Effects of pyrazinamide: A Synthesis of Findings from 15 Studies

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Original Abstract of the Article

Major Research Findings

Pyrazinamide is an antituberculosis drug with a variety of effects and side effects. Pyrazinamide does not affect the gene expression of the enzyme ACMSD (alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase) in the liver, 6 , while peroxisome proliferators such as clofibrate suppress ACMSD gene expression. This suggests that pyrazinamide and peroxisome proliferators may have different effects on NAD synthesis pathways in the liver.

Pyrazinamide can cause side effects such as liver damage, rash, and joint pain. These side effects are more common in people over 60 years old or with a history of hepatitis. 11 . Pyrazinamide can also enhance the effects of uricosuric agents, which promote uric acid excretion. This is probably because pyrazinamide enhances uric acid reabsorption in the kidneys, thereby increasing the effectiveness of uricosuric agents. 2 In addition, pyrazinamide has been shown to affect the excretion of purine bases (such as uric acid, hypoxanthine, and xanthine) in the kidneys.

Pyrazinamide is thought to work by inhibiting the synthesis of lipids in the cell wall of Mycobacterium tuberculosis. However, it was reported that pyrazinamide does not directly inhibit fatty acid synthase I (FAS-I), which is an enzyme involved in the fatty acid synthesis in Mycobacterium tuberculosis. 8 . Pyrazinamide is also believed to exert its antibacterial effect against Mycobacterium tuberculosis by stimulating the biosynthesis of niacin. 9 The study reported that pyrazinamide promotes the metabolism of tryptophan to niacin in rats. 9

Pyrazinamide is often combined with other drugs to enhance its effectiveness against Mycobacterium tuberculosis. Side effects of pyrazinamide combined with other antituberculosis drugs were reported in the study. 5 It was reported that liver damage and immunosuppression can occur when pyrazinamide is combined with other antituberculosis drugs. 5 However, the study suggests that some herbs may mitigate these side effects. 5

Benefits and Risks

Benefits Summary

Pyrazinamide is an effective drug for treating tuberculosis. Pyrazinamide inhibits the growth of Mycobacterium tuberculosis and slows the progression of the disease. 8 , 9 , , 1 . Pyrazinamide can also enhance the effectiveness of treatment when combined with other antituberculosis drugs. , 5 In addition, pyrazinamide may enhance the effectiveness of uricosuric agents. 2

Risks Summary

Pyrazinamide poses a risk of side effects such as liver damage, rash, and joint pain. 11 , , 5 . These side effects are more common in people over 60 years old or with a history of hepatitis. 11 . Pyrazinamide should not be used by pregnant or breastfeeding women. 11 Pyrazinamide should not be used by individuals with impaired kidney function. Pyrazinamide can interact with other drugs. Consult a physician before using pyrazinamide.

Comparison of Studies

Commonalities of Studies

Multiple studies have shown that pyrazinamide may affect the liver, kidneys, bones, and DNA. 11 , , 12 , , 4 , 3 . Many studies have also shown that pyrazinamide inhibits the growth of Mycobacterium tuberculosis. 8 , 9 , , 1

Differences of Studies

Studies differ in their findings on whether pyrazinamide affects the gene expression of ACMSD. 6 suggests that pyrazinamide does not affect ACMSD gene expression. However, other studies have shown that pyrazinamide may inhibit ACMSD activity. 15 There are several hypotheses about the mechanism of action of pyrazinamide against Mycobacterium tuberculosis. 8 , 9 , 1

Consistency and Discrepancies of Results

Multiple studies have shown that pyrazinamide carries a risk of side effects such as liver damage, rash, and joint pain. 11 , , 5 . However, the incidence and severity of these side effects may vary depending on the study. Moreover, the mechanism by which pyrazinamide acts against Mycobacterium tuberculosis is not yet fully understood. These results suggest that further research on the effects and side effects of pyrazinamide is needed.

