CHEMISTRY AND THERAPEUTIC EFFECTS OF ANALGESICS

CHAPTER ONE

INTRODUCTION

Background to Study

Analgesics are among the most frequently used medicines all over the world for the treatment of various types of pain, including vulnerable populations such as children, pregnant women, and the elderly [1–4]. Pain is a highly prevalent symptom, with a great impact on patients’ life [5, 6]. The availability nowadays of various types of analgesics and the potential for some of them to be misused drew more attention on the management of pain [7, 8].

Adverse drug reactions (ADRs) are a well-known cause of mortality and morbidity among patients, being between the fourth and sixth leading cause of death [9]. They represent a significant cause of hospital admissions in most countries [10–12]. France was found between the countries with a high analgesic consumption in comparison with other European countries [13]. Furthermore, analgesics are be- tween the drugs most frequently responsible for ADRs in France [11, 14]. Analyzing the ADRs of analgesics and under- standing their causes could be thus useful for implementing risk-minimizing strategies. Spontaneous reporting system is an invaluable way to collect safety information on medicines after their approval, with details on the ADR cases most often not available in the results of clinical trials or pharmacoepidemiological studies. The aims of the present study were to characterize patterns of spontaneous ADR reports for analgesics and to assess their preventability and contributing factors.

Statement of Problem

Chronic daily headaches (CDH) are frequently associated with the daily use of nonprescription "pain killer” drugs, and the low efficacy of single preparations also leads physicians to prescribe combination analgesic drugs. Physicians experienced in the treatment of headaches commonly note that, after a variable period, the dosage of analgesic compounds is gradually increased until drug dependence and analgesic-induced headache results.

These patients are commonly encountered in headache centers,1 and there are reports in which 3% to 10% of patients have CDH2–4 which fulfills the clinical criteria for drug-induced headaches according to the International Headache Society (IHS) classification.5–8 The exact prevalence of drug-induced headaches in the general population is under debate, but a recent review by Rasmussen indicates a lifetime prevalence of 3%9; while a representative sample of the Swiss population, 2.3% of the sample used analgesic drugs everyday.10 An Italian epidemiological study reported an incidence of 4.3% over 3000 consecutive headache patients attending a headache center.11

A retrospective study by Manzoni et al of 150 patients examined the clinical features of CDH and reported that about 60% of patients suffering from CDH reported daily drug use.12 They proposed a revision of the IHS classification, taking into account the evolution of the headache pattern.

Based on the number of analgesic tablets sold, it has been calculated that possibly about 1% of the German population take up to 10 pain tablets every day.13 Similarly, basing their calculation on evaluation of analgesics sold, Sternieri and Bavutti have calculated that all adults living in the urban area of Modena (Italy) take on average 15 mixed barbiturate-analgesic tablets or 18 packages of mild analgesics per year.14

Common opinion is that headache associated with daily use of analgesics is most likely sustained or caused by chronic drug use, and will reduce or disappear if patients withdraw from the analgesics. In 1988, the IHS classified headaches associated with or following withdrawal of analgesics on the basis of these parameters.8 On the other hand, it should be noted that patients consuming daily nonsteroidal anti-inflammatory drugs (NSAIDs) for diseases other than headache develop daily headache only at a rate ranging from 2% to 5%.15,16

It has been reported that about 72% of patients with CDH began their history with paroxysmal migraine attacks, about 10% with tension-type headaches, and the others began as chronic headache sufferers.5,6,17,18 Sandrini et al19 in a series of 90 patients suffering from chronic headache reported that 16.7% of patients considered their headaches to be chronic ab initio, reporting symptoms which fulfilled the criteria for tension-type headache or combined tension and migraine type. The reported rates are similar among the various studies; in our experience, in a series of 65 patients, we found that 84% of patients began their history of headache suffering from migraine attacks, 12% from tension-type headaches, and only 2% of cases were classified as mixed headaches.20

Lag time between onset of headache and CDH with daily drug intake (DDI) averages 15 years, ranging between 6 months to 25 years.3,15,16,20 Contributing factors to this evolution are still debated3,15,16,20: a comparative study of patient variables, as risk factors in hospitalization for chronic headache, did not show significant differences between inpatients and outpatients.21

The types of abused drugs are largely variable among studies, countries, and times. In studies from Anglo-Saxon countries, the prevalence of abuse of ergot derivatives is higher.12 In Switzerland, Germany, Austria, and Italy, the commonly abused drugs were mixtures containing caffeine and/or barbiturates.1,10,11,23

The main problem in CDH remains the therapeutic approach, which has not yet been systematically determined, so that a widely cited experience is the simple abrupt outpatient withdrawal of medication, as performed by Hering and Steiner.24 No treatment for tension-type headache can be successful in the presence of analgesic abuse, so that drug-dependent patients must first successfully withdraw before their tension-type headache can be effectively managed.23

Purpose of Study

The aim of this study is to analyse Chemistry and Therapeutic Effects of Analgesics. However, the specific objectives are as follows;

1. To determine the patterns of analgesic adverse drug reactions (ADRs)

2. To assess their preventability and contributing factors.

Scope of Study

This study analyses Chemistry and Therapeutic Effects of Analgesics. This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported.