without ASCVD history and not on statin

What are risk enhancing factors for ASCVD?

family history of premature ASCVD, elevated LDL 160 or higher, metabolic syndrome, CKD, premature menopause, chronic inflammatory disorder, ethnic group, elevated TGs 175 or higher

What are diabetes specific risk enhancing factors for ASCVD?

long duration, albuminuria 30 mcg or higher, eGF <60 mL/min/1.73 m2, retinopathy, neuropathy, ABI < 0.9

What are the secondary ASCVD prevention groups?

ASCVD not at very high risk, very high risk ASCVD

What are examples of clinical ASCVD?

ACS, history of MI, stable/unstable angina, stroke, TIA, PAD

What are examples of major ASCVD events?

recent ACS, history of MI, history of ischemic stroke, symptomatic PAD

What are high risk conditions for ASCVD?

65+, heterozygous FH, hx of HF, hx of coronary bypass, DM, HTN, CKD, smoker, elevated LDL 100 or above

What should dietary cholesterol be per day?

< 200 mg/day

What should your total fat range be per day?

25%-35%

How much viscoius fiber should be taken every day?

10-25 g

How much physical activity should a person get per week to avoid ASCVD?

150 mins of moderate/high intensity

Which drugs works by inhibiting conversion of HMG-CoA to L-mevalonic acid and subsequently cholesterol?

statins

Which drug works by blocking biliary and dietary cholesterol as well as phytosterol absorption by interacting with NPC1L1 transporter?

ezetimibe

Which drugs work by resins binding to bile acids in the gut and the complex is excreted in the feces?

bile acid sequestrats

Which drug works by inhibiting FA release from adipose tissue and FA and TG production in the liver cells?

niacin

Which drugs work by activating peroxisome proliferator-activated receptor alpha (PPAR-a), which reduces TG-rich lipoproteins (VLDL and IDL) and an increase in HDL?

fibrates

Which drugs work by reduction in hepatic synthesis and release of VLDL TGs, increased B-oxidation of FA, enhanced TG clearance from TG-rich lipoproteins?

long-chain omega-3 fatty acids

Which drug works by inhibiting microsomal TG transfer protein, thereby inhibiting the normal transfer of TG to Apo B in the lumen of the ER and preventing the assembly of Apo B-containing lipoproteins in enterocytes and hepatocytes?

lomitapide

Which drug works by inhibiting Apo B synthesis?

Mipomersen

Which drug works by inhibiting binding of PCSK9 to the LDL receptors on hepatocyte surfaces and increasing the number of LDLRs available to clear LDL?

PCSK9 inhibitors

What percent do low-intensity statins lower LDL cholesterol?

<30%

What percent do moderate-intensity statins lower LDLs?

30-50%

What percent do high-intensity statins lower LDLs?

>50%

What are the high intensity statins?

Atorvastatin 40-80 mg, Rosuvastatin 20-40 mg

What is the dose of atorvastatin that makes it a moderate-intensity?

10-20 mg

What is the dose of rosuvastatin that makes it a moderate-intensity?

5-10 mg

What is the dose of simvastatin that makes it a moderate-intensity?

20-40 mg

What is the dose of Pravastatin that makes it a moderate-intensity?

40-80 mg

What is the dose of Lovastatin that makes it a moderate-intensity?

40 mg

What is the dose of Fluvastatin XL that makes it a moderate-intensity?

80 mg

What is the dose of Fluvastatin that makes it a moderate-intensity?

40 mg bid

What is the dose of Pitavastatin that makes it a moderate-intensity?

2-4 mg

What is the dose of simvastatin that makes it a low-intensity?

10 mg

What is the dose of pravastatin that makes it a low-intensity?

10-20 mg

What is the dose of Lovastatin that makes it a low-intensity?

20 mg

What is the dose of Fluvastatin that makes it a low-intensity?

20-40 mg

What is the dose of pitavastin that makes it a low-intensity?

1 mg

What is the recommendation for secondary prevention with history of multiple ASCVD events?

maximum tolerated statin

What is the recommendation for secondary prevention with history of 1 major ASCVD event + multiple high risk conditions?

maximum tolerated statin

What is the recommendation for primary prevention LDL >/- 190 mg/dL?

maximum tolerated statin; if LDL > 100 mg/dL adding zetia is reasonable; if LDL > 100 mg/dL, adding PCSK9-I can be considered

What is the recommendation for primary prevention LDL 70-189 mg/dL without diabetes?

assess 10-year ASCVD risk to begin discussion

What is the recommendation for primary prevention LDL 70-189 mg/dL without diabetes if they are at high risk (20%)?

high intensity statin

What is the recommendation for primary prevention LDL 70-189 mg/dL without diabetes for intermediate risk (7.5-20%)?

moderate intensity statin

What is the recommendation for primary prevention LDL 70-189 mg/dL without diabetes for borderline risk (5-7.5%)?

lifestyle, selective moderate statin

What is the recommendation for primary prevention LDL 70-189 mg/dL without diabetes for low risk (<5%)?

lifestyle and risk discussion

What is the recommendation for primary prevention if LDL 70-189 mg/dL with diabetes?

moderate intensity statin

What is the recommendation for primary prevention if LDL 70-189 mg/dL with diabetes and if there are ASCVD risk factors and person is 50-75?

high intensity statin

What is the recommendation for primary prevention when LDL <70 mg/dL?

assess lifetime risk

When should Zetia be used for secondary prevention?

hx of major ASCVD events, high risk, and LDL is over 70

When should Zetia be used in primary prevention?

