Seizure Management

 Epilepsy is defined as a disorder of the brain characterized by an ongoing derangement towards recurrent epileptic seizures. An epileptic seizure is defined as an excessive burst of abnormally synchronized neuronal activity affecting small or large neuronal networks that results in clinical manifestations. Such clinical manifestations could be sudden, transient or usually of short duration.

Incidence of an unprovoked seizure is approximately around one in one thousand (0.1%) children every year. Medical treatment of a first seizure is controversial. Recurrence of subsequent seizures has been observed approximately in more than 50% cases. Antiepileptic drug therapy after the first episode of seizure does not alter the long-term prognosis for episodes of epilepsy. Many drugs may reduce the risk of second seizure.

Why antiepileptic treatment?

The risk of having a third seizure after the two previous episodes is higher, and due to these reasons most neurologists advocate a treatment with antiepileptic drugs after the second seizure. Neurolgists clearly suggest individualized treatment in patients of epilepsy; as the recurrence risk is affected in such patients depends on variable etiology. Patients with structural brain abnormality are said to be high risk patients.

Brain Stimulation:

Seizure generation could be indirectly inhibited by stimulation of subcortical structures of brain. There are several reports representing that chronic anterior thalamic stimulation reduces seizure frequency in patients with partial and generalized seizures, in small clinical trials.

Stimulations of the centromedian nucleus was beneficial in some studies. Direct cortical stimulation has been observed to shorten or terminate electrographic discharges induced by stimulations during brain mapping.

Ketogenic Diet:

High-fat, low-carbohydrate and low protein diet after the brief period of fasting has been observed to result in ketosis. In a meta-analytical study, the diet showed clear effect of >50% seizure reduction in patients on ketogenic diet in comparison to others.

Happy New Year - 2018

Dr. CS Rayat wishes his Followers & Friends “A Very Happy & Prosperous New Year-2018”.

“May every ray of the Sun fill your life with Success and Ultimate Happiness in 2018”

CS Rayat

Management of Tuberculosis: Therapeutic Approach

Pulmonary tuberculosis (Tuberculosis of lungs) or Extra-pulmonary tuberculosis (Tuberculosis of organs other than lungs) in humans is caused by Mycobacterium tuberculosis, a human tubercle bacillus. Mycobacterium tuberculosis is an obligate anaerobic bacterium, whose natural reservoir is human beings. Mycobacterium tuberculosis (MTB) is non-motile and does not produce spores. The generation time of MTB is 15 to 20 hours, so it is also called slow growing bacterium.

Tuberculosis (TB) of any type remains a challenging clinical problem and important public health issue the world over. In the recent past the World Health Organization (WHO) has documented an annual incidence of 9.27 million new cases of TB with a prevalence of 13.7 million cases. Majority of TB cases exist in Africa and South East Asia. The annual incidence rate in Africa and South East Asia has been reported as 356 and 182 cases per 100,000 population respectively that is much higher than the global incidence rate.

The ‘gold standard’ in the diagnosis of TB has been the detection of Mycobacterium tuberculosis in the sputum smear or in the pathological lesions (by histopathological methods). The rapid diagnosis of TB is fundamental to clinical outcome. On general physical examination careful attention should be given to the presence of lymphadenopathy (swollen/enlarged lymphnodes), draining sinuses, non-healing ulcers, spinal or joint lesions etc.

Extensive research has been going on in the field of management of TB through anti-tubercular treatment (ATT) ever since the discovery of rifampicin in 1960s. The major objectives of research in anti-tubercular treatment (ATT) include the shortening of duration of therapy, preventing the emergency of drug resistance, avoiding toxicity and shortening the period of infectivity. Direct Observation Therapy-Short Course (DOTS) is the most effective strategy propagated for the management of tuberculosis. Several new drugs and non-pharmacological therapeutic modalities are under extensive study for the effective management of tuberculosis.

A)  Pharmacological Approach to Management of TB:

Pharmacological drugs can be classified as

Ø  Drugs susceptible for MTB.

Ø  Drugs susceptible for conventional ‘drug-resistant bacilli’, which include the followings:

·         Re-purposed drugs (e.g. Fluoroquinolones)

·         New dosages of already available drugs (e.g. Rifampicin rifamycin or high dose isoniazid)

·         New drugs (e.g. Bedaquiline for ‘multi drug resistant-TB).

B)  Preventive Approach to Management of TB:

Ø  Vaccination: The use of BCG vaccination is recommended. Recombinant BCGs are also under clinical trials.

Ø  Chemoprophylaxis for Latent-TB: Chemoprophylaxis is recommended for new born babies born to ‘sputum smear positive’ mothers. Chemoprophylaxis should also be recommended for the cases having ‘Latent-TB’. Interferon gamma release assay test (IGRAs) and Mantoux Test (a Skin Test) are useful tests for establishing a diagnosis of Latent-TB. However, these tests do not necessarily indicate the presence of active tuberculosis and requirement of ATT.

C)  Non-pharmacological Approach to Management of TB:

Ø  Non-pharmacological advances are based on immunomodulation and immunotherapy. Use of protective cytokines, anti-cytokine agents (such as thalidomide pentoxiphylline) and immune-enhancement with ‘heat killed Mycobacterium vaccine’ and other recombinant BCGs have been under clinical trials. These modalities have not been recommended for standard clinical practice.

Ø  Strategies for Airborne Infection Control:  ‘International Guidelines on Airborne Infection Control in Healthcare Settings’ should be adopted. These guidelines are very important in the isolation wards, multi-drug resistant-TB (MDR-TB) wards and the Medical Laboratories conducting TB tests, for prevention of spread of infection among health workers in hospitals.

 

 

Jaundice: Should the Drugs be Used ?

