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                           Drug Information Bulletin
                                                       (Inaugural Issue)
     Drug Information Center, Manipal Teaching Hospital, MCOMS, Pokhara, Nepal.
                    (In collaboration with United States Pharmacopoeia)
    Vol: 1 Issue: 1                                                                                              Nov 2003
    Guest editor : Dr. S.K. Dham                     Chief editor: Mr. Pranaya Mishra
    Editorial board : Dr. P. Ravi Shankar, Dr. Arun Kumar Dubey, Mr. P. Subish,
                      Mr. Dinesh Kumar Upadhyay, Mr. Kadir Alam
    Address for correspondence: dicmth@fewanet.com.np

                                          Message from the Dean
        Establishing a Drug Information Center is another feather in the cap of the prestigious Manipal Teaching Hospital.
The armamentarium of drugs is ever increasing and necessitates their use in a judicious manner with full knowledge of the
pharmacokinetics, adverse drug reactions and drug interactions. It is in this context that the Drug Information Center will
prove a boon to all practicing clinicians.
         I exhort all specialists to utilize the immense potential of the Drug Information Center for the practice of Evidence
Based Medicine.
        I wish this venture all success.
                                                                               Dr. S.K. Dham
                                                                               CEO (MEMG, Nepal)
                                                                               Dean, MCOMS, Pokhara
                                                                               Nepal

                       Message from the Medical Superintendent
        It is with immense pleasure that I have come to know that we are starting a Drug Information Center in our hospital.
This will help all the consultants to know about the newer drugs being introduced, their uses, side effects, doses and other
information about the drugs. It will be helpful for all the consultants if they utilize the services provided by the Drug Information
Center. I would like all the medical officers and interns to utilize the facilities available in the Drug Information Center. I
wish this project all the success. Keep up the good work.
                                                                               Dr. S. Ramachandran
                                                                               Medical Superintendent
                                                                               Manipal Teaching Hospital.

                Message from HOD Medicine and Chairman DTC
          I am pleased to know that the Drug Information Center of Manipal Teaching Hospital is being inaugurated on 16th
Nov 2003. With the ever-increasing number of molecules being added to the clinician’s armamentarium it is absolutely
essential that reliable, authentic and updated information is available on each and every drug in the shortest possible time.
The center will help to provide such information.
        In this connection the Drug Bulletin will also serve to disseminate knowledge to clinicians and general practitioners on
latest trends in therapeutics, drug alerts, adverse drug reactions etc.
        I would like to compliment Mr. Pranaya Mishra and his team for commencing this venture and wish the project all the
success.
                                                                               Prof. (Dr.) V.M. Alurkar
                                                                               MD, DM (Cardiology)
                                                                               Head, Department of Medicine
                                                                               Manipal Teaching Hospital and
                                                                               Chairman
                                                                               Drugs and Therapeutics Committee.
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                                      From the Chief Editor’s desk
          It is a matter of great pleasure that a Drug Information Center (DIC) has been established in our hospital. At the
outset, I would like to express my gratitude to the United States Pharmacopoeia (USP) without whose help and support this
would not have been possible. It has been the practice to have a DIC at all tertiary care hospitals, where a plethora of drugs
are being used for the treatment of patients. Being a not for profit, non-governmental organization, USP has been involved in
information development through evidence-based consensus of volunteer experts. It supports the practice of evidence-based
medicine (EBM). The practice of medicine is changing very fast with the development of new molecules, formulations and
new guidelines. Our clinicians and paramedical staff are well versed and competent in their professions. Our attempt is to
help them regarding drug related queries, if any. Our mission is not to correct, but to complement by giving drug related
information.
          It is a matter of pride to be associated with USP, which has been advocating practice of evidence-based medicine,
particularly in developing countries. It is a matter of satisfaction that our center is one of the few in Nepal. We hope that our
clinicians, nursing staff, paramedical staff will utilize this facility to the fullest. This center is open for all. We would appreciate
it if we get queries from the clinicians practicing elsewhere as well as medical and paramedical staff working at the primary
care level. On the eve of the inauguration of the Drug Information Center we are happy to release the first issue of our Drug
Bulletin. I hope this bulletin will be of great help to our clinicians and paramedical staff in assimilating and disseminating the
information about drugs.
