Clinical Pharmacy and Pharmacotherapeutics 2 (PHCP312) Dyslipidemia PDF

CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM tinatawag na...

CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM tinatawag na thrombogenic. Naghahatak siya ng platelets so DYSLIPIDEMIA magbubuo buo then cmagcclog sa ➔ Defined as elevated total cholesterol, low-density blood vessels lipoprotein (LDL) cholesterol, or triglycerides; low ○ mechanical injury to endothelium, high-density lipoprotein (HDL) cholesterol; or a ○ and excessive homocysteine can lead to combination of these abnormalities. endothelial dysfunction and cellular ◆ Pwede tayo magka problema if naoxidized interactions culminating in atherosclerosis ang LDL sa ating blood vessels which can further result to atherosclerosis. And kapag Kapag tayo ay nangyari to, it somehow irreversible kasi nagkakaroon ng oxidized nagcclog na sa blood vessel LDL, naiipon yan or LDL: bad cholesterol nagsisingit singit sa HDL: scavengers ng LDL or Good cholesterol tuninca media. Chronic ito. Then eventually habang tumatanda tayo Pathophysiology parami siya ng parami, mag iipon yan dyan Cholesterol, triglycerides, and phospholipids are (atherosclerotic plaque) transported in blood as complexes of lipids and hanggang mastretch yung proteins (lipoproteins). tunica intima hanggang Adrenal gland is responsible for the production of several sa mapunit si tunica hormones such as androgens, cortisol and aldosterone which intima. is made up of cholesterol as well. It means cholesterol is important to make up other hormones. So ayun, as we grow But excessive cholesterol and triglycerides would be old, na iipon yan lalo detrimental to the body. DAPAT SAPAT LANG yung nasa na kapag napabayan. katawan natin. Then magggrow and rupture yan, masisira Elevated total and LDL cholesterol and reduced HDL yung tunica intima. cholesterol are associated with development of Then yung fats coronary heart disease (CHD). wherein nacclog ng maeexposed siya. fats yung blood vessels natin. So kapag nangyari ito, These fats ang soft mahihirapan dumaloy ang dugo sa blood vessel fats and thrombogenic which can cause hypertension and eventually kapag which is magtatawag nasobrahan ng nasarahan ang daanan ng dugo, wala ng platetes. So kapag nang oxygenation sa mga nabarahan so pwedeng naexpose yung fats, magkaroon ng Ischemia wherein there is a loss of aatakihin ng katawan oxygenation mamamatay yung tissues natin don and natin dahil akala niya eventually mag degrade yung katawan natin.And ito is foreign substance. yung pinipigilan natin So yung mga platelets, The development of atherosclerosis is chronic. Hindi agad nag magcclog siya don hanggang eventually mapupuno siya ng kakaroon nito, instead, nagkakapatong patong ito kapag clot. So lumiliit yung space ng daanan ng dugo natin. So yung kumain ka or as aged. Kapag di natin inaalagaan ang sarili mga dugo na naggagaling don, maiipon and tataas yung natin pressure so it can induced hypertension and if left untreated it can caused ischemia or loss of oxygenation dahil wala nang Risk factors such as dugo na lumalabas. Remeber: yung dugo natin yung nagccarry ○ oxidized LDL ng oxygen, so if walang dugong dumaan, wala nang oxygen na Dito nagsisimula ang production ng dadaloy sa kabilang part ng katawan ng clog na yun so atherosclesis and eventually mamatay yung tissue which could lead to angina or Myocardial magaaccumulate ito hanggang sa infarction, or arrhythmia or ischemic stoke or even death. magkakaroon ng rupture and then yung ruptured area na yun ay Lalo & Tobias 1 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM Maging maingat sa kinakain natin,. Pwede rin naman genetic, Primary or genetic lipoprotein disorders are which is tinatawag na familial hypercholesterolemia which classified into six categories: means mataas ang cholesterol level because of the genes of ○ I (chylomicrons) our body. ○ IIa (LDL) ○ IIb (LDL + very-low-density lipoprotein Yung mga fats na nakaclot, hindi na yun matatanggal. Hindi na [VLDL]) macconvert to energy kasi naoxidized na siya. So habang ○ III (intermediate-density lipoprotein) buhay na or ooperahan, like bypass surgery or angioplasty. ○ IV (VLDL) ○ V (VLDL + chylomicrons) So para malaman kung optimum ang level ng cholesterol Secondary forms of dyslipidemia also exist, and titignan natin yung Lipid panel several drug classes may elevate cholesterol levels (eg, progestins, thiazide diuretics, glucocorticoids, Eventual clinical outcomes may include angina, β-blockers, isotretinoin, protease