Futuristic face of resuscitative Centhaquine for hypovolemic shock: A Review

Noorul Shain

Clinical Pharmacist, Kauvery Hospital, Tennur, Trichy

Abstract

Hypovolemic shock is a medical emergency that happens when our body loses too much blood or fluid. Severe fluid loss makes it very difficult for the heart to beat efficiently which can lead to organ failure. This requires immediate emergency medical attention. I review here a drug in the Indian market that may help to substantially reduce the morbidity and mortality of hypovolemic shock in patients.

Keywords: Centhaquine, Haemorrhage, Hypovolemia, Resuscitative agent, Shock

Background

Centhaquin citrate (PMZ-2010) is a novel first-in-class resuscitative agent that has been shown to reduce blood lactate, increase cardiac output and mean arterial pressure, and decrease vascular resistance, in hemorrhage. Centhaquine converts the venous unstressed blood volume to stressed blood volume and improves cardiac output and blood circulation. Centhaquine (Lyfaquin®) as marketed as a resuscitative agent in Hypovolemic Shock Patients. [1]

IUPAC Name: 2-hydroxypropane-1,2,3-tricarboxylic acid;2-[2-[4-(3-methylphenyl)piperazin-1-yl]ethyl]quinolone.

Therapeutic Area: Trauma (Emergency, Injury, Surgery)

Generic Name: Centhaquine citrate

Dosage form and strength

Sterile Intravenous Injection (Lyophilized) Centhaquine citrate 1.0 mg to be reconstituted in 10 ml of Sodium Chloride Injection I.P. (0.9% w/v).

Therapeutic indication

Hypovolemic Shock: LYFAQUIN® is indicated as a resuscitative agent for the treatment of patients with hypovolemic shock as an adjuvant to standard of care.

Posology

LYFAQUIN® should be administered at a dose of 0.01 mg/kg body weight as an intravenous infusion over 1 hour in 100 ml normal saline.

Contraindications

Hypersensitivity to centhaquine or to any of the excipients listed in section 2

Drugs interactions none

No drug-drug interaction or drug-food interaction was observed during clinical development phase.

Special warnings and precautions for use

Lyfaquin® administration with precautions in hepatic failure, renal failure and decompensated heart failure patient as safety and efficacy of Lyfaquin® not established in the same cases. The safety and efficacy of Lyfaquin® is also not established in pregnancy, lactating women, pediatric and geriatric population.

Storage and handing instructions

  • LYFAQUIN® injection should be stored at 2-8 °C, protected from light and moisture.
  • Do not freeze.

Overdose

At significantly higher (10 times or more) doses, hypotension, drowsiness, dry mouth and fall in respiratory rate can occur. Also, increased blood lactate levels may be observed. Treatment of overdose should be symptomatic. Effects are expected to be brief as the half-life of LYFAQUIN® is short i.e. 0.71-1.62 hr and no accumulation has been reported.

Method of Administration

LYFAQUIN® should be administered at a dose of 0.01 mg/kg body weight as an intravenous infusion over 1 hr in 100 ml normal saline. The next dose of LYFAQUIN® should be administered if systolic blood pressure falls below or remains below 90 mm Hg, but not before 4 hr of previous dose and total number of doses per day should not exceed 3. LYFAQUIN® administration, if needed, may continue for two days subject to a maximum of 6 doses within the first 48 hr of treatment and more than 6 doses of LYFAQUIN® is not recommended.

Mechanism of Action

Centhaquine has a unique mechanism compared to other resuscitative agents. Centhaquine increases blood pressure and cardiac output by augmenting venous blood return to the heart (alpha-2B adrenergic stimulation) and enhances tissue blood perfusion by arterial dilatation (sympatholytic due to central alpha-2A adrenergic stimulation). Enhancing tissue blood perfusion is a significant advantage in reducing the volume of resuscitation and preventing extravasation of fluid and adverse effect of lung edema. Centhaquine does not act on beta adrenergic receptors, and therefore the risk of arrhythmia’s is mitigated.[2]

Description

  1. Phase II results demonstrate highly significant efficacy in improving blood pressure (p<0.0001), lactate levels (p=0.0012) and base-deficit (p<0.0001). There was also improvement in reduction in use of vasopressors and reduced mortality. Similarly, results of phase III study confirmed the safety and efficacy of centhaquine as an adjuvant to standard of care for hypovolemic shock. Therefore, to assess safety of centhaquine in large population a phase IV study (post-authorization safety study) has been designed.[3]
  2. In this phase II study, centhaquine (Lyfaquin®) was safe and well-tolerated in hypovolemic shock patients.
  3. An improvement in all the above clinical and biological markers appears to contribute towards improved outcomes and reduced deaths with centhaquine.[4]

Conclusion

Centhaquine is an efficacious resuscitative agent for treating hypovolemic shock. The efficacy of centhaquine in distributive shock is being explored.It improves the clinical outcome of patients with hypovolemic shock. [5]

References

Noorul Shain
Clinical Pharmacist

Nightingale Journals

Kauvery Hospital
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