          The Drug Information Center aims to start following programs on the near future: adverse drug reaction monitoring
program, developing standard treatment guidelines, formulary development and review, continuing education programs,
disseminating information on infectious diseases such as tuberculosis and local drug resistance patterns. I am hopeful that all
concerned will utilize this facility to its fullest. I would also take this opportunity to thank every one involved directly and
indirectly in our Drug Information Center as well in the Drug Bulletin.
                                                                                 Pranaya Mishra
                                                                                 In charge
                                                                                 Drug Information Center.


                                            Using drugs rationally
P-Drug concept and Rational Use of Drugs                              copy the P-drug lists of others. You are responsible for the
         In the recent decades there has been a ‘drug                 health and well being of your patients. You can draw on expert
explosion’. At present, we have more than a thousand drugs            opinions and the views of committees but you should always
in our therapeutic armamentarium. As doctors and doctors to           draw up your own list.
be, you may be confronted with a bewildering array of                           One of the main objectives behind the P-drug concept
molecules. You may spend an average of 3 to 5 minutes with            is to promote the rational use of drugs. What is meant by the
the patient. How can you choose the right drug for the patient        term ‘Rational use of drugs’? Different people have their own
in such a short interval of time? The solution may be by using        ideas and perceptions. In 1985, the Conference of Experts on
P-drugs. What are these P-drugs?                                      Rational Use of Drugs in Nairobi defined that ‘Rational use
         P-drugs stand for personal drugs. These are a list of        of drugs requires that patients receive medicines appropriate
drugs, which you will be using, in your day-to-day practice.          to their clinical needs, in doses that meet their own individual
The list of P-drugs depends on many factors. It depends on            requirements for an adequate period of time, and at the lowest
your field of specialization, the common illnesses in your area,      cost to them and their community.’
the availability of drugs, the socioeconomic status of the                      How do you go about the process of selecting P-drugs?
population and other factors. When using antibiotics, the list        Remember P-drugs are for a particular disease and not a
will also depend on the sensitivity pattern of microorganisms         particular patient. After selecting a P-drug for a particular
in your area of practice.                                             disease then we can tailor the treatment to a particular patient.
         You should become thoroughly familiar with the P-            The steps in choosing a P-drug are:
drugs; their dosage forms, dosage schedule and duration of                 1) Define the diagnosis
treatment should be noted. The adverse effects,                            2) Specify the therapeutic objective
contraindications and special precautions to be taken while                3) Make a list of effective group of drugs
using these drugs are important.                                           4) Choose an effective group according to criteria and
         How do you go about compiling your list of P-drugs?               5) Choose a P-drug.
The easiest way may be by copying the list of your teachers                     Let us consider the clinical illenss LRTI. The
or from the National formularies. But you should NEVER                therapeutic objective is to cure the patient. But in other
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conditions like hypertension it might be to control the blood        sputum. We can use drugs for symptomatic relief but to cure
pressure or in cancer it may be palliative care. The third step      the patient we must eliminate the microorganism causing the
is to list out the drugs likely to be effective in the condition.    disease. Keeping in mind the sensitivity patterns of the bacteria
In LRTI, the effective group of drugs maybe sulfonamides             and other factors the P-drug, cotrimoxazole was chosen. The
(cotrimoxazole), fluoroquinolones (ciprofloxacin), newer             next step in rational treatment is to ensure that the P-drug
macrolides (azithromycin) or maybe other groups. After               (cotrimoxazole) is suitable in our 32-year old lady patient.
choosing the effective groups of drugs you have to choose an         The drug must be effective; contraindications have to be ruled
effective group according to criteria. We have to choose             out. The pharmacokinetics of the drug must be suitable.
between sulfonamides, fluoroquinolones and newer                              After checking the suitability, start the treatment and
macrolides. To do a proper comparison we need information            inform the patient about the disease and how to take the drug.