Jaundice is a symptom of a liver disease wherein the level of a yellow colored pigment called bilirubin increases in blood. The cause of jaundice may be infectious, pathological, obstructive or therapeutic. However, the most prevalent cause of jaundice is due to viral infection. Till 1940 this disease was considered catarrhal (catarrhal jaundice), due to catarrh of bile passages responsible for transporting bile from the liver to the intestine. It was during World War-II (1939-1945), the attending physicians discovered that the disease is due to some infection; and it was labeled as 'infectious hepatitis'. Many soldiers died due to infectious hepatitis during the World War-II. It was also observed during the period of war that there are two viruses infecting the soldiers with relatively shorter and longer incubation periods.

Now, these hepatitis viruses are called hepatitis virus-A and hepatitis virus-B. We can accurately diagnose the cause of jaundice and classify the causative virus. Hepatitis-B is severer of the two. Disease is transmitted not only through transfusion of infected blood or blood products but also through saliva, tears, breast milk, and seminal fluid and rarely by feces and urine of the patient.

Fatigue, loss of appetite, nausea, vomiting, joint and muscle pains, cough, coryza and headache may precede for one to two weeks preceding the onset of jaundice. Dark colored urine and light colored stools are other visible signs in addition to yellow coloration of eyes. There may be pain in the upper right quadrant of tummy along with discomfort in the tummy. Progress of recovery is very encouraging in cases of Hepatitis-A.


The medical management in cases of viral hepatitis/jaundice is just symptomatic and maintenance of nutrition is taken care of in these patients. There is no specific treatment for viral hepatitis/jaundice. Restriction of physical activity is advisable. A high calorie diet is generally recommended but special care is required in diabetics. Drugs should be avoided to avoid adverse effect on the liver. Patient should be isolated to a room (and a bathroom too) and routine hygiene measures should be observed. Serious patients should be hospitalized.

Inimical Interaction of Tobacco with Drugs

Consumption of tobacco in any form is bad as it has inimical interaction with a majority of drugs/medicines in addition to its other bad effects and health hazards. There are thousands of chemical substances in the tobacco and the smoke of its products like cigarette and bidi. Nicotine, tar and carbon monoxide are three most damaging chemical substances present in the smoke of cigarette and bidi. Smoking and chewing of tobacco would affect your metabolism and physiology. Like cocaine and morphine; nicotine causes addiction to tobacco. Cigarette smoking speeds up your heart beat and increases blood pressure. It is major cause of emphysema (chronic obstructive lung disease leading to damage of alveoli), chronic bronchitis, coronary heart disease (CHD) and lung cancer. Carbon monoxide along with nicotine increases the prevalence of heart attack in smokers.

The tar present in the smoke of cigarette or bidi damages the delicate epithelial lining of lungs. The brown and sticky deposit produced by the tar is a cause of lung cancer in smokers. The nicotine content per cigarette has been estimated to 20-30 mg. The carbon monoxide remains in the blood of a smoker for 5-6 hours after he finishes a cigarette and keeps interacting with body metabolites and drugs. The tobacco that is chewed, kept in the mouth or snuffed has equally bad effects. The consumption of tobacco is like ‘slow motion suicide’ due to its bad effects and inimical interaction with large number of drugs taken for various health ailments:


Tobacco has been found to reduce the effectiveness of pain killers (analgesics), anti-asthma drugs, anti-coagulants and drugs used to treat heart ailments. The risk of cardiovascular diseases increases in women taking oral contraceptives.

Immunity and Effect of Emotions

You would find that one is more disease-prone when under stress. Many of us tend to catch eye flu, colds, or viral fever when exposed to prolonged periods of emotional stress or tension. It has been proved experimentally that immunological functions of animals get altered if stressful environments are created. In humans too significant change in lymphocytes' count and function had been documented in subjects whose spouses were died within previous six to eight weeks. Lowered values of cellular and humoral immunity parameters have also been documented in students during examination periods. The science of 'psychoimmunology' has well established experimental models to demonstrate the effect of emotions on immunological parameters. Theoretically, the stress could affect the immune system in two ways; it may suppress the immune system or may make it hyperactive.


The suppressed immune system may invite more viral infections or may flare-up the autoimmune disorders like rheumatoid arthritis. Assessment of links between the emotions and immunity has gained a great clinical importance. Psychological support and counseling in addition to therapeutic measures have been helpful in improving the health of many with autoimmune diseases, allergic asthma, acquired immunodeficiency syndrome (AIDS) etc. You must have observed that many patients visiting overcrowded hospitals get upset seeing a different doctor or attitude of an over busy doctor. The emotional stress of patients in response to doctor’s attitude has been found altering the drug response of patients. The therapeutic treatment in totality needs a balance between the emotions and immunity of a patient for quick recovery.

Geriatric Medicine

Geriatric Medicine was recognized as separate discipline of medicine in the year 1950. When we become old is a big question with multiple answers? It is 65 years of age arbitrarily in majority of the countries of the world. Depending on the physical and emotional state of health, most people above the age of 75-80 years do fall in the category of old. Quality of healthcare measures has changed the global scenario and extended life span is a global feature now. Special efforts are needed to be mounted to ensure the independence of elderly for as long as possible in their family/home environment.

In many countries geriatric medicine has become one of the largest medical specialties in terms of number of consultants. Geriatricians believe that they are more efficient and better trained in the healthcare of elderly patients than the general physicians. You would find that average length of stay of a geriatric patient in a geriatric ward is less than in a general medical ward. The integration of geriatric medicine with other medical services is necessary to provide appropriate medical expertise to elderly patients.

The old age people suffer unduly from incapacitating illness. Many people suffer from a decline in their higher functions when they get old. Personal cleanliness and comfort is must for the old people. We do not yet have geriatric wards for the old in majority of our hospitals, leave aside the specialty of geriatric medicine. Significant age related financial facilities should be made available from the public exchequer for the healthcare of elderly people. The cultural traditions in many nations include the care and respect of elderly people of the family. In early eighties the then Director General of the World Health Organization (W.H.O.), Dr. Halfdon Mahler, quoted the fifth commandment "To honour thy father and mother". The specialty of geriatric medicine needs to be fully developed worldwide to overcome the crisis of old age.