inhibitors, myocardial infarction (MI), arrhythmias, stroke, cyclosporine, mirtazapine, and sirolimus - peripheral arterial disease, abdominal aortic immunomodulator na ginagamit ng mga tao na need aneurysm, and sudden death. magundergo ng organ tranplantation ). Atherosclerotic lesions arise from transport and The primary defect in familial retention of plasma LDL through the endothelial cell hypercholesterolemia is inability to bind LDL to the layer into the extracellular matrix of the subendothelial LDL receptor (LDL-R). space. ○ Mataas ang LDL because of genes Once in the artery wall, LDL is chemically modified ○ This leads to a lack of LDL degradation by through oxidation and nonenzymatic glycation. ¨ cells and unregulated biosynthesis of Mildly oxidized LDL recruits monocytes into the artery cholesterol. wall, which transform into macrophages that accelerate LDL oxidation. Oxidized LDL provokes an Clinical Presentation inflammatory response mediated by chemoattractants and cytokines. ¨ Repeated injury and repair within an atherosclerotic Most patients are asymptomatic for many years. plaque eventually lead to a fibrous cap protecting the Symptomatic patients may complain of chest pain, underlying core of lipids, collagen, calcium, and palpitations, sweating, anxiety, shortness of breath, or inflammatory cells. Maintenance of the fibrous plaque abdominal pain. They may also experience difficulty is critical to prevent plaque rupture and coronary with speech or movement or loss of consciousness thrombosis baka affected na yung brain or may ischemic stroke. Patients with atherosclerosis cardiovascular diseases are ischemic stroke- there is loss of oxygenation in our brain given aspirin to inhibit platelet aggregation. Dahil ung platelet because of the clogged blood vessels in the brain. Pwedeng aggregation ang pwede mag increase ng risk of having galing siya sa atherosclerosis. Example yung natuklap na clot nhtromboisis. Maiipon yung platelet and fats, which could lead sa ibang part na may atherosclerosis, so dadaloy sa blood to blockages in blood vessels. vessels hanggang mapunta sa brain which is maliit lang kasi blood vessel don. So that area, mawawalan ng oxygenation which is ISchemia then eventually will lead to necrosis. Ischemic stroke give alteplase which is a tissue plasminogen activator. Tutunawin yung plaque. Thrombus: blood clot Embolus: yung gumagala na blood clot Depending on the lipoprotein abnormality, signs on physical examination may include cutaneous xanthomas, peripheral polyneuropathy, high blood pressure, and increased body mass index or waist size. Diagnosis HDL: good cholesterol LDL: bad cholesterol Lalo & Tobias 2 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM Measure fasting (preferred) lipoprotein profile (total TREATMENT cholesterol, LDL, HDL, and triglycerides) in all adults 20 years of age or older at least once every 5 years. ○ Especially if we have a sedentary lifestyle. ➔ Goals of Treatment: Lower total and LDL cholesterol to reduce the risk of first or recurrent events such as Measure plasma cholesterol, triglyceride, and HDL MI, angina, heart failure, ischemic stroke, or levels after a 12-hour fast because triglycerides may peripheral arterial disease. Or increase the HDL level be elevated in non fasting individuals; total cholesterol if mababa ito. is only modestly affected by fasting. ○ Sabay na rin yung FBS STUDY THIS MATRIX Two determinations, 1 to 8 weeks apart are recommended to minimize variability and obtain a reliable baseline. ○ Normal: 5.17 mmol/L), a second determination is recommended, ○ and if the values are greater than 30 mg/dL (>0.78 mmol/L) apart, use the average of three values. History and physical examination should assess: 1. presence or absence of cardiovascular risk factors or definite cardiovascular disease; 2. family history of premature cardiovascular disease or lipid disorders; Liver function: Test yung Alanine aminotransferase 3. presence or absence of secondary causes If mataas ang ALT, di pwede bigyan ng STATIN of dyslipidemia, including concurrent CAC (coronary calcium scan) medications; and 4. presence or absence of xanthomas (skin Intensity of statin therapy condition wherein there is a skin tags), abdominal pain, or history of pancreatitis, renal or liver disease, peripheral vascular disease, abdominal aortic aneurysm, or cerebral vascular disease (carotid bruits, stroke, or transient ischemic attack) Diabetes mellitus is a CHD risk equivalent; its presence in patients without known CHD