Rabu, 29 Februari 2012

Why You Should Consider Pharm.D Programs


Different people have different career dreams. Just like any other career, pharmacy is not as easy as it seems. This is especially considering the fact that you will have to work really hard first before you can get your degree. Nevertheless, it is correct to say that every moment of it is worth your effort. This is because pharmacy offers you a wide range of career opportunities in the different health sectors.
Pharm.D simply refers to a six year doctorate program in pharmacy. Different countries have different policies and in some countries this is considered as a first professional doctorate degree in pharmacy and the grandaunts can be given the license to exercise their profession. The health care industry is very vital. A doctor of pharmacy is intended to prepare the students for different responsibilities as pharmaceutical care, research, pharmaceutical science and health policy and management among others.
With the many job opportunities contracted for this career, it is correct to say that the Pharm.D programs are one of the most marketable syllabuses globally. Positions are usually available in research facilities in different universities, hospitals, pharmaceutical companies, government agencies and advisory boards among many other places. Such programs will usually differ from the regular PhD which is usually theoretical to a research based degree.
You can get your doctorate in pharmacy from the different universities across the globe. While a simply degree in pharmacy is acceptable, today, more and more people would prefer to graduate with a Doctors in pharmacy especially due to the tight competition in the career opportunities available.
A Pharm.D degree is intended to equip you with all the knowledge necessary for any pharmaceutical field of practice. What is more, students are also endowed with the necessary health care skills which are going to come in handy once they start practicing.
by
Akshaya Srikanth
Pharm.D Internee
Hyderabad, India

Understanding and Management Of ECG


Clinical uses of ECG
Gold standard for diagnosis of arrhythmias                                               
Often an independent marker of cardiac disease (anatomical, metabolic, ionic, or haemodynamic)                    
Sometimes the only indicator of pathological process
Limitations of ECG
It does not measure directly the cardiac electrical source or actual voltages
It reflects electrical behavior of the myocardium, not the specialised conductive tissue, which is responsible for most arrhythmias
It is often difficult to identify a single cause for any single ECG abnormality
Cardiac Electrophysiology
Cardiac cellular electrical activity is governed by multiple transmembrane ion conductance changes
3 types of cardiac cells
Pacemaker cells     - SA node, AV node
Specialised conducting tissue-Purkinjie fibres
Cardiac myocytes 
Cardiac Ion Channels
They are transmembrane proteins with specific conductive properties
They can be voltage-gated or ligand-gated, or time-dependent
They allow passive transfer of  Na+, K+, Ca2+, Cl- ions across cell membranes
Cardiac Ion Channels: Applications
Understanding of the cardiac action potential and specific pathologic conditions
e.g. Long QT syndrome                        
Therapeutic targets for antiarrhythmic drugs 
e.g. Azimilide (blocks both components of delayed rectifier K current)
Mechanisms of Arrhythmias
Important to understand because treatment may be determined by its cause
1.Automaticity
Raising the resting membrane potential
Increasing phase 4 depolarization
Lowering the threshold potential
e.g. increased sympathetic tone, hypokalamia, myocardial ischaemia
2.Triggered activity    
from oscillations in membrane potential after an action potential
Early Afterdepolarization
Torsades de pointes induced by drugs
Delayed Afterdepolarization
Digitalis, Catecholamines
3.Re-entry
from slowed or blocked conduction
Re-entry circuits may involve nodal tissues or accessory pathways

Selasa, 28 Februari 2012

Be Aware of Rabies Disease

 Rabies is a viral disease. The virus travels from the site of entry (the bite or scratch) via the nerves to the brain and spinal cord and eventually spreads to the salivary glands. In humans, once symptoms have developed it is invariably fatal (there are reports of one or two people surviving once symptoms had developed). Symptoms may start with itching or tingling at the site of the bite or scratch. These may then develop to include headache and fever progressing to paralysis, agitation, spasm of the muscles used for swallowing, delirium and convulsions.
Symptoms
The incubation period for rabies is typically 1–3 months, but may vary from <1 week to >1 year. The initial symptoms of rabies are fever and often pain or an unusual or unexplained tingling, pricking or burning sensation (paraesthesia) at the wound site.
As the virus spreads through the central nervous system, progressive, fatal inflammation of the brain and spinal cord develops.

Two forms of the disease can follow. People with furious rabies exhibit signs of hyperactivity, excited behaviour, hydrophobia and sometimes aerophobia. After a few days, death occurs by cardio-respiratory arrest.
Paralytic rabies accounts for about 30% of the total number of human cases. This form of rabies runs a less dramatic and usually longer course than the furious form. The muscles gradually become paralyzed, starting at the site of the bite or scratch. A coma slowly develops, and eventually death occurs. The paralytic form of rabies is often misdiagnosed, contributing to the underreporting of the disease.
Diagnosis
No tests are available to diagnose rabies infection in humans before the onset of clinical disease, and unless the rabies-specific signs of hydrophobia or aerophobia are present, the clinical diagnosis may be difficult. Post mortem, the standard diagnostic technique is to detect rabies virus antigen in brain tissue by fluorescent antibody test.
Transmission
Rabies can be transmitted in a number of ways to humans. Dog bites are by far the most common source of infection—though mostly in undeveloped countries where vaccination programs are not in place. A scratch to the skin, a lick on a fresh skin break or contact of the infected saliva with intact mucous membranes may also transmit rabies. Cats, bats, foxes, skunks, raccoons, monkeys and many other animals can be infected with this virus. Animals may be infectious for five days before they develop symptoms. More unusual routes of infection have also been documented. Aerosol transmission has been reported in a bat infested cave in South America and corneal transplants taken from undiagnosed rabies sufferers have also transmitted this infection to others. 
The incubation period for rabies in humans varies from 4 days to 7 years (usually between 20–90 days). The size and location of the bite or scratch, ie, proximity to the brain and the richness of the nerve supply to the area are thought to be important factors that influence the length of the incubation period. A deeply penetrating bite to the face or neck is likely to cause problems quicker than a scratch to the ankles.
Treatment and Prevention
Thoroughly cleanse all bites with soap and water and do not allow the wound to be stitched. Limited bleeding should be encouraged. Apply alcohol if possible. Once symptoms develop, death is inevitable in all cases. There is no cure. However, the disease can almost always be prevented, even after exposure, if rabies vaccine is administered without delay. Travelers should seek one of the modern cell culture vaccines. These can be difficult to obtain abroad. Some countries are using less effective locally produced vaccines that have to be administered into the abdomen; these are best avoided where possible. Travelers who have had a full course of pre-exposure vaccines still need to seek post exposure vaccines if they are bitten. However, they should only need two vaccines over 2 days and they will not need the human rabies immunoglobulin (HRIG) injection (HyperRAB S/D), which is in short supply in many countries. Those who have not had any pre-exposure vaccines or had an incomplete course of vaccine before travel should be given five post-exposure vaccines over 28 days plus the human rabies immunoglobulin (HRIG). 
The antibody response to the first post exposure vaccine is expected to be rapid in those who have been “primed” with any rabies vaccines before they travel (even if they have not had a full 3 dose course). As the incubation period of the disease can in rare circumstances be as short as 4 days, the vaccines should always be sought as soon as possible. However, as the incubation period can be as long as several years in exceptional circumstances, it is still worthwhile getting vaccines if you were bitten in a risk area some time ago. 
Never approach or handle animals you don't know, particularly if they are acting strangely. Pre-exposure immunization against rabies is recommended for long-stay travelers/residents and those who intend to travel to rural and remote areas in areas where rabies is common. In the event of a bite, your body's responses could be quickly activated by booster doses of vaccine. A full course of pre-exposure vaccines is three doses given on Days 0, 7 and 21–28. All travelers to risk areas should know what to do if they are bitten.
FIRST AID TREATMENT
Effective treatment soon (within a few days, but as soon as possible) after exposure to rabies can prevent the onset of symptoms and death.
Post-exposure prevention consists of local treatment of the wound, administration of rabies immunoglobulin (if indicated), and immediate vaccination.
Local treatment of the wound
Removing the rabies virus at the site of the infection by chemical or physical means is an effective means of protection. Therefore, prompt local treatment of all bite wounds and scratches that may be contaminated with rabies virus is important. Recommended first-aid procedures include immediate and thorough flushing and washing of the wound for a minimum of 15 minutes with soap and water, detergent, povidone iodine or other substances that kill the rabies virus.
Please watch this video
                                           