Toxic Effects of Antiworm or Antihelminthic Drugs

There are a variety of antiworm/antihelminthic drugs used to treat worm infestations/infections. Though the effects and side effects of antiworm/ antihelminthic drugs are well evaluated before the clinical trials but the real time toxic effects with respect to age, sex and associated medication of patients should always be kept in mind. For your benefit, toxic effects of some commonly used antiworm/antihelminthic drugs are summarized below.

1. Piperazine:  Piperazine is considered safe and cheap and widely used in large scale treatment programs for roundworm infestations/infections. It acts by producing a neuromuscular block in Ascaris (roundworm) through anticholinergic action at myoneural junction and decrease the succinic acid production by worm. Piperazine is easily absorbed from the gastrointestinal tract. Around 20% of it is metabolized and rest is excreted in the urine. Its mild side effects are: Intestinal discomfort, dizziness, nausea and vomiting may occur occasionally. Over dose can cause urticaria or allergic respiratory reaction. Severe toxic effects could be referable to the 'central nervous system' (CNS) leading to confusional states, inordination, dropping of objects, vertigo, muscular weakness and myoclonic contractions. Severe epileptic seizures have also been reported. Piperazine should not be prescribed to patients with history of epilepsy, renal or liver disease and neurological disease. Use of piperazine should be avoided during the first trimester of pregnancy.
2. Pyrantel pamoate:  Pyrantel pamoate is highly effective broad spectrum antihelminthic. Pyrantel pamoate induces paralysis of roundworms. It is very effective as single dose therapy with moderate side effects. Adverse reactions such as abdominal disturbance, headache and dizziness occur occasionally.
3. Tetramisole:  Tetramisole is very effective against nematodes especially Ascaris lumbricoides or roundworms. It acts by inhibiting the action of enzyme succinate dehydrogenate in the muscles of Ascaris lumbricoides or roundworms, inhibiting the conversion of fumerate to succinate, resulting in paralysis of muscles of worms. Nausea, vomiting, abdominal disturbance, headache and dizziness are minor side effects of tetramisole.
4. Mebendazole:  Mebendazole is extremely effective and well tolerated broad spectrum antihelminthic like pyrantel pamoate. Cure rates of 100% have been documented in the treatment of roundworm infections. Mebendazole inhibit the glucose intake by worms and thus kill them. Mebendazole also kills the ova of nematodes. Only 5-10% drug is absorbed from intestine and excreted in urine as metabolite. Around 90% of drug is utilized to kill the worms in the intestine. Mebendazole is embryotoxic and teratogenic. Its use should be avoided in children below 2 years of age and during pregnancy.

Rational Drug Combinations

The combination of two or more drugs with near about identical plasma half-life, in the same pharmaceutical formulation is termed as 'fixed dose combination' (FDC). The formulation may be in the form of tablet, capsule, syrup, powder or injection. The ratio of dose depends on peak plasma concentration and body mass of the patient. Some of the fixed dose combinations (FDCs) discussed below are 'rational drug combinations' as these have been found advantageous in terms of better therapeutic efficiency, reduced adverse effects, convenience of dose and better patient compliance.

Some rational drug combinations as per WHO's essential drug list and other lists:

1. Amoxycillin + Clavulanic Acid

The combination is indicated in bacterial infections producing b-Lactamase. Amoxycillin is inactivated by b-Lactamase if given alone. Clavulanic acid is b-Lactamase inhibitor and thus restores the sensitivity of Amoxycillin against the b-Lactamase producing bacteria. Escherechia coli, Klebsiella, H. influenzae, N. gonorrhoe, Staphylococci, Proteus, M. catarrhalis and Bacteroid species are known b-Lactamase producing bacteria.

2. Cotrimoxazole (Sulfamethaxazole +Trimethoprim)

Cotrimoxazole is prescribed to treat bacterial infections. We know that a variety of bacteria survive and proliferate in our body by synthesis of folate. Sulfamethaxazole inhibits folate's synthesis while Trimethoprim inhibits dihydrofolate reductase which converts folate
to tetrahydrofolate. Thus the combination is synergistic and potent bactericidal and provides wider spectrum of antibacterial activity. The combinations is a rational drug combination in terms of drug action.

3. Imipenem + Cilastatin

This combination drug is an antibiotic and used to treat bacterial infection. The drugs we take orally or through injection, are exposed to the metabolic enzymes present in our stomach as well as other organs. Imipenem is a broad-spectrum antibiotic but the enzyme dehydropeptidase present in kidney destroys it. The Cilastatin present in the combination inhibits the dehydropeptidase present in kidneys and thus prevents the inactivation of Imipenem.

4. Neomycin + Bacitracin

This combination is used in powder, solution and ointment form to treat bacterial infections of skin, ulcers of mucous membranes, infected wounds and conjunctivitis. Infected dermatosis and infected corneal ulcers are also treated by this rational drug combination.

5. Benzoic Acid + Salicylic Acid

The Benzoic acid is an antifungal agent, very effective in acidic pH. The Salicylic acid is a keratolytic agent, and thus improves the penetration of Benzoic acid and provides additional acidic environment.

6. Sulfadoxine + Pyrimethamine

This FDC is indicated for the treatment of chloroquine resistant falciparum malaria (Plasmodium falciparum) along with quinine therapy or artemisinin therapy. The combination is justified as sulfadoxine inhibits folate synthesis by the malarial parasite while pyrimethamine inhibits the action of dihydrofolate reductase which converts folate to
tetrahydrofolate thus blocks the growth and survival of malarial parasite.

7. Artemether + Lumefantrine

This FDC is indicated for the treatment of chloroquine resistant falciparum malaria (Plasmodium falciparum). One tablet of this combination contains Artemether (20 mg) and Lumefantrine (120 mg). The combination drug is very effective against blood schizonts and prevents relapse of malaria. It has been reported that Lumefantrine is less cardio-toxic drug in
comparison to side effects of halofantrine.

