Dyslipidemia drugs Flashcards
statin MOA
primarily works by interruption of the conversion of HMGCoA to mevalonate, which is the rate limiting step in cholesterol biosynthesis; Also reduce CoQ10; if pt takes CoQ10 supplements, that can reduce chance of myalgia
bile acid sequestrants MOA
Binds bile acid in the intestinal lumen, which reduces enterohepatic circulation of bile acids. Indirectly increases clearance of LDL and decreases absorption; can bind co-administered drugs in the gut -> take 1hr before or 4hr after dimer
niacin MOA
Reduces hepatic synthesis of VLDL which leads to reduces synthesis of LDL; Reduces HDL catabolism; Nicotinic acid affects lipids but nicotinamide does not
fibrates MOA
Not fully understood, but appears related to PPARα which may increase lipoprotein lipase enhancing TG clearance and increase apoA expression which will increase HDL
ezetimibe MOA
blocks cholesterol absorption across intestinal border
omega-3 fatty acids MOA
EPA and DHA compete for the enzymes that cause TG synthesis less TG synthesis, enhance TG clearance
PCSK9 inhibitors MOA
Human monoclonal antibody to PCSK9 (proprotein convertase subtilisin kexin type 9, a protein that degrades the LDL receptor). Binds to PCSK9 and increases the number of LDL receptors available to clear circulating LDL.
omega-3-acid ethyl esters brand name
Lovaza
omega-3-acid ethyl esters dose
2-4 g/day (in 1 or 2 daily doses)
omega-3-acid ethyl esters ADR’s
- Dyspepsia and belching
- Thrombocytopenia and bleeding disorders (especially in high doses)
omega-3-acid ethyl esters precautions / contraindications
- Caution with agents which can increase bleeding risk (drug interaction)
- CI: allergy to fish or shellfish
safety monitoring for omega-3-acid ethyl esters
monitor LFTs at baseline and 6-12 months after initiation
cholestyramine brand name
Questran
cholestyramine dose
- initial: 4 g 1 to 2 times/day
- maintenance: 8 to 16 g/day divided in 2 doses
- max 24g/day
cholestyramine ADR’s
- constipation
- bloating
- epigastric fullness
- nausea
- flatulence
cholestyramine precautions / contraindications
- constipation
- complete biliary obstruction
safety monitoring for cholestyramine
no specific labs required b/c no systemic effects; completely in gut (no liver)
drug interactions with cholestyramine
decreases F
- warfarin
- niacin
- ezetimibe
- thyroxine
- acetaminophen
- hydrocortisone
- HCTZ
- loperamide
- iron
vitamin B3 (aka nicotinic acid) brand name
Niacin
vitamin B3 dose
- Start at 500 mg QHS
- titrate up 250-500 mg monthly
- target 1.5-2g daily
vitamin B3 ADR’s
- cutaneous flushing and itching
- dyspepsia
- elevated LFT’s
- hyperuricemia
- hyperglycemia
vitamin B3 precautions / contraindications
- Active liver disease
- Active peptic ulcer disease
- Active bleeding
- Pregnancy
How can you manage flushing caused by vitamin B3?