Precautions for Application in Real Life

Pyrazinamide is an effective drug for treating tuberculosis, but it comes with the risk of side effects. It is important to follow your doctor's instructions when using pyrazinamide. Pyrazinamide poses a risk of side effects such as liver damage, rash, and joint pain. 11 , , 5 . These side effects are more common in people over 60 years old or with a history of hepatitis. 11 . When using pyrazinamide, it is important to consult a physician and carefully monitor for side effects. Pyrazinamide should not be used by pregnant or breastfeeding women. 11 Pyrazinamide should not be used by individuals with impaired kidney function. Pyrazinamide can interact with other drugs. Consult a physician before using pyrazinamide.

Limitations of Current Research

Research on pyrazinamide is not yet comprehensive. In particular, there are many unknowns about the long-term effects and side effects of pyrazinamide. Furthermore, the mechanism of action of pyrazinamide against Mycobacterium tuberculosis is not yet fully elucidated. Further research on pyrazinamide is needed.

Future Directions for Research

Future research on pyrazinamide should focus on the long-term effects and side effects of pyrazinamide, the mechanism of action of pyrazinamide against Mycobacterium tuberculosis, and the interaction of pyrazinamide with other drugs. These studies will contribute to a deeper understanding of the safety and efficacy of pyrazinamide.

Conclusion

Literature analysis of 15 papers

Positive Content

Neutral Content

Negative Content

Article Type

Randomized Controlled Trial0

Meta-Analysis0

Systematic Review0

Review0

Journal Article15

'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?

Author: AnthonyR M, den HertogA L, van SoolingenD

Tuberculosis treatment

This article proposes that PanD is the primary target of pyrazinoic acid, the active form of pyrazinamide, an anti-tuberculosis drug. An intact stress response is also required for pyrazinoic acid susceptibility.

Language : English

Enhancement of pharmacological effects of uricosuric agents by concomitant treatment with pyrazinamide in rats.

Author: TaniguchiTetsuya, AshizawaNaoki, MatsumotoKoji, IwanagaTakashi

Urate handling

Uricosuric effects

This study investigated the effects of uricosuric agents in rats co-treated with pyrazinamide, an anti-tubercular agent. The pyrazinamide-treated model showed increased sensitivity to uricosuric agents compared to intact rats, likely due to enhanced urate reabsorption.

Language : English

Pyrazinamide potential effects on male rats DNA fragmentation, bone type I collagen amino acid composition, reproductive capability and posterity antenatal and postnatal development.

Author: BondarenkoLarysa B, ShayakhmetovaGanna M, ByshovetsTaisiya F, KovalenkoValentina M

Tuberculosis treatment

Reproductive harm

Current therapeutic regimens with first-line antitubercular agents are associated with a high rate of adverse effects. This study investigated pyrazinamide potential effects on male rats DNA fragmentation, amino acid composition of bone type I collagen, reproductive capability and their posterity antenatal and postnatal development. Pyrazinamide, at different doses, demonstrated dose-dependent quantitative and qualitative changes in male rat reproductive organs DNA and extracellular matrix proteins.

Language : English

Pyrazinamide Effects on Cartilage Type II Collagen Amino Acid Composition.

Author: BondarenkoLarysa B, KovalenkoValentina M

Cartilage changes

This study examined the effects of pyrazinamide, a drug used to treat tuberculosis, on the amino acid composition of type II collagen, a protein found in cartilage. Pyrazinamide was found to cause changes in the amino acid composition of type II collagen in a dose-dependent manner. These findings highlight the potential for pyrazinamide to impact the structure and function of cartilage.

Language : English

Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs.

Author: AdhvaryuMeghna-R, ReddyNarsimha, ParabiaMinoo H

Hepatoprotective

Immunomodulatory

Curcuma longa, Ocimum sanctum, Tinospora cordifolia and Zizyphus mauritiana all showed hepatoprotective and immunomodulatory effects in guinea pigs with liver injury and immunosuppression.

Language : English

Differential effects of pyrazinamide and clofibrate on gene expression of rat hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase, a key enzyme of the tryptophan-NAD pathway.

Author: EgashiraYukari, SatoMakiko, SatoMayuki, SugawaraRyoko, TanabeAtsushi, ShinMariko, SanadaHiroo

NAD biosynthesis regulation

This study found that peroxisome proliferators, such as clofibrate, can suppress the expression of hepatic ACMSD mRNA in rats. Pyrazinamide, on the other hand, did not affect ACMSD mRNA expression, but did suppress ACMSD activity.

