**12. Biochemical findings of tramadol**

Bleeding time (BT), clotting time (CT), prothrombin time, partial thromboplastin time, and body temperature were not affected by tramadol [17]. But, leukocytosis has been reported [44]. Tramadol overdose may result in increased creatine phosphokinase (CPK) which may be seen with or without seizure and can be accompanied by acute renal failure (Table 2) [13].



**11. Carcinogenic effects**

108 Toxicology Studies - Cells, Drugs and Environment

beings, either [17].

**Authors Publication**

Afshari and Ghooshkhanehee

Eizadi -Mood et al. [21]

[14]

**year**

2009 Case

In long-term studies on rats and mice, no tramadol-attributed carcinogenic changes were detected. Histopathologic evaluations showed increased risk of hepatic adenoma in the males and non dose-related pulmonary adenoma in females. No specific mutations or chromosomal impairments were detected in rats, mice, or hamsters due to tramadol use. In skin and eye tests, tramadol had weak corrosive effects on the white rabbits' eyes but no irritating changes on their skin [2]. Oral administration of tramadol was reported to have no carcinogenic effects on the mice and rats. No mutations or increased risk of gene toxicity were detected in human-

Tramadol can cause urinary retention because of opioid agonistic effects that can increase the tonicity of the bladder sphincter [68]. Also, it was shown to have hazardous effects on the growth, survival, and reproduction system of Daphnia Magna with the most effects on the latter. Long-term exposures decreased expression of the *vtg* gene which is an important

In a study by Matthiesen et al, low dose of tramadol had no effect on the fertility, giving birth, and lactation of the rats and had no teratogenic effects on the fetus [17]. These results are however in contrast to the results withdrawn by Bornas who mentioned that laboratory studies had confirmed the teratogenic effects of tramadol on the animals. Tramadol and M1 metabolite

Bleeding time (BT), clotting time (CT), prothrombin time, partial thromboplastin time, and body temperature were not affected by tramadol [17]. But, leukocytosis has been reported [44]. Tramadol overdose may result in increased creatine phosphokinase (CPK) which may be seen

> **administration or comorbidity**

in 41%, psychotic disorder in 30.4%, cardiac disease in

male \_ \_ Seizure, confusion,

**Mortality Findings Dosage or**

miosis, dramatic rise of CPK, LDH,

57%, bradypnea in 18%, tachycardia in

Cr

1.1% CNS depression in

**concentration**

Mean dosage of 2006±7466 mg

4000 mg

with or without seizure and can be accompanied by acute renal failure (Table 2) [13].

**Sex Co-**

2011 186 Male=76.6% Addiction history

biomarker in the reproduction of the oviparous animals [64,95].

**12. Biochemical findings of tramadol**

**Number of patients**

report

can cross the placenta easily because of their low molecular weights [55].