on efficacy, safety, suitability and cost. The pharmacokinetics      Tell the patient about the adverse effects she may experience
of the drug should ensure that the drug reaches its site of action   and what action is to be taken. Always ask the patient to
in an adequate amount. The drug should have an adequate              summarize in his/her own words, the key information like
safety margin. Taking all these factors into consideration and       how to take the medicines, the precautions to be taken and the
keeping in mid the sensitivity patterns of the pathogens, a          important adverse effects.
sulfonamide may be the logical choice.                                        In LRTI we have to emphasize that symptomatic relief
          The last step is to choose a P-drug. You have to select    is not synonymous with cure and the patient should not stop
a proper drug and then select an active substance and a dosage       taking the drug on feeling better. Monitoring is a important
form. The dosage form may influence the compliance of the            part of the therapeutic process. Many patients do not come
patient. Cotrimoxazole is our P-drug for LRTI and tablets are        back if they feel better. Patients may come back if they think
the preferred dosage form. Prescribe drugs by generic name           the treatment was not effective, the treatment was not safe or
only. After choosing a dosage form, choose a standard dosage         the treatment was not convenient. If the patient is not getting
schedule and a standard duration of treatment. The dose for          relief then consider whether the diagnosis, treatment,
our patient is 960 mg twice a day and the duration of treatment      adherence to treatment and monitoring procedures were
should be at least 7 days.                                           correct. In chronic disease like hypertension monitoring is
          Having chosen the P-drug, the next objective is to         important for ensuring patient compliance with your treatment.
use the P-drug for the rational treatment of a patient with LRTI.             In Nepal, inappropriate prescribing practices are
The steps in rational treatment using a P-drug are:                  encountered in many health care settings. The common
    1)     Define the patients problem                               examples are overuse of antibiotics and antidiarrheals for non-
    2)     Specify the therapeutic objective                         specific childhood diarrhea, indiscriminate use of injections
    3)     Verify the suitability of your P-treatment                and excessive use of antibiotics for treating no pneumonia.
    4)     Start the treatment                                       Proper choice and rational use of drugs will be a great help in
    5)     Give information, instructions and warning and            ensuring appropriate and affordable care and should be
    6)     Monitor (and stop?) the treatment.                        incorporated into daily clinical practice.
          Imagine a general practitioner in Jomsom (Mustang          Sources:
district) located at the foot of the majestic Nilgiris. A 32-year-   1) WHO guide to good prescribing. WHO/DAP/94.11
old lady comes to him with lower respiratory tract infection         2) Training manual, 16th National Training Course on Rational Use
(LRTI). She is not pregnant, is not breast-feeding her child,           of Drugs. INRUD, Nepal, 2003.
and has no history of liver or kidney disease or allergy to any                                     Dr. P.Ravi Shankar
drugs.                                                                                              Assistant Professor
                                                                                                    Department of Pharmacology.
          Our patient is suffering from LRTI and her main
problems are fever and cough with foul smelling yellow

                                                   Drugs revisited
Potential Cardioprotective effects of                                55% depending on the dose and Statin used. A similar
                                                                     reduction in triglycerides is observed with the more potent
Statins other than LDL lowering??                                    Statins (Simvastatin and Atorvastatin). In addition, Simvastatin
         The Statins (Lovastatin, Pravastatin, Simvastatin,          in high doses has been found to increase HDL level more
Atorvastatin, & Fluvastatin) are most widely used agents for         than Atorvastatin in comparable doses.
treating dyslipidemias. These drugs are competitive inhibitors                Although statins clearly exert their major effects on
of HMG Co-A reductase and inhibit cholesterol synthesis in           Coronary Heart Disease (CHD) by lowering LDL cholesterol
the liver. This results in increased number of LDL receptors         and improving the lipid profile, recently, a multitude of
on the surface of hepatocytes and hence enhanced removal of          potentially cardioprotective effects have been ascribed to these
LDL from the blood. Statins lower LDL cholesterol by 20 to           drugs. Some of these effects are:
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Statins and endothelial function: Statins stabilize                     vivo. Furthermore, Atorvastatin has been reported to stabilize
endothelial cell nitric oxide synthase enzyme and enhance               or increase plasma level of paraoxanase, the antioxidant
synthesis of nitric oxide. It is thought to cause coronary              enzyme associated with plasma HDL.
