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Treatment of dyslipidemia

The document outlines various treatments for dyslipidemia, including non-pharmacological measures and classifications of drugs such as statins, ezetimibe, bile acid sequestrants, fibrates, and niacin, detailing their mechanisms of action, side effects, and therapeutic uses. It emphasizes the importance of combination therapy and preventive measures, including lifestyle changes. Additionally, it highlights the need for regular monitoring of liver function and specific considerations for certain populations, such as pregnant women.

Health & Medicine◦
Treatment of dyslipidemia Asma mutni ID 33121670
Objectives : 1)list non-pharmacological measures for treatment of dyslipidemia . Classify drugs used in treatment of dyslipidemia .2) 3) Mention the MOA , most common side effect and the effect on lipid profile of each class . 4) outline preventive measure of dyslipidemia .
1. HMG-CoA Reductase Inhibitors: statins Simvastatin, Fluvastatin, lovastatin, pravastatin,, atorvastatin, rosuvastatin 2. Specific cholesterol absorption inhibitors: ezetimibe 3. BILE ACID BINDING (RESINS): Cholestyramine and Colestipol, colesevelam 4. FIBRATES: Gemfibrozil, Clofibrate,, Bezafibrate,and Fenofibrate, ciprofibrate 5. Nicotinic Acid (NIACIN), Acipimox 6. Others: Omega-3-FA, orlistat, CETP inhibitors (Torcetrapib)▲ BP & mortality, Prubucol,
HMG-CoA Reductase Inhibitors: statins MOA : Statin will inhibit HMG-CoA reductase prevent catalyses the conversion of HMG-CoA to mevalonic acid inhibit cholestrol synthisis intracellular cholestrol LDL receptor LDL.c , VLDL remnants . synthesis of VLDL TG , LDL HDL 5-20 %
Cont. atorvastatin, rosuvastatin long acting inhibitor . Simvastatin, Fluvastatin, lovastatin, pravastatin short acting inhibitor giving by mouth at night ? To reduce peak cholesterol synthesis in the early morning . absorption with food . They are well absorbed and excreted by liver ,their site of action, and are subject to extensive presystemic metabolism via cytochrome p450 and glucoronidation pathway . Excretion : 80% metabolized and excreted in bile and 20% excreted unchanged drug in urine Importance ?? Frequent checkup liver and kidney function
Clinical uses of HMG-CoA reductase inhibitors (statins) 1) Secondary prevention of CHD (e.g. angina, following myocardial infarction or stroke). 2) Primary prevention of arterial disease in patients who are at high risk of atherosclerosis. 3) Atorvastatin lowers serum cholesterol in patients with homozygous familial hypercholesterolaemia. 4) In severe drug-resistant dyslipidaemia (e.g. heterozygous familial hypercholesterolaemia), ezetimibe is combined with statin treatment. 5) 2ry hyperlipidemia e.g DM , nephrotic syndrome 6) # in pregnancy .
cont.. side effect : most common : muscle pain (myalgia )1) 2) GIT disturbance 3) raised concentration of liver enzyme in plasma 4) insomnia 5) rash rarly : 1)myositis ( common in lean body mass and uncorrected hypothyroidism pt . 2) angio-oedema
Specific Cholesterol Absorption Inhibitors(Ezetimibe= zetia) MOA : inhibit absorption of cholesterol from duodenum by blocking transport protein (NPC1L1) in the brush border of enterocyte without affecting the absorption of fat soluble vitamins , TG or bile acid . Adverse effect : 1. GIT: Diarrhea, abdominal pain, hepatitis if combined with statins, rarely myositis alone or with statins 2. CNS: Headache, fatigue, dizziness 3. Skin: Allergic reactions (rare)
Therapeutic uses of ezetimibe 1) In compination with statin to treat hypercholesterolemia. 2) Alone in mild cases or when statin is contraindication Patients with moderate to severe hepatic insufficiency should not be treated with ezetimibe.
Bile Acid Sequestrants (Resins) and colesevelamCholestyramine and colestipol MOA : These drugs bind to bile acid (cholesterol metabolite) and bile salts in small intestine form resins bile acid complex which is insoluble complex excreted in feces preventing the bile acid reabsorption and returning to liver bile acid concentration increase conversion of cholesterol to bile acid by hepatocyteintracellular cholesterol uptake of LDL LDL level in plasma .