is associated with the same level of risk as patients without diabetes but having confirmed CHD ASIAN cannot tolerate a high level of Rosuvastatin. Lipoprotein electrophoresis is sometimes Hindi pwede lumagpas ng 40mg lang dapat. performed to determine which class of lipoproteins is involved. If the triglycerides are less than 400 mg/dL Atorvastatin and Rosuvastatin: long acting and can be taken (4.52 mmol/L), and neither type III dyslipidemia nor any time of the day. chylomicrons are detected by electrophoresis, then one can calculate VLDL and LDL concentrations: The rest of the statins must be taken before sleeping. Dahil ○ VLDL = triglycerides ÷ 5 ang production ng cholesterol is when we are sleeping or de ○ LDL = total cholesterol – (VLDL + HDL) novo synthesis. Yung hindi nagamit na carbohydrates matturn to cholesterol. Lalo & Tobias 3 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM IV Fibrates Niacin Niacin Fibrates V Fibrates Niacin niacin Fish oils (BAR, bile acid reins; fibrates include gemfibrozil or fenofibrate.) BAR are not used as first-line therapy if triglycerides are elevated at baseline since hypertriglyceridemia may be worsen with BAR alone. Mipomersen and lomitapide are used in combinations with other lipid lowering therapy, in particular, statins for patients with familial hypercholesterolemia (homozygotes or heterozygotes) and in patient who cannot be managed adequately with maximally tolerated statin therapy Niacin: for hyperglycinemia Gemfibrozil: first fibric acid salt, so maraming ADR. do not Mipomersen and lomitapide, hindi gano ginagamit sa combined with other cholesterol medications Philippines. Di raw naencounter ni sir Ken. Fenofibric: can combine with statins but can cause Ezetimibe: together with statins. Kasi mabilis magaroon ng rhabdomyolysis and myopathy. tachyphylaxis wherein a medication has a very high level of Statins: inhibits the first step in the cholesterol synthesis kaya tolerance. sila ang first line treatment. Ezetimibe: inhibit cholesterol absorption. Dinudumi natin Homozygote: one parent meron Heterozygote: both parents meron Apolipoprotein B-100 makikita sa hepatocytes or liver cells which help in making or utilizing VLDL which is released by endoplasmic reticulum found in the hepatocytes. Bile Acid Resins PCSK9 part of production of cholesterol in the body Bile acids: Lipoprotein Phenotype and Recommended Drug ○ gawa sa cholesterol Treatment ○ emulsify the fats Lipoprotein type Drug of choice Combination ○ Narerecycle ng katawan therapy ○ Kapag gagawa ng bile acids, gagamitin yung cholesterol na nasa I Not indicated - katawan natin, so bababa yung IIa Statins Niacin or BAR cholesterol Cholestyramine Statins or niacin ○ The problem is it can affect the or colestipol Statins or BAR absorption of vitamins that are lipid Niacin Ezetimibe soluble such as vitamin ADEK. Mipomersen, lomitapide BARs (cholestyramine, colestipol, and colesevelam) bind bile acids in the intestinal IIb Statins Statins or niacin lumen, with a concurrent interruption of Fibrates Statins or enterohepatic circulation of bile acids, which Niacin fibrates decreases the bile acid pool size and stimulates Ezetimibe hepatic synthesis of bile acids from cholesterol. III Fibrates Statins or niacin Niacin Statins or ○ Depletion of the hepatic cholesterol pool fibrates increases cholesterol biosynthesis and the Ezetimibe number of LDL-Rs on hepatocyte Lalo & Tobias 4 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM membranes, which enhances the rate of Niacin may cause itching. catabolism from plasma and lowers LDL levels. The principal use of niacin is for mixed dyslipidemia or as a second-line agent in combination therapy ○ Increased hepatic cholesterol biosynthesis for hypercholesterolemia. may be paralleled by increased hepatic It is a first-line agent or alternative for treatment of VLDL production; consequently, BARs hypertriglyceridemia and diabetic dyslipidemia. may aggravate hypertriglyceridemia in patients with combined dyslipidemia Cutaneous flushing and itching appear to be prostaglandin mediated and can be reduced by BARs are not given if there is hypertriglyceridemia. taking aspirin 325 mg shortly before niacin ingestion. Taking the niacin dose with meals and BARs are useful in treating primary slowly titrating the dose upward may minimize hypercholesterolemia (familial these effects. hypercholesterolemia, familial combined ○ Aspirin- irreversibly binds to cox1 and dyslipidemia, and type IIa hyperlipoproteinemia). cox2 therefore