vasodilatation and improves coronary blood flow.                   Statins and coagulation: Statin reduces platelet aggregation
                                                                   and show variable effect on plasma fibrinogen level, the
Statins and plaque stability: There are reports that Statins
                                                                   significance of which remains to be determined.
affect plaque stability in a beneficial way (decreased rupture
and thrombosis). These actions are attributed to decreased                All these effects of statins are based on small in vitro
monocyte infiltration into the arterial wall and decreased studies and ex vivo data. The mechanism of action for these
proliferation of smooth muscles of the arteries.                   non-lipid roles of Statins have not been established and it is
                                                                   not known whether these effects represent a class-action effect
Statins and inflammation: Recently there has been a better
correlation between understanding of inflammation and the or are biologically relevant. These early clues require thorough
process of atherogenesis. In a number of in vitro studies, Statins investigation and large well-designed clinical trials to firmly
have been suggested to be anti-inflammatory. In a small study, establish their efficacy.
C-reactive protein was taken as a marker for inflammation Sources:
and Statin therapy decreased C-reactive protein level Goodman and Gillman’s – The pharmacological basis of
independently of cholesterol lowering in patients with CHD. therapeutics: 10th edition.
                                                                        Martindale- The complete drug reference: 33rd edition.
Statins and lipoprotein oxidation: Oxidative modification
                                                                                                          Dr A.K.Dubey
of LDL plays a key role at several steps in the process of
                                                                                                          Lecturer
atherogenesis. A number of animal and human studies have                                                  Department of Pharmacology
shown that Statins reduce LDL oxidation both in vitro and in

                                          Drugs and the laboratory
Drugs affecting blood glucose testing
   Drugs are known to affect the laboratory tests in many ways. The drug can cause abnormal laboratory tests by:
   1. Interference with the assay
   2. Change in the concentration of the measured substance due to the drug
   3. Toxic effect of the drug itself can cause abnormal laboratory tests.
   Blood glucose monitoring is one of the essential parameters for the management of Diabetes mellitus. It is also the main
component in self-monitoring of diabetes. Many drugs are known to affect the blood glucose testing. Some of them are as follows:
    S.No     Drug           Effect         Mechanism                                Laboratory abnormality
      1 Ascorbic acid  Decreased serum     Analytical      At conc. above 150mg/l it lowers glucose conc. measured by GOD method.
                       glucose level
     2   Cefuroxime    Decreased serum     Analytical      False negative test may be observed when ferricyanide methods are used
                       glucose level                       to measure glucose
     3   Metronidazole Decreased serum     Analytical      With hexokinase reaction involving enzymatic coupling with oxidation-reduction
                       glucose level                       of NAD. Interference may occur due to the similarity of absorbance peaks
                                                           of NAD and metronidazole (322nm) at pH 7.
     4   Ciprofloxacin Decreased serum Physiological       Concurrent administration of ciprofloxacin with glyburide has on rare
                       glucose level                       occasions been associated with severe hypoglycemia.
     5   Propranolol   Decreased serum Physiological       Has slight effect like that of prolonging insulin. Rare cases due to inhibition
                       glucose level                       of glycogenolysis in nondiabetics.
     6   Ramipril      Decreased serum Physiological       Slight but significant reduction from mean baseline conc. of 8.5 m.mol/L
                       glucose level                       to 8.0m.mol/L in 21 hypertensive patients with noninsulin dependent diabetes
                                                           mellitus treated with 5mg/day for 12 weeks. Incidence of 1.6 % observed in
                                                           French pharmacovigilance database
     7   Sildenafil     Decreased serum Physiological      Hypoglycemic reaction observed in some patients when administered with
                        glucose level                      sildenafil.
     8   Furosemide     Increased serum Physiological      Hyperglycemia and alterations in glucose tolerance may occur with treatment.
                        glucose level                      Diabetogenic like action of drug affects glucose tolerance tests.
         Hence, it becomes necessary to take the medication history of the patient before testing for blood glucose level.