by
Akshaya Srikanth
Pharm.D*
Hyderabad, India
Please feel free to share your comments for my handwork

Senin, 27 Februari 2012

Career options for those with a degree in pharmacy

Most of us think of pharmacists as the persons who are behind the counter when we go to a drug store with a prescription. While retail pharmacy is a common career choice for pharmacists, there are many other options available to those who have completed their Pharm.D degree and the necessary licensure requirements. Although there are a variety of practice settings, compensation remains relatively consistent across all of these employment options with minor variations according to hours of work and call.
Here are the some career options in this field:
Retail Pharmacy/ Chemists 
A pharmacist in medical retail store prepares and dispenses drugs on prescription to the general consumer. With the growing availability of pre-packaged doses, the pharmacists now monitor the drug sale on the basis of prescriptions and dosage and give over-the-counter advice on how to use the prescribed drugs.
In the retail sector pharmacists run chemist's shops. As medical representatives, they inform and educate medical practitioners about the potential uses of the drug or health product and its administration along with the side effects or precautions for its use. The job entails regular visits to medical practitioners, hospitals, clinics, nursing homes, health centres. There is usually a lot of touring to be done in this case.
Hospital Pharmacy
The primary role of a hospital pharmacist is to provide medication and medication management services to patients who are hospitalised or are visiting hospital-based clinics, and to provide medication services to health professionals who care for patients in the hospital set up.
Hospital pharmacists have exposure to many complicated and unique therapy needs, including intravenous medication therapy, nutrition, and the specific needs of newborns and the elderly. Pharmacists in the practice find working with other health professionals, work variety and focused clinical care opportunity rewarding. This is the second most common practice area.
Industrial Pharmacy 
While most firms are involved in the production of pre-formulated preparations, a growing number of firms are developing new formulations through autonomous research work. Industrial pharmacists carry out clinical trials, where drugs are tested for safety and effectiveness work in research and development to develop new formulations the production job entails management and supervision of the production process, packaging, storage and delivery work in marketing, sales and quality control.
In addition to the many opportunities for graduates in the many areas of pharmacy practice there are increasing numbers of opportunities within the pharmaceutical industry in advanced and specialised areas, as the depth and breadth of education in pharmacy increases opportunities in industry. This includes the promotion of pharmaceuticals to health professionals, marketing, development of new drugs and dosage forms, clinical studies in patients, monitoring pharmaceutical use on a population scale, and managing regulatory and legal issues.
Government Services
Pharmacists are hired within the central and state government departments - the Health Protection Branch of the Department of Health and Welfare, the Pest Control Division of Agriculture, the Department of National Defense, Provincial Research Councils, and the Provincial Departments of Agriculture or Environment. There are employment opportunities available also within the food and cosmetic industries or within any other industry that requires an assurance that new products are as safe and effective as possible. In government departments, a pharmacist maintains proper records according to various Acts governing the profession.
Pharmaceutical Education 
Many pharmacists work as faculty in colleges of pharmacy. These pharmacists enjoy influencing the future of pharmacy by educating future pharmacists and may participate in direct patient care and/or scientific research as well. Academic pharmacist practice has its rewards in disseminating and discovering new ideas that change medication use, pharmacist practices and healthcare policy. Career as a teacher is satisfying as it allows interaction with people, especially students, and provides them with the flexibility to pursue their own ideas in the field.

Nuclear Pharmacy 
Nuclear pharmacists are responsible for measuring and delivering radioactive materials which are used in digital imaging (MRI, CT, etc) and other procedures in medical offices and hospitals. Due to the nature of the radioactive materials and how they are handled, nuclear pharmacists are typically required to start each work day very early, sometimes pre-dawn, as the radioactive materials must be delivered within a few hours of their use, or they lose their effectiveness
Clinical Research
Recently, Clinical research has also opened its door for B.Pharma graduates as medical underwriter, CRO, data validation associate, clinical research associate etc. A clinical research associate plays an important role in monitoring and overseeing the conduct of clinical trials, which are conducted on healthy human volunteers. They have to see that the trials meet the international guidelines and the national regulatory requirements.
Community pharmacy
The primary role of a community pharmacist is to provide medication and medication related services to patients. In most settings, pharmacists provide prescription drug services to their community of patients, working with the patients and a broad spectrum of healthcare providers to achieve the best possible healthcare outcome of medication.
Quality Control & analysis
A pharmacy graduate can play a crucial role in controlling product quality as an analytical chemist or a quality control manager. The Drug and the Cosmetics Act (1945), Rules 71(1) and 76(1) says that the manufacturing activity should be taken up under the supervision of a technical man whose qualification should be B PharmA, B Sc, B Tech or medicine with Bio-Chemistry.