LDL is greater than 190

When should a PCSK9 inhibitor be used for secondary prevention?

hx of major ASCVD event, high risk, LDL >70, non HDL > 100

When should a PCSK9 inhibitor be used as primary prevention?

LDL is greater than 190

What is a normal TG?

<150

What is a high TG?

200-499

What is a very high TG?

500+

What drugs should be given if TGs are greater than 1000?

niacin, fibrates, OM3FA

Which drugs should be given if TGs are 500-999?

TG lowering agent, statin

When should a repeat lipid panel be drawn?

4-12 weeks after statin initiation or dose adjustment

Which medications should monitor creatinine?

statins

Which medications should monitor CK?

statins, fibrates

Which medications should monitor uric acid?

niacin

Which medications should monitor glucose?

niacin

At what level of labs would discontinuation of drug therapy be warranted?

10x upper limit of normal CK, 3x upper limit of normal LFTs

What BMI is considered underweight?

<18.5

What BMI is considered normal weight?

18.5-24.9

What BMI is considered overweight?

25-29.9

What BMI is considered obesity class I?

30-34.9

What BMI is considered obesity class 2?

35-39.9

What BMI is considered extreme obesity class III?

40 and above

What are 3 drug therapies that can contribute to weight gain?

antidepressants, insulin, lithium

How many calories reduced will equal one pound of weight loss?

3500 cal

When should pharmacotherapy be discontinued for weight loss?

if 4-5% of weight loss is not achieved after 12 weeks of target dose therapy

Which medication works by inhibiting pancreatic and gastric lipases, and undigested triglycerides aren't absorbed --> calorie deficit and weight loss?

orlistat

Which medication works by decreasing food intake by increasing NE and dopamine release in the CNS which suppresses appetite?

phentermine-topiramate

Which medication works by decreasing food intake and weight with an unknown mechanism?

naltrexone-bupropion

Which drug works by stimulating GLP1 receptors in brain, receive signals of satiety and delayed gastric emptying?

liraglutide

What is the percentage of total calories we should be getting from saturated fats every day?

<7%

What is the amount of LDL-lowering plant stanols/sterols we should be getting every day?

2 g/day

If a patient is discontinued from a statin therapy, can we retrial on that medication and what are the challenges with this?

ideally put back on same statin or maybe reduced dose; patient may not want to go back on med that caused symptoms

What components are used in the assessment of an overweight or obese patient?

BMI, WC, comorbidities, readiness to lose weight

What is a high risk waist circumference for men? For women?

greater than 40 inches; greater than 35 inches

What is the recommended initial weight loss goal and in what time frame should this occur?

5-10% of weight loss in 6 months

What are some non-pharmacologic therapy options for weight loss?

reduced calorie diet, increased physical activity, behavioral

When should pharmacotherapy be initiated in addition to lifestyle modifications for weight loss and before treatment what do many experts recommend?

BMI 27-29.i + comorbidity present; 6 months lifestyle modifications

Who is weight loss indicated for?

patients with BMI of 25-29.9 with one or more indicators of increased CVD risk, patient with BMI of 30 or greater, elevated WC with two or more comorbidities

What comorbidities and risk factors heighten the need for treatment of the overweight or obese patient?

CHD, atherosclerosis, DM2, sleep apnea, cardiovascular risk factors

What are some cardiovascular risk factors that are comorbidities for obesity?

smoking, HTN, low HDL, high LDL, impaired fasting glucose, FH, premature CHD, age

What are some risk-enhancing lipid/biomarkers associated with increased ASCVD risk?

elevated high-sensitivity C-reactive protein, elevated Lp(a), elevated apoB

What does it mean if a person has a coronary artery calcium (CAC) score of zero?

treatment with statin therapy may be withheld or delayed, except in smokers, DM, and strong family history of premature ASCVD

What does a CAC score of 1-99 favor?

statin therapy, esp in 55+

What does a CAC score of 100+ indicate?

statin therapy is indicated unless otherwise deffered

Which statins are more lipophilic?

atorvastatin, lovastatin, simvastatin, pitavastatin

Which statins are metabolized solely by CYP3A4?

atorvastatin, lovastatin, simvastatin

Which CYP enzyme is fluvastatin metabolized by?

CYP2C9

Which CYP enzyme is rosuvastatin metabolized through?

CYP2C9

Which CYP enzymes are pitavastatin metabolized through?

CYP2C9, 2C8