Faculty of Pharmacy

Department of Pharmacology

Course Name: Clinical Pharmacology

Course Code: PO512

Assignment topic: Anti-Hyperlipidemia Drugs

Student Name: Nancy Hesham

Student ID: 173421

Tutorial group: W2 Group D

Submitted to: Dr. Mai Abdelhafez

Assignment Due-date: 13-11-2020

 Anti-Hyperlipidemia Drugs

Introduction:

Hyperlipidemia is a disease where excessive accumulation of any type of lipid that are present in
the plasma such as triglyceride, cholesterol which are produced within the mucosal layer of the
liver or the intestine, then transported through the plasma. Naturally, lipids are insoluble in any
aqueous media, thus it is connected to a protein moiety acting as a carrier forming together a
lipoprotein. Also, on the surface of the lipoproteins there are apo-lipoproteins that are
responsible for regulating the mechanism and uptake of the lipoproteins into the cells.

Moreover, anti-hyperlipidemia drugs are generally used in decreasing the lipid serum
concentrations in the blood “Hyperlipidemia” and in preventing associated atherosclerosis. Also,
in the case of “hypertriglyceridemia”, these drugs prevent pancreatitis. Generally, anti-
hyperlipidemia drugs are effective and safe, however, adverse drug reactions such as drug-drug
interactions and rare toxic side effects might happen in skeletal muscles and liver. In the figure
below the five different classes of drugs are showed:

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As shown in the figure above there are five classes of drugs that finally do the same effect by
lowering the lipids in the serum and blood:

-Statins (e.g. lovastatin, fluvastatin , pravastatin, simvastatin, atrovastatin): HMG CoA

reductase inhibitor that have the ability to modify the cholesterol synthesis . Statins might
adversely affect the body causing: rhabdomyolsis, GIT upset, myopathy, cataracts, and
increased risk of diabetes.

-Ezetimibe: they work by inhibiting the absorption of the cholesterol. Ezetimibe adversely
affects the body causing: diarrhea, drowsiness, stuffy nose, and joint pain.

-Niacin (nicotinic acid): they work by decreasing the secretion of lipoproteins. It adversely
affects the body through: hepatotoxicity, worsening diabetes, pruritis, and dyspepsia.

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-Fibrates (e.g. fenofibrate, gemfobrozil, clofibrate): they work by by increasing peripheral
clearance of lipoproteins. They adversely affect the body making: GIT discomfort, increase
the liver transaminases, myopathy, and gall stone formation.

-Resins (e.g. colestipol, cholestyramine, colesevelam): they work by reducing bile acid
absorption “bile acid sequestrants”. It adversely affect the absorption of other drugs taken
with it in the same time.

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  Drug-(drug, food, and herb) interactions for anti-hyperlipidemia medications:
-Statins:
+Anti-fungal drugs (Azoles)  increased absorption of statins  increasing risk of
myopathy or rhabdomyolsis.
+Macrolide antibiotics (e.g. erythromycin)  inhibiting CYP3A4  increasing
plasma concentrations of statins  increased risk of myopathy or rhabdomyolsis.
+Anti-viral (protease inhibitors e.g. ritonavir)  inhibiting CYP3A4  increasing
plasma concentrations of statins  increased risk of myopathy or rhabdomyolsis.
+Fibrates (e.g. gemfobrozil)  inhibiting CYP3A4  increasing plasma
concentrations of statins  increased risk of myopathy or rhabdomyolsis.
+Potent CYP3A4 inhibitors (e.g. cyclosporine)  inhibiting CYP3A4  increasing
plasma concentrations of statins  increased risk of myopathy or rhabdomyolsis.
+CYP3A4 inducers (e.g. carbamazepine)  inducing CYP3A4  decreasing plasma
concentrations of statins  decreased drug efficacy  we need to increase the dose
of statins then.
+Warfarin  competing on the cytochrome P450  increased risk of bleeding.
+Grapefruit juice  inhibiting CYP3A4  increasing plasma concentrations of
statins  increased risk of myopathy or rhabdomyolsis.
+Cranberry juice  inhibiting CYP3A4  increasing plasma concentrations of
statins  increased risk of myopathy or rhabdomyolsis.

-Ezetimibe:

+Fibrates  both increase secretion of cholesterol into the bile acid  increased risk of
cholestiasis.

+Bile acid sequestrants  decreasing absorption of ezetimibe  decreased plasma concentration

of Ezetimibe.

+Warfarin  inhibiting NPC1L1 which is important for vitamin K absorption  increased

prothrombin time or INR.

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+Cyclosporine  alteration of glucuronidation  increased plasma concentration of ezetimibe
and cyclosporine.

-Niacin:

+Statins  increased plasma level of both of them  increased risk of myopathy or

rhabdomyolsis.

+Warfarin  decreased metabolism of warfarin through niacin metabolites  increased risk of

bleeding.

+Niacin requires the presence of vitamins B1, B6 and B12 for better conversion or absorption.

-Fibrates:

+Ciprofibrate  increased risk of myopathy and rhabdimyolsis  contraindicated.

+Sulfonylurea antidiabetics (e.g. Glipizide)  increased blood glucose lowering effect 

increased risk of delayed severe hypoglycemia.

+Repaglinide + gemfobrozile  increased concentration of repaglinide in plasma  increased

risk of hypoglycemia.

+Dasabuvir + Gemfobrozil  inhibition of CYP2C8 mediated Dasabuvir metabolism by

gemfobrozil  increased Dasabuvir exposure  increased risk of QI prolongation 
contraindicated.

+Colchicine  synergistic myo-toxicity effect  increased risk of myopathy or rhabdomyolysis

 contraindicated.

+Anti-coagulants  increased effect on anti-coagulation  increased risk of bleeding.

+Bile acid sequestrants  impaired absorption of fibrates  decreased effect of fibrates.

-Resins (bile acid sequestrants):

+Defrasirox  binding together with bile acid sequestrants in the GIT  decreasing absorption
of defrasirox.

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+Bizafobrate  binding together with bile acid sequestrants in the GIT  decreasing absorption
of bizafibrate.

+Ezetimibe  binding together with bile acid sequestrants in the GIT  decreasing absorption
of ezetimibe.

+Mycophenolate  binding together with bile acid sequestrants in the GIT  decreasing
absorption of mycophenolate and its exposure.

+Levothyroxine  binding together with bile acid sequestrants in the GIT  decreasing
absorption of levothyroxine.

+Vitamins A, E, D, and K  reducing their availability in the plasma and impairing their
absorption.

References:

accessphysiotherapy.mhmedical.com. (n.d.). Chapter 26. Antihyperlipidemic Drugs |

Pharmacology for the Physical Therapist | AccessPhysiotherapy | McGraw-Hill Medical. [online]
Available at:
https://accessphysiotherapy.mhmedical.com/content.aspx?bookid=442&sectionid=40184164
[Accessed 11 Nov. 2020].

authorSTREAM. (n.d.). Drug Interactions of Fibrates. [online] Available at:

http://www.authorstream.com/Presentation/nainamohamedpakk-2847793-drug-interactions-
fibrates/ [Accessed 11 Nov. 2020].

authorSTREAM. (n.d.). Drug Interactions of Statins. [online] Available at:

http://www.authorstream.com/Presentation/nainamohamedpakk-2829098-drug-interactions-
statins/ [Accessed 11 Nov. 2020].

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