Research and Development
New and expanding knowledge in healthcare and biomedical sciences provides tremendous opportunities for the pursuit of research careers for pharmacists. Graduates with Pharm.D degree can pursue a research career directly or go in for additional education either in the form of residency and fellowship training or in formal graduate programmes leading to the M.S. and Ph.D. degrees.
With a clinical focus one can be involved in the conduct and analysis of large-scale human drug studies in academic, industrial, and governmental settings. Pharmacists are also highly qualified to pursue additional training in business, public health, or pharmaceutical socioeconomics in order to become involved in research in drug utilisation, healthcare outcomes, and the provision of pharmacy services.
Sales and Marketing
Ambitious achievers with pleasant personality and good communication skills can opt for the job of Medical Sales Representative. Companies prefer pharmacy graduates for this job, as they have a good knowledge about the drug molecules, their therapeutic effects and the drug -drug interactions.
by
Akshaya Srikanth
Pharm.D Intern
Hyderabad, India

Minggu, 26 Februari 2012

Central Nervous System Infections



Central nervous system infections are usually:
Blood-borne invasion; most common
(e.g. polioviruses or Neisseria meningitidis)
Invasion via peripheral nerves; less common      
 (e.g. herpes simplex, varicella-zoster, rabies)
Blood-borne invasion takes place across: 
     - blood-brain barrier (encephalitis)
     - blood-cerebrospinal fluid (CSF) barrier (meningitis)
Invasion via peripheral nerves:
* Herpes simplex virus (HSV) and varicella-zoster virus (VZV) present in skin or mucosal lesions travel up axons to reach the dorsal root ganglia. 
* Rabies virus, introduced into muscle tissues by:   
     - bite of a rabid animal 
   - It enters peripheral nerves and travels to CNS, to reach the neurons
Pathologic consequences of CNS infection
In CNS; viruses infect neural cells, sometimes showing a marked preference
Polio and rabies viruses invade neurons. CJD virus invades oligodendrocytes
Spread of infection is direct from cell to cell along established nervous pathways
Bacteria and protozoa induce brain abscesses 
Meningitis
* Meningitis is one of the most terrifying disease
* It can be fatal in hours
* Early symptoms resemble, self-limiting condition (flu and colds)
Most common causes of meningitis are:
  a) Bacterial infections (Septic meningitis) may result in death or brain damage. 
  b) Viral infections (Aseptic meningitis) usually resolve without treatment. 
Bacterial Meningitis (Septic Meningitis)
Pneumococcal, Streptococcus pneumoniae (38%)
Meningococcal, Neisseria meningitidis (14%)
Haemophilus influenzae (4%)
Staphylococcal, Staphylococcus aureus (5%)
Tuberculous, Mycobacterium tuberculosis
Viral Meningitis (Aseptic meningitis)
Etiological Agents: 
Enteroviruses, most common (Coxsackie and Echovirus)
Adenovirus
Arbovirus
Measles virus
Herpes Simplex virus
Varicella Zoster virus
by
Akshaya Srikanth, Sunil Jain*
Pharm.D Intern, *Chief Pharmacist
Hyderabad, India

Physiology of SLEEP


How do we Measure Sleep?Electroencephalogram (EEG) measures the electrical changes in the brain. The electrodes are placed on the scalp. The wavy lines recorded by the EEG are called brain waves.
Electrooculogram (EOG) measures the electrical changes as the eyes rotate in its socket. The electrodes are placed either above and below the eye or left and right of the eye. 
Electromyogram (EMG) measures the electrical changes generated during muscle contraction. The electrodes are placed under the chin. 
EEG, EOG and EMG are recorded simultaneously and the patterns of activity in these three systems provide basic classification for the different types of sleep.  
Placement of electrodes to determine EEG,EOG and EMG
Brain, eye and muscle wave in NREM sleep have greater amplitudes and lower frequencies as compared to REM and wakefulness. The amplitude increases continuously, while their frequency decreases correspondingly from the time a normal person falls asleep, till he or she reach the deepest NREM sleep. 
Classification of Brain Waves
EEG associated with sleep from the highest to the lowest frequency: 
Beta waves (β) The frequency of beta waves range from 13-15 to 60 hertz (Hz) and an amplitude of 30 microvolt (μV). Beta waves are associated with wakefulness. 
Alpha waves (α) The frequency range from 8 to 12 Hz and an amplitude of 30 to 50 μV. These waves are found in people who have their eyes closed and relax or meditating.
Theta waves (θ) Frequency in the range of 3 to 8 Hz and amplitude of 50 to 100 μV. These waves are related with memory, emotions and activity in the limbic system. 
Delta waves (δ) It ranges from 0.5 to 4 Hz in frequency and amplitude of 100 to 200 μV. Scientists had observed delta waves in deep sleep and in coma patients because normal and healthy adults will not show large amount of delta waves. 
    Flat-line trace occurs when no brain waves are present and this is the clinical sign of brain death. 
STAGES OF SLEEP
Sleep is characterized by two distinct cycles, 
NREM sleep. Non-Rapid Eye Movement Sleep (NREM) is further classified into 4 stages: 
Rapid Eye Movement Sleep (REM) sleep
Stages 3 and 4 in humans are homologous to animal sleep stage of slow-wave sleep (SWS). A normal human sleep cycle starts with NREM stage 1, stage 2, stage 3, stage 4 and progresses to REM. This cycle is repeated several times throughout the night (between 4 to 5 cycles). The duration for each cycle has been identified ranging between 60 to 90 minutes. The next section explains the characteristics of each of the four stages in detail. 
Circadian Rhythms
Circadian Rhythm is one of the several intrinsic body rhythms modulated by the hypothalamus. The suprachiasmatic nucleus sets the body clock to 24 hours and is modulated by light exposure. The retino-hypothalamic tract allows light cues to directly influence the suprachiasmatic nucleus. 
Circadian rhythm allows the brain to regulate periods of rest during sleep (equivalent to battery re-charging) and periods of high activity during the wakefulness (equivalent to battery discharging). The nadir of the rhythm is in the early morning. The downswing in circadian rhythm after the apex in early evening is thought to initiate sleep and maintain sleep overnight for full restoration by preventing premature awakening. The morning upswing then facilitates awakening and acts as a counterbalance to the progressive discharge of wake neuronal activity, enabling cognitive function throughout wakefulness.

