Flushing, nicotinic acid

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

Nicotinic acid may cause nausea, vomiting, abdominal pain, diarrhea, severe generalized flushing of the skin, a sensation of warmth, and severe itching or tingling. 

Nicotinic acid has been used to treat hyperlipidemia when of the order of 1—6 g/d are required, causing dilation of blood vessels and flushing, with skin irritation. Intakes of both nicotinic acid and nicotinamide in excess of 500 mg/d can cause liver damage. 

Niacin should be instituted at the lowest dose and gradually titrated to a maximum dose of 2 grams daily for ER and SR products and no more than 5 grams daily for IR products. FDA-approved niacin products are preferred because of product consistency. Moreover, niacin products labeled as no flush don t contain nicotinic acid and therefore have no therapeutic role in the treatment of lipid disorders.28 The time until maximum effect on lipids for niacins is generally 3 to 5 weeks. 

Nicotinic acid in large doses used to treat hyperlipoproteinemia causes a cutaneous flush. The vasodilator) effect is due to... 

The answer is b. (Hardman, pp 890-891.) Nicotinic acid in large doses stimulates the production of prostaglandins as shown by an increase in blood level. The flush may be prevented by the prior administration of aspirin, which is known to block synthesis of prostaglandins... 

Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, acipimox) activate endothelial lipoprotein lipase and thereby lower triglyceride levels. At the start of therapy, a prostaglandin-mediated vasodilation occurs (flushing and hypotension) that can be prevented by low doses of acetyl-salicylic acid. 

Compliance with nicotinic acid therapy can be poor because the drug can produce an intense cutaneous flush. This can be reduced by beginning the drug in... 

Nicotinic acid (niacin) Yes Reduces LDL Reduces VLDL Raises HDL IV Ik with fibrates severe IV with fibrates Cutaneous flush, GI distress, liver dysfunction, hyperglycemia, hyperuricemia... 

Nicotinic acid (5.18), and related derivatives such as pyridylcarbinol (5.19), xanthinol nicotinate (5.20), acipimox (5.21), given in large doses, influence the lipoprotein ratio, decreasing the concentrations of very low and low-density lipoprotein, but have no effect on HDL-cholesterol complexes. Acipimox (5.21) is a new pyrazine derivative that is 20 times more active than nicotinic acid. When first administered, the use of these agents is associated with flushing and hypotension. 

Nicotinic acid is also a potent vasodilator, probably by a direct action on smooth muscle cells. It produces cutaneous vasodilatation, itching of the skin, facial flushing, a sensation of feeling hot, pounding in the head, gastric irritation, diarrhea, raised transaminases, hyperglycemia, and hyperuricemia. These unpleasant adverse effects limit its acceptability for many patients. Nicotinic acid as such is not used in the treatment of vascular disorders, but some of its derivatives are, albeit with poor evidence of clinical efficacy. 

Modified-release formulations of nicotinic acid do not appear to be better tolerated than regular formulations, flushing and itching being the most common adverse effects (SEDA-19, 206). There have also been several reports of hepatotoxicity with this form of the drug (SEDA-16,438). Other adverse effects are hepatotoxicity (apparently a dose-related direct toxic effect), hyperglycemia, and hyperuricemia. It has been questioned whether the modified-release formulation, which is available over the counter in some countries, ought to continue to be available for self-medication in view of its serious adverse effects (2,3). 

The beneficial and adverse effects of nicotinic acid (niacin) have been reviewed (12). Standard nicotinic acid from an immediate-release formulation is metabolized primarily by conjugation, which results in a high frequency of flushing. Long-acting nicotinic acid is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Modified-release nicotinic acid, on the other hand, has a more balanced metabolism and causes fewer of both types of adverse effects. 

Severe toxicoderma has been reported with xanthinol nicotinate and confirmed by a provocation test (SEDA-1, 333). Flushing is claimed to be less frequent with xanthinol nicotinate than with nicotinic acid, but has nevertheless been repeatedly observed, and its other adverse effects are likely to be the same as those of nicotinic acid. 

Of 61 patients with ischemic heart disease and dyslipi-demia treated with nicotinic acid 1.5 and 3.0 g/day, 32 patients were withdrawn, 18 because of adverse effects and 14 for reasons not related to nicotinic acid (32). Of the 29 patients who finished the study, adverse effects included dryness of the skin (14%), acanthosis nigricans (10%), fatigue (6.9%), nausea (6.9%), abdominal pain (3.4%), diarrhea (3.4%), and anorexia (3.4%) the figures in parentheses were the incidences at 33 weeks. Flushing occurred more often at 18 weeks than at 33 weeks (24 versus 6.9%), as did pruritus (35 versus 28%), suggesting tolerance to these effects. 

Since nicotinic acid can cause unpleasant flushing and other symptoms of vasodilatation, attempts have been made to develop modified-release formulations. Modified-released nicotinic acid formulations may be better tolerated than the immediate-release formulation, because they reduce the vasodilatory effects of the drug. However, the low frequency of flushing produced by modified-release formulations may be offset by an increased risk of hepatotoxicity. Some reports have suggested a higher frequency of hepatic dysfunction with traditional modified-release nicotinic acid formulations compared with immediate-release products (2, 40). 

An interaction between nicotinic acid and nicotine trans-dermal patches has also been observed, causing flushing and dizziness (47). 

Warady B, Kriley M, Alon U, Hellerstein S. Nicotinic acid-induced flush. Perit Dial Int 1989 9(l) 81-2. 

Nicotinic acid (hut not nicotinamide) causes a marked vasodilatation, with flushing, burning, and itching of the skin. Very large single doses of nicotinic acid may cause sufficient vasodilatation to lead to hypotension after the administration of 1 to 3 g of nicotinic acid daily for several days, the effect wears off to a considerable extent. A number of nicotinoyl esters have been developed to permit sensitive patients to benefit from the hypoUpidemic effect of... 

Adverse effects do not occur with standard doses of nicotinamide. Nicotinic acid, which is converted into nicotinamide, causes peripheral vasodilatation accompanied by an unpleasant flushing and itching, and the patient may faint. 

The physical effects of the nicotinic acid (facial flushing and prickly sensations) set in very quickly, leading the controls to believe for a time that they were the ones receiving the psilocybin. Shortly after, when others began remarking on such details as the spectacular candlelight,... 

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