Download study on identification and assessment of drug interactions in

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXURE- II
PROFORMA OF REGISTRATION OF SUBJECT FOR DISSERTATION
1
1)
NAME OF THE CANDIDATE
AND ADDRESS
ALIREZA SAHEBDEL BORHAN
NO 96/SATYANARAYANA LAY-OUTKURUBARAHALLI/J.C NAGAR/NEAR TO
AMBEDKAR PHARMACY
COLLEGE/BANGALORE:560086
2)
NAME OF THE INSTITUTION
VISVESWARAPURA INSTITUTE OF
PHARMACEUTICAL SCIENCES, BANASHANKARIII STAGE, BANGALORE-70
3)
COURSE OF THE STUDY AND
SUBJECT
MASTER OF PHARMACY
IN
PHARMACY PRACTICE
4)
DATE OF ADMISSION TO THE
COURSE
1 JUNE 2011
5)
TITLE OF THE TOPIC
STUDY ON IDENTIFICATION AND
ASSESSMENT OF DRUG INTERACTIONS IN
PSYCHIATRIC DEPARTMENT AT KIMS
HOSPITAL AND RESEARCH CENTRE
6.0
BRIEF RESUME OF THE INTENDED WORK
6.1) Need for the study
Drug-drug interaction (DDI) may be defined as the pharmacological or clinical response to the
administration of a drug combination that is different from the anticipated known effects of the two
agents when given alone and that can result in reduced effectiveness or increased toxicity1.
A DDI can be the consequence of various situations that reflect the growing number of drugs available
in the market and increasing complexity of polytherapy is a cause of DDIs.
The very widespread practice of self-medication makes the situation more severe and difficult.
Most of the studies on drug interactions have analyzed patients in hospitals, and it has been estimated
that drug interactions may affect up to 63% of all hospitalized patients.2,3,4
These may occur due to several reasons. For example, accidental misuse or younger people tend to
metabolize drug faster than older people or those who smoke the cigarettes metabolize clozapine and
olanzapine faster than those who do not. Co morbid medical condition that decrease the hepatic
function, such as cirrhosis or congestive heart failure ,are likely to decrease the rate of drug
metabolism.CytochromeP450 enzymes are polymorphic, there exist ethnic differences in hepatic
enzymes that influence the pharmacokinetics of drugs and also due to lack of knowledge about the
active ingredients involved in the relevant substances. These processes may cause alterations in
the pharmacokinetics of the drug, such as Absorption, Distribution, Metabolism, and Excretion
(ADME)
of
a
drug.
Alternatively
drug
interactions
may
be
the
result
of
the pharmacodynamic properties of the drug, e.g. the co-administration of a receptor antagonist and
an agonist for the same receptor.
Drug interactions are to be avoided, due to the possibility of poor or unexpected outcomes. A
contemporary example: selective serotonin reuptake inhibitors (SSRIs) inhibit the metabolism of
tricyclic antidepressant (TCAs) dangerous toxicity can occur if the two are given concurrently, like:
fluoxetine and imipiramine.
Co-administration of SSRIs and mono amine oxidize inhibitors (MAOIs) are contraindicated because
they cause severe depression.
Combination
of
SSRIs
with pimozide (an antipsychotic diphenylbutylpiperidine
derivative), or
Tramadol hydrochloride, produce seizures and Liver impairment is an another contraindication for
medications of this type.
2
Drugs like lithium, diuretics and CNS depressants increase the toxicity and NSAIDS interferes with
SSRIs and reduces its efficiency.5
The major impact problem associated with psychotic medication due to drug interactions causes,
adverse drug reactions, drug resistance, side effect, improper drug use, delay in proper diagnosis,
treatment and cost effectiveness of medicine. Hence the present study is aimed on antipsychotics at
psychiatric dept., KIMS Hospital and research centre.
6.2) REVIEW OF LITERATURE:
Sabers A, Gram L. has conducted the drug interaction study at hottun collage and aimed for
identification of the tolerability and drug interaction profiles of six new anticonvulsants:
oxcarbazepine, vigabatrin, lamotrigine, gabapentin, tiagabine and topiramate, are minor with
the exception of the risk of failure of oral contraceptives during treatment with oxcarbazepine
or topiramate and so causes specific problems related to the epilepsy and sometimes include
impaired fertility, failure of oral contraceptives and the risk of birth defects in pregnant women
and concluded that co-administration of antipsychotic drug should not given with
contraceptive medicine and should not given into pregnant women.6

P G Gilman conducted a study at British college of pharmacy in Britannia to identify action of
tricyclic antidepressants and therapeutic drug interactions and found that TCA are the often
have interaction with SSRIs and MAOIs. This interaction involving with CYP450enzyme and
cause seizure, cardiac toxicity, CNS toxicity. The data indicate that nortriptylin &
desiperamine has the most neither pharmacologicaly desirable characteristic as nor adrenalin
reuptake inhibitors (NRIs).7

