Pharmacology- Cardio 1

Atovastatin (Lipitor)

Class: HMG-CoA reductase inhibitors

Indications: hyperlipidemia

MoA: inhibition of HMC-CoA reductase causing reduced formation of cholesterol

SE/ADRs: arthralgia, N, myopathy, rhabdomyolysis

Contra: liver disease, major substrate of CYP450 metabolism

Dx-Dx: decreased Dabigatran; St. John’s wort, decrease Atorvastatin serum concentrations

Monitor: Creatinine kinase (CK), AST, ALT baseline and later if symptoms; lipid panel

PG: X

Lactation: no

Best combo LDL/trig reduction of statins, take in PM, “rule of 6,” CYP3A4 metabolism

Lovastatin (Mevacor)

Class: HMG-CoA reductase inhibitors

Indications: hyperlipidemia

MoA: inhibition of HMC-CoA reductase causing reduced formation of cholesterol

Contra: liver disease

PG: X

Lactation: no

Cautious use in decreased renal function (GFR <30mL/min)

Pravastatin (Pravachol)

Class: HMG-CoA reductase inhibitors

Indications: hyperlipidemia

MoA: inhibition of HMC-CoA reductase causing reduced formation of cholesterol

SE/ADRs: myalgia, diarrhea, arthralgia, N

Contra: PG, breastfeeding, active liver disease

Dx-Dx: multiple including Warfarin

Monitor: lipid panel, hepatic function panel; A1c, eGFR

PG: X

Lactation: no

Reduce starting dose (10mg daily) if chronic liver disease, minor substrate of CYP3A4 system, 70% fecal excretion, 20% renal, not CYP450 metabolized

Rosuvastatin (Crestor)

Class: HMG-CoA reductase inhibitors

Indications: hyperlipidemia

MoA: inhibition of HMC-CoA reductase causing reduced formation of cholesterol

SE/ADRs: hyperglycemia, elevated ALT, arthralgia, increased CPK

Contra: active liver disease, PG, breastfeeding

Dx-Dx: multiple, see Lexicomp

Monitor: creatinine kinase (CK), AST, ALT baseline and later if symptoms; lipid panel

PG: X

Lactation: no

Avoid use with Gemfibrazol; CrCl <30 mL/min max dose is 10mg daily

Simvastatin (Zocor)

Class: HMG-CoA reductase inhibitors

Indications: hyperlipidemia

MoA: inhibition of HMC-CoA reductase causing reduced formation of cholesterol

Contra: active liver disease

PG: X

Lactation: no

No longer use the 80mg dose; caution in renal dysfunction

Fluvastatin (Lescol)

Class: HMG-CoA reductase inhibitors

Indications: hyperlipidemia

MoA: inhibition of HMC-CoA reductase causing reduced formation of cholesterol

Contra: active liver disease

PG: X

Lactation: no

Daily or twice daily dosing

Cholestyramine (Questran)

Class: bile-acid sequestrants

Indications: hypercholesterolemia

MoA: binds bile acids inhibiting enterohepatic circulation of cholesterol

SE/ADRs: constipation (20%), heartburn, N, belching, bloating; long term may decrease folate absorption

Extra

Contra: hypersensitivity, bowel obstruction, biliary obstruction

Dx-Dx: not absorbed from bowel

Monitor: lipid panel

PG: B

Lactation: caution

caution with constipation; usually adjunct; moderately effective lowering cholesterol but doesn’t lower triglycerides, start low and titrate up

Colesevelam (WelChol)

Class: bile-acid sequestrants

Indications: LDL reduction; T2DM; usually adjunct

MoA: binds bile acids inhibiting enterohepatic circulation of cholesterol

SE/ADRs: constipation (20%), heartburn, N, belching, bloating; long term may decrease folate absorption

Extra

Contra: hypersensitivity, bowel obstruction, biliary obstruction

Dx-Dx: not absorbed from bowel

Monitor: lipid panel

PG: B

Lactation: caution

caution with constipation; usually adjunct; moderately effective lowering cholesterol but doesn’t lower triglycerides, start low and titrate up