                                                                                               P. Subish
                                                                                               Lecturer
                                                                                               Department of Pharmacology
Source: Effects of drugs on clinical laboratory tests: Donald S Young; Fifth edition; Vol II
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                                                      Drug alerts
Seizures associated with Fluoroquinolones                           GABA; this results in CNS stimulation. Binding to this
        Fluoroquinolones are widely used and are                    receptor is strongly influenced by the side chain in the 7th
administered by several routes. Although the introduction of        position: quinolones with bulky moieties such as temafloxacin
fluoroquinolones has increased the treatment options, their         and sparfloxacin binds less efficiently to GABA receptors.
wide spread use has also revealed a wide spectrum of adverse        (1)
reactions. Several new members of this group were marketed                   It was noted that convulsions could occur both in
with great enthusiasm, but after the occurrence of serious          patients with epilepsy and in those with no previous history
adverse events during the early post marketing phase, some          of convulsions (2). However seizures have occurred
had to be withdrawn.                                                predominantly in patients who were also receiving
Eg: Temafloxacin (1992) Temafloxacin syndrome.                      theophylline or a nonsteroidal anti-inflammatory drug
       Trovafloxacin(1999) Lethal hepatic effects.                  (NSAID). NSAIDs may augment displacement of GABA from
       Grepafloxacin(1999) Torsade de pointes (1).                  its receptors by the quinolones (3). The risk factors for
In Nepal, currently ciprofloxacin, ofloxacin and norfloxacin        fluoroquinolone-induced seizure may include seizure history,
are approved for use.                                               electrolyte imbalances, lack of dosage adjustment for renal
        The fluroquinolones have a broad spectrum of side           insufficiency, and concomitant treatment with agents that
effects ranging from the milder ones that rarely require            lower the seizure threshold (4).
attention to the life threatening ones. The most common                    Hence these agents should be used with caution in
adverse reactions involve the gastrointestinal tract and are seen   patients with known or suspected CNS disorders (seizure
in 3% to 17% of patients The central nervous system effects         disorders, severe arteriosclerosis) that predispose to seizures
are seen in 0.9% to 11% of the patients. These effects include      or lower the seizure threshold and should be used with caution
mild headache, dizziness, hallucinations, delirium, seizures        in the presence of other factors (eg, certain drug therapies,
etc. The ability of fluoroquinolones to cause seizures has          renal dysfunction, alcohol consumption etc) that predispose
gained attention these days. Isolated reports of seizures have      to seizures or lower the seizure threshold. If seizures occur
been reported with ciprofloxacin and ofloxacin. The risk of         during quinolone therapy, the drug should be discontinued
seizures during treatment with individual quinolones is             and appropriate measures should be instituted. (5)
currently unknown. Electrophysiological field potentials in         Sources:
                                                                    1.Meylers side effects of drugs 14 th edition
animals are affected to varying degrees by different
                                                                    2. Martindale- The complete drug reference: 33rd edition
quinolones; the smallest effect was observed with ofloxacin,         3.Goodman and Gillman’s – The pharmacological basis of
followed by ciprofloxacin and nalidixic acid, whereas there         therapeutics: 10th edition
was an increasing excitatory effects with clinafloxacin,            4. Annals of pharmacotherapy. 2001 Oct; 35(10): 1194-98
enoxacin, fleroxacin, lomefloxacin, moxifloxacin, and               5. AHFS Drug Information 2003
trovafloxacin.                                                                                     P. Subish
        The pathophysiologic basis for the triggering of                                           Lecturer
seizures probably lies in the binding of fluoroquinolones to                                       Department of Pharmacology.
GABAA receptors in the brain, blocking the natural ligand



Interaction between Warfarin and                                    developed an increased prothrombin time. One woman took
                                                                    warfarin and used vaginal miconazole suppositories for 2 days
Miconazole vaginal cream and                                        showed an increased prothrombin time and developed bruises,
suppositories                                                       gingival bleeding, and nose bleed. These reports suggest that
        Miconazole is an imidazole antifungal drug that has         there is a probable interaction between warfarin anticoagulants
been available by prescription and over the counter in different    and intravaginal miconazole. It is important for physicians
formulations for many years. The interaction between systemic       and patients to understand that this interaction may occur with
miconazole and warfarin is well established. Recently the FDA       these topical miconazole products so that patients who need
received two adverse event reports of women who                     to use both products simultaneously will be appropriately
concomitantly took anticoagulant therapy with warfarin and          monitored.