- take ASA 325 30min before niacin
- take with food
- titrate dose
- use SR
drug interactions with vitamin B3
- Bile acid sequestrants bind niacin and must separate administration
- statins w/ niacin increase risk of myopathy
safety monitoring for vitamin B3
- measure CK at baseline and if clinically indicated based on signs and symptoms
- measure LFTs, uric acid, and glucose at baseline and repeated in 6-12 weeks if on 1000 mg/day or more
fenofibrate brand name
Tricor
fenofibrate dose
48 and 145 mg daily
fenofibrate ADR’s
- Cholesterol gallstones (0.5-7%)
- GI complaints (3-5%)
- rash (2%), transient increases in LFTs
- myositis
fenofibrate precautions / contraindications
- inhibitor of CYP2C9 -> increased INR
- Gallbladder disease
- Severe renal disease
- Active liver disease
drug interactions with fenofibrate
- warfarin (b/c Tricor inhibits CYP2C9 -> increase activity of warfarin)
- should not be used with statins (increased side effects)
safety monitoring with fenifibrate
- Safety monitoring: LFTs at baseline and 6-12 weeks after initiation
- CK (b/c of muscle break down) and renal function
atorvastatin brand name
Lipitor
atorvastatin dose
10-80 mg daily
atorvastatin ADR’s
- Myalgia
- myositis
- Rhabdomyolysis (increased Scr, discolored urine)
- elevation in LFT
- small increase in glucose levels
- interacts with CYP3A4
atorvastatin precautions / contraindications
- Prior myopathy with statin use
- Chronic / dormant liver disease
- Renal insufficiency
- pregnancy
- acute liver disease or elevations of liver enzymes
drugs interactions with atorvastatin
avoid with gemfibrozil -> enhanced side effects
safety monitoring for atorvastatin
check LFT’s and CK before therapy
rosuvastatin brand name
Crestor
rosuvastatin dose
5-40 mg daily
rosuvastatin ADR’s
- Myalgia
- myositis
- Rhabdomyolysis (increased Scr, discolored urine)
- elevation in LFT
- small increase in glucose levels
- interacts with CYP2C9
rosuvastatin precautions / contraindications
- Prior myopathy with statin use
- Chronic / dormant liver disease
- Renal insufficiency
- pregnancy
- acute liver disease or elevations of liver enzymes
drug interactions with rosuvastatin
avoid with gemfibrozil -> enhanced side effects
safety monitoring for rosuvastatin
check LFT’s and CK before therapy
pravastatin brand name
Pravachol
pravastatin dose
10-40 mg at bedtime
pravastatin ADR’s
- Myalgia (small chance)
- myositis
- Rhabdomyolysis (increased Scr, discolored urine)
- elevation in LFT
- small increase in glucose levels
pravastatin precautions / contraindications
- Prior myopathy with statin use
- Chronic / dormant liver disease
- Renal insufficiency
- pregnancy
- acute liver disease or elevations of liver enzymes
simvastatin brand name
Zocor
simvastatin dose
5-40 mg at bedtime
simvastatin ADR’s
- Myalgia
- myositis
- Rhabdomyolysis (increased Scr, discolored urine)
- elevation in LFT
- small increase in glucose levels
- interacts with CYP3A4
simvastatin precautions / contraindications
- Prior myopathy with statin use
- Chronic / dormant liver disease
- Renal insufficiency
- pregnancy
- acute liver disease or elevations of liver enzymes
- CI: if patient is on ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, cyclosporine, grapefruit juice
Which drug has a black box warning and what is it?
- simvastatin
- don’t dose at 80mg because risk of myopathies were too high
safety monitoring for simvastatin
check LFT’s and CK before therapy
drug interactions with simvastatin
- CI: if patient is on ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, cyclosporine, grapefruit juice
- Do not exceed 10 mg of simvastatin when taking: verapamil, diltiazem, dronedarone
- Do not exceed 20 mg of simvastatin when taking amiodarone, amlodipine, ranolazine, lomitapide
- avoid with gemfibrozil -> enhanced side effects
ezetimibe brand name
Zetia
ezetimibe dose
10 mg daily
ezetimibe ADR’s
- Fatigue
- arthralgias
ezetimibe precautions / contraindications
Pregnancy
drug interactions with ezetimibe
- If given with fibrates -> increased risk of gallbladder disease
- cannot be combined with bile acid sequestrants because it binds to ezetimibe
safety monitoring for ezetimibe
check LFT’s and CK before therapy
evolocumab brand name
Repatha
evolocumab dose
140 mg SQ every 2 weeks or 420 mg SQ once a month
evolocumab ADR’s
- rash
- eczema
- erythema
- urticarial
- injection site pain
- excess LDL reduction has unknown effects
evolocumab precautions / contraindications
Hypersensitivity reactions
simvastatin + ezetimibe brand name
Vytorin
simvastatin + ezetimibe dose
- Familial: ezetimibe 10 mg/simvastatin 40 mg once daily in the evening
- primary & mixed: 10/10 – 10/40 daily
What are the high intensity statins and what are the goals?
- Daily dose lowers LDL by > 50%
- Atorvastatin 40-80mg
- Rosuvastatin 20-40mg
What are the moderate intensity statins and what are the goals?
- Daily dose lowers LDL 30-<50%
- Atorvastatin 10-20mg
- Rosuvastatin 5-10mg
- Simvastatin (Zocor) 20-40mg
- Pravastatin (Pravachol) 40-80mg
- Lovastatin (Mevacor) 40mg
- Fluvastin XL (Lescol XL) 80mg
- Fluvastatin (Lescol) 40 mg BID
- Pitavastatin (Livalo) 2-4mg
