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1. BY
ACC
8/17/2021 ACC 1

2. Antilipemic drugs
• Antilipemic drugs are used to lower abnormally
high blood levels of lipids (Cholesterol,
Triglycerides, and Phospholipids.
5 classes of antilipemic drugs:
1. Bile-sequestering drugs
2. Fibric acid derivatives
3. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-
CoA) reductase inhibitors
4. Nicotinic acid
5. Cholesterol absorption inhibitors.
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3. Bile-sequestering drugs
• These drugs are resins.
Mechanism of action
• Combine bile acids in the
intestines leading to ↓
bile acid in gallbladder
triggers the liver to
synthesize more bile
acids.
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4. Bile-sequestering drugs
Pharmacokinetics
• Aren’t absorbed from the GI tract.
Drug in class
• Cholestyramine (4g oral powder sachets)
• Colestipol (5g granules sachets sugar-free;
Tablets 1g tablets)
• Colesevelam (Colesevelam hydrochloride 625mg
tablets).
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5. Cholestyramine
Hyperlipidaemias| Prevention of CHD in men
aged 35–59 years with hypercholesterolaemia
• Adult: Initially 4 g daily PO, ↑ 4 g every week
(max 36 g daily)
Pruritus due to partial biliary obstruction and
primary biliary cirrhosis
• Adult: 4–8 g once daily PO
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6. Cholestyramine
Diarrhoea due to Crohn’s disease, ileal resection,
vagotomy, diabetic vagal neuropathy or radiation
• Adult: 4 g daily PO, ↑ of 4g weekly (max 36g
daily)
Accelerated elimination of teriflunomide
• Adult: 8 g 3 times a day for 11 days; ↓ to 4g 3
times a day.
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7. Colestipol
Hyperlipidaemias not responding adequately to
diet and other appropriate measures
• Adult: Initially 5 g 1–2 times a daily PO, ↑ of 5 g
monthly (30g daily)
Colesevelam
Hypercholesterolaemia as an adjunct to dietary
measures
• Adult: 2.5–3.75g daily PO in 1–2 divided doses
(max 4.375g daily)
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8. Bile-sequestering drugs…
Drug interactions
• Bind with acidic drugs e.g barbiturates,
phenytoin, penicillins, cephalosporins, thyroid
hormones and digoxin.
• ↓ absorption of propranolol, tetracycline,
furosemide, penicillin G, hydrochlorothiazide
and gemfibrozil.
• ↓ absorption of lipid-soluble vitamins A, D, E,
and K.
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9. Bile-sequestering drugs…
Adverse reactions
• Severe fecal impaction
• GIT effects
• Hemorrhoids
• Rarely, peptic ulcers, gallstones, and
inflammation of the gallbladder.
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10. Fibric acid derivatives
Mechanism of action
• Activation of peroxisome proliferator-activated
receptor-α (PPAR-α), modulating proteins
expression (lipoprotein lipase).
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12. Fibric acid derivatives
Pharmacokinetics
• Fenofibrate and gemfibrozil are absorbed
readily from the GI tract and are highly
protein-bound.
• Fenofibrate and gemfibrozil are
metabolised in the liver and excreted in
urine.
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13. Fibric acid derivatives
Drug examples
• Fenofibrate (160mg tablets; 67mg, 200mg and
267mg capsules)
• Bezafibrate (200mg Tablets)
• Gemfibrozil (300mg, 600mg tablets)
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14. Fenofibrate
Hyperlipidaemia if statin CI or not tolerated
• Adult: 200mg 3 times a day PO
Bezafibrate
Hyperlipidaemia if statin or not tolerated
• Adult: 200 mg 3 times a day PO
Gemfibrozil
Hyperlipidaemia if statin/Prevention of CVD in
men with hyperlipidaemias if statin CI or not
tolerated
• Adult: 0.9–1.2 g daily PO
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15. Fibric acid derivatives
Drug interactions
• Displace acidic drugs, such as barbiturates,
phenytoin, thyroid derivatives, oral
anticoagulants and cardiac glycosides.
• Hypoglycemic effects of repaglinide may be
increased and prolonged if taken with
gemfibrozil.
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16. HMG-CoA reductase inhibitors
• 3-hydroxy-3-methylglutaryl coenzyme A (HMG-
CoA) reductase inhibitors (Statins).
Drug examples
• Atorvastatin
• Fluvastatin
• Lovastatin
• Pravastatin
• Rosuvastatin
• Simvastatin.
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17. HMG-CoA reductase inhibitors
Mechanism of action
• HMG-CoA reductase inhibitors inhibit the
enzyme responsible for the conversion of HMG-
CoA to mevalonate, an early step in the
synthesis of cholesterol.
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19. HMG-CoA reductase inhibitors
Pharmacokinetics
• Highly bound to plasma proteins
• Undergo extensive first-pass metabolism.
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20. HMG-CoA reductase inhibitors
PharmacologicaI activity
• ↓ LDL cholesterol and total blood cholesterol
levels.