DIA to organize 2-day conference on pharmacovigilance in Bengaluru on March 3 & 4


Drug Information Association (DIA) is organizing a two-day Pharmacovigilance conference in Bengaluru on March 3 and 4, 2012  The event will be held at The Park hotel. The theme of the event is  “Future Perspectives in Pharmacovigilance.’
The key objective of the event is to explain the current global safety reporting requirements for prescription and over the counter drugs.
There is also need to discuss the new pragmatic approaches to pharmacovigilance as proposed in the Council for International Organizations of Medical Sciences (CIOMS) working group. Over the two days, experts will deliberate and provide inspection program of regulatory agencies in the area of clinical safety from US and Europe, stated Kaushik Desai, director DIA India.
The key note speakers are from India and abroad. They are Dr YK Gupta, department of clinical pharmacology, All India Institute of Medical Sciences, Moin Don, executive director PVCON, Pharmacovigilance Consulting Services, Stewart Geary, vice president, and deputy director of Corporate Regulatory Compliance, Safety & QA, Eisai Co. Ltd and Dr Vivek Ahuja, director, Pharmacovigilance, Asia Pacific, Baxter Healthcare.
While Programme co-chairs are Moin Don and Dr Ahuja, the programme committee members constitute Dr BR Jagashetty, Karnataka drugs controller, Dr Gupta, Prof. Parathasarthy Gurumurthy, professor and head of the department of clinical pharmacy, JSS College of Pharmacy Medical College Hospital, Mysore, RK Giridhar, vice president, BPO Pharma Services, Accenture, Dr Chitra Lele, chief scientific officer, Sciformix Corp.
International speakers panel covers Dr Sidney Kahn, principal scientist, Sciformix Pharmacovigilance Services, Dr Sumit Munjal, consultant, (oncology), Global Medical Safety, Johnson & Johnson, a division of Janseen-Cilag Ltd., Johnson & Johnson, UK and Angela Pitwood, VP, Pharmacovigilance, Indipharm Inc. US.
Some of the topics are safety and management during early drug development programme, US &EU safety regulations upsides-New FDA Rule/ DSURs, safety and regulatory writing, medical device vigilance, panel discussion on Schedule Y and Empowerment to Ethics Committees(ECs) and Institutional Review Boards (IRBs), India: as pharmacovigilance outsourcing destination, safety during clinical trials through medical monitoring, integrating pharmacovigilance in medical and para medical curriculum., Utility of Cloud Computing in pharmacovigilance data base domain.
The organizers recommend that the conference should be attended by those from clinical research, risk management, compliance, medical information, regulatory affairs, academia and pharmacology.

Sabtu, 25 Februari 2012

ANEMIA AND ITS TREATMENT

Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells provide oxygen to body tissues.

Causes, incidence, and risk factors 
While many parts of the body help make red blood cells, most of the work is done in the bone marrow. Bone marrow is the soft tissue in the center of bones that helps form blood cells.
Healthy red blood cells last between 90 and 120 days. Parts of your body then remove old blood cells. A hormone called erythropoietin made in your kidneys signals your bone marrow to make more red blood cells.
Hemoglobin is the oxygen-carrying protein inside red blood cells. It gives red blood cells their red color. People with anemia do not have enough hemoglobin.
Possible causes of anemia:
Certain medications
Chronic diseases such as cancer, ulcerative colitis, or rheumatoid arthritis
Genetics: Some forms of anemia, such as thalassemia, can be inherited
Kidney failure
Blood loss (for example, from heavy menstrual periods or stomach ulcers)
Poor diet
Pregnancy
Problems with bone marrow such as lymphoma, leukemia, or multiple myeloma
Problems with the immune system that cause the destruction of blood cells (hemolytic anemia)
Surgery to the stomach or intestines that reduces the absorption of iron, vitamin B12, or folic acid
Too little thyroid hormone (underactive thyroid, or hypothyroidism)
Testosterone deficiency
Symptoms
Possible symptoms include:
Chest pain
Dizziness or light-headedness (especially when standing up or with activity)
Fatigue or lack of energy
Headaches
Problems concentrating
Shortness of breath (especially during exercise)
Some types of anemia may have other symptoms, such as:
Constipation
Problems thinking
Tingling
Signs and tests
Pale skin
Rapid heart rate
Heart murmur
Blood tests used to diagnose:
Blood levels of vitamin B12, folic acid, and other vitamins and minerals
Red blood count and hemoglobin level
Reticulocyte count
Ferritin level
Iron level
Iron deficiency Anemia
Iron deficiency anemia occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed.The principal cause of iron deficiency anemia in premenopausal women is blood lost during menses. Iron deficiency anemia can be caused by parasitic infections, such as hookworms. Intestinal bleeding caused by hookworms can lead to fecal blood loss and heme/iron deficiency. Chronic inflammation caused by parasitic infections contributes to anemia during pregnancy in most developing countries.Iron deficiency anemia is an advanced stage of iron deficiency.Iron deficiency ranges from iron depletion, which yields little physiological damage, to iron deficiency anemia, which can affect the function of numerous organ systems.
Hemolytic Anemia
Hemolytic anemia occurs when the bone marrow is unable to increase production to make up for the premature destruction of red blood cells and the abnormal breakdown of red blood cells  either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired. Treatment depends on the cause and nature of the breakdown.Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications such as gallstones and pulmonary hypertension.
Megaloblastic anemia
Megaloblastic anemia is a disorder of the bone marrow. There is a presence of erythroblasts in the bone marrow with delayed nuclear maturation because of defective DNA synthesis.
In megaoblastic anaemia Erythrocytes are larger and have higher nuclear-to-cytoplasmic ratios compared to normoblastic cells. Neutrophils can be hypersegmented, and megakaryocytes are abnormal. Risk Factors for Megaloblastic anaemia are Vitamin B12 deficiency ,Folic acid deficiency and Conditions with neither B12 nor folate deficiency, e.g. orotic aciduria, where there is a defect in pyrimidine synthesis, therapy with drugs interfering with DNA synthesis and myelodysplasia. 
Anemia of chronic disease
Anemia of chronic disease is a form of anemia seen in chronic illness e.g. from chronic infection, chronic immune activation, or malignancy.In Anemia of chronic disease,In response to the inflammatory cytokines (IL-6) the liver produces increased amounts of hepcidin. Hepcidin in turn stops ferroportin from releasing iron stores. Inflammatory cytokines also appear to affect other important elements of iron metabolism, including decreasing ferroportin expression, and probably directly blunting erythropoiesis by decreasing the ability of the bone marrow to respond to erythropoietin.Anemia of chronic disease may also due to the neoplastic disorder and non infectious inflammmatory diseases. Neoplastic disorder include Hodgkin’s disease lung and breast carcinoma and non infectious inflammmatory diseases include Rheumatoid arthritis and systemic lupus erythematosus.
Anemia of chronic disease is often a mild normocytic anemia, but can sometimes be more severe, and can sometimes be a microcytic anemia.