8. Drug Combinations for Anti-Tuberculosis Therapy (ATT)

• INH + Rifampicin


• INH + Ethambutol


• INH + Rifampicin + Pyrazinamide


• INH + Rifampicin + Pyrazinamide + Ethambutol

The treatment of tuberculosis is very critical. Antitubercular drugs are used in combination for better efficacy, to shorten duration of therapy, to prevent emergence of resistant organisms and for better patient compliance.

Important Tips:

i.) During intensive care phase, 3-5 drugs are used for 2-3 months. These drugs reduce bacterial load, ameliorate the acute symptoms and make patient non-contagious.

ii.) During continuation phase, 2 or 3 drugs are used for 4-7 months. These drugs kill all the persisters and thus sterilize all the organ and tissues.

iii.) Complete cure of tuberculosis should be ensured to prevent relapse.

9. Drug Combinations for Anti-retroviral Therapy (ART)

• Zidovudine + Lamivudine


• Zidovudine + Lamivudine + Navirapine


• Stavudine + Lamivudine + Navirapine


• Emtricitabine + Tenofovir


• Efavirenz + Emtricitabine + Tenofovir


• Lopinavir + Ritonavir

These are highly active antiretroviral drugs used in the treatment of AIDS (HIV infection). Antiretroviral drugs are combined to prevent resistance, limit toxicity and for synergistic effect. There are four groups of antiretroviral drugs depending on their anti-viral actions as:

• Zidovudine, Lamivudine, Stavudine and Emtricitabine are nucleoside reverse transcriptase inhibitors (NRTIs).


• Navirapine and Efavirenz are non nucleoside reverse transcriptase inhibitors (NNRTIs).


• Tenofovir is very effective nucleotide reverse transcriptase inhibitor.


• Lopinavir and Ritonavir are protease inhibitors (PIs).

10. Ethinyl estradiol + Norethisterone

Used for female contraception as FDC pill from 5^th day of menstrual cycle for 21 days.

Justified role of ingredients in combination:

Estrogen (Ethinyl estradiol) and progesterone (Norethisterone) by exerting negative feedback over the pituitary gland, reduce the secretion of Follicle Stimulating Hormone (FSH)
and Luetinizing Hormone (LH). In the absence of LH, the ovulation does not occur and the ovulatory cycle becomes an anovulatory cycle. Estrogen with progesterone make endometrium unfit for implantation of ovum. Progesterone ensures withdrawal bleeding after stoppage of medication. Progesterone also prevents risk of endometrial carcinoma due to estrogen (if used alone as contraceptive).

11. Lignocaine + Adrenaline

This is used as local anesthetic in the ratio of 1:50,000 - 1:200,000. The combination drug is administered for infiltration anesthesia, nerve block, spinal anesthesia and epidural anesthesia.

Justification for the combination:

i.) Adrenalin is a vasoconstrictor, so it reduces the absorption of Lignocaine and prevents its early clearance.

ii.) Adrenalin prolongs duration of action of local anesthetic, reduces its toxicity and provides almost blood less zone for the surgery.

Limitations:

This combination is not indicated for anesthetizing organs and tissues supplied by end arteries. So, ear lobes, finger tips, toes, nose tip and penis should not be anesthetized with this combination anesthesia.

12. Glucose (5%) with Saline (0.9%)

This glucose saline fluid is used as intra-venous maintenance fluid for dehydration. Dextrose provides energy and saline covers the deficiency of sodiumand chloride in extracellular compartments.

13. Acriflavin + Glycerin

Acriflavin in glycerin is used as anti-infective agents for dressing the wounds, cuts, ulcers, burns and umbilical cord.

14. Aluminium Hydroxide + Magnesium Hydroxide

This rational drug combination is used in hyperaciditym peptic ulcer, upper GI bleeding and gastro-esophageal reflux disease (GERD) to neutralize gastric acid.

Advantage: Aluminium hydroxide causes constipation but Magnesium hydroxide causes diarrhoea if used alone. So, the combination would not cause any intestinal upset.

15. Metronidazole + Diloxanide Furoate

Metronidazole is a pan-amoebicidal drug to which Diloxanide Furoate is added to make it effective to kill the cysts also. The combination drug is used in the management of amoebiasis.

16. b₂-Agonist + Inhaled Corticosteroid

• Salbutamol + Beclomethasone


• Formeterol + Budesonide

Salbutamol and Formeterol are b₂ -agonists and cause bronchodilation. Inhaled corticosteroid (Beclomethasone or Budesonide) helps to control the bronchial asthma by its anti-inflammatory and immunosuppressive action.

Irrational Drug Combinations !

When two or more drugs are combined in a fixed dose formulation like tablet, capsule, syrup, powder or injection, then their plasma half-life should approximately be same. The ratio of dose would depend on the volume of distribution and peak plasma concentration. If the combination of drugs is illogical in terms of plasma half-life and pharmacokinetics of the drug, the combination should be termed as irrational drug combination. Large number of such irrational drug combinations are available in the market which unnecessarily increase the cost of medication and add to the side effects of the therapy. Some of these combinations have been discussed below:

1. Ampicillin + Cloxacillin:

Ampicillin is effective against Gram negative bacilli but Cloxacillin is an Anti-staphylococcal penicillin and not effective against Gram negative bacilli. Mixed Gram negative and Staphylococcal (Gram positive) infection rarely coexists. So, in a patient with a single infection, one of the drug of the combination would be useless. In addition to the cost of therapy it would add to adverse side effects and resistance of bacteria to the drug. On the other hand the combination would reduce the dose of effective drug to the half and the patient would need longer course of therapy.

2. Antibacterial + Antiamoebic Combinations:

Ciprofloxacin + Metronidazole, Norfloxacin + Tinidazole and Ofloxacin + Ornidazole are such commonly available fixed dose drug combinations. In bacterial diarrhoea only anti bacterial drug is effective and antiamoebic drug is useless. Similarly, in intestinal amoebiasis only antiamoebic drug is effective while antibacterial drug is useless. Amoebiasis and bacterial diarrhoea rarely coexist. The therapy should be based on the diagnosis to reduce the cost of treatment since in a given case, only one drug of the combination would be effective and the other one would be useless.

