Assessment of Analgesics Induced Adverse Drug reactions in a Tertiary Care Hospital

 

Sumit Kumar¹, Badruddeen²*, S. P. Singh¹, Juber Akhtar², Mohammad Irfan Khan², Mohammad Ahmad²,

Usama Ahmad²

¹Department of Pharmacology and Therapeutics, GSVM Medical College, Kanpur (U.P.), India.

²Faculty of Pharmacy, Integral University, Lucknow (U.P.), India.

 

ABSTRACT:

The objective of the study was to ascertain the different type of adverse drug reactions associated with analgesics, used for treating pain associated with different ailments in a tertiary care hospital and determine their causal relationship with the offending drug. This observational, non-interventional study was conducted in a tertiary care hospital at GSVM medical college Kanpur (U.P), India. Adverse drug reactions were reported by the physicians of different department and ADRs were assessed for different parameters-causality assessments, outcome and seriousness of ADRs as per World health organization (WHO), Expanded Rawlins and Thompson’s classification scale was used for determining type of ADRs, Predictability using CIOMS guidelines, severity using modified Hartwig’s scale and preventability as per Schumock and Thornton criteria. A total of 192 adverse drug reactions were reported from analgesics during treatment in tertiary care hospital. The Burden of ADRs in each patient was 2.25. Most of the adverse drug reactions were observed in the age group of 40–60 year. Gastritis (22.4%) was commonly reported reaction. Among analgesics, Aceclofenac + Paracetamol leads to 10.94% ADRs followed by Piroxicam (10.43%). Most of the adverse drug reactions on causality assessment were of Probable (96.35%) and possible (3.65%) nature. Type -A ADRs account for more than 50% of the total reported ADRs, followed by Type-B, C and D. Severity of most ADRs was found to be mild (94.80%) followed by severe and moderate and serious ADRs account in 4.69% cases and among serious ADRs most common were hematemesis (33.33%) and rash (22.22%). Most of the ADRs were of not-predictable type (69.27%) and not preventable type (96.34%). Digestive system was the most common organ system associated with Analgesics –ADRs.

 

 

 

INTRODUCTION:

An adverse drug reaction (ADR) is any noxious, unintended, and undesired effect of a drug that occurs at doses used for prophylaxis, diagnosis, or therapy or for modification of physiological function^[1,2,3]. In estimation approximately 2.9–5.6% of all hospital admissions are caused by ADRs and as many as 35% of hospitalized patients experience an ADRs during their hospital stay ^[4]. Algesia or pain is an unpleasant sensory and emotional experience related with actual or potential tissue damage or described in terms of such damage^[5].

 

Analgesic is drug that selectively relieves pain by acting in the CNS (opioids) or on peripheral pain mechanism, without significantly altering consciousness. Broadly classified as Opioids/narcotics analgesics and Non-opioids/non-narcotic analgesics/Non-steroidal anti-inflammatory drugs (NSAIDs)/antipyretic- analgesics, having analgesic, antipyretic and anti-inflammatory actions. NSAIDs act primarily on peripheral pain mechanisms, inhibit cyclooxygenase enzyme (COX-1 and COX-2) but also raises pain threshold in the CNS and widely used as over the counter drugs. ADRs associated with opioid analgesics are tolerance, dependence, respiratory depression, blurred vision, sedation, constipation, apnoea (in newborn) etc., whereas non-opioids are free from physical dependence and abuse but causes ADRs such as gastric erosion/bleeding, asthma exacerbation, angioedema etc.

 

MATERIAL AND METHOD:

A prospective, observational, non-interventional study carried out at in-Patient and out-Patient setting in various depart­ment of GSVM medical college Kanpur U.P for a period of three year. Permission was obtained prior to the initiation of this study.

 

Inclusion criteria’s:

·       Patients of all age groups and either sex.

·       All the suspected ADRs that may be due to the medications, both prescribed and over the counter, taken by patients either as inpatients or outpatients.

 

Exclusion Criteria’s:

·       Patients who could not recall the name of the suspect medicines consumed.

·       Patients who were mentally retarded and unconscious.

·       Patients who consumed alternative system of medicine.

·       Patients who developed ADRs due to intentional or accidental poisoning, ADRs due to the fresh blood/ blood products, patients with drug abuse and intoxication.