ANEMIA PHARMACOLOGY 
ANDROGENS (eg, oxymetholone): Anabolic steroids are synthetic derivatives of testosterone. These drugs enhance the production and urinary excretion of erythropoietin in patients with anemias due to bone marrow failure and often stimulate erythropoiesis in anemias due to deficient red cell production. The actions of anabolic steroids are similar to those of male sex hormones, therefore the possibility of causing serious disturbances of growth and sexual development in young children does exist.
COMPLEMENT INHIBITOR (eg, eculizumab): Eculizumab is a monoclonal antibody which binds with high specificity and affinity to the complement protein C5. When bound to C5, eculizumab prevents the protein from cleaving into C5a and C5b and inhibits the formation of the terminal complement complex C5b-9. This action inhibits the terminal complement-mediated intravascular hemolysis of abnormal red blood cells (RBCs) found in paroxysmal nocturnal hemoglobinuria (PNH). PNH patients are deficient in terminal complement inhibitors which make PNH RBCs susceptible to continuous terminal complement-mediated destruction.
ERYTHROPOIESIS-STIMULATING AGENTS (ESAs): Erythropoietin is a glycoprotein that stimulates red blood cell production. Endogenous production of erythropoietin is normally regulated by the level of tissue oxygenation. Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis. 
Recombinant erythropoietin (eg, epoetin alfa) and erythropoiesis-stimulating proteins (darbepoetin alfa) stimulate red blood cell production by the same mechanism of action as endogenous erythropoietin. Darbepoetin alfa differs in that it has a longer circulatory survival (half-life: 21hours) than recombinant erythropoietin (half-life: 4–13hours).
Sufficient time should be allowed to determine a patient's responsiveness to ESAs before adjusting the dose. Because of the time required for erythropoiesis and the RBC half-life, an interval of 2-6 weeks may occur between the time of a dose adjustment and a significant change in hemoglobin.
GONADOTROPIN-RELEASING HORMONE (GnRH) ANALOGUES: Leuprolide acetate is a long-acting GnRH analogue that is used in combination with iron therapy to treat anemia caused by acute or chronic blood loss associated with uterine leiomyomata. Repeated dosing of leuprolide acetate causes reduced secretion of pituitary gonadotropins leading to inactivity of dependent tissues and functions. This effect has been shown to reduce uterine and fibroid volume and excessive vaginal bleeding, thereby alleviating anemia caused by uterine leiomyomata.
HEMATINICS: 
Iron supplements: Iron is essential for the maintenance of normal hemoglobin synthesis and erythropoiesis. Treatment of iron deficiency anemias can generally be managed with oral iron supplementation. Oral iron supplements are available as carbonyl iron [elemental iron (eg, Ferralet 90)] or as various salt formulations which are similar in absorption and bioavailability, but differ in their percentage of elemental iron. 
Ferrous fumarate - 33% elemental iron
Ferrous gluconate - 12% elemental iron 
Ferrous sulfate - 20% elemental iron
Ferrous sulfate; exissicated - 32% elemental iron
Proper dosing of these supplements is based on the elemental iron content. Liquid formulations of iron may stain teeth.
Parenteral therapy is used when oral iron therapy is not feasible, cannot be tolerated, or iron losses are large. Preparations for parenteral therapy include iron dextran, iron sucrose, and sodium ferric gluconate. Use caution when administering parenteral iron therapy as acute hypersensitivity and anaphylactic reactions may occur; iron sucrose and sodium ferric gluconate have a lower incidence of these reactions. Of these agents, sodium ferric gluconate has the fastest onset of action but may require more frequent dosing. 
Vitamins: Vitamin B12 (eg, cyanocobalamin) is a vitamin essential for erythropoiesis. Rapidly dividing cells (eg, bone marrow and myeloid cells) have the highest requirement for Vitamin B12. Cyanocobalamin is available as an injection and as topical nasal preparations for the treatment of pernicious anemia and other megaloblastic anemias due to Vitamin B12 deficiency.
Folic acid and folic acid derivatives: Folic acid, which is necessary for the maintenance of normal erythropoiesis, is reduced by dihyrofolate reductase to tetrahydrofolic acid. Tetrahydrofolic acid is involved in the formation of thymidylates of nucleic acids and subsequently DNA synthesis. Folic acid deficiency impairs this process, resulting in megaloblastic and macrocytic anemias. Leucovorin is a folic acid derivative composed of a mixture of active tetrahydrofolic acid derivatives that do not require enzymatic reduction. Caution should be used if megaloblastic and pernicious anemias due to Vitamin B12 deficiency are suspected as folic acid and its derivatives may mask the signs of this condition.
SUBSTITUTED UREA (eg, hydroxyurea): Although the exact mechanism of action of hydroxyurea in treating sickle cell anemia is unknown, it is believed that the agent causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid. Known pharmacologic effects of hydroxyurea that may contribute to its beneficial effects include increasing hemoglobin F levels in RBCs, decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.
by
Akshaya Srikanth, Dr.Chandra Babu*
Pharm.D Intern, *Asst.Prof of Medicine
RIMS Medical College, Kadapa, A.P
INDIA