3. NSAIDs Combinations

Nimesulide, diclofenec, ibuprofen and paracetamol are some non-steroidal anti-inflammatory drugs (NSAIDs). There is no justification in combining one NSAID (nimesulide, diclofenec, ibuprofen) with another NSAID (paracetamol) having same pharmacological actions. The increased risk of hepatotoxicity has been reported due to the use of combination of nimesulide with paracetamol. There is increased risk of nephrotoxicity with NSAIDs combinations.

4. H₂ Blocker + Domperidone

Ranitidine and Famotidine are H₂ blockers. H₂ blockers reduce gastric acid production in peptic diseases and give symptomatic relief. The combination of these drugs with antiemetic drug (Domperidone) is an irrational drug combination as peptic ulcer is not always associated with vomiting. Even in gastro-esophageal reflux disease (GERD), the domperidone is less effective as compared to metoclopramide, so combining H₂ blockers with domperidone seems to be an irrational choice.

5. Domperidone + Proton Pump Inhibitors

Omeprazole, Pantroprazole and Lansoprazole are proton pump inhibitors. Proton pump inhibitors reduce gastric acid production in peptic diseases and give symptomatic relief. The combination of these drugs with antiemetic drug (Domperidone) is an irrational drug combination as peptic ulcer is not always associated with vomiting. Even in gastro-esophageal reflux disease (GERD), the domperidone is less effective as compared to metoclopramide, so combining proton pump inhibitors with domperidone seems to be an irrational choice.

6. Ondensetron + Proton Pump Inhibitor or H₂ Blocker

Such combination drugs are prescribed for the acid peptic disease, but the disease is not always associated with vomiting. So, the combination of Ondensetron, an antiemetic drug with antisecretary drugs like H₂ blocker (Ranitidine) or proton pump inhibitor (Omeprazole, Pantoprazole or Lansoprazole) seems to be an irrational drug combination.

7. H₂ Blocker (Ranitidine) + Antispasmodic Drug (Dicyclomine)

The pain of peptic ulcer is due to high level of gastric acid but not due to spasm of smooth muscles and will subside only with reduction in gastric acid in stomach by use of H₂ blocker (Ranitidine) or proton pump inhibitor drugs (Omeprazole, Pantoprazole or Lansoprazole). So there is no justification in combining H₂ blocker (Ranitidine) with antispasmodic drug (Dicyclomine).

8. Antacid + Antianxiety Drug

The acid peptic disease is rarely associated with psychosomatic basis. So, there is no justification of combining antianxiety drug like diazepam with antacids. The simultaneous use of antacids with antianxiety drugs should always be avoided as antacids reduce the absorption of antianxiety drugs.

9. Antacid + Antispasmodic Drug (Dicyclomine)

There is no justification in combining antacids with antispasmodic drug like Dicyclomine, because the pain of peptic ulcer is not due to the spasm of the smooth muscles.

10. Mucolytic Agent + Antibacterial

Ambroxol + Ciprofloxacin or Cefadroxil or Roxithromycin. Ambroxol is a mucolytic agent used to liquefy thick respiratory secretions. There is no justification in combining mucolytic agent with antibacterial, as thick secretions in respiratory tract are always not due to respiratory infections. Also the antibacterial therapy always does not require an associated dose of mucolytic agent

11. Mebendazole + Pyrantel-pamoate or Levamisole

Dosages' schedule of both the drugs mismatch so the combination of such two anthelminthic drugs is irrational. The Mebendazole is required to be administered twice a day for three days whereas Pyrantel-pamoate or Levamisole should be administered as a single dose.

12. Leukotrine Antagonist (Montelukast) + Bambuterol or Levocetirizine

Montelukast, the leukotrine antagonist is used as alternative to inhaled steroid in the management of mild persistent asthma. Levocetirizine is an antihistaminic drug and has limited role in the control of asthma as it is not only histamine that triggers the asthma attack. Bambuterol is a long acting beta-2 agonist having role in the management of moderate persistent asthma as well as severe persistent asthma. There is no justification in combining of Montelukast with Bambuterol or Levocetirizine.

13. Metformin + Glimeperide + Pioglitazone

Metformin is indicated drug in obese type -2 diabetes mellitus whereas Sulfonylurea (Glimeperide) is indicated drug in non-obese type-2 diabetes mellitus. As per pharmacological principle, other drug should be added only when monotherapy fails. Metmorfin (biguanide) is to be administered after meal whereas Glimeperide (sulfonylurea) drug is to be administered before meal, therefore even when both the drugs are required, it would be better to administer them separately. Pioglitazone is indicated in suspected cases of insulin resistance. So, the combination of all these drugs in one formulation is an irrational drug combination.

Common and Serious Side Effects of Vaccines !

Vaccines are for preventing disease but any vaccine can cause side effects. The risks of use of immunization are adjudged to be acceptable in relation to the benefits and safety during the life. Majority of the vaccines have minor side effects like low grade fever, pain at the site of administration and sore arm, but sometimes there can be severe and life threatening anaphylactic reactions. Almost half of the persons experience fever after the administration of vaccines. The fever may be around 100^oF. Pain, redness, swelling and itching around the site of administration are common with injectable-vaccines. Muscle pain and tiredness are also commonly seen. The minor and common side effects usually subside within a few days and respond well to common antipyretics and analgesics. Cooling the injection site and topical application of lignocaine emulsion is generally recommended for decreasing pain. Some less common side effects like headache, nausea, vomiting and mild rash are also seen with most of the vaccines. The rota virus vaccine may cause self limiting diarrhoea.