used vaginal miconazole for three days. Their INR was
increased. One woman taking acenocoumarol used miconazole Source: www.fda.gov
vaginal cream for an indeterminate length of time and


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                           Hospital Pharmacy in the Past quarter
New drugs introduced in the hospital pharmacy
During the period of last three months the following drugs have been introduced in the hospital pharmacy:
    S.No Generic name           Brand name            Manufacturer                    Category           Recommending
                                                                                                           department
     1    Bambuterol      Tab.Betaday 10 mg      Sun Pharmaceuticals      Beta 2 receptor agonist        Medicine
          Hydrochloride
     2.   Pamidronate     Inj. Pamifos 90mg      Dabur Pharmaceuticals Aminobisphosphonate                Oncology
     3.   Fludrocortisone Tab. Floricot 0.1mg    Samarth Pharma         Corticosteroid with glucoco-
                                                                        rticoid and highly potent
                                                                        mineralocorticoid activity.      Medicine
     4    Carbachol       Inj. Miostat 0.1%      Alcon labs             Quarternary ammonium             Ophthalmology
                                                                        parasympathetic with the
                                                                        muscarinic and nicotinic
                                                                        actions of acetylcholine.
     5    Glipizide       Tab. Bimide SR         Emcure pharmaceuticals Sulfonylurea antidiabetic        Medicine
     6    Docetaxel       Inj. Daxotel 20mg      Dabur Pharmaceuticals Semisynthetic taxane              Oncology
                          and 80 mg
     7    Ambroxal        Tab. Ambrodil 30 mg Aristo pharmaceuticals Mucolytic                           ENT
          hydrochloride

Note: The Drug And Therapeutic Committee of the hospital governs the entry and deletion of drugs in the hospital pharmacy.
                                                                                          Kadir Alam
                                                                                          Bulk Pharmacy



                                                 From the DIC
Even though the Drug Information Center (DIC) has not fasting triglyceride levels of less than 400 mg/dl (4.5mmol/l)
started officially, there are some drug information queries were recruited.
received by the DIC. For a period of one month the DIC has            Patients were randomly assigned to receive treatment
received eight queries.                                         with fluvastatin 80mg/d (n=844) or placebo (n=833) on
                                                                discharge for a period of 3-4 years.
Query of the quarter                                                  The survival time free of MACE, defined as cardiac
                                                                death, nonfatal myocardial infarction, or reintervention
                                                                procedure were compared between the treatment and placebo
What is LIPS Trial?                                             groups. The median time between PCI and first dose of study
Enquirer category: Physician                                    medication was 2.0 days, and median follow-up was 3.9 years.
                                                                      MACE- free survival time was longer in the fluvastatin
       LIPS (Lescol Intervention Prevention Study) is a group (p=0. 01). 21.4% of individuals in the fluvastatin group
randomized, double blind, placebo controlled trial conducted and 26.7% in the placebo group had at least one MACE. In
to determine whether treatment with fluvastastin (HMG COA the sub group analysis, the risk of MACE was reduced in
reductase inhibitor) reduces major adverse cardiac events patients with diabetes and in those with multivessel disease
(MACE) in patients who had undergone first percutaneous who received fluvastatin compared with those who received
coronary intervention (PCI).                                    placebo.
       A total of 1667 patients aged 18-80 years with stable or       There were no instances of creatine phosphokinase
unstable angina or silent ischemia following successful elevation above 10 times the upper limit of normal or
completion of their first PCI and who had baseline cholesterol rhabdomyolysis in the fluvastatin group.
levels between 135 and 270 mg/dl (3.5-7.0 mmol/l) with




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                                      Complementary Medicine
β-Boswellic acid in the treatment of                              which is mostly concentrated in tropical parts of Asia and
                                                                  Africa. In India it occurs in the dry hilly forests of Rajasthan,
Rheumatoid arthritis                                              Madhya Pradesh, Gujarat, Bihar, Assam, Orissa as well as in
                                                                  the central peninsular regions of Andhra Pradesh.. The gum
         Inflammatory diseases such as rheumatoid arthritis,      is tapped from the incisions made on the trunk of the tree (1).