Language : English

Investigation of the effects of concomitant caffeine administration on the metabolic disposition of pyrazinamide in rats.

Author: MehmedagicAida, VeritePhilippe, MenagerSabine, TharasseChristine, ChabenatChristiane, AndreDominique, LafontOlivier

Caffeine was found to increase the excretion of the PZA metabolite 5-hydroxypyrazinoic acid (5-OH-PA), which is the most water-soluble and least toxic PZA metabolite.

Language : English

Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I.

Author: BoshoffHelena I, MizrahiValerie, BarryClifton E

Inhibition of fatty acid synthesis

Pyrazinoic acid is an effective treatment for tuberculosis, but it does not directly inhibit fatty acid synthesis.

Language : English

Effects of dietary pyrazinamide, an antituberculosis agent, on the metabolism of tryptophan to niacin and of tryptophan to serotonin in rats.

Author: ShibataK, FukuwatariT, SugimotoE

This study investigates the effect of pyrazinamide, an anti-tuberculosis drug, on the metabolism of tryptophan, an amino acid. Pyrazinamide increased the production of niacin, a vitamin, from tryptophan. The increased niacin levels could be due to an increased conversion ratio of tryptophan to niacin and higher levels of NAD, a coenzyme involved in many biochemical reactions. The study suggests that pyrazinamide’s effectiveness against tuberculosis might be linked to its effect on NAD turnover and levels.

Language : English

10.

Effects of dietary pyrazinamide on the metabolism of tryptophan to niacin in streptozotocin-diabetic rats.

Author: ShibataK, IshikawaA, KondoT

Increased nicotinamide formation

This study investigated the effects of feeding with a pyrazinamide (PYR) diet on the metabolism of L-tryptophan (Trp) to nicotinamide in streptozotocin (STZ)-diabetic rats. Feeding with the PYR diet increased nicotinamide formation, but did not improve blood glucose levels or prevent the diabetic action of STZ.

Language : English

11.

Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis.

Author: SchabergT, RebhanK, LodeH

Tuberculosis treatment

Arthralgia

Exanthema

Hepatotoxicity

Side-effects of standard antituberculosis therapy were frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis.

Language : English

12.

Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol.

Author: YamamotoT, MoriwakiY, TakahashiS, SudaM, HigashinoK

Pyrazinamide decreased the renal excretion of oxypurinol, while probenecid and benzbromarone increased it. This suggests that oxypurinol is secreted by an organic acid system and reabsorbed in the renal tubules.

Language : English

13.

Effects of dietary pyrazinamide, tryptophan, or nicotinic acid and gamma-ray irradiation on levels of NAD and NADP in various organs of mice.

Author: InoueK, SanadaH, WadaO, AokiN

NAD content increase

NAD content decrease

Dietary supplementation with tryptophan or nicotinic acid increased NAD content in the spleen, thymus, and kidney of mice. Gamma-irradiation generally decreased NAD content in these organs, except in the spleen and thymus of the tryptophan and nicotinic acid supplemented groups, where NAD levels remained higher than the irradiated control group.

Language : English

14.

Renal excretion of purine bases. Effects of probenecid, benzbromarone and pyrazinamide.

Author: YamamotoT, MoriwakiY, TakahashiS, HadaT, HigashinoK

This study investigates the renal transport mechanisms of oxypurines (uric acid, hypoxanthine, and xanthine) by using uricosuric agents and pyrazinamide. The results suggest that each purine base has a distinct renal transport mechanism.

Language : English

15.

Tryptophan and glucose metabolism in rat liver cells. The effects of DL-6-chlorotryptophan, 4-chloro-3-hydroxyanthranilate and pyrazinamide.

Author: CookJ S, PogsonC I

Decreases quinolinate formation

Less sensitive to tryptophan inhibition

Increased quinolinate formation with pyrazinamide

Potentiates tryptophan inhibition with pyrazinamide

DL-6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate decreased quinolinate formation in liver cells, while pyrazinamide increased quinolinate formation. These findings have implications for understanding tryptophan metabolism and its impact on gluconeogenesis.

Language : English

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