Jumat, 24 Februari 2012

Peripartum cardiomyopathy

HEART FAILURE DURING PREGNANCY was recognized as early as 1849, but it was first described as a distinctive form of cardiomyopathy only in the 1930s.1 In 1971, Demakis et al2 described 27 patients who presented during the puerperium with cardiomegaly, abnormal electrocardiographic findings, and congestive heart failure, and named the syndrome peripartum cardiomyopathy. 
The European Society of Cardiology3 recently defined peripartum cardiomyopathy as a form of dilated cardiomyopathy that presents with signs of heart failure in the last month of pregnancy or within 5 months of delivery.
Peripartum cardiomyopathy is defined on the basis of four criteria:
  1-  Development of cardiac failure in the last month of pregnancy or within five months of delivery
  2-  Absence of an identifiable cause for the cardiac failure 
  3-  Absence of recognizable heart disease prior to the last month of pregnancy
 4-  Left ventricular systolic dysfunction demonstrated by classic echocardiographic criteria, such as depressed  shortening fraction or ejection fraction
The true incidence of PPCM is unknown; estimates proposed over the last several decades range from 1 per 1300 to 1 per 15,000 live births.
Unknown etiology
No hormonal disorder has been identified in patients with PPCM, even though estrogen, progesterone, and prolactin have significant effects upon the cardiovascular system
Inflammatory cytokines may play a role in PPCM ( TNF, IL6, Fas receptor, ….)
Myocarditis , evidence by endomyocardial biopsies
A maternal immunologic response to a fetal antigen has been proposed as another potential etiology of PPCM 
Familial or genetic etiology can not be excluded 
Risk Factors
Age greater than 30 years 
Multiparity
Women of African descent 
Pregnancy with multiple fetuses 
A history of preeclampsia, eclampsia, or postpartum hypertension
Association with maternal cocaine abuse or selenium deficiency 
Long term (>4 weeks) oral tocolytic therapy with beta adrenergic agonists such as : Terbutaline.
Diagnosis    
The development of CHF signs and symptoms
EKG: sinus tachy, a-fib, low voltages , prolong PR/QRS, non specific ST-T wave changes
CXR: enlargement of the cardiac silhouette with evidence of pulmonary venous congestion and/or interstitial edema, pleural effusions.
The echocardiogram and Doppler usually reveal left ventricular enlargement with significant global reduction in overall performance without LVH  
The role of endomyocardial biopsy remains unclear. 
Viral and bacterial cultures, as well as selected viral titers (eg, Coxsackie B) should also be considered.
Management
Heart failure treatment during pregnancy
When considering tests or treatments in pregnancy, the welfare of the fetus is always considered along with that of the mother. Coordinated management with specialists (an obstetrician and maternal-fetal medicine team) is essential, with fetal heart monitoring.
  • Angiotensin-converting enzyme (ACE) inhibitors and ARBs are contraindicated in pregnancy because they can cause birth defects, although they are the main treatments for postpartum women with heart failure. The teratogenic effects occur particularly in the second and third trimester, with fetopathy characterized by fetal hypotension, oligohydramnios-anuria, and renal tubular dysplasia. However, a recent study suggested a risk of malformations even after first trimester exposure to ACE inhibitors.
  • Digoxin, beta-blockers, loop diuretics, and drugs that reduce afterload such as hydralazine and nitrates have been proven to be safe and are the mainstays of medical therapy of heart failure during pregnancy.Beta-blockers have strong evidence of efficacy in patients with heart failure, but they have not been tested in peripartum cardiomyopathy. Nevertheless, beta-blockers have long been used in pregnant women with hypertension without any known adverse effects on the fetus, and patients taking these agents prior to diagnosis can continue to use them safely.
  • Heart failure treatment postpartum
  • After delivery, the treatment is identical to that for nonpregnant women with dilated cardiomyopathy. ACE inhibitors and ARBs. The target dose is one-half the maximum antihypertensive dose.
Diuretics are given for symptom relief
Spironolactone or digoxin is used in patients who have New York Heart Association class III or IV symptoms. The goal with spironolactone is 25 mg/day after dosing of other drugs is maximized. The goal with digoxin is the lowest daily dose to obtain a detectable serum digoxin level, which should be kept at less than 1.0 ng/mL. In the Digitalis Investigation Group trial,55 serum digoxin levels of 0.5 to 0.8 ng/mL (0.6–1.0 nmol/L) were most beneficial, and levels of 1.1 to 1.5 ng/mL (1.4–1.9 nmol/L) were associated with an increase in deaths related to heart failure.
Beta-blockers are recommended for peripartum cardiomyopathy,44 as they improve symptoms, ejection fraction, and survival. Nonselective beta-blockers such as carvedilol (Coreg) and selective ones such as metoprolol succinate (Toprol XL) have shown benefit. The goal dosage is carvedilol 25 mg twice a day (50 mg twice a day for larger patients) or metoprolol succinate 100 mg once a day.
Anticoagulation treatment
During pregnancy, the risk of thromboembolic complications increases due to higher concentrations of coagulation factors II, VII, VIII, and X, and of plasma fibrinogen. The risk may persist up to 6 weeks postpartum.1 Cases of arterial, venous, and cardiac thrombosis have been reported in women with peripartum cardiomyopathy, and the risk may be related to the degree of chamber enlargement and systolic dysfunction and the presence of atrial fibrillation.
Patients with evidence of systemic embolism, with severe left ventricular dysfunction or documented cardiac thrombosis, should receive anticoagulation. Anticoagulation should be continued until a return of normal left ventricular function is documented.
We await the results of the Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction trial, which should determine which drug will best prevent death or stroke in patients with ejection fractions of less than 35%.
Warfarin can cause spontaneous fetal cerebral hemorrhage in the second and third trimesters and therefore is generally contraindicated during pregnancy. However, guidelines from the American College of Cardiology and the American Heart Association on the management of patients with heart valve disease say that “warfarin is probably safe during the first 6 weeks of gestation, but there is a risk of embryopathy if the warfarin is taken between 6 and 12 weeks of gestation.” The guidelines also say warfarin is “relatively safe” during the second and third trimesters but must be stopped and switched to a heparin several weeks before delivery. Unfractionated heparin or low-molecular-weight heparin can be used during pregnancy. However, should warfarin be needed for any reason, we believe a cesarian section should be performed to reduce the risk to the infant.
by
Akshaya Srikanth, Dr. Archana
Pharm.D Intern, Asst.Prof. of Obs & Gyn
RIMS Medical College, Kadapa
India

Overdose Prevention Programs Using Opioid Antagonist


Naloxone, an opioid antagonist, is being used by at least 188 overdose prevention programs in the United States, but many states with high death rates due to heroin or other opioid overdose do not include naloxone distribution in their programs, according to research published in the Feb. 17 issue of the US Centers for Disease Control and Prevention's Morbidity & Mortality Weekly Report. 
Eliza Wheeler, MPA, of the Harm Reduction Coalition in Oakland, CA, and colleagues compiled a report based on surveys regarding naloxone distribution and overdose reversal that were completed by 48 US programs representing 188 local programs.
The researchers found that, since 1996, when naloxone was first distributed by a prevention program, the programs completing the survey indicated that they provided training and distributed naloxone to more than 53,000 people and reversed overdoses in 10,171. However, 19 of 25 states with higher than median drug overdose fatalities did not have a program that distributes naloxone, and 43.7% of programs that do distribute the agent reported difficulty in obtaining the drug.
"Providing opioid overdose education and naloxone to persons who use drugs and to persons who might be present at an opioid overdose can help reduce opioid overdose mortality, a rapidly growing public health concern," the authors write.
Full text can be available at
by
Akshaya Srikanth,
Pharm.D Intern
Hyderabad, India

