Diabetic Neuropathy

Diabetic Neuropathy is a neurometabolic disorder that is found in diabetic patients.

• About 60-70% of people with diabetes have mild to severe forms of nervous system damage, including:                                                                                                                                                                -Impaired sensation or pain in the feet or hands                                                                          -Slowed digestion of food in the stomach                                                                                        -Carpal tunnel syndrome                                                                                                                   -Other nerve problems

• More than 60% of nontraumatic lower-limb amputations in the United States occur among people with diabetes.

Risk Factors
-Glucose control
-Duration of diabetes
-Damage to blood vessels
-Mechanical injury to nerves
-Autoimmune factors
-Genetic susceptibility
-Lifestyle factors
-Smoking
-Alcohol
-Increased Height
-Pathogenesis of Diabetic Neuropathy
Metabolic factors
-High blood glucose
-Advanced glycation end products
-Sorbitol
-Abnormal blood fat levels
-Ischemia
-Nerve fiber repair mechanisms
Pathophysiology-biochemical and vascular factors

Ways of Diagnosis
-Assess symptoms - muscle weakness,
-muscle cramps, prickling, numbness or pain, vomiting, diarrhea,
- poor bladder control and sexual dysfunction
-Comprehensive foot exam
-Skin sensation and skin integrity
-Quantitative Sensory Testing (QST)
-X-ray
-Nerve conduction studies
-Electromyographic examination (EMG)
-Ultrasound

Classification of Diabetic Neuropathy
-Symmetric polyneuropathy
-Autonomic neuropathy
-Polyradiculopathy
-Mononeuropathy
-Symmetric Polyneuropathy

Most common form of diabetic neuropathy 
Affects distal lower extremities and hands (“stocking-glove” sensory loss) 
Symptoms/Signs
-Pain
-Paresthesia/dysesthesia
-Loss of vibratory sensation
Complications:
-Ulcers
-Charcot arthropathy
-Dislocation and stress fractures
-Amputation

Foot Ulceration

Treatment of Symmetric Polyneuropathy

-Glucose control
-Pain control
-Tricyclic antidepressants
-Topical creams
-Anticonvulsants
-Foot care
                                                                             -Visual inspection of feet at every visit with a health care professional
-Use lotion to prevent dryness and cracking
-Cut toenails weekly or as needed
-Always wear socks and well-fitting shoes
-Notify their health care provider immediately if any foot problems occur

Autonomic neuropathy

Affects the autonomic nerves controlling internal organs
-Peripheral
-Genitourinary
-Gastrointestinal
-Cardiovascular
Symptoms/Signs:
-Neuropathic arthropathy (Charcot foot)
Aching, pulsation, tightness, cramping, dry skin, pruritus, edema, sweating abnormalities
Weakening of the bones in the foot leading to fractures
-Treatment: Symptomatic therapy due to have foot ulceration, pain, edema and so on.

Polyradioculopathy
-Lumbar polyradiculopathy (diabetic amyotrophy)
-Thigh pain followed by muscle weakness and atrophy
-Thoracic polyradiculopathy
-Severe pain on one or both sides of the abdomen, possibly in a band-like pattern
-Diabetic neuropathic cachexia
-Polyradiculopathy + peripheral neuropathy
-Associated with weight loss and depression
-Polyradiculopathies are diagnosed by electromyographic (EMG) studies
Treatment
-Foot care
-Glucose control
-Pain control

Mononeuropathy
-Peripheral mononeuropathy
-Single nerve damage due to compression or ischemia
-Occurs in wrist (carpal tunnel syndrome), elbow, or foot (unilateral foot drop)
-Cranial mononeuropathy
-Affects the 12 pairs of nerves that are connected with the brain and control sight, eye movement, hearing, and taste
Symptoms/Signs
-paratesia
-Edema
-unilateral pain near the affected eye
-paralysis of the eye muscle
-double vision
So we should concern about diabetes

Article Written By: Md. Enamul Hoque Khan
Student of MPharm,Department of Pharmacy,
East West University,Dhaka.

Read more »

Posted in: Clinical Pharmacy,Diseases Information

Precautions and Directions during use of Medication

 Drug Safety and Availability
Information for consumers and health professionals on new drug warnings and other safety information, drug label changes, and shortages of medically necessary drug products.

Precautions
-Patients previous history;ensure that the patients have no genetics or other allergic problems with the medicine.
-Patients body functions;ensure that the patients body functions is well tolerated with that particular medicine.
Food habit;Check the patients food habit is not contraindicated with the medicine;
-Financial effort;ensure that the patients is able to buy the medicine.
-Check the patients cure and awareness about that particular disease as well as taking medicine.
-Others factors.
Directions
-Side effects,adverse effects should be mentioned as leaflet.
-Dose and route of administration should be mentioned.
-Storage conditions should be followed.
-Full dose should be completed.
-Life style during taking medicine should be counseled.
-If any problemetic conditions arise during taking medicine then the medicine should be stopped and take advice of doctors.
-Proper monitoring should be maintained.
-Others.

