7. Comments and conclusions

4. Probability and causality assessment of drug-induced hepatotoxicity:

the score obtained, a range of causal probability is established.

86 Pharmacokinetics and Adverse Effects of Drugs - Mechanisms and Risks Factors

5. Hepatotoxic medicines during pregnancy

To solve the difficulty of identification of hepatotoxicity and to try to estimate the probability that a therapeutic agent is associated with a hepatic injury, clinical scales have been developed; these assess aspects such as absence or presence of confounding factors, temporal relation of hepatotoxicity with drug consumption, coexistence of risk factors, previous description in the literature, exclusion of other causes and effects of readministration of the drug. According to

In this sense, there are scales, such as the Roussel Uclaf Causality Assessment Method scale (RUCAM) and the Clinical Diagnostic Scale (M&V CDS), considering that the RUCAM scale is more appropriate than M&V CDS [12], besides, facilitates to distinguish when patient is using concomitants drugs. However, despite their theoretical utility and being validated, these scales are hardly used in clinical practice [22]. To promote its use, it is advisable to have knowledge of the possible agents associated with hepatotoxicity and to reduce subjectivity bias at the time of

Twelve hepatotoxic agents were identified as drugs with probability to cause injury in pregnant women are as follows: acetaminophen, alpha-methyldopa, labetalol, methotrexate, saquinavir, nevirapine, propylthiouracil, methimazole, carbimazole, nitrofurantoin, acetylsalicylic acid and piperidolate. Some characteristics associated with these drugs were the time of reaction onset, weeks of pregnancy (between 3 and 36 weeks), risk factors (age and chronic diseases), clinical manifestations (elevation of transaminases, pruritus, vomiting, anorexia and jaundice) and outcomes (liver transplantation and death of mother and/or fetus). In this sense, pregnant women between the second and third decade of age may have an increased risk of liver problems due to the use of medications such as methotrexate, alpha-methyldopa and propylthiouracil. For drugs such as acetaminophen, acetylsalicylic acid, piperidolate, nitrofurantoin, methotrexate and alpha-methyldopa, information about frequency of hepatotoxic reactions during gestation is limited, whereas for antithyroid drugs, the frequency of occurrence of hepatotoxicity can be found between 0.1 and 0.2% of the pregnant population using these drugs [44]. The management in cases of hepatotoxicity in pregnant women must be the suspension of the offending drug, which in most cases afford to improve the symptomatology and prevent fatal

6. Pharmacist and prevention of drug-induced hepatotoxicity

Currently, there is a need to discuss about interdisciplinary groups to provide comprehensive patient care; and the pharmacist is a part of this. Through knowledge of the important aspects of hepatotoxicity (hepatotoxic drugs, symptoms, risk factors, pathological antecedents and

scales and proposals

its application.

outcomes.

Many drugs are hepatotoxic agents, most of these drugs generate idiosyncratic reactions and cause hepatocellular damage in a wide range of patients in different age groups; and moreover, concomitant medications may deteriorate the clinical features of patients. Elevation of liver enzymes, fever and jaundice are common signs and symptoms, with identification and suspension of offending drug, patients present an adequate evolution.

On the other hand, it is important to have in mind that some patients are asymptomatic and the liver injury identification is based only on the elevation of liver enzymes; therefore, monitoring of liver tests is important to prevent serious effects. In addition, knowing the risk factors and habits of patient can improve the response time in a possible case.

It is advisable to use RUCAM scale to obtain a correct judgment when the probability of hepatotoxicity or any doubt exists. While there are other scales present, RUCAM allows

Hepatotoxicity by Drugs

89

http://dx.doi.org/10.5772/intechopen.72005

Research Group on Pharmaceutical Prevention and Promotion, University of Antioquia,

[1] Tejada F. Hepatotoxicidad por Fármacos. Revista Clínica de Medicina de Familia. 2010;3

[2] Andrade R, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega M-C, Lucena M-I. Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for

[3] Bell LN, Chalasani N. Epidemiology of idiosyncratic drug-induced liver injury. Seminars

[4] Danan G, Benichou C. Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: Application to drug-induced liver injuries. Journal of Clinical Epidemiology. 1993;46(11):1323-1330

[6] Ramachandran R, Kakar S. Histological patterns in drug-induced liver disease. Journal of

[7] Fisher K, Vuppalanchi R, Saxena R. Drug-induced liver injury. Archives of Pathology &

[8] Martí L, Olmo J, Tosca J, Ornia E, Serra M, Rodríguez F, et al. Clinical evaluation of druginduced hepatitis. Revista Espanola De Enfermedades Digestivas. 2005;97(4):258-265 [9] García-Cortés M, Andrade R, Lucena M, González-Grande R, Camargo R, Fernández-Bonilla E, et al. Hepatotoxicidad secundaria a fármacos de uso común. Gastroenterología y

[10] Ibáñez L, Pérez E, Vidal X, Laporte J. Prospective surveillance of acute serious liver disease unrelated to infectious, obstructive, or metabolic diseases: Epidemiological and clinical features, and exposure to drugs. Journal of Hepatology. 2002;37(5):592-600

gastroenterologists. World Journal of Gastroenterology. 2007;13(3):329-340

discern when confusing factors or concomitant drugs are present.

\*Address all correspondence to: pedro.amariles@udea.edu.co

Alejandra Cano Paniagua and Pedro Amariles\*

in Liver Disease. 2009;29(4):337-347

Clinical Pathology. 2009;62:481-492

Hepatología. 2005;28(8):461-472

Laboratory Medicine. 2015;139:876-887

[5] Reuben A. Hy's Law. Hepatology. 2004;39(2):574-578

Author details

Medellin, Colombia

(3):177-191

References

ALT: alanine-aminotransferase; ALP: alkaline phosphatase; ULN: upper limit of normal

Diagram 1. Identification of hepatotoxicity.

It is advisable to use RUCAM scale to obtain a correct judgment when the probability of hepatotoxicity or any doubt exists. While there are other scales present, RUCAM allows discern when confusing factors or concomitant drugs are present.