DRUGS USED IN BACTERIAL INFECTIONS - A BRIEF REVIEW


Antiinfectives should never be given casually for mild infections. Ideally, a culture & sensitivity should be done before administering the antiinfective of choice. Antibiotics are ineffective against viruses. The product labeling should be consulted for specific information about organism sensitivity and resistance and for detailed microbiological indications. Advise patients to continue taking medication until course of treatment is finished (usually 7–10 days) unless severe allergic reactions occur. When selecting antibiotics for the prevention of bacterial endocarditis, the physician or dentist should read the full joint statement of the American Heart Association and the American Dental Association. Treatment of strep infections usually requires at least 10 days of therapy.
Interactions: Antibiotics may reduce efficacy of oral contraceptives. Bactericidal drugs are primarily active against actively dividing cells. Therefore, bacteriostatic antibiotics (eg, tetracyclines) may interfere with the action of bactericidal antibiotics (eg, penicillins).
Adverse Reactions: Pseudomembranous colitis may occur following the administration of antibacterial agents. This may range in severity from mild to life-threatening. This diagnosis should be considered in patients who present with diarrhea subsequent to antibiotic therapy. Mild cases usually respond to discontinuing the drug; more severe cases may need supportive care and/or therapy with an agent effective against Clostridium difficile. Anti-motility drugs should be avoided since they may precipitate toxic megacolon. Also, overgrowth of nonsusceptible organisms, including fungal overgrowth (superinfection) may occur with the prolonged use of antibiotics.
AMINOGLYCOSIDES: The aminoglycosides (eg, gentamycin, tobramycin, streptomycin, amikacin) bind to the 30S ribosomal subunit of bacteria resulting in decreased protein synthesis and misreading of mRNA. These agents exert concentration-dependent bactericidal effects and demonstrate a post-antibiotic effect to persistently suppress bacterial growth after concentrations fall below the MIC. Aminoglycosides are active against gram-negative aerobic and facultative bacilli, including Pseudomonas aeruginosa. Aminoglycosides have limited activity against gram-positive organisms when used alone; however, when combined with a cell wall-active agent (eg, penicillins, vancomycin), in vitro synergistic bactericidal activity against enterococci and staphylococci is observed. Aminoglycosides are not active against anaerobes or atypicals.
β-LACTAMS: β-lactam antibiotics inhibit bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins to exert time-dependent bactericidal activity. The β-lactam antibiotics can be divided into penicillins, cephalosporins, carbapenems, and monobactams, which are further divided into different groups according to spectra of activity.
Penicillins are primarily active against gram-positive cocci and some gram-negative bacilli. These agents can be subdivided into 5 distinct groups: natural penicillins, penicillinase-resistant penicillins, aminopenicillins, carboxypenicillins, and ureidopenicillins. β-lactamase inhibitors (eg, clavulanic acid, sulbactam sodium) may be formulated in combination with penicillins to restore the spectrum of activity of the corresponding β-lactam to include pathogens that were resistant due to their production of β-lactamases. 
Natural penicillins (eg, penicillin G, penicillin V) are active against non-β-lactamase-producing gram-positive bacteria, anaerobes, and select gram-negative cocci. Penicillinase-resistant penicillins (eg, nafcillin, oxacillin) are semi-synthetic penicillins stable against staphylococcal penicillinase. 
Aminopenicillins (eg, ampicillin, amoxicillin) have a spectrum of activity similar to penicillin G with added activity against gram-negative cocci and Enterobacteriaceae that do not produce β-lactamase. 
Carboxypenicillins (eg, ticarcillin) have an expanded spectrum of activity against non-β lactamase-producing gram-negative aerobic bacilli. 
Ureidopenicillins (eg, piperacillin) have a broader spectrum of activity compared to carboxypenicillins. Relative to carboxypenicillins, piperacillin offers activity against Enterococcus faecalis and Klebsiella and has greater efficacy against Pseudomonas. In addition, piperacillin has excellent activity against non-β-lactamase-producing anaerobic cocci and bacilli.
Cephalosporins
Cephalosporins are divided into 4 different generations based on microbiologic activity. In general, gram-positive activity diminishes while gram-negative activity increases moving from the first- to third-generations. Fourth-generation cephalosporins demonstrate similar activity to first-generation agents against gram-positive cocci and are also active against most gram-negative bacilli (including Pseudomonas). All cephalosporins are considered inactive against methicillin-resistant staphylococci, enterococci, Listeria, Legionella, Chlamydia, Mycoplasma, and Acinetobacter species. 
First-generation cephalosporins (eg, cefazolin, cephalexin, cefadroxil, cephradine) are most often used as alternatives to penicillins for infections caused by methicillin-sensitive staphylococci and streptococci.
Second-generation cephalosporins can be further subdivided into true cephalosporins and the cephamycins. True cephalosporins (eg, cefuroxime, cefprozil, cefaclor) have similar activity against staphylococci and noneterococcal streptococci compared to first-generation agents but have increased activity against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria. The cephamycins (eg, cefotetan and cefoxitin) have reduced activity against gram-positive pathogens but enhanced activity against certain Enterobacteriaceae and are active against anaerobes, especially Bacteriodes fragilis. 
Third-generation cephalosporins (eg, ceftriaxone, cefotaxime, cefixime, cefdinir) have enhanced activity against gram-negative bacilli that are resistant to other β-lactams. 
Fourth-generation cephalosporins (eg, cefepime) have the widest activity spectrum. Cefepime has enhanced activity against Enterobacter, Citrobacter, and Serratia and is active against Pseudomonas while maintaining potency against gram-positive cocci.
Carbapenems
The carbapenems (eg, imipenem, meropenem, ertapenem, doripenem) are primarily active against gram-positive cocci, gram-negative bacilli, and anaerobes. These agents are not active against atypicals.
Monobactams
Aztreonam is active only against gram-negative aerobic bacilli. Because of structural differences, aztreonam can be safely given to patients with immediate hypersensitivity reactions to other β-lactams.
FLUOROQUINOLONES: Fluoroquinolones (eg, ciprofloxacin, levofloxacin, moxifloxacin) exert concentration-dependent bactericidal activity. These agents inhibit bacterial DNA synthesis and promote cleavage of DNA leading to bacterial cell death. These agents inhibit the activity of DNA gyrase and topoisomerase IV to prevent uncoiling of DNA strands and decatenation of daughter DNA strands during the replication process, respectively. In general, fluoroquinolones primarily inhibit DNA gyrase in gram-negative bacteria, whereas topoisomerase IV is the main target in gram-positive bacteria. Fluoroquinolones are most active against aerobic gram-negative bacilli and gram-negative cocci and have some activity against atypicals but provide poor anaerobic coverage.
FOLATE SYNTHESIS INHIBITORS: Sulfonamides (eg, sulfamethoxazole, sulfisoxazole), trimethoprim, and pyrimethamine are bacteriostatic agents that inhibit microbial synthesis of folate, a necessary component of bacterial nucleotide synthesis. Only bacteria which must self-synthesize folic acid are susceptible to these agents. Sulfonamides and trimethoprim/pyrimethamine exert their inhibitory effects at different stages of the folate synthesis pathway. Sulfonamides competitively inhibit dihydropteroate synthase which acts to incorporate para-aminobenzoic acid (PABA) into dihydropteroic acid, the precursor to folic acid. Trimethoprim and pyrimethamine inhibit dihydrofolate reductase, which is responsible for the conversion of dihydrofolic acid to the active tetrahydrafolic acid. Thus, the combination of sulfonamides with trimethoprim or pyrimethamine acts synergistically to reduce intracellular folate and subsequently inhibit nucleotide synthesis and bacterial cell growth.