 

Patient demographic data like patient initial, OPD/IPD number, age, sex, medical history, medication history, surgery history, allergies, management and outcome of ADR had been recorded on the Suspected ADRs reporting form of Indian Pharmacopoeia commission. Causality of ADRs was evaluated by WHO-UMC assessment scale^[6], outcome and seriousness of ADR as per WHO^[7], type of ADR using Expanded Rawlins and Thompson’s classification^[8,9], preventability as per Schumock and Thornton criteria^[10] , Predictability using CIOMS guidelines^[11,12] and severity as per modified Hartwig’s scale^[13]. Descriptive statistics were used for data analysis.

 

RESULTS AND DISCUSSION:

A total of 85 patients encountered 192 ADRs, therefore burden was found to be 2.25 ADRs per patient. Female patient encountered maximum ADRs (51.56%) followed by male (48.74%) with no significant difference between group. Maximum ADRs occurred in age between 40y -60y (43.23 %){Fig 1}.

 

Fig 1: Occurrence of ADRs in different age group

 

On WHO causality scale, causality of ADRs was probable (96.35%) followed with possible, this result was in line with study of Rejimon et. al^[14]. As per Rawlins and Thompson's classification Type -A ADRs account for 55.21% followed by Type -B (25.52%), type- C (18.75%) and single case of Type –D, no case of E, F ADRs. Severity of ADRs as per Hartwig’s scale was found to be of mild category (94.80%). Most ADRs cases were of non-serious nature (95.31%) and few serious ADRs (4.69%). As per CIOMS most ADRs are of not predictable type (69.27%) and on preventability as per Schumock and Thornton criteria maximum ADRs belong to not-preventable type (96.34%). ADRs mostly affected digestive system (60.42%) followed by integumentary (16.14%) and lymphatic system (7.29%) {Table 1}. In most of case single drug therapy was given to patient accounting – 60% among whole population receiving analgesics.

 

 

Table 1: Assessment of ADRs-Analgesics

Causality		ADRs	%
	Possible	7	3.65
	Probable	185	96.35
Type of ADRs
	A	106	55.21
	B	49	25.52
	C	36	18.75
	D	1	0.52
Severity
	Mild	182	94.80
	Moderate	2	1.04
	Severe	8	4.16
Seriousness
	Non-serious	183	95.31
	Serious	9	4.69
Predictability
	Predictable	59	30.73
	Not-predictable	133	69.27
Preventability
	Probably preventable	7	3.66
	Not preventable	185	96.34
Outcome
	Recovered	165	85.94
	Not recovered	4	2.08
	Recovering	23	11.98
	Unknown	0	0
	Fatal	0	0
Organ system
	DS	116	60.42
	CVS	3	1.56
	ES	0	0
	HS	0	0
	IS	31	16.14
	LS	14	7.29
	MSS	2	1.04
	MOS	1	0.52
	NS	11	5.73
	RS	7	3.65
	US	7	3.65
Drug Therapy		No. of Patient	%
	Single drug	51	60
	Two drug	34	40
	Three drug	0	0
	> Three drug	0	0

 

Most common ADRs in our population were gastritis (43, 22.40%) followed by vomiting (18, 9.37%), rash (15,7.80%) and nausea (12, 6.24%) {Fig 2}. In Rejimon et.al study nausea and diarrhea was most common reaction. Serious ADRs account for only 4.69% of total 192 ADRs. Among serious ADRs most common was hematemesis (33.33%), followed by rash (22.22%). Most common drug leading to maximum ADRs was aceclofenac + paracetamol (21,10.94%) followed by piroxicam (20, 10.43%) {Table-2 and 4}.The outcome of most ADRs was recovered (85.94%) as the most of them relieved after drug withdraw / and appropriate treatment, with few on recovering stage (11.98%) and no case of fatal nature.

