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These drugs include: - acipimox
- synthetic nicotinic acid
Actions (and proposed mechanisms) include: - inhibition of synthesis
and secretion of VLDL - reduces the rate of mobilisation of free fatty acids from
adipose tissue to the liver and therefore a reduction in hepatic synthesis of
of VLDL
- increases the rate of VLDL breakdown
- reduction in plasma
cholesterol, triglycerides, VLDL, LDL - as VLDL is a precursor to LDL, the effects
of nicotinic acid on VLDL also lead to a reduction in LDL
- increases HDL
- the pathway by which nicotinic acid increases HDL is thought to be via the binding
of HDL to apoA-1 - nicotinic acid decreases the rate of removal of apoA-1 by the
liver but does not seem to effect the rate of synthesis of this protein - this
means that HDL particles can persist for extended periods leading to an increase
in HDL levels
- reduces Lp (a) - the mechanism for this is currently unknown
- it is not directly related to the decrease in LDL as neither statins or fibrates
decrease Lp (a)
- a meta-analysis has evaluated the effect of nicotinic
acid on lipid profile (1):
- 10% reduction in total cholesterol
- 20%
reduction in triglycerides
- 14% reduction in low-density lipoprotein cholesterol
-
16% increase in HDL-C for fibrates and niacin, respectively. Apart from flushes
in the niacin group, both fibrates and niacin were shown to be well-tolerated
and safe
Side effects include: - flushing - may
be reduced if a small dose of aspirin (or another prostaglandin inhibitor) is
taken before nicotinic acid treatment
- modified-relase nicotinic acid
is administered as a once-daily dose in the evening or at bedtime - it is associated
with a lower rate of flushing than immediate-release nicotinic acid, and a lower
risk of hepatotoxicity in comparison with sustained release nicotinic acid (1,2)
- other
possible side effects include
- hepatitis, exacerbation of peptic ulcer
disease, gastritis
- hyperglycaemia - there is evidence that modified-release
nicotinic acid can be used safely in patients with controlled type 2 diabetes
(1,3) - modified-release nicotinic acid has been shown to be an appropriate treatment
for dyslipidaemia associated with type 2 diabetes and metabolic syndrome (1)
- hyperuricaemia - treatment with nicotinic acid has been associated with
hyperuricaemia - it should therefore be used with caution in patients with gout,
pre-existing hyperuricaemia or those receiving other treatments that may increase
uric acid levels
Combination with statins: - the
combination of modified-release nicotinic acid/statin therapy has been shown to
have complimentary lipid-modulating effects, and is safe and effective even in
patients with diabetic dyslipidaemia, despite earlier concerns about hyperglycaemia
(2)
Synthetic nicotinic acid can be used to treat deficiency states such as pellagra.
Notes:
- nicotinic acid plus the prostaglandin D2 receptor 1 antagonist laropiprant
(LRP)
- in a phase three trial extended release nicotinic acid (ERN) was coadministered
with the prostaglandin D2 receptor 1 antagonist LRPT (4)
- given according to a new paradigm of initiation at ERN 1 g/day
for 4 weeks and then advanced to 2 g/day for another 4 weeks in dyslipidemic
patients
- treatment with LRPT plus ERN was well tolerated and led to a significant
reduction in ERN-induced flushing at the initiation of therapy and
with the long-term maintenance of therapy, without affecting niacins
beneficial effects on lipids. In addition, there was a lower incidence
of discontinuations because of flushing with LRPT plus ERN compared
with ERN alone
The summary of product characteristics should be consulted
before prescribing this drug. Reference:
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