Cardiology final

How does cigarette smoking impact the lipid panel?

Reduces HDL

Impacts cholesterol retrieval, increases oxidation of lipoproteins

Cytotoxic to endothelium

Increases thrombogenesis

Who do we calculate a ASCVD risk score for?

all pts 40 and older who have not had an ASCVD event to determine if lipid lowering therapy is necessary for primary prevention

Who should receive a baseline lipid panel for both primary and second prevention?

All pts

Which statins should not be taken at night?

Atorvastatin

Rosuvastatin

Fluvastatin brand name

Lescol XL

Lovastatin brand name

mevacor

Pitavastatin brand name

livalo

Pravastatin brand name

pravachol

Simvastatin brand name

zocor

What are the high intensity statins

Atorvastatin 40-80

Rosuvastatin 20-40

What are the low intensity statins

Fluvastatin 20-40mg

lovastatin 20

pravastatin 10-20

Pitavastatin 1mg

Simvastatin 10 mg

What are the non lipophilic statins

Pravastatin

Rosuvastatin

What statins have the longest half life/

Atorva (20-30)

Rosvu (19)

What causes rhabdomyolysis in statin use?

Increase in CPK (enzyme)

HMGCA stands for

Hepatotoxicity

Myopathy

GI (diarrhea)

CPK

Avoid in Breast feeding

What does statin monitoring include?

Fasting lipid panel

Transaminases

Monitor for new onset diabetes

What gene encodes OAT1B1?

SLCO1B1

Which haplotype of SLCO1B1 indicates low activity?

388G*5 and *15 - potential increase for myalgias

Which haplotype of SLCO1B1 indicates high activity?

388G*1b

If the haplotype is low functioning, what can we do to the pts statin dosing?

avoid simvastatin or use lower doses

What are the contraindications to ezetimibe (zetia)

gallbladder disease

severe hepatic dysfunction

Which drugs plasma concentrations are significantly increased when administered with fibrates or cholestyramine?

Ezetimibe

Which drugs can cause nasopharynghitis, influenza, and/or URTI?

PCSK-9i

Alrocumab (Praluent)

Evolocumab (Repatha)

What is inclisiran (leqvio)?

RNAI inhibitor of PCSK9

What are the contraindications of inclisiran?

Pregnancy

how is inclisiran dosed?

Once then in 3 months, then every 6 months

What is unique about inclisiran?

Cannot be administered at home/pharmacy

What is the MOA of bempedoic acid (nexletol)?

Adenosine triphosphate citrate lyase inhibitor

What are the adverse effects on bempedoic acid (nexletol)?

Hyperuricemia

Tendon rupture

bempedoic acid (nexletol) increases which statins concentrations?

pravastatin (max dose =40 mg)

Simvastatin (max dose = 20 mg)

What are the contraindications of bile acid sequestrants?

history of bowel obstruction

Triglycerides >500

Hypertriglyceridemia induced pancreatitis

How are bile acid sequestrants dosed?

Impacts drug absorption, most medications need to be taken 1 hr before or 2 hours after the BAS to ensure adequate absorption

Must be titrated

BAS can cause

increased seizure activity

decreased INR

increase TSH in pts taking thyroid hormone replacement therapy

BAS have what impact on cholesterol?

Increase VLDL

May increase TGs

Omega-3s are used to lower

TG (25-45%)

fibric acid derivatives activate

peroxisome proliferator activated receptor alpha which increases lipolysis and elimination of triglyceride rich particles

What is the contraindication of fibric acid?

gall bladder disease

Which drug can cause increased transaminases?

Fenofibrates (antara, fenoglide), gemfibrozil (lopid)

Which fibric acid has the longest half life?

Fenofibrate - 20 hrs

What drug when in combination with statins increases the risk of myopathy?

fibrates - worse with gemfibrozil than fenofibrate (CHOOSE FENOFIBRATE IF STATIN)

Fibric acids and niacin have what impact on cholesterol?

TG 20-50%

Exercise and physical activity lifestyle changes in hyperlipidemia?