osteoarthritis, ankylosing spondylitis etc can produce pain and          β-boswellic acid inhibits the leukotriene biosynthesis
adversely affect the quality of life. These diseases usually set  in neutrophils by a non-redox, noncompetitive inhibition of
in after or during the third or fourth decade of life, although   5-lipoxygenase. A series of chronic inflammatory diseases are
in some instances, people of the younger age group are also       thought to be perpetuated by leukotrienes (2).
affected. The disease condition progresses with age and there            In the anti-arthritic study on the mycobacterial adjuvant-
will be immobility in one or more joints. In extreme cases the    induced poly-arthritis in rats, ‘salai guggul’ showed 34% and
patients may be crippled and bed ridden.                          49% inhibition of paw swelling with 50 and 100 mg/kg (p.o)
         Despite the rapid strides made in the development of     doses respectively as compared to controls. Thus the hope on
synthetic drugs in the last several decades, we are still         alternative medicine seems to be fairly good in management
searching for newer remedies from plant sources. The primary      and treatment of inflammatory disorders.
reason for this could be the lesser adverse effects of drugs of
plant origin. A large number of drugs are commonly used in References
Indian medicine for treating chronic inflammatory diseases. 1. Hande SS, Kaul MK, Supplement to cultivation and utilization
Boswellia serrata is one of them, which is used, in a chronic    of medicinal plants, 1996, RRL, Jammu, page 526-35.
inflammatory disease like rheumatoid arthritis. Anti- 2. Ammon HP. Boswellic acid (component of frankincense) as
inflammatory activity is mainly due to boswellic acid, which     the active principle in the treatment of chronic inflammatory
is the active constituent of Boswellia serrata.                  disease. Wien Med Wochenschr 2002; 152 (15-16): 373-8.
         Boswellia serrata is also known as salai guggul,
Sallaki, Indian olibanum, white guggul and frankincense and                                     Mr. Dinesh Kumar Upadhayay
                                                                                                Lecturer
belongs to the family Burseraceae.
                                                                                                Department of Pharmacology
         Boswellia serrata is a deciduous middle-sized tree,

                                                   Drug profile
    Glipizide                                                   Mechanism of action: It acts by stimulating pancreatic beta
                                                                cells and thereby releasing insulin. Glipizide also appears to
Category: Sulfonylurea antidiabetic (Second generation)         enhance peripheral insulin action at postreceptor (probably
Therapeutic advantage:                                          intracellular) site(s) during long term administration, and this
Glipizide stimulates insulin action through extra pancreatic appears to be a principal mechanism of action during
effects that affect insulin receptor binding and enhance tissue prolonged therapy.
responsiveness to insulin. Another beneficial effect of
Glipizide is that fasting hypoglycemia is less.                 Side effects: Hypoglycemia, weight gain, allergic reactions
Uses: Used in the treatment of type 2 diabetes                  including pruritis, urticaria and hematological effects like
                                                                leukopenia, thrombocytopenia, aplastic anemia and central
Pharmacokinetics: Glipizide is readily absorbed from the nervous system effects like dizziness, drowsiness and head
gastrointestinal tract with peak plasma concentration occurring ache etc are reported. Like other sulfonylureas, hyponatremia
with in 1 to 3 hours after a single dose. It is extensively and SIADH have occurred in patients receiving Glipizide
bounded to plasma proteins and has a half-life of 2-4 hours. It therapy.
is metabolized mainly by liver and excreted chiefly in urine,
largely as inactive metabolites.                                Precautions and contraindications: It should not be used in
                                                                type I diabetes mellitus. Use in type II diabetes is
Dose: The usual dose is 2.5 –5 mg daily given as single dose contraindicated in patients with ketoacidosis and in those with
15 to 30 mins before breakfast. Dosage may be adjusted at severe infections, trauma or other conditions where the
intervals of several days by amounts of 2.5 to 5mg daily to a sulfonylurea is unlikely to control hypoglycemia.
maximum of 20 mg daily. Doses up to 40mg have been used.