Rare and serious side effects of vaccines:

Vaccines like MMR, MMRV, Hib and HPV can cause high grade fever (>100^oF) in some cases. The fever has to be controlled quickly and effectively by antipyretics and cold sponging to prevent febrile seizures. In some adolescents, fainting episodes have been reported after administration of HPV, H1N1-inactivated influenza vaccine and MCV_4 (meningococcal vaccine). Arthralgia and Arthritis have been reported in young women after administration of MMR vaccine. Rabies vaccine may also cause arthralgia and arthritis in around 6% cases. Thrombocytopenia (low count of platelets in blood) has also been reported with MMR, varicella vaccine and Yellow fever vaccine. The most serous side effect of Yellow fever vaccine is multi-organ failure or viscerotropic reaction. The varicella vaccine may also cause pneumonia. The BCG vaccine has been reported to cause disseminated tuberculosis and regional adenitis in immnocompromised people. Oral Polio Vaccine (OPV) can cause paralytic polio if administered to already ailing infant/child. The BCG vaccine has also been reported to be associated with the development of Type-1 and Type-2 diabetes mellitus with metabolic syndrome. Life threatening, anaphylactic reactions have been reported with anti-viral vaccines probably due to egg protein of embryonated eggs used to grow various viruses.

Important tips:

• Live vaccines should not be given to pregnant women as there are chances of risk of active disease to the fetus.


• Live vaccines are also contraindicated in patients on immunosuppressive therapy as the risk of developing active disease is there.


• Breast feeding mothers should also not be administered live vaccines and small pox vaccine.


• General health status of infants and children should be assessed before administration of a vaccine.

Why vaccination is necessary ?

The World Health Organization (WHO) is concerned for the world's health and always put emphasis on the availability and supply of clean drinking water and immunization or vaccination. The word vaccine is of Latin origin. The word vacca in Latin means cow. The word vaccine was coined from vacca because Edward Jenner first used fluid from the cowpox to prevent smallpox. Though the word vaccination and immunization are interchangeable but don't mean exactly the same. The administration of vaccines could be called vaccination but the immunization is the induction or acquiring of immunity by using pharmacological agents other than vaccines too. Immunization may be active (production of antibodies after administration of antigen or vaccine) or passive (administration of readymade/preformed antibodies). Vaccination is the active immunization. Vaccination may not provide active immunity to all the individuals. Under the Universal Immunization Programme (UIP) launched by WHO in 1985, free vaccination is available for tuberculosis, diphtheria, pertussis (whooping cough), tetanus, poliomyelitis and measles. The vaccines for these six vaccine-preventable diseases should be administered as per WHO schedule for UIP. The vaccination is necessary for healthy human race all over the world. By timely vaccination we can save our younger generations from major disabling and fatal diseases. Vaccines are considered safe when the side-effects of use are judged to be acceptable in relation to the benefits.

Risks for a Pregnant Smoker !

The period of gestation, number of pregnancy and general health of a pregnant woman with smoking habit are the important factors which could influence the effect of smoking on the unborn baby. When a pregnant woman smokes, her unborn baby does the same. The carbon monoxide and nicotine are passed onto unborn baby through blood stream. The maternal blood laced with nicotine and enriched with carbon monoxide lessens the oxygen supply and accelerate the heart beat of unborn baby. The child is likely to be premature or under weight. The growth of the toddler would be affected and the child may be more susceptible to infectious diseases. The chances of spontaneous abortions and still-births are three times more in pregnant smoker as compared to non smoker pregnant. The risks are more pronounced in pregnant smokers with anemia and poor nutrition.

A non-smoker pregnant woman, whose husband smokes, would be having identical risks for her unborn baby. In fact a non-smoking wife of a smoker husband thus becomes a non-smoking smoker or passive smoker. Pregnant smokers and the husbands of non-smoker pregnant women should quit smoking for the better outcome of pregnancy and the health of their baby. Excessive smoking during first trimester of pregnancy may lead to abortion. Primigravida women ( women with first pregnancy) would be at more risk as compared to multigravida due to pregnancy associated physiological and metabolic changes as well as psychological and emotional factors.

Tobacco – An addiction forming drug and its implications

A doctor who smokes today must be a fool. There are many medical men who have not made much effort to give up smoking habit though they full knowledge of harmful effects and consequences of smoking. The role of tobacco in producing morbidity and mortality is well known. It is we proved that cigarette smoking is related with higher risk of lung cancer, ischemic heart disease, emphysema and chronic bronchitis. The risk of young one suffering from pneumonia and bronchitis is much higher if the parents smoke. The children of smoking parents also develop the habit of smoking.

Cigarette smoking carries special risks for women. Smoking during pregnancy has been observed to retard fetal growth. The habit may also lead to genetic disorders in babies born to smoker mothers. Spontaneous abortion rate is higher in women who smoke. However, outcome of pregnancy is not affected if smoking is given up as early as possible after conception. Smokers are more susceptible to infectious diseases also. There are many chemical substances in the smoke of cigarette and biri, but nicotine, carbon monoxide and tar are most harmful and hazardous for health. The tobacco that is not smoked but chewed or left in the mouth or snuffed is called smokeless tobacco. Smokeless tobacco is no alternative to smoking and is equally harmful. Chewable tobacco leads to tooth decay and mouth cancer.

A smoker who can not quit smoking is essentially an addict. Youngsters develop tobacco addiction during pre-teen years as they are not aware of its harmful effects and consequences. Youngsters fall prey to seductive advertising and sales promotion drives. More than one billion kilograms of tobacco is produced and consumed world wide every year. Around 40% of males above the age of 15 years smoke cigarettes or chew or eat tobacco. Around 3 million people die of tobacco-related diseases, worldwide yearly. The incidence of cancer of mouth, esophagus and the pharynx is 10 times higher in smokers as compared to non-smokers. Biri smoking carries a higher risk of lung cancer than cigarette smoking due to higher amount of tar sucked by the smokers.

Tobacco reduces the effectiveness/efficiency of a wide range of drugs used for the treatment of various ailments. The efficiency of analgesics, anti-asthmatic and anti-coagulants has been found to be reduced. Cigarette smoking increases the risk of cardiovascular diseases in women taking oral contraceptives. Female smokers are at higher risk if their blood pressure and cholesterol levels are high. Be determined to quit smoking for the sake of your own health and for the health of your family. Smoking is a slow-motion suicide attempt. If you are not able to quit smoking through determined will power, consult your physician and take de-addiction therapy and counseling.

Can we eradicate smoking ?