At least 150 mins per week of moderate-intensity or 75 mins of vigorous intensity aerobic

What groups will not benefit from lipid lowering therapy?

Age 0-19 (unless familial hypercholesterolemia)

Age 20-39 (unless family history of premature ASCVD or LDL >160)

Pts over 75 yrs (unless risk discussion warrants tx)

Pt who will benefit from lipid lowering therapy

All pts with LDL >190

Pts 40-75 with diabetes

Pts 40-75 with LDL >70 and <190 without diabetes

What is tx for primary prevention for pt with LDL >190?

First: High-intensity statin

Second line: Consider ezetimibe and/or PCSK-9i

• ezetimibe if <25% lowering is needed

• PCSK-9i if >25% lowering is needed

Third line: may consider bempedoic acid or inclisiran

• bempedoic if <17% additional LDL lowering required

• Inclisiran >17% lowering is required

When are pts 40-75 years with diabetes, what classifies them as high risk?

ASCVD >7.5%

Diabetes specific risk factors

Pts 40-75 with diabetes, not at high risk

Primary prevention

First line: Moderate intensity statin

Second line: high intensity

Third line: add ezetimibe

Pts 40-75 with diabetes, at high risk

Primary prevention

First line: High intensity statin

Second line: ezetimibe

Pts 40-75 with LDL 70-190 classifications

ASCVD:

<5%

5-7.5

7.5-20

>20

What is primary prevention for Pts 40-75 with LDL 70-190 that are low risk (<5%)?

Primary: Risk discussion emphasize lifestyle to reduce ASCVD risk

If risk enhancing factors: can consider moderate intensity statin

What is primary prevention for Pts 40-75 with LDL 70-190 that are borderline risk (5-7.5%)?

First line: If risk enhancers, moderate intensity statin

Second line: high intensity statin

What is primary prevention for Pts 40-75 with LDL 70-190 that are intermediate risk (7.5-20)?

First line: if risk enhancers, moderate intensity statin

Second line: high intensity statin

What is primary prevention for Pts 40-75 with LDL 70-190 that are high risk (>20%)?

First line: high intensity statin

Second line: Ezetimibe

What is true statin intolerance?

Unacceptable muscle-related symptoms that resolve with d/c and recur with rechallenge on at least 2 statins that are metabolized by different pathways, have different lipo/hydrophilicity and at lowest approved dose

What is tx, For pts unable to tolerate statins and have a LDL >190

First line: Ezetimibe or PCSK-9i

Second: Bempedoic acid or inclisiran

What is tx, for pts 40-75 with diabetes?

First line: Ezetimibe

Second: BAS

Third line: bempedoic acid

What is tx, for pts with LDL 70-190?

First: ezetimibe

Second: BAS

Third: Bempedoic acid

Which drug may have an increased effect due to induction of CYP1A2 in smoking?

Clopidogrel (prodrug) - smoking cessation will reverse these effects

Smokers who use combined hormonal contraceptives have an increased risk of

Stroke

MI

Thromboembolism

Does smoking decrease the efficacy of CHC?

No - smoking does not

Nicotine gum dosing

cigarette >30 mins after waking = 2 mg q 1-2 hrs for 6 weeks

cigarette <30 mins after waking = 4 mg q 1-2 hrs for 6 weeks, then decrease to 2mg q 2-4 hr in weeks 7-9, then q 4-8 hrs in weeks10-12

AEs of nicotine gum?

Mouth soreness/irritation

How do we minimize AEs of nicotine gum?

Chew and park technique

What are the advantages of using nicotine gum?

May satisfy oral cravings

Delay weight gain

Can titrate therapy to manage withdrawal

Nicotine lozenge dosing

cig >30 mins after waking: 2 mg q 1-2 hrs for 6

cig <30 mins after waking: 4 mg q 1-2 hrs for 6 weeks, then decrease to q2-4 hrs in weeks 7-9, then 4-8 hrs in weeks 10-12

What are the advantages of nicotines lozenges ?