magddecrease din yung prostaglandin synthesis Common GI complaints include constipation bloating, epigastric fullness, nausea, and Concomitant alcohol and hot drinks may flatulence. They can be managed by increasing magnify the flushing and pruritus from niacin, and fluid intake, increasing dietary bulk, and using stool they should be avoided at the time of ingestion. softeners The gritty texture and bulk may be minimized by GI intolerance is also a common problem. mixing the powder with orange drink or juice. Laboratory abnormalities may include elevated Colestipol may have better palatability than liver function tests, hyperuricemia, and cholestyramine because it is odorless and hyperglycemia. Niacin-associated hepatitis is tasteless. Tablet forms may help improve more common with sustained release preparations, adherence and their use should be restricted to patients intolerant of regular-release products. Other potential adverse effects include impaired absorption of fat-soluble vitamins A, D, E, and K; Niacin is contraindicated in patients with active hypernatremia and hyperchloremia; GI obstruction; liver disease, and it may exacerbate pre existing and reduced bioavailability of acidic drugs such gout and diabetes. as warfarin, nicotinic acid, thyroxine (esp. If may hyperthyroidism), acetaminophen, hydrocortisone, Niaspan is a prescription-only, extended-release hydrochlorothiazide, loperamide, and possibly iron. niacin formulation with pharmacokinetics intermediate between prompt- and sustained Drug interactions may be avoided by release products. It has fewer dermatologic alternating administration times with an interval reactions and a low risk of hepatotoxicity. of 6 hours or more between the BARs and other Combination with statins can produce large drugs. reductions in LDL and increases in HDL. ○ Nicotinamide should not be used in the Niacin treatment of dyslipidemia because it does not effectively lower cholesterol or Niacin is Vitamin B3. triglyceride levels. Niacin (nicotinic acid) reduces hepatic synthesis of VLDL, which in turn reduces synthesis HMG-CoA Reductase Inhibitors of LDL. Niacin also increases HDL by reducing its catabolism. Lalo & Tobias 5 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM Reduced LD synthesis and enhanced LDL catabolism mediated through LDL-Rs appear to be the principal mechanisms for lipid-lowering effects When used as monotherapy, statins are the most potent total and LDL cholesterol– lowering agents and among the best tolerated. Total and LDL cholesterol are reduced in a dose-related fashion by 30% or more when added to dietary therapy Combination therapy with a statin and a BAR is rational because the numbers of LDL-Rs are increased, leading to greater degradation of LDL cholesterol; intracellular synthesis of cholesterol is inhibited; and enterohepatic recycling of bile acids is interrupted. ○ As much as possible hindi siya masyadong pinagcombine ○ Mas common ang combination of statin The first step in the production of cholesterol is the and ezetimide. conversion of HMG-CoA to Mevalonate via the Combination therapy with a statin and enzyme HMG-CoA reductase. So Statins will inhibit ezetimibe is also rational because ezetimibe HMG-CoA reductase para no formation of cholesterol. inhibits cholesterol absorption across the gut border and adds 12% to 20% further reduction Also take note: There are many signaling pathways na when combined with a statin or other drug. pwede maproduce. And ang main product is cholesterol Constipation occurs in less than 10% of patients taking statins. Other adverse effects include STATINS SHOULD BE GIVEN BEFORE SLEEPING elevated alanine aminotransferase, elevated because the de novo synthesis or production of creatine kinase levels, myopathy, and, rarely, rhabdomyolysis. cholesterol happens when we are sleeping. Sa pinaka mahimbing na tulog. So avoid eating before Fibric Acid sleeping.yung kanin pwede maging cholesterol sa gabi kasi di nagamit. If carbohydrates ay hindi Fibrate monotherapy (gemfibrozil, fenofibrate, and ginagamit, nasstore sa katawan so nagiging clofibrate) is effective in reducing VLDL, but a cholesterol. reciprocal rise in LDL may occur, and total cholesterol values may remain relatively Fats can be used if kulang na ng energy. unchanged. Plasma HDL concentrations may rise Gluconeogenesis is the production of energy from 10% to 15% or more with fibrates. non carbohydrates such as fats. Gemfibrozil reduces synthesis of VLDL and, to a lesser extent, apolipoprotein B with a