Statins Flashcards
Considerations for the following special populations: 1) Children 2) Pregnancy 3) Asians 4) Kidney Function 5) Breastfeeding 6) Prediabetes 7) Older Adults 8) Hypothyroidism 9) Viral or Alcoholic Hepatitis
1) Children- lovastatin, simvastatin, pravastatin, and atorvastatin are approved. No statin use under 10 y/o 2) Pregnancy- contraindicated. Ezetimibe & fibrates can be used, benefit should outweigh risk 3) Asians- same dose of rosuvastatin given to other subjects, produces twofold higher blood levels in this population. Start with lowest dose and monitor closely 4) Kidney Function- atorvastatin and fluvastatun are preferred with renal impairment since there is no need to adjust dose 5) BF- effects have not been studied. Possible harm, but benefits should outweigh the risks 6) Prediabetes- statins can accelerate advancement from prediabetes to diabetes 7) Older Adults- cost-benefit evaluation of treatment 8) Hypothyroidism- increases risk of myopathy with use of statins in high doses 9) Viral or Alcoholic Hepatitis- avoid statins due to liver injury by elevations in serum transaminase levels
HMG-CoA Reductase Inhibitors (statins); screening & lab work
Baseline LFTs prior to starting treatment and then repeat if clinically indicated (some sources recommend another LFT 3 months after starting and again at 12months). If serum transaminase levels rise to >x3 the upper limit of normal and remain, the statin should be discontinued. Avoid statins in patients with viral or alcoholic hepatitis. Statins can be used in pts w NAFLD.
Potential side effect of statins and treatment
Side effects are not common and are generally tolerated well by patients. Side effects that can occur include headache, rash, or GI problems like dyspepsia, cramps, flatulence, constipation, or abdominal pain. Side effects tend to be mild. Hepatotoxicity and myopathy are serious adverse effects that rarely occur.
Interactions with other medications: Interactions Statins and drugs that inhibit CYP3A4
Drugs that inhbit CYP3A4 can raise levels of lovastatin and simvastatin substantially and can raise levels of atorvastatin moderately, by slowing their inactivation. Inhibitors of CYP3A4 include macrolide antibiotics, azole antifungal drugs, HIV protease inhibitors, amiodarane, and cyclosporine.
Screening laboratory work prior to initiation of therapy and through treatment
Total cholesterol, LDL, HDL, and Triglycerides. Baseline LFTs and a CK level. Cholesterol levels should be monitored monthly early in treatment and at longer intervals thereafter.
Special Considerations: Pregnancy
Special Considerations: Statins are contraindicated in pregnancy. Any benefits of therapy are outweighed by risk to the fetus. Because statins inhibit cholesterol synthesis and cholesterol is necessary for cell membrane synthesis and synthesis of fetal hormones, there is concern for harm to human fetuses with statin use during pregnancy. Women of childbearing age should be counseled regarding the potential for statins to cause fetal harm if they become pregnant.
Interactions with other Medications
Combining a statin with other lipid-lowering drugs can increase the incidence and severity of the most serious statin-related adverse events: muscle injury, liver injury, and kidney damage. Statins can also interact with drugs that inhibit CYP3A4. Drugs that inhibit CYP3A4 can raise levels of lovastatin and simvastatin substantially and can raise levels of atorvastatin moderately by slowing their inactivation. Some authorities recommend an automatic reduction in statin dosage if these inhibitors are used.
Special Considerations: Asian heritage
Rosuvastatin reaches abnormally high levels in people of Asian heritage. When given the same dose to Asian and white subjects, it may produce twofold higher blood levels in the Asians. At usual therapeutic doses, rosuvastatin levels in these people are about twice those in whites. If rosuvastatin is used by Asians, dosage should be reduced. Start with the lowest available dosage and monitor diligently.
Potential side effect of statins and treatment
Statins are generally well tolerated and side effects are uncommon. Mild and transient side effects can include headache, rash, or GI disturbances. Two potentially rare and serious adverse effects are hepatotoxicity and myopathy. Hepatotoxicity occurs in 0.5% to 2% of patinets treated 1 year or more and packaging recommends baseline LFTs and subsequent monitoring. Statins should be avoided in patients with viral or alcoholic hepatitis, but are safe to use in patients with nonalcoholic fatty liver disease. Mild myopathy occurs in 5%-10% of patients and fatal rhabdomyolysis is rare. Rosuvastatin has the highest risk for rhabdomyolysis. Other factors that increase the risk for myopathy are advanced age, small body frame, multisystem disease, high dose statin use, low vitamin D and coenzyme Q levels, hypothyroidism, and concurrent use of fibrates.
Drug Interactions.
“Combining a statin with other lipid lowering drugs can
increase the incidence and severity of the most serious
statin-related adverse events; muscle injury, liver injury
and kidney damage. Statins can also interact with
drugs that inhibit CYP3A4. This inhibitions can raise
levels of atorvastatin moderately by slowering their i
inactivation. Asians are recomended on intiating lower
dose due to the risk of elevating blood levels compared
to white patients.”
What is an interaction with other medications?
Pravastatin and Pilavastatin are not metabolized significantly by CYP450 system, but still interact with several medications including Cyclosporines and macrolide antibiotics.
Labs that should be monitored prior to statin initiation of therapy and throughout treatment include 1) VLDL 2) LDL 3) HDL 4)Total Cholesterol 5) Triglycerides
1) VLDL - contains many triglycerides and they account for nearly all the TGs in the blood. Deliver triglycerides from the liver to adipose tissue and muscle. 2) LDL - contains cholesterol as primary core lipid and accounts for 60-70% of all cholesterol in the blood. Delivers cholesterol to nonhepatic tissues. The “bad” cholesterol. 3) HDL - Contains cholesterol as primary core lipid and accounts for 20-30% of all cholesterol in the blood. Carry cholesterol from peripheral tissues back to the liver. HDLs promote cholesterol removal. The “good” cholesterol. 4) Total cholesterol - The combined level of LDL and HDL in your blood. 5)Triglycerides - A type of fat found in your blood.