Gemfibrozil (Lopid)

Class: fibric acids

Indications: hypertriglyceridemia, low HDL

MoA: not known; theories on changes in various enzymes involved in VLDL and IDL metabolism

SE/ADRs: fatigue, N/V, dyspepsia, flatulence, caution with HMG-CoA RI; potentiates Warfarin

Contra: hypersensitivity; hepatic or severe renal disease; GB disease

Dx-Dx: avoid with Clopidogrel, Repaglinide, Warfarin, Ezetimibe, statins

Monitor: hepatic function, LDH, Alk Phos, eGFR, lipid panel, glucose, CK

PG: C

Lactation: no

Decrease triglycerides and increase HDL, class is most effective triglyceride lowering agents; max impact ~3-4 weeks, Fenofibrate usually preferred

Fenofibrate (Fibricor)

Class: fibric acids

Indications: hypertriglyceridemia >500mL/dL, low HDL

MoA: not known; theories on changes in various enzymes involved in VLDL and IDL metabolism

SE/ADRs: fatigue, N/V, dyspepsia, flatulence, caution with HMG-CoA RI; potentiates Warfarin

Contra: hypersensitivity; hepatic or severe renal disease; GB disease

Dx-Dx: avoid with Clopidogrel, Repaglinide, Warfarin, Ezetimibe, statins

Monitor: hepatic function, LDH, Alk Phos, eGFR, lipid panel, glucose, CK

PG: C

Lactation: no

Decrease triglycerides and increase HDL, class is most effective triglyceride lowering agents; max impact ~2 weeks, preferred fibrate, renal dose adjustment

Niacin (Niaspan)

Class: nicotinic acid

Indications: hypertriglyceridemia >500mL/dL, low HDL, high LDL

MoA: inhibits fatty acid release from adipose tissue and hepatic triglyceride production

SE/ADRs: itching, flushing, arrhythmia, decrease glucose tolerance, blurred vision, increased uric acid

PG: C

Lactation: no

Ezetimibe (Zetia)

Class: cholesterol absorption inhibitor

Indications: hypercholesterolemia, adjunct to statin or substitute if unable to take statin

MoA: decreases absorption of cholesterol from GI tract

SE/ADRs: minimal

Contra: active hepatic disease, hypersensitivity

Dx-Dx: fibrates (Gemfibrozil) increases risk of gallstones; increases effect of Warfarin

Monitor: liver function

PG: C

Lactation: no

average 54% reduction of cholesterol absorption; LDL reduction max effect ~2 weeks; some concerns with Simvastatin use

Evinacumab (Evkezza)

Class: angiopoietin-like protein 3 (ANGPTL3) inhibitor, monoclonal antibody

Indications: add-on treatment for homozygous familial hypercholesterolemia in pts =/> 12 years old

MoA: inhibition of ANGPTL3 results in increased lipid metabolism leading to decreases in LDL-C, HDL-C, and triglycerides

SE/ADRs: severe hypersensitivity reactions possible; local infusion reactions

Contra: hypersensitivity

Dx-Dx: see Lexicomp

Monitor: LDL-C level; R/O PG, Sn/Sm of hypersensitivity reaction

PG: no

Lactation: individualize

IV, renal/hepatic dosing not studied; expensive

Lomitapide (Juxtapid)

Class: microsomal triglyceride transfer protein (MTP) inhibitor

Indications: only pts with homozygous familial hypercholesterolemia; BBW and REMA program

MoA: inhibits microsomal triglyceride transfer protein (MTP) resulting in reduced production of chylomicrons and VLDL and subsequently reduces plasma LDL-C concentrations

SE/ADRs: many: chest pain, fatigue, diarrhea, fatty liver, increase in AST/ALT, infection (flu), muscle pain, angina, impedes fat soluble vitamin absorption

Contra: Child-Pugh moderate to severe hepatic impairment; PG

Dx-Dx: see Lexicomp

Monitor: initial and periodically ALT/AST, alkaline phosphatase, total bilirubin, PG test