Side effect : Minimal systemic effect because it dose not absorbed from GIT . in high doses and elderly ::Local effect -Bulky unappetizing and inconvenient . - GIT : abdominal fullness , diarrhea , constipation , nausea , bloating in colesevelam is less . - decrease absorption of fat soluble vit. (ADEK) but not colesevelam . - Hypernatremia and Hyperchloremia
Therapeutic uses Drug of choice in TTT of hyperlipidemia In children & pregnant women Hypercholestrolemia; Type IIA, and IIB Alone or + Statins or Niacin .
4. FIBRATES: Gemfibrozil, Clofibrate,, Bezafibrate,and Fenofibrate, ciprofibrate MOA : • -peroxisome proliferator activated receptor (PPAR) which is nuclear receptor that regulate lipid metabolism. • -activation of this receptor  bind to peroxisome proliferator response elements fibrates-mediated gene expression increase expression of lipoprotein lipase • decrease triacylglycerol concentration. also increase HDL level by increase expression of apo AI and apo AII.
:Adverse effect of fibrates 1) Muscles: rare Myalgia & Myositis (▲Kidney,Liver) ▲if +Statins (Simvastatin+Gemfibrozil) less with fenofibrate 2) GIT: (the most common) 5% Dyspepsia, abdominal pain, nausea, diarrhea, (▲Liver enzymes 3% 3) Skin 2%: Rash, urticaria, hair loss 4) Blood: ▼WBCS, anemia, ▼ K► Arrhythmias 5) Others; Headache, fatigue, impotence.
Therapeutic uses : 2nd line of TTT hypertriacylglycerolemuas after statin . Fenofibrate and gemfibrozil are particularly useful in treating Type III hyperlipidemia (dysbetalipoproteinemia) - Patients with hypertriacylglycerolemia (Type IV [elevated VLDL] or Type V [elevated VLDL plus chylomicron] disease) who do not respond to diet or other drugs
5. Nicotinic Acid (NIACIN), Acipimox • 1-strongly inhibition of lipolysis in adipose tissue decrease circulating free fatty acids  decrease triacylglycerol synthesis in liver decrease VLDL production  decrease plasma LDL concentration. • 2-niacin cause highly increase in HDL level by : • increase secretion of tissue plasminogen activator. • Decrease the level of plasma fibrinogen. • So .. It’s decrease triglyceride and LDL including Lp(a), and increase HDL
Adverse Effects: 1. CVS: flushing arrhythmias. Postural hypotnsion 2. Skin: pruritis, rash, dry skin, ↑pigmentation, acanthosis nigricans 3. GI: nausea, vomiting, diarrhea, flatulence, dyspepsia, activation of peptic ulcer 4. Liver; Hepatotoxicity 5. Endocrine: Insulin resistance and hyperglycemia. Not acipimox 6. ▲Uric acid: Hyperuricemia 20% (gout) 7. CNS: headache, dizziness. Blurring vision (Macular edema).
Therapeutic uses •Niacin lowers plasma levels of both cholesterol and triacylglycerol. Therefore, it is particularly useful in the treatment of familial hyperlipidemia 1. Not widely used due to ADR 2. Useful in all forms of dyslipidemia (# type1) 3. In hypertriglyceridemia (III, IV, V) with or without levated LDL. 4. Mostly used to lower VLDL & raise HDL 5. Adjunct to; statins, fibrates; (Niacin + Statins)► myopathy 6. Prevention of pancreatitis
Other drugs used to lowering lipid 1) Omega 3 fatty acid (fish oil ) reduce plasma triglyceride concentrations but increase cholesterol . - Antiarrhythmic risk of cardiac death in MI -inhibition of platelet function & plasma fibrinogen  prolonged bleeding time. - anti-inflammatory effect  alteration leukotriene biosynthesis - Anti-plaques adhesion of molecule 2) CETP inhibitors: Torcetrapib ▲HDL
non-pharmacological measures for treatment of dyslipidemia Our goal is increase HDL and decrease LDL 1 ) supplement healthy habit . 2) Moderate alcohol consumption raise HDL. 3) Regular exercise also increase circulating HDL . 4) Antioxidants (e.g vit. C and vit E ) . 5) Oestrogen (has antioxidant property) in women protect them from atherosclerosis . 6) Fish oil : supply omega 3 FA that decrease LDL .
effect of drugs on lipid profile TGHDLLDLType of drugs 14-29%6-12%25-60%HMG-coA reductase inhibtor (statin) 30-50%14-35%10-20%Niacin 30-60%11-13%4-21%fibrates Nutral3%10-18%Bile acid sequestrants (Resins) 9%1%18%Ezetimibe
preventive measures of dyslipidemia Primary prevention (Risk factors) 1- Diet control ; ↓protein intake , CHO, fat, salt . Total cholesterol should be < 200 . Antioxidants as vit.E , C , nuts,cereals, fresh fruit & vegetables . Fish oil : supply omega 3 FA that decrease LDL . 2- Regular check body weight , BP . 3- quit smoking and alcohol . 4- Physical activity . 5- Control oral contraceptive . 6) TTT of hypertension and , to lesser extent , DM 7) Reduce the incidence of symptomatic atheromatous disease . 8) Reduce atrial thrombosis by antithrombotic drugs .
Secondary prevention (Early stage) 1- Screening : A- All adult > 20 y (Fasting lipid profile) B- High risk group (Fasting lipid profile) 2-↓complications .. Tertiary prevention (Late stage) ↓impairments . Rehabilitation ..
My references :
Usesmetabol ism Lipid profile ADReffectMOAdrug 1ry hyperlipidemia 2ry hyperlipedemia 1ry and 2ry prevention of CHD # pregnancy , children <8 L and K disease In liver by cytochrom e p450 LDL 20-35% TG 10-35% HDL 10% Hepatotoxici ty Myopathy The most potent C agent ( Rosuvastatin the most potent one ) HMG- coA reductase inhibiter Statins In combination with statin in hypercholes terolemia or alone in mild cases or when statins is contraindica tion Metabol ized in gout and liver by conjugat ion and excreted in bile to feces 80% and C 50 % LDL 20 % Mild side effect . Has no serious ADR unless if it’s combined with statin (hepatitis Dec. C absorption in 50%( but not TG,bile acid , fat soluble vit) C absorption by dec. NPC1L1 transport protein Ezetimibe
UsesmetabolismLipid profileADRMOAdrug In children and pregnancy - Hypertriglyce ridemia alone or + stastin or niacin Not absorbed or metabolite and totally excreted by feces LDL 15-30% TG 20 % HDL 5% GIT Dec. absorption of fat soluble vit. And folic acid but not colesevelm Inc. hypertriglycer idemia in pt with CHL Bind with bile acid to form non- soluble non- absorpable complex Resins -In sever inc. in TG -Combined with otheer drugs in Sever resistance dyslipidemia -Mixed dyslipidemia ( ^ in C and TG) - In pt with low HDL and risk of atheromatus disease (e.g type 2 DM -Albumin binding 90 % -In liver glucoronoide  EHC -kideny 70% as glucoronoid e HDL 15-20% TG 50% -- GIT (most commo n) -Gallstones Anemia leukopenia rash peroxisome proliferator activated receptor Fibrates
UsesMetabolis m Lipid profile ADRMOADrug As adjunct to a statin and diet in dyslipidem ia especially when associated with low HDL and raised TG - Used when statin containdica tion. Conjugatio n with glycin to form nicotinuric acid then excreted in urine TG 33- 45% LDL 20- 30% HDL 30- 40% -CVS  flushing , postural hyperte Ntion -skin:pruritis , rash Liver : hypatotoxcic ty - hyperglycim ea strongly inhibition of lipolysis in adipose tissue decrease circulating free fatty acids  decrease triacylglycerol synthesis in liver decrease VLDL production  decrease plasma LDL concentration niacin
Thank you !
Questions ^,^ The most effective TG lowering drug is fibrates The drug causing hepatitis is statin Best drug to increase HDL is niacin TTT od dyslipidemia in pregnant women resine Drug can be used in primary previntion of dyslipidemia statin . Ezetimibe is contraindication in hepatic insufficiency . The least drug cause abdominal side effect from bile acid sequestrant is colesevelam The most common side effect of fibrate is GIT problem