• Mild increase in HDL cholesterol levels.
Indications
• Primary hypercholesterolemia.
• Prevent risk of CAD, MI or stroke in patients with
high cholesterol levels.
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21. Atorvastatin (10,20,40,60,80mg Tablets)
Indications
1. Primary hypercholesterolaemia
2. Mixed hyperlipidaemia
3. Prevention of CVD in patients at high risk of a
cardiovascular event
• Adult: 10 mg once daily PO; ↑ every 4 weeks
(max 80 mg once daily)
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22. Rosuvastatin (5,10,20,40mg Tablets)
Indications
1. Hypercholesterolaemia
2. Mixed dyslipidaemia
• Adult: 5–10 mg once daily PO (up to 40 mg once
daily).
3. Prevention of CVD in high risk patients with risk
factors for myopathy or rhabdomyolysis
• Adult: 5mg once daily PO, ↑ gradually at
intervals of 4 weeks up to 20mg once daily.
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23. Simvastatin (10,20,40,80mg tablets)
Indications
Hypercholesterolaemia
Mixed hyperlipidaemia
• Adult: 20–40mg once daily PO, increased at
intervals of at least 4 weeks up to 80 mg once
daily.
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24. HMG-CoA reductase inhibitors
Drug interactions
• Statin with amiodarone, clarithromycin,
cyclosporine, erythromycin, fluconazole,
gemfibrozil, itraconazole, ketoconazole, or niacin
increases the risk of myopathy or
rhabdomyolysis.
• Lovastatin, rosuvastatin and simvastatin ↑ risk of
bleeding when administered with warfarin.
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25. HMG-CoA reductase inhibitors…
Adverse reactions
• ↑ aspartate aminotransferase, alanine
aminotransferase, alkaline phosphatase, and
bilirubin levels.
• Pancreatitis, hepatitis and cirrhosis.
• Musculoskeletal effect.
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26. Nicotinic acid
• Also known as niacin.
• Water-soluble vitamin that decreases
cholesterol, triglyceride, and apolipoprotein B-
100 levels and increases the HDL level.
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27. Nicotinic acid…
Mechanism of action
• Inhibit hepatic synthesis of lipoproteins that
contain apolipoprotein B-100.
• Promoting lipoprotein lipase activity.
• Reducing free fatty acid mobilization from
adipose tissue.
• ↑ fecal elimination of sterols.
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28. Nicotinic acid…
Pharmacokinetics
• Absorbed well from GIT.
• 60% to 70% bound to plasma proteins.
• Metabolized by the liver.
• Excreted in urine.
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29. Nicotinic acid (100mg, 500mg
Capsules)
Indication
Adjunct to statin in dyslipidaemia or used alone if
statin not tolerated.
• Adult: 1.5 to 3 g daily.
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30. Nicotinic acid
Indications
• Lower triglyceride levels in patients with type IV
or V hyperlipidemia at high risk of pancreatitis.
• Lower cholesterol and LDL levels in patients
with hypercholesterolemia.
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31. Nicotinic acid
Drug interactions
• Nicotinic acid and an HMG-CoA reductase
inhibitor may increase the risk of myopathy or
rhabdomyolysis.
• Bile-sequestering drugs can bind with nicotinic
acid and ↓ its effectiveness.
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32. Nicotinic acid
Adverse reactions
• High doses may produce vasodilation and cause
flushing (Aspirin 30 min or extended release at
night).
• Hepatotoxicity.
• Epigastric or substernal pain.
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33. Cholesterol absorption inhibitors
Drug examples
• Ezetimibe
Mechanism of action
• A transport protein, NPC1L1, is the target of the
drug
• Inhibiting the absorption of cholesterol.
• ↓ delivery of intestinal cholesterol to the liver,
↓ hepatic cholesterol stores and ↑ plasma
clearance.
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34. Cholesterol absorption inhibitors…
Pharmacokinetics
• Rapidly and extensively absorbed following oral
administration.
• Highly bound to plasma proteins.
• Metabolized in the small intestine and excreted
by the liver and kidneys.
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35. Ezetimibe (Ezetimibe 10mg tablets)
Indication
1. Primary hypercholesterolaemia
2. Homozygous familial hypercholesterolaemia
3. Homozygous sitosterolaemia
• Adult: 10 mg daily PO
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36. Cholesterol absorption inhibitors…
Drug interactions
• Cholestyramine decreased effectiveness of
ezetimibe.
• Cyclosporine, fenofibrate, or gemfibrozil
increase levels of ezetimibe.
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37. Cholesterol absorption inhibitors…
Adverse reactions
• Fatigue
• GIT effects
• Pharyngitis and sinusitis
• Arthralgia
• With HMGCoA reductase inhibitor results in;
• Chest pain, dizziness, headache, upper
respiratory tract infection, back pain and
myalgia.
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38. THANK YOU
THE END
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