pharm unit 3 cholesterol lowering meds

what do statins inhibit

HMG-CoA reductase inhibitors - stops cholesterol synthesis

examples of statins (3)

PAS -statin

Pravastatin (Pravachol)

Atorvastatin (Lipitor)

Simvastatin (Zocor)

statins MOA

prevents production of cholesterol = increased number of LDL receptors = reduction in circulating LDL and total cholesterol

minimal impact on HDL

timeline for peak affects of statins

around 4 weeks of use will see reduction in LDL

what to check before and during statin use

lipid panels- checks total cholesterol/HDL/LDL/triglycerides @ baseline then after 3 months of use to see impact of statins

indications for statins

1st line treatment for managing hyperlipidemia

-risk reduction for coronary events (pts @ risk for stroke and heart attack)

- secondary prevention for stroke after already having one (used w/ aspirin)

contraindications for statins

pregnancy or plans to get preg

liver disease

history of alcoholism

elevated liver functions

what supplement should be used in caution w/ statins

red yeast rice - this lowers cholesterol and adding a statin can increase liver enzymes

statins side effects

generally well tolerated

myalgias/muscle pains

if a patient on statins reports muscle pain what should you check

creatine phosphokinase (CPK) levels - increased muscle cell inflammation can cause myositis or rhabdomyloysis

serious side effects of statins

myositis or rhabdomyloysis - muscle cell death

hepatotoxicity

depletion of coenzyme Q10- may beed supplement to decrease muscle symptoms

what to advise patients about when taking statins

avoid grapefruit juice

photosensitivity risk

statins metabolization

atorvastatin, simvastatin = CYP3A4 enzyme pathway (pravastatin not metabolized here) - watch for drug metabolism interaction

what medications should you use caution with when prescribing statins due to CYP3A4 metabolism

gemfibrozil

protease inhibitors

niacin

erythromycin

example of cholesterol absorption inhibitor med

ezetimibe (Zetia)

cholesterol absorption inhibitor MOA

decreased absorption of cholesterol in small intestine = decreased amount taken to liver = reduced liver enzyme stores

decreased cholesterol in blood = decreased atherosclerosis risk

how are cholesterol absorption inhibitors generally prescribed

as add on therapy to statins who cannot get to target LDL levels on statins alone

monotherapy only in pts unable to tolerate statins due to side effects

contraindication of cholesterol absorption inhibitors

acute liver disease

- when used as combo ezetimibe w/ statin

side effects of cholesterol absorption inhibitors

generally well tolerated

- can have GI upset/diarrhea, muscle pain, fatigue

serious side effects of cholesterol absorption inhibitors

hypersensitivity (angioedema/rash)

increased liver function tests

drug-induced myopathy

rhabdomyolysis (rare w/ monotherapy and increased risk w/ combo of statin)

drug interactions of cholesterol absorption inhibitors

bile acid sequestrants - decreases absorption

cyclosporine - increases serum levels of ezetimibe

fibrates - increases cholesterol excretion into bile = gall bladder probs (cholelithiasis)

bile acid sequestrants example

questran/prevalite

MOA od bile acid sequestrants

binding to bile acid in gut disrupts recycling through liver circulation and is excreted in feces

hepatic cells convert cholesterol into bile acid = increased LDL receptors = increased hepatic uptake of LDL = lowered serum LDL

what is the role/MOA of bile acids

secreted into intestine through the bile

cholesterol is precursor of bile acids that are needed for digesting fats and soluable vitamins (A,D,E,K)

drugs that bile acid sequestrants can prevent absorption of

thiazide diuretics

furosemide - loop diuretic

propranalol - beta blocker

digoxin - antiarrhythmic

warfarin - blood thinner

fat soluable vitamins - A,D,E,K

how should bile acid sequestrants be seperated from the drugs it affects absorption of

1 hour before taking questran or 4 hours after taking questran

indications for bile acid sequestrants

hypercholesterolemia

contraindications of bile acid sequesterants

hypertriglyceridemia

liver disease

severe constipation/bowel obstruction

bile acid sequesterants side effects

GI - constipation, nausea, bloating/gas, pain

increase in liver enzymes

vitamin A,D,E,K deficiency

fibrates examples (2)

gemfibrozil (Lopid)

fenofibrate (Tricor) - most common

MOA of fibrates

regulating gene transcrption of enzymes involved in VLDL/fatty acid breakdown to facilitate reverse cholesterol transport and uptake of LDL by liver

indications of fibrates

patients with high triglycerides, low HDL, high LDL

- reduces risk of CV complications in these pts who have failed dietary/other cholesterol pharm treatments

contraindications of fibrates

renal dysfunction

hepatic failure

gallbladder disease

side effects of fibrates

rash

GI symptoms (especially taken w/ statins)

cholelithiasis

hepatic dysfunction (check liver function/enzymes)

rare side effects of fibrates

pancreatitis

reversible decreased renal function (increases serum creatinine)

myositis/myopathy/rhabdomyositis -check CPK levels if worried when using w/ statins

vitamin B3 medication name

Niacin (nicotinic acid)

MOA of vitamin B3 meds

niacin is converted to NAD and NADP that are coenzymes for lipid + protein metabolism = decreases VLDL and increases HDL

indication for vitamin B3

hypercholesterolemia

side effects of vitamin B3

flushing (from vasodilation)- using aspirin w/ niacin can reduce this

hepatic dysfunction (check liver function)

nausea/abdomen discomfort

orthostatic hypotension

exacerbation of gout

what symptoms should you educate patients to report when taking niacin/vitamin B3

darkening of urine

light gray stool

loss of appetite

stomach pain

yellow eyes/skin

repathia (evolocumab) MOA

Injectable taken once every 2 weeks

reduces cholesterol by binding to LDL receptors = increases receptors = increased clearance of LDL from blood

repathia indications

reduce risk of MI and stroke in pts w/ CV disease

- used as adjunct and not 1st or 2nd line treatment

repathia contraindications

hypersensitivity to REPATHA

repathia side effects

diabetes

upper respiratory tract infection

injection site irritation

allergic reaction