 

Fig 2: Most common ADRs with analgesics

 

Table 2: List of Analgesics and ADRs share

S. No	Drug	No. of patient	No. of ADRs %
1.	Aceclofenac+ Paracetamol	8	21(10.94)
2.	Aceclofenac + Tizanidine	1	1(0.52)
3.	Aspirin	7	19(9.90)
4.	Diclofenac	4	9(4.69)
5.	Diclofenac+ Paracetamol	7	19 (9.90)
6.	Etodolac	2	6(3.12)
7.	Etodolac + Paracetamol	4	10(5.22)
8.	Etoricoxib	4	7(3.65)
9.	Etoricoxib+ Paracetamol	5	14(7.29)
10.	Ibuprofen	11	16(8.33)
11.	Ibuprofen + Paracetamol	7	19 (9.90)
12.	Indomethacin	1	2(1.04)
13.	Metamizole	1	2 (1.04)
14.	Naproxen	1	3(1.56)
15.	Nimesulide	3	4 (2.08)
16.	Nimesulide+ Paracetamol	1	2 (1.04)
17.	Paracetamol	5	6(3.12)
18.	Piroxicam	8	20(10.43)
19.	Tramadol	4	11(5.73)
20.	Tramadol+ Paracetamol	1	1(0.52)

 

Most common organ system associated with analgesics ADRs was digestive system accounting 60.42% of total ADRs followed by ADRs of integumentary system (16.14%), lymphatic system (7.29%), RS and US each with 3.65% ADRs, with no ADRs of endocrine system and hematological system {Table-3}. Among integumentary system most common ADRs were Rash, itching and angioedema, among DS ADRs were gastritis and vomiting and among LS ADRs pedal edema and swellings were common.

 

Table 3: Analgesics-ADRs associated with different organ system

Organ System	ADRs No.	Percentage ADRs	ADRs
DS	116	60.42	Nausea-12, Vomiting-18, Diarrhoea-9, Abdominal Pain-1, Constipation-3, Anorexia-9, Mucositis-4, Flatulence-3, Gastritis-43, Melena-4, Hematochezia-4 , Hematemesis-3, Polydipsia-1, Xerostomia- 2
CVS	3	1.56	Tachycardia-1, High B.P-2
ES	0	0	-
HS	0	0	-
IS	31	16.14	Rash-15, Angioedema-1, Itching-11, Increased Sweating -1, SJS-1, Pigmentation Lip-2
LS	14	7.29	Generalized Swelling-2 , Leg Swelling-2, Swelling Face-2 , Edema Mouth-2, Edema Pedal-4, Edema Periorbital-2
MSS	2	1.04	Joint Pain-1, Fatigue-1
MOS	1	0.52	Epitaxis-1
NS	11	5.73	Headache-6, Dizziness-2, Confusion-1, Drowsiness-1, Tinnitus-1
RS	7	3.65	Throat Pain-1, Apnoea-6
US	7	3.65	Dysuria-1, Oliguria-5, Hematouria-1

DS-Digestive system, CVS-cardio-vascular system, ES-Endocrine system, HS Hematological system, IS-Integumentary system, LS-Lymphatic system, MSS-Musculoskeletal system, MOS-Multi-organ system, NS- Nervous system, RS-Respiratory system, US-Urinary system

 

Table 4: Serious ADRs- Analgesics

S. No	Serious ADRs	No.of ADRs  (n=9) %	Analgesic drug
1	Angioedema	1 (11.11)	Tramadol+ Paracetamol
2	Apnoea	1 (11.11)	Naproxen
3	Rash	2 (22.22)	Ibuprofen-1; Naproxen-1
4	SJS	1 (11.11)	Nimesulide
5	Hematemesis	3 (33.34)	Diclofenac+ Paracetamol-1 Aspirin-1 Etodolac+ Paracetamol-1
6	Edema -periorbital	1 (11.11)	Naproxen

CONCLUSION:

Digestive system was most common organ system affected with use of analgesic causing gastritis, vomiting, nausea, diarrhea etc. and serious ADRs like hematemesis, mostly with use of paracetamol-based drug therapy. ADRs may be prevented with proper monitoring and timely management. ADRs associated with opioids are less reported, as these drugs were less commonly prescribed. Similar studies with larger population size are highly essential and a vigilant ADRs monitoring unit in every hospital is requisite.

 

ACKNOWLEDGEMENT:

Authors are highly thankful to all the departments of GSVM Medical College, Kanpur and Faculty of Pharmacy Integral University, Lucknow for providing suitable facilities and support for the successful completion of this study.

 

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Received on 25.10.2019           Modified on 20.12.2019

Accepted on 13.02.2020         © RJPT All right reserved