PG: no

Lactation: no

PO, dose adjust if ALT/AST > 3x upper limit of normal (ULN); need fat soluble vitamin supplements; hepatic and renal dose adjustments

Omega 3 Fatty Acids (Lovaza)

Class: other (omega-3 fatty acid, (O3FA) (PUFA))

Indications: high trig despite diet, alcohol restriction and fibrates

MoA: unknown

SE/ADRs: diarrhea, belching, dyspepsia, change in taste; angina, flu type syndrome; excess bleeding

Contra: fish allergy

Dx-Dx: anticoagulants

Monitor: lipids

PG: C

Lactation: no

Decr triglycerides despite lowering Trig, Lovaza not shown to reduce risk for pancreatitis

Evolocumab (Repatha)

Class: monoclonal antibody PCSK9 inhibitor

Indications: drug resistance hyperlipidemia (tried statin and ezetimibe), especially in homozygous familial hypercholesterolemia

MoA: human monoclonal antibody that bind to proprotein convertase subtilisin kexin type 9 (PCSK9) inhibiting degradation of LDLR; this increases the number of functioning LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels

SE/ADRs: nasopharyngitis, HTN, gastroenteritis, URIs

Contra: hypersensitivity, otherwise as yet unknown

Dx-Dx: unknown

Monitor: lipid profile

PG: unknown

Lactation: unknown

SQ used as adjunct with max tolerated dose of statin

Icosapent ethyl (E-EPA) (Vascepa)

Class: omega-3 fatty acid

Indications: CVD: adjunct to max tolerated statin therapy in patients with mild hypertriglyceridemia >150 mg/mL, hyperglyceridemia: adjunct to diet therapy to reduce severe triglyceride levels > 500mg/dL

MoA: reduces hepatic synthesis of triglycerides and VLDL

SE/ADR: hemorrhage, eructation, A fib or A flutter

Contra: coagulopathy, fish allergy, a fib, a flutter

Dx-Dx: antiplatelet meds, anticoags

Monitor: lipids, liver enzymes (ALT), Sns, Sms, bleeding

PG: caution

Lactation: caution

Reduces triglycerides and CVD risk, may elevate LDL levels; recent FDA approval to decrease CVD in patients with high triglycerides and CVD or increased CVD risk

Bempidoic acid (Nexletol)

Class: adenosine triphosphate lyase (ACL) inhibitor

Indications: used in conjunction with statin, ezetimibe for additional LDL reduction

MoA: inhibits LDL production upstream of HMG-CoA reductase so amplifies impact of statins in reducing LDL

SE/ADR: hyperuricemia (4%), leukopenia (9%), thrombocytopenia (10%), increase BUN (4%)

Contra: none known; relative contra gout

Dx-Dx: may increase Pravastatin (keep max dose 40mg), Simvastatin (keep max dose 20mg) levels, see Lexicomp

Monitor: lipid levels, serum uric acid levels, indicators of tendon injury, CBC

PG: no

Lactation: no

avoid in >60 y/o taking corticosteroids, fluoroquinolones, renal failure; caution with gout, adjunct to max tolerated statin and ezetimibe, renal and hepatic dosing not yet studied

Propranolol (Inderal)

Class: sympatholytics; peripheral adrenergic ‘R’ blockers- beta blockers

Indications: angina, HTN, tachyarrhythmias, essential tremor, migraine px, anxiety

MoA: adrenergic B1 and B2 receptor inhibitor; reduction in myocardial oxygen demand

SE/ADR: fatigue, sleep disturbance, depression

Contra: hypersensitivity, bradycardia, heart block, uncompensated heart failure, severe depression, bronchospasm

Dx-Dx: ethanol

Monitor: BP, chest pain, HR, LFTs

PG: C

Lactation: unknown

May mask hypoglycemia, titrate to HR 50-60bpm or increase HR 20bpm with exercise, titrate down when stopping, 2x bioavailability in elderly

Metoprolol Tartrate (Lopressor), Metoprolol Succinate (Toprol XL)

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