John A and Yagiel.D.D.S, conducted the study on adrenergic vasoconstrictor drugs which are
commonly used by dentist to enhance the pain-relieving action on focal anesthetics and to
control local bleeding and they found vasoconstrictor drug has interaction with involving
ticyclic antidepressant/ non selective B-selective adrenergic- blockage drugs, general
anesthetics causes thyroid hormone deficiency and comorbidity and even death in some cases,
careful administration of small doses of vasoconstrictor will permit these drugs to be used with
no risk or minimally increased risk only in the case of cocaine intoxication adrenergic
vasoconstrictor must be avoided.8

Markovitz J S, Patrik K S, conducted the study at institute of psychiatry in medicinal
department of university of South Carolina in department of pharmaceutical science aimed for
3
pharmacokinetic and pharmacodynamic drug interaction in the treatment of attention deficit
hyperactivity disorders. Methylphenidate/amphetamine/pemolin are among the most common
medication which are used to day in child & adolescence psychiatry for treatment, often
implicated in pharmacokinetics interaction like suggestive of possible metabolic inhibition
/affecting cytochrom450 which if co-administrate with alpha-adrenergic agonists clonidin will
be implicated in several interaction. Hence they concluded psychostimulent drugs should give
to patient with more care and co-administration with MAOIs agonists and it appears that this
agent may be safety co-administrated with alpha adrenergic agonists.9

Amir H rezvani, conducted a study in the department of psychiatry and behavioral science at
Dura university medical center about nicotine antisycotic drug interaction, which are used to
treat schizophrenia with psychiatric symptoms patient like hallucination. Nicotine commonly
self administrated by people with schizophrenia and the current study was conducted to
determine the effect and interaction of typical (haloperidol) and atypical (clinazpine and
resperidone) with Nicotine. Both typical and atypical antipsychotic drugs significantly
impaired sustained action.10

Umbrunnen T L, Jann M W, conducted a study of drug interactions with antipsychotics at
Atlanta Georgia USA in Mercer university aimed for Incidence and Therapeutic Implications
which the mainstay of treatment for psychotic disorders. Both the newer atypical
antipsychotics and their more traditional counterparts are subject to drug-drug interactions
amongst themselves, with other psychotropic’s and with agents used in the treatment of
various physical ailments Pharmacokinetic interactions occur when the combination of drugs
results in alterations in the absorption, distribution, metabolism or excretion of either agent. As
a consequence, interactions can arise from combining antipsychotics with other agents are
highly protein bound. Antipsychotics undergo phase I and II metabolism to more water-soluble
compounds to aid in excretion from the body. Research has dramatically expanded in the area
of metabolism by the cytochrome P450 (CYP) system. Most antipsychotics are metabolized by
the CYP system and potential drug interactions could occur when they are administered with
other agents that affect or are metabolized by the same isozymes and concluded that
antipsychotic drug interactions come from case reports and limited uncontrolled studies,
making assessment of the clinical significance of the interactions difficult. However, with
further insight into the metabolic interactions of the CYP isozyme systems.11