But doses larger than 15 mg daily are given in two daily Use in pregnancy: US FDA pregnancy category C
divided doses before meals. Modified release formulations Although the use of Glipizide may be beneficial for decreasing
are given in a dose of 5-10 mg as a single dose with breakfast. the incidence of fetal and newborn morbidity and mortality in
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developing countries where the proper use of insulin is
                                                                   Dose adjustment in renal failure:
problematic, insulin is still the treatment of choice for the
                                                                   In individuals with normal renal and hepatic function 60-90
disease during pregnancy. Oral hypoglycemics are not
                                                                   % of Glipizide is excreted in the urine in unchanged form and
indicated for the pregnant diabetic because they will not
                                                                   as metabolites within 24-72 hrs and 5-20% is excreted in feces,
provide good control. If Glipizide is used during pregnancy,
                                                                   Less than 10% is excreted in urine in unchanged form within
it should be changed to insulin and Glipizide should be
                                                                   24 hrs. It requires dosage adjustment as follows:
discontinued before delivery.
Lactation: Information on Glipizide in lactation is lacking.          GFR (ml/min)                          Dose
Preparations available: Glynase Tab 5 Mg and Bimode SR                    > 50                      No adjustment required
Tab 10 Mg                                                                10-50                      50% of the usual dose
                                                                          <10                       50% of the usual dose
Drug interactions:
        Drug                                                     Effect
  Antacids                Magnesium hydroxide and sodium bicarbonate have been reported to increase the rate of absorption,
                          although not the total amount absorbed of a dose of Glipizide in healthy subjects.
    ACE inhibitors        Combination is associated with an increased risk of developing hypoglycemia
    Antibacterials        Sulphonamides including cotrimoxazole may enhance the hypoglycemic effect. Rifampicin
                          enhances metabolism of Glipizide.
    Anti fungal           Hypoglycemia is reported in patients taking Glipizide with fluconazole & Ketoconazole.
                                                                                                 Kadir Alam
                                                                                                 Bulk Pharmacy.

                                         Drug Delivery Systems
Enteric coated drugs                                               to 4. It is released after one hour when the drug is passed
         Enteric coatings preparations are those that              to the intestine where the pH is basic ranging from 6.5 to
remain intact in the stomach but will dissolve and release         7. The intended drug disintegrates in the specified time
the contents once it reaches the small intestine. The              in the intestine where it is better absorbed also. Thus, it
purpose of such coating is to delay the release of drugs           is not always esential to take these preparations before
which are inactivated by the stomach contents eg.                  food (as even in case of NSAIDS).
Pancreatin and erythromycin, or to prevent nausea or               Some of the commercially marketed brands of drugs
bleeding caused by drugs due to irritation of the gastric          available in the market are :
mucosa eg.aspirin, steroids. These preparations are                ⇑ Aspirin: Each enteric-coated tablet containing
designed in such a way that they remain undissociated                   aspirin 50mg, 75mg, 100mg, 150mg.
in the low pH of the stomach but readily ionize when the           ⇑ Diclofenac sodium: Each tablet containing
pH rises above 4 or 5. Enteric coating is designed in such              diclofenac sodium 50mg.
a way that they should remain atleast one hour without                                        Ram Bdr Bhandari
disintegrating in the stomach fluids i.e a pH of about 1                                      Hospital Pharmacist

                                                 Five Questions
1. The isomer of one of the drug is used in the treatment of 4. Cyclo phosphamide nephrotoxicity can be reduced by
   hypertension:                                                giving:
   A. Labetolol                  B.Furosemide                   A. Ginkgo biloba              B. Normal Saline
   C. Propranolol                D. Amlodipine                  C. Folic acid                 D. MESNA
2. Long term use of thiazolidinediones can lead to           5. One of the following drugs is a specific opioid antagonist
   A. Congestive cardiac failure B. Carcinogenicity             A. Nalorphine                 B. Naloxone
   C. Impotence                  D. Teratogenicity              C. Fentanyl                   D. Pethidine
3. One of the following drug is a steroidal antibiotic
   A. Imepenem                   B. Amphotericin                              (Answers in the next issue)
   C. Fusidic acid               D. Vancomycin
              For any drug related queries, please contact DIC or mail dic@fewanet.com.np or dial 526416, Ext. 221
                                                               8
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