Lozenge may satisfy oral cravings

Lozenge is easy to use and conceal

Pts can titrate easily

Nicotine patches dosing

>10 cigs per day: 21 mg qd for 6 weeks, then 14 mg patch for 2 weeks, then 7 mg patch for 2 weeks

<10 cigs per day: 14 mg qd for 6 weeks, then 7 mg patch for 2 weeks

AEs of nicotine patches

Local skin reactions

Insomnia and/or vivid dreams

Remove before MRI

Nicotine nasal spray dosing

1-2 doses per hour increasing prn for symptom relief

Do not exceed 40 mg (80 sprays) per day or 5 mg (10 sprays) per hour

Prescribing instructions of nicotine nasal spray

Do not inhale or sniff through nose when spraying

Prime before use, blow nose prior to use, spray with head tilted slightly back

Contraindications of nicotine nasal spray

Nasal spray products higher peak concentrations of nicotine and has highest dependency potential

Some reactive airway disease or chronic disorders

Nicotine inhaler dosing

6-16 cartridges per day for 3 months

can be used up to 6 months

What are the currently recommended combination products?

Bupropion SR + nicotine patch

Nicotine patch (>14 weeks) + other NRT prn

Nicotine patch + inhaler

Clincial effects of bupropion

decreases cravings for cigarettes

Decreases symptoms of nicotine withdrawal

What is the dosing of bupropion SR?

Start 150 mg po x 3 days then increase to bid for 7-12 weeks can be taken for 12 months

When do we start bupropion?

Pt should begin therapy 1-2 weeks prior to their quit date to ensure that therapeutic plasma levels of the drug are achieved

When do we d/c using bupropion?

No significance progress toward abstinence is seen by week 7 therapy unlikely to be effective

Contrainidcations for bupropion?

Current or prior anorexia

Bulimia

undergoing abrupt d/c of alcohol or sedatives

pts taking wellbutrin, SR, XL

MAOIs

What is BBW of Bupropion

Suicidal thoughts and behaviors

Why do we titrate bupropion?

To lower risk of precipitating a seizure

Varenicline dosing

Day 1-3 0.5 mg qd

Day 4-7 0.5 mg bid

Day 8 to end of tx 1mg bid

Taken after eating with a full glass of water

Do not use with NRT

When do we evaluate pt response to varenicline?

12 weeks

if fails therapy may reattempt

Oral dosing of clonidine?

Range: 0.15 mg to 0.75 mg/day

start: 0,1 mg bid

Transdermal dosing of clonidine?

Range 0.1 mg to 0.3 mg/day

Start: 0.1 mg patch C

Clonidine requires

dose tapering

Nortriptyline dosing

75-100 mg/day start 25 mg qhs

6-14 weeks

tapered the dose over 1-2 weeks

start prior to quit date

What factors can increase cardiac output?

Increased cardiac output - sodium and water retention from excess sodium and intake

What factors increase TVR?

Vascular constriction - excess stimulation of RAAS, sympathetic overactivity, endothelial derived factors

What factor decreases HR?

PSNS

What factor decreases TVR?

B2

NO

PG

What is the clinical presentation of HTN?

Asymptomatic

stimulation of a1 receptors in arterioles and venules, causes

vasoconstriction = increase TVR

stimulation of a2 receptors in the CNS causes

decreased release of peripheral catecholamines

Stimulation of B1 receptors in the heart, causes

Increase in HR and force of contraction = increase BP

Stimulation of B2 receptors in arterioles and venules cause

vasodilation

decreases TVR

In response to decreased volume the baroreceptor reflex system causes

vasoconstriction

In response to increased volume the baroreceptor reflex system causes

vasodilation

Kidneys regulate BP through regulation of plasma volume. When there is an acute defect in the kidney, what happens?the

Increased BP due to reversible increased TVR

Kidneys regulate BP through regulation of plasma volume. When there is a chronic defect in the kidney what happens?

Arteriolar hypertrophy and thickening causing irreversible increase in TVR resistance

Which endothelial derived factors cause vasodilation?

NO

Prostacyclin

Bradykinin