196 Section 4/ Drugs Acting on Cardiovascular & Urinary Systemand IDL are atherogenic, while HDL is
protective because it facilitates removal of
cholesterol from tissues.
The drugs used in the treatment of
hyperlipidemia are classified as in table 4.5.1.
HMG CoA REDUCTASE INHIBITORSAlso known as statins. HMG CoA reductase
(Hydroxymethyl-Glutaryl Coenzyme A
Reductase) inhibitors block the synthesis of
cholesterol in liver by competitively
inhibiting HMG CoA reductase activity, also
cause depletion of critical intracellular pools
of sterols and increased transcription of LDL
receptors leading to enhanced removal from
plasma of LDL cholesterol and LDL
precursors. They also reduce hepatic
synthesis of VLDL, increase plasma HDL.
Reduction of LDL occurs over 4-6 weeks.
LOVASTATIN
It is a potent HMG CoA reductase
inhibitor. This enzyme catalyzes the
conversion of HMG CoA to mevalonate in
liver which is an important early and rate
limiting step in the cholesterol synthesis. It
causes marked reduction in LDL
cholesterol and also raise HDL level and
may lower the triglyceride level. After oral
administration it is extensively metabolised
in liver and metabolites are excreted in bile.
Adverse reactions include arthralgia,
myopathy, vertigo, tremor, memory loss,
alteration of taste, peripheral neuropathy,
anxiety, insomnia, depression, hepatitis
cholestatic jaundice, abdominal pain,
alopecia, blurred vision etc.
It is indicated in primary hypercholesterol-
emia and hyperglyceridemia.
SIMVASTATIN
Simvastatin, is twice as potent as
lovastatin.
Simvastatin has been shown to reduce
both normal and elevated low-density
lipoprotein (LDL) cholesterol concentrations.
Apolipoprotein B, VLDL cholesterol and
plasma triglycerides also reduce and can
produce increase in HDL cholesterol.
Simvastatin reduces total cholesterol,
LDL cholesterol and triglycerides by 25%,
35%, and 10% respectively. The increase in
HDL is upto 12%.
Adverse effects are flatulence,
diarrhoea, constipation, nausea, abdominal
pain, cramps, heart burn and dysgeusia.
Rarely myopathy, rhabdomyolysis with
acute renal failure may also occur.
Other adverse effects include headache,
dizziness, rashes/pruritus, impotence
insomnia, blurring of vision and lens opacities.
Simvastatin is indicated in patients with
coronary heart disease and
hypercholesteremia, for the reduction of
elevated total and LDL cholesterol in
patients with primary hypercholesterolemia
(type IIa and IIb hyperlipoproteinemia),
combined hypercholesterolemia and
hypertriglyceridemia.
Simvastatin is also used in combination
with nicotinic acid. It is found to be the most
useful drug combination for the treatment of
dyslipidemias associated with coronary
artery disease. It is particularly effective in
normalizing the lipid profiles of patients with
familial combined dyslipidemia.ATORVASTATIN
Atorvastatin reduces total cholesterol,
LDL-cholesterol and apolipoprotein B