The smoking habit is not natural but acquired one as one has to learn smoking. How does one get initiated to smoking ? Social influence such as parental example, sibling, friends' pressure and motivation by industrial promoters, initiate youth to smoking. Seductive tobacco advertisements by the cigarette manufacturers play a vital role in the initiation of new smokers. The tobacco industry is very powerful the world over. Tobacco industries spend US$ 25-30 billion every year to promote smoking as they need to add 2-3 million new smokers every year to run their business successfully. The smoking is an addictive habit and the danger posed by use of tobacco is not recognized by most of smokers as well as governments the world over. Non-smokers also suffer because of contaminated atmosphere.

Nicotine is the active agent behind the drug dependence of tobacco. A smoker experiences withdrawal symptoms after considerable time and gets stimulation through smoking. Habits can not be checked by force but through determination and medical and psychological counseling. Can we eradicate smoking ? Yes, probably we can eradicate smoking with political determination, public participation and community counseling. Tobacco perhaps is the more abused drug than alcohol but less dependence inducing. The cultural, commercial and economical factors are involved in addiction to cigarette (or biri) smoking. There is a need for strong governance and policies to bring social transformation to eradicate smoking.

Lithotripters, Stones and Lithotripsy

Stones in kidneys, urinary tract, urinary bladder and gall bladder could be treated with open surgery, percutaneous laproscopic surgery or lithotripsy. Treatment of stones in organs with drugs is of limited scope. A lithotripter is an instrument which breaks up stones in situ by shockwaves, which are focused on them. There are a variety of lithotripters available worldwide. Kidney stones or renal calculi are effectively treated with extracorporeal shockwave lithotripsy (ESWL), though sometimes percutaneous nephrolithotomy (PCNL) or open surgery is also required to remove renal stones. The lithotripsy treatment is said to be successful if stones are eliminated or reduced to <2 mm size. Comparative total cost of treatment by lithotripsy is almost half than by open surgery. ESWL has its own advantages as there is no blood loss and very little morbidity. Extracorporeal shockwave lithotripsy (ESWL) is the cheapest and quickest way of returning patient to normal life.

Extracorporeal shockwave lithotripsy is the best option as a mono-therapy for a medium-size stone (1-2 cm). However, for larger and stag-horn type stones, the best results could only be achieved by multi model approach. After nephrolithotripsy, the fragments of stones are expected to be passed in the urine within about 3 months time. The success rate varies with the size of stones but is always above 80% with ESWL and >90% for percutaneous nephrolithotomy (PCNL). Depending on the location, volume and composition, ureteral and kidney stones need endoscopic treatment via uretero-renoscopy (URS) and/or percutaneous nephrolithotomy.

Childcare and Hospitals for Children

Children constitute around 40% of the world population. Pediatric medicine is a broad specialty embodying all the organ specialties of adult medicine such as cardiology, dermatology, endocrinology, gastroenterology, hepatology, neurology, pulmonology, rheumatology etc. Pediatric surgery and its specialties also make a list as long as in the case of adults' specialties. All hospitals worldwide do have pediatric departments but special hospitals for sick children could provide better care of children by child specialists or pediatricians. The childcare begins at birth with mandatory vaccination planning which could be handled well by specialized vaccinologists. Vaccination and preventive medicine should be allocated special funds, as that would be an investment for the children's welfare and community health. All the countries and states on this earth should have special hospitals for children since childcare is the foundation of a healthy nation.

Usage of Antibiotics in Pediatric Practice

Antibiotics are very potent weapon to kill a variety of bacteria, but should be used judiciously to avoid life threatening complications. Attempts to treat symptoms of infections without identifying the bacteria or site of infection could be very harmful in infants and children. Selection of antibiotic and its optimal use is the key to effective treatment. There is a need to understand the pharmacologic principals to select an antimicrobial agent and to avoid allergic reactions and toxicity in the patient being treated. The penetration and diffusion of antibiotics in various tissues and spaces should be taken into account while deciding the dose and mode of administration of an antibiotic. All antibiotics cannot treat pyogenic meningitis and purulent exudates. Antibiotics could be classified into three groups for treatment of infectious agents in infants and children:-

1. Penicillins: Ampicillin, amoxicillin, penicillinase, penicillin G &V.
   
2. Alternative of penicillin for patients allergic to penicillin: Cotrimoxazole, erythromycin, tetracyclines, lincomycin etc.
   
3. Antibiotics effective against Gram-negative bacteria: Gentamycin, kanamycin, tobramycin, amikacin etc.
   

Situations where antibiotics should be avoided:

1. Viral infections: Usually viral infections are self limiting and the patient may recover within a week's time. Use of antibiotics for the treatment of chickenpox, measles, mumps and viral URI (upper respiratory infection). However, antibiotics may be helpful in controlling/preventing secondary bacterial infections during viral infections.
   
2. Treatment of pyogenic exudates without surgical drainage: Extensive use of antibiotics to treat purulent exudates without surgical drainage should be avoided since the infection will not come under control without drainage.
   
3. Improper dosage: Both the suboptimal and large doses of antibiotics are harmful and should be avoided.
   
4. Prophylactic use of antibiotics: Antibiotics should be used to treat established disease only and not as prophylactic therapy to prevent infection in patients/children at high risk. However, chemoprophylaxis is helpful in preventing the spread of singe microorganism with single drug but to use multiple antibiotics for prophylaxis could be hazardous.
   

Usage of Steroids in Pediatric Practice

A child is not a compressed or mini man, so the method of scaling down the adult dose of a drug on the basis of body weight is not an accurate method for treating children. The pediatric pharmacology is a complex science since the drug requirements of neonates, older infants and children are quite different from adults due to difference in the absorption, biotransformation and renal excretion of drugs. Steroids are the most important drugs discovered after antibiotics. Though the steroids are not actual therapy but they provide immediate symptomatic relief. Steroids have been used both for their systemic action as well as topical actions. Steroids should not be misused and used only when indicated. Proper doses are very important for effective therapeutic effect.