concurrent Statins (atorvastatin, fluvastatin, increase in the rate of removal of triglyceride-rich lovastatin, pitavastatin, pravastatin, lipoproteins from plasma. Clofibrate is less effective rosuvastatin, and simvastatin) inhibit than gemfibrozil or niacin in reducing VLDL 3-hydroxy-3- methylglutaryl coenzyme A production. (HMG-CoA) reductase, interrupting conversion of HMGCoA to mevalonate, the rate limiting step in GI complaints occur in 3% to 5% of patients. cholesterol biosynthesis. Rash, dizziness, and transient elevations in Lalo & Tobias 6 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM transaminase levels and alkaline phosphatase may also occur. Diets high in omega-3 polyunsaturated fatty ○ If mataas ang alkaline phosphatase, may acids (from fish oil), most commonly problem sa liver or bones eicosapentaenoic acid (EPA), reduce cholesterol, ○ If sa bones, need pa ng Gamma glutamyl triglycerides, LDL, and VLDL and may elevate HDL transpeptidase. cholesterol. Fish oil supplementation may be most useful in ALP GGT patients with hypertriglyceridemia, but its role in liver ↑ ↑ treatment is not well defined. bones ↑ - LOVAZA (omega-3-acid ethyl esters) is a prescription form of concentrated fish oil ¨ Gemfibrozil and probably fenofibrate enhance EPA 465 mg and docosahexaenoic acid 375 mg. gallstone formation rarely. The daily dose is 4 g, which can be taken as four 1-g capsules once daily or two 1-g capsules twice A myositis syndrome of myalgia, weakness, daily. This product lowers triglycerides by 14% to stiffness, malaise, and elevations in creatine kinase 30% and raises HDL by ~10%. ¨ and aspartate aminotransferase may occur and may be more common in patients with renal Complications of fish oil supplementation such as insufficiency. thrombocytopenia and bleeding disorders have been noted, especially with high doses (EPA 15–30 Fibrates may potentiate the effects of oral g/day). anticoagulants (enhanced Warfarin which leads to bleeding), and the international normalized ratio (INR) should be monitored very closely with this Mipomersen combination. Mipomersen (Kynamro) is an antisense oligonucleotide inhibitor of apolipoprotein B-100 Ezetimibe synthesis. ○ APO B- 100: n Produced in the liver and Ezetimibe interferes with absorption of cholesterol is necessary for the assembly and from the brush border of the intestine, making it a secretion of VLDL good choice for adjunctive therapy. It is approved as monotherapy and for use with a statin. It is indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-cholesterol, The dose is 10 mg once daily, given with or without apolipoprotein B, total cholesterol, and non-HDL food. When used alone, it results in ~18% cholesterol in patients with homozygous familial reduction in LDL cholesterol. hypercholesterolemia. When added to a statin, ezetimibe lowers LDL by The dose is 200 mg once weekly given by an additional 12% to 20%. subcutaneous (SC) injection. When given in combination with maximum tolerated doses of lipid A combination product (Vytorin) containing lowering therapy, mipomersen can produce an ezetimibe 10 mg and simvastatin 10, 20, 40, or 80 additional 25% reduction in LDL cholesterol. mg is available. Ezetimibe is well tolerated; ~4% of patients experience GI upset. Because Adverse reactions include injection site reactions, cardiovascular outcomes with ezetimibe have not flu like symptoms, nausea, headache, and been evaluated, it should be reserved for patients elevations in serum transaminases. unable to tolerate statin therapy or those who do not achieve satisfactory lipid lowering with a statin alone. Lomitapide Lalo & Tobias 7 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM Lomitapide (Juxtapid) is a microsomal TREATMENT RECOMMENDATIONS triglyceride transfer protein (MTP) inhibitor that reduces the amount of cholesterol that the liver and ★ Treatment of TYPE I HYPERLIPOPROTEINEMIA is intestines assemble and secrete into the directed toward reduction of chylomicrons derived circulation. from dietary fat with the subsequent reduction in plasma triglycerides. Total daily fat intake should be It is indicated as an adjunct to diet and other lipid no more than 10 to 25 g, or ~15% of total calories. lowering treatments to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-HDL The longer the fatty acid chain, mas malinamnam cholesterol in patients with homozygous familial We have to avoid yung mantika na natutulog or mabubuo. hypercholesterolemia. Lomitapide may reduce From animal fats yun. LDL cholesterol by about 40% in patients on maximum tolerated lipid-lowering therapy and LDL 1 tablespoons of palm oil = 120 calories apheresis. 