4
Berecz et al., conducted the study at Department of Pharmacology and Psychiatry, Medical
School, University of Extremadura aimed for study on the Role of Cytochrome P450 Enzymes
in the Metabolism of Risperidone and Its Clinical Relevance for Drug Interactions.
Risperidone in humans is mainly metabolized to 9-hydroxyrisperidone by the polymorphic
cytochrome enzyme P450 2D6 (CYP2D6) in spite of this information which show Plasma
concentrations of risperidone and 9-hydroxyrisperidone show large interindividual variability,
which may be partly related to the activity of the CYP2D6 enzyme and Around seven percent
of Caucasians have a genetically inherited impaired activity of the CYP2D6 enzyme.
Debrisoquine metabolic ratio (a marker of CYP2D6 activity) and the number of CYP2D6
active genes have been related to risperidone plasma concentrations among patients during
steadystate conditions. Large number drugs have been described to be metabolized by
CYP2D6, and it is therefore important to evaluate the clinical significance of the impaired
metabolism and possible drug interactions on the enzyme.12
 S.J.C Davies, S.Ecagres, P.pratt conducted the study at Carolina, department of psychiatric in
pharmaceutical science, U.S.A.,
aimed to assess the potential for interactions involving
cytochromes P450 2D6 (CYP2D6) and 3A4 (CYP3A4) between drugs prescribed in a city inpatient psychiatric service. The proportion of patients on functional elderly wards prescribed at
least one drug interacting with CYP3A4 (87%) was significantly greater than that for patients
on adult wards (57%, P < 0.001). The frequency of interactions involving CYP3A4 was
significantly greater on functional elderly than adult wards and they concluded that confirm
extensive polypharmacy on general adult psychiatric and functional elderly psychiatric wards.
A substantial proportion of patients were receiving combinations of drugs that interact with
CYP2D6 and/or CYP3A4, many of which are known to produce clinically important
interactions.13
6.3) OBJECTIVES OF THE STUDY :
 To identify and assess drug interactions at psychiatry department of KIMS hospital and
research center.
 To study any adverse drug reaction (ADRs) observed with the above antipsychotic treatment
7.0)
MATERIALS AND METHODS :7.1) Source of Data :
Medication chart & discharge patients medication order in KIMS.
5
7.2) INCLUSION CRITERIA:
 In patients on antipsychotic drug therapy in psychiatric department
7.3) EXCLUSION CRITERIA
Patient discharge against medical advice.
7.4) METHOD AND COLLECTION OF DATA:
A prospective study will be conducted on inpatients of psychiatric department at KIMS hospital &
research center who have been diagnosed and on therapy. The patient consent form will be taken from
the patient caretaker. The Medical records, case sheets of patients will be reviewed and the drug data
will be collected.
Any identified DDIs assessment will be done for their mild, moderate and severity of reactions and
analyze the mechanism
and time of onset of DDIs using recourses like drudge, stockley’s drug
interaction, patient drug facts etc.
Any medical outcomes, change of therapy due to DDIs will be assessed and monitored.
7.5) Duration of the study:
The study will be conducted for a period of 9 months and around 200 samples will be included for the
study.
7.6) Place of Study:
In KIMS hospital and research center.
7.7)
Does the study require any investigation or intervention to be conducted on patient or
other humans or animals if so, please describe briefly
-No7.8) Has ethical clearance been obtained from your Institution?
Yes, copy attached.
6
8.0)
LIST OF REFERENCES
1.Magro L, et al., Identification of severe potential drug-drug interactions using an Italian generalpractitioner databasec. Eur J Clin Pharmacol. 2007; 10.1007:234
2. Grönroos PE, Irjala K M, Huupponen R K, Scheinin H, Forsström J, Forsström JJ (1997) A
medication database-a tool for detecting drug interactions in hospital. Eur J Clin Pharmacol 53(1):13–
17
3. Glintborg B, Andersen SE, Dalhoff K (2005) Drug-drug interactions among recently hospitalized
patients-frequent but mostly clinically insignificant. Eur J Clin Pharmacol 61(9):675–681
4 . Cruciol-Souza JM, Thomson JC (2006) Prevalence of potential drug-drug interactions and its
associated factors in a Brazilian teaching hospital. J Pharm Pharm Sci 9(3):427–433
5 . Tripathi KD, Essential of medical pharmacology .5th Ed. page no 410
6.Sabers A.; Gram L. Newer Anticonvulsants: Comparative Review of Drug Interactions and Adverse
Effects.2000:60(1):23-33.
7. P K Gillman .Tricyclic antidepressant pharmacology and therapeutic drug interactions
updated.2009:151(6):737-748.
8. John a. Yagiela, d.d.s. associated with vasoconstrictors Part v of a series.
9. Markowitz J.S.; Patrick K.S. Pharmacokinetic and Pharmacodynamic Drug Interactions in the
Treatment of Attention-Deficit Hyperactivity Disorder. 2001:40: 753-772.
10. Amir H Rezvani , Edward D Levin. Nicotine–antipsychotic drug interactions and attentional
performance in female rats. 2003.
11. ZumBrunnen T.L.; Jann M.W. Drug Interactions with Antipsychotic Agents: Incidence and
Therapeutic Implications.1998: 9:381-401.
12. Berecz R, Dorado P, Rubia A D L, Caceres M C, Degrell I, LLerena A. The Role of
Cytochrome P450 Enzymes in the Metabolism of Risperidone and Its Clinical Relevance for Drug
Interactions.2004:5(6):573-579.
13. Davies S J C, Eayrs S, Pratt P, Lennard M S, Potential for drug interactions involving cytochromes
P450 2D6 and 3A4 on general adult psychiatric and functional elderly psychiatric wards.
2004:57(4):464-472.
1.
7
9.0
NAME & SIGNATURE OF THE
CANDIDATE
10.0
REGISTRATION NUMBER
11.0
SHEKAR H.S.
NAME AND DESIGNATION OF THE GUIDE
Assistant Professor
VIPS, Bangalore.
11.1
REMARKS OF THE GUIDE
11.2
SIGNATURE OF THE GUIDE
12.0
Mrs.Githa Kishore
NAME OF THE HEAD OF THE
Assistant Professor
DEPARTMENT
VIPS, Bangalore.
12.1
SIGNATURE OF THE HEAD OF THE
DEPARTMENT
13.0
NAME AND DESIGNATION OF CO-GUIDE
13.1
SIGNATURE OF THE CO-GUIDE
14.0
NAME OF THE PRINCIPAL
Dr. Harish Kumar DH.
M.Pharm, Ph.D
14.1
REMARKS OF THE PRINCIPAL
14.2
SIGNATURE OF PRINCIPAL WITH SEAL
8