In pediatric practice systemic use of steroids is indicated in many conditions. Three major dose related categories for systemic use of steroids are: (1) Replacement Therapy, (2) Therapeutic Doses (For treating hematological, renal and immunological disorders) and (3) Massive Doses (For treating hematological and renal disorders).

1) Steroids as replacement therapy:

Use of steroids as replacement therapy in congenital adrenal hyperplasia (CAH) and Addison's disease is very much indicated. The CAH is caused due to deficiency of 21-hydroxylase, so that 17-hydroxy progesterone is not converted into cortisol but is converted into adrenal androgens. Female babies with congenital adrenal hyperplasia (CAH) will be having ambiguous genitalia and male babies will show precocious puberty. The patients with CAH may also have mineralocorticoid deficiency. The other common type of CAH is represented by 11-hydroxylase deficiency and these patients are hypertensive and have masculinized looks. Both types of patients with CAH need replacement therapy with prednisolone (5mg/m² body surface area in two divided doses) or cortisone (20mg/m²body surface area in three divided doses). The dose of steroid is monitored by the estimation of 17-ketosteriod excretion, skeletal maturation and growth rate.

2) Therapeutic doses of Steroids :

Use of steroids is extremely indicated for treating hematological, renal and immunological disorders.

1. Use of Steroids in Hematological Disorders: Steroids have important role in the treatment of acute lymphatic leukemia, idiopathic thrombocytopenic purpura (ITP). Remission of acute lymphatic leukemia can be achieved with prednisolone (40mg/m² body surface area) within 4-6 weeks. However, success rate is around 80%. A success rate of around 95% is achievable if prednisolone is combined with Vincristine. In acute ITP steroids are the drug of choice to save life and are administered at a dose of 1-2mg/kg body weight for about 3 weeks or till the platelet count improves. Around 25% of patients may develop chronic ITP and may need steroid therapy (on alternate days) for about 3-6 months.
   
   


2. Use of Steroids in Renal Disorders: Treatment of nephrotic syndrome with steroids shows remarkable results. Prednisolone is given at a dose of 2mg/kg body weight daily for 4 weeks and the same dose is given at alternate days for another 4 weeks. Around 60-65% of patients show significant response in 4 weeks another 20-25% of cases will go into remission within 8 weeks of treatment. Around 8% cases may require prolonged treatment, while 3-5% may need other modes of therapy.
   
   


3. Use of Steroids in Immunological Disorders: Steroids remain the therapy of great importance in the treatment of Lupus nephritis, SLE, dermatomyositis, polyarteritis nodosa. Prednisolone is given at a dose of 2mg/kg body weight till the remission and then tapered off to minimum maintenance dose.
   
   


4. Use of Steroids in other diseases: Severe cases of asthma and status asthmaticus, where bronchodilators alone fail to control the disease; treatment with hydrocortisone and prednisolone is indicated. Steroids have been found to be useful in the treatment of ulcerative colitis. Acute cases of ulcerative colitis can be managed well with retention enema with steroids.
   
   

3) Massive Doses:

Massive doses of steroids are administered in patients affected by endotoxic shock. In these cases, steroids decrease the peripheral resistance, increase tissue perfusion and venous return. Such cases need Hydrocortisone in doses of 50-100mg/kg body weight initially and there may be need to repeat the dose 4-6 hourly for 24-48 hours. In 'rapidly progressive glomerulonephritis' (RPGN) and 'idiopathic apastic anemia' remarkable results have been achieved with higher doses of methyl prednisolone.

Understanding Drug Action, Interaction and Reaction

Monitoring of physical, cellular, biochemical, immunological and psychological parameter during the course of any drug therapy imparts us valuable information regarding drug action (expected relief), interaction (action in association dietary items and other drugs) and reaction (adverse effect of the drug or adverse drug reaction or ADR). Let us take the treatment of psoriasis, a chronic, immunological and inflammatory disease of skin for understanding drug, action, interaction and reaction. Psoriasis presents with erythematous, scaly (pustular) or indurated plaques over the extensor aspects of limbs, trunk, head and face and is widely treated with acitretin (synthetic aromatic analogue of retinoic acid).

Action of acitretin:

Systemic treatment with acitretin promotes cellular differentiation of epidermis and decrease proliferation rate in psoriatic plaques. It also exerts anti-inflammatory effect by modulating lymphocyte functions and inhibition of neutrophil migration. Psoriatic inflammation generally subsides within 6-12 weeks' period of treatment with acitretin. It is indicated for the treatment of moderate to severe psoriasis in adult patients. Pregnancy should be ruled out in female patients and they should be advised to use effective contraception at least for a period of three years to avoid pregnancy.

Interactions of acitretin:

• Acitretin interferes with the contraceptive action of minipill contraceptives and may result in failure of contraception.


• Use of alcohol during acitretin treatment should be avoided as ethanol converts acitretin to etretinate and thus prolongs clearance of acitretin.


• There is a risk of hypervitaminosis-A if acitretin is given along with vitamin-A.


• Risk of hepatitis increases if acitretin is administered in combination with methotrexate.


• Use of tetracyclines or its derivatives should be avoided in patients on acitretin therapy as there are chances of development of pseudotumor cerebri.


• Acitretin may decrease night vision, so patients should be advised to avoid driving at night.


• Acitretin should not be used in lactating mothers as it is excreted in the breast milk and may harm the baby as the drug is teratogenic.


• Acitretin sensitizes the skin to UV light so patient should be advised to avoid excessive exposure to sunlight.

Adverse drug reactions:

• Use of acitretin is contraindicated in pregnancy and during lactation. Fetal deformities like dysmorphia and cardiovascular malformations have been reported with the use of acitretin and/or etretinate.


• The drug has teratogenic.


• Commonly encountered adverse effects with acitretin are mucocutaneous effects like chelitis, xerosis, rhinitis, skin peeling over palms & soles, nail dystrophy, and hair loss.


• Dryness and irritation of eyes.


• Use of tetracycline or minocycline along with acitretin may lead to the development of pseudotumor cerebri.