2000 calories a day lang dapat. Because of the risk of hepatotoxicity, lomitapide ★ Secondary causes of hypertriglyceridemia should is available only through the Risk Evaluation and be excluded, and, if present, the underlying disorder Mitigation Strategy (REMS) program. should be treated appropriately. Proprotein Convertase Subtilisin/Kexin Type 9 ★ Primary hypercholesterolemia (familial (PCSK9) Inhibitors hypercholesterolemia, familial combined dyslipidemia, and type IIa hyperlipoproteinemia) is treated with PCSK9 promotes intracellular degradation of BARs, statins, niacin, or ezetimibe. hepatic LDL, prevents LDL recycling to the cell surface, and reduces LDL clearance from the ★ Combined hyperlipoproteinemia (type IIb) may be circulation; inhibiting PCSK9 substantially lowers treated with statins, niacin, or gemfibrozil to lower LDL cholesterol. LDL-C without elevating VLDL and triglycerides. Niacin is the most effective agent and may be These drugs are indicated as an adjunct to diet and combined with a BAR. maximally tolerated lipid-lowering therapy for adults ○ A BAR alone in this disorder may elevate with heterozygous familial hypercholesterolemia or VLDL and triglycerides, and their use as ASCVD who require additional lowering of LDL single agents for treating combined cholesterol. ¨ hyperlipoproteinemia should be avoided. The typical LDL reduction ranges from 40% to over 60%. ★ Type III hyperlipoproteinemia may be treated with fibrates or niacin. Although fibrates have been The most common adverse effect reported in suggested as the drugs of choice, niacin is a clinical trials was injection site pain. reasonable alternative because of the lack of data supporting a cardiovascular mortality benefit from Not common in philippines fibrates and because of potentially serious adverse effects. The drugs are administered by SC injection into the ○ Fish oil supplementation may be an thigh, abdomen, or upper arm as follows: alternative therapy. ○ Alirocumab (Praluent) 75 mg SC every 2 weeks; if the response is inadequate, the ★ Type V hyperlipoproteinemia requires stringent dose may be increased to 150 mg SC restriction of dietary fat intake. Drug therapy with every 2 weeks fibrates or niacin is indicated if the response to diet ○ Evolocumab (Repatha) 140 mg SC alone is inadequate. every 2 weeks or 420 mg once monthly ★ Medium-chain triglycerides, which are absorbed without chylomicron formation, may be used as a Lalo & Tobias 8 CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS 2 (PHCP312) TOPIC 6: DYSLIPIDEMIA MIDTERM dietary supplement for caloric intake if needed for associated with CHD. Alternative therapies include both types I and V. gemfibrozil or fenofibrate, statins, and fish oil. ★ The goal of therapy is to lower triglycerides and COMBINATION DRUG THERAPY VLDL particles that may be atherogenic, increase HDL, and reduce LDL. ★ Combination therapy may be considered after adequate trials of monotherapy and for patients ★ Very high triglycerides are associated with documented to be adherent to the prescribed pancreatitis and other adverse consequences. regimen. Two or three lipoprotein profiles at 6-week Management includes dietary fat restriction (10–20% intervals should confirm the lack of response prior to of calories as fat), weight loss, alcohol restriction, and initiation of combination therapy. ¨ Screen carefully for treatment of coexisting disorders (eg, diabetes). Drug contraindications and drug interactions with combined therapy includes gemfibrozil or fenofibrate, niacin, and therapy, and consider the extra cost of drug product higher potency statins (atorvastatin, pitavastatin, and monitoring. rosuvastatin, and simvastatin). ★ In general, a statin plus a BAR or niacin plus a ★ Successful treatment is defined as reduction in BAR provides the greatest reduction in total and LDL triglycerides to less than 500 mg/dL (5.65 cholesterol. Regimens intended to increase HDL mmol/L). levels should include either gemfibrozil or niacin, bearing in mind that statins combined with either of these drugs may result in a greater incidence of TREATMENT OF LOW HDL CHOLESTEROL hepatotoxicity or myositis. ★ Low HDL cholesterol is a strong independent risk ★ Familial combined dyslipidemia may respond better to predictor of CHD. a fibrate and a statin than to a fibrate and a BAR. ★ ATP III redefined low HDL cholesterol as less than 40 mg/dL (