Sulfonamides and trimethoprim are active against gram-positive and gram-negative bacteria, Actinomyces, Nocardia spp., Chlamydia, Plasmodium, and Toxoplasma. Trimethoprim is 20100 times greater in potency than a sulfonamide, making the synergistic combination of sulfisoxazole/trimethoprim more effective therapy than a sulfonamide alone. Pyrimethamine is highly selective against Plasmodium and Toxoplasma gondii; its activity against Toxoplasma is enhanced when combined with a sulfonamide.
GLYCOPEPTIDES: Vancomycin exerts time-dependent bactericidal activity by inhibiting cell wall synthesis. Vancomycin forms stable complexes with cell wall precursor units to prevent polymerization (transglycosylaton) of precursor units for the formation of a functional cell wall. Vancomycin is active only against gram-positive organisms. Vancomycin is not absorbed when given orally and is not appropriate for treatment of systemic infections. However, it achieves high concentration within the gastrointestinal tract and therefore is used for the treatment of pseudomembranous colitis caused by C. difficile or pseudomembranous enterocolitis caused by Staphylococcus aureus.
GLYCYLCYCLINES: Glycylcyclines (eg, tigecycline) are derivatives of minocycline that bind to the 30S subunit of bacterial ribosome to inhibit bacterial protein synthesis to exert bacteriostatic activity against gram-positive and gram-negative organisms, atypicals, and anaerobes.
KETOLIDES: Ketolides (eg, telithromycin) are derivatives of erythromycin that bind to the 50S subunit of bacterial ribosome and inhibit RNA-dependent protein synthesis of susceptible bacteria, similarly to macrolides. Telithromycin differs from macrolides in that it is more acid stable and demonstrates a higher binding affinity for the ribosome, which may contribute to its improved activity against macrolide-resistant pathogens. Telithromycin is bacteriostatic and has improved activity against gram-positive aerobic bacteria compared to macrolides. It is also active against gram-positive and gram-negative bacteria, atypicals, and some anaerobes.
LICOPEPTIDES: Daptomycin is a lipopeptide antibiotic that exerts concentration-dependent bactericidal activity. Daptomycin binds to the cell membrane of gram-positive bacteria in a calcium-dependent manner, resulting in loss of cell membrane depolarization. This action results in inhibition of protein, DNA, and RNA synthesis, leading to cell death. Daptomycin has a spectrum of activity that resembles that of vancomycin while maintaining activity against pathogens with reduced susceptibility to vancomycin (eg, vancomycin intermediate S. aureus and vancomycin-resistant enterococci).
LINCOSAMIDES: Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis through interactions with the 50S bacterial ribosomal subunit. Clindamycin primarily exhibits bacteriostatic activity against anaerobes and gram-positive organisms; it has been shown to be bactericidal against Streptococcus pneumoniae, Streptococcus pyogenes, and S. aureus.
MACROLIDES: Macrolides (eg, erythromycin, clarithromycin, azithromycin) bind to the 50S subunit of the prokaryotic bacterial ribosome and inhibit RNA-dependent protein synthesis of susceptible bacteria to exert bacteriostatic effects. Macrolides are active against gram-positive cocci and bacilli and atypicals and have some activity against gram-negative bacteria.
NITROIMIDAZOLES: Nitroimidazoles (eg, metronidazole) are prodrugs that exert their antibacterial actions by interfering with DNA synthesis to induce apoptosis; they are amebacidal, bactericidal, and trichomonacidal. By passive diffusion, these agents cross bacterial cell membranes and undergo nitro reduction to form free radicals. These reactive intermediates exert their cytotoxic effects via damage to nucleic acids and proteins. Metronidazole is active against anaerobic cocci, anaerobic gram-negative bacilli, anaerobic spore-forming gram-positive bacilli and microaerophilic pathogens. Due to its excellent penetration, metronidazole is used for the treatment of brain abscess or other central nervous system infections, as well as anaerobic infections involving the bones and joints, soft tissues, oral cavity, head and neck. 
OXAZOLIDINONE: Linezolid is an oxazolidinone that binds to the 50S ribosomal subunit of the 30S unit to prevent the formation of the 70S initiation complex. Linezolid is generally bacteriostatic, however it is bactericidal against some strains of S. pneumoniae and S. pyogenes. It is active against gram-positive pathogens including gram-positive anaerobic cocci, as well as mycobacteria. Linezolid lacks activity against most gram-negative aerobes and anaerobes. In addition to its antibiotic effects, linezolid is also a weak monoamine oxidase inhibitor, thus concomitant use with adrenergics, serotonergics, or consumption of tyramine-rich foods may lead to palpitations, headache, hypertensive crisis, fever, and mental status changes.
RIFAMYCINS: Rifamycins (eg, rifampin and rifaximin) are broad-spectrum antibacterials. These agents bind to DNA-dependent RNA polymerase, resulting in a drug-enzyme complex. Formation of this complex inhibits activity of the RNA polymerase, preventing the initiation of chain formation in the synthesis of RNA, but not chain elongation. Rifamycins are most active against gram-positive organisms, but are also active against gram-negative pathogens. Additionally, rifampin is moderately active against slow-growing mycobacteria and has some activity against Legionella.
STREPTOGRAMINS: Quinupristin and dalfopristin are streptogramins that bind to the 50S ribosomal subunit of the 70S unit in the elongation phase of protein synthesis. Quinupristin acts at the same site as macrolides and causes protein synthesis termination at a later phase, whereas dalfopristin directly blocks the addition of amino acids into the peptide chain to inhibit early polypeptide elongation. The streptogramins are active against most gram-positive aerobic pathogens. Available as combination therapy, the synergistic activity of quinupristin/dalfopristin accounts for its bactericidal activity; it is bacteriostatic against Enterococcus faecium.
TETRACYCLINES: Tetracyclines (eg, tetracycline, doxycyline, minocycline) are bacteriostatic antibiotics that bind to the 30S subunit of bacterial ribosome to inhibit bacterial protein synthesis. Tetracyclines primarily exhibit activity against atypicals and have some activity against gram-positive and gram-negative bacteria.
OTHER CLASSES: Fosfomycin exerts its antibacterial effect by inhibiting the enzyme enolpyruvyl transferase to irreversibly block an initial step in bacterial cell wall synthesis and, additionally, decreasing bacteria adherence to uroepithelial cells. Fosfomycin has a broad spectrum of activity against gram-positive and gram-negative pathogens.
Nitrofurantoin is used exclusively for prophylaxis against recurrent urinary tract infections (UTI); and treatment of uncomplicated cystitis or uncomplicated UTIs. Nitrofurantoin is rapidly eliminated and thus only achieves adequate concentrations in the urine. Reduction of nitrofurantoin by bacteria in the urine leads to formation of reactive intermediates that subsequently damage bacterial DNA; the antibacterial activity of nitrofurantoin is enhanced in the presence of acidic urine. Macrocrystalline preparations of nitrofurantoin (eg, Macrodantin, Macrobid) are absorbed and excreted more slowly than microcrystalline preparations (eg, Furadantin).
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by
Akshaya Srikanth, 
Pharm.D Intern,
Hyderabad, India.