Things To Know
It’s also important to follow any storage instructions, such as the need for refrigeration, that are on the prescription label. Most medications can be stored at room temperature, away from any moisture or light.
 
Last thing to do

1. If your medication does not have any specific disposal instructions and there are no available take-back programs near you,  you can dispose of them in your household trash:
1. Remove or scratch off any personal information on your prescription vial label.
2. Do NOT crush tablets or capsules when throwing away.
3. Mix your medications with an undesirable substance such as coffee grounds or cat litter. Place this mixture in a plastic, sealable bag or container.
4. Ask your local retail pharmacist if his or her company has a drug take back if possible.

Read more »

Posted in: Pharmacy Law & Ethics

Principle of Pelletization

DEFINITION OF PELLETISATION
      Pelletization is an agglomeration process, that converts fine powder blend of drug(s) and excipients into small, free flowing, spherical units, referred to as pellets. (Ref. L. Hellen 1992)
The pelletizing process for the production of pharmaceutical pellets - including extrusion and spheronization, production of pellets by powder layering and liquid layering and pelletization via melt and wet granulation processes.

Why Pellet
-Excellent Stability
-Dust free Round pellets
-Good flow behavior
-Easy to dose
-Compact structure
-Very Low hygroscopicity
-High bulk density
-Dense, uniform surface
L-ow abrasion
-High active ingredient content possible
-Optimum starting shape for subsequent coating
-Controlled-release applications
- The risks of the local damage to the GI-tract mucosal 

Some Type of Pellets
Liquid layering of pellets-coater systems can all be used to make pellets by layering the active material onto an inert core. Non-pareil starter pellets are sprayed with a solution or suspension of theactive material, and dried simultaneously.
Powder layering of pellets-Layering a drug onto starter pellets.When the active ingredient is in powder form, pelletization can be achieved by spraying starter pellets with the active powder and at the same time a liquid binder solution. The layered pellets are then dried. 
Melt granulation pelletization-Pelletization by heating and massing a powder mixture.Melt pelletization is performed in the active and binder powders are mixed and heated to a temperature above the melting point of the binder. Granulation and pelletization are then carried out in a single operation.
Wet granulation pelletization-Granulating and spheronizing a powder mixture.The active substance is mixed with 5-30% microcrystalline cellulose and the mixture granulated with water or an organic solvent. During the process the granules are compacted and spheronized.

PREPARATION OF PELLETS

-Drum/pan pelletization
- Extrusion-spheronization
 -Centrifugal drug-layering
 -Fluidized-bed pelletization
- High-shear melt pelletization



A-FLUID BED COATING BY WURSTER TECHNOLOGY

Extrusion-Spheronizations of pellets

Innovative processes for Pellets / Particles coating
-Film coating /Enteric/ extended Release, and -lipid/hot melts coating.
-Coating of micro particles, granules, pellets

BATCH FLUID BED SYSTEMS categorized in different manufacturing Techniques:
-Top Spray Coating
-Bottom Spray Coating (Wurster Pellets Coating)
-Tangential Spray Coating (Rotor Pellet Coating)


PRINCIPLE OF OPERATION
With fluid bed coating, particles are fluidized and the coating/ Binder fluid sprayed on and dried. Small droplets and a low viscosity of the spray medium ensure an even product coating.

Fluid Bed Operation

1-POWDER LAYERING PROCESS (ROTO SYSTEM)

2- COATING SUSPENSION AND SOLUTION LAYERING PROCESS

 

2- COATING SUSPENSION AND SOLUTION LAYERING PROCESS

 

PROCESS PRINCIPLES

1- LAYERING PROCESS-Film Coating

Article Written By: Md. Enamul Hoque Khan
Student of Mpharm,Department of Pharmacy,
East West University,Dhaka

Read more »

Posted in: Pharmaceutical Technology

Getting the drug to market

 Getting the Drug

Three main issues are involved in getting the drug to the market.

First, the drug has to be tested to ensure that it is not only safe and effective, but can be administered in a suitable fashion. This involves preclinical and clinical trials covering toxicity, drug metabolism, stability, 
formulation, and pharmacological tests.
Second, there are the various patenting and legal issues.
Third, the drug has to be synthesized in ever-increasing quantities for testing and eventual manufacture. This is a field known as chemical and process development.

Preclinical and clinical trials 
Toxicity testing
One of the first priorities for a new drug is to test if it has any toxicity.

This often starts with in vitro tests on genetically engineered cell cultures and/or in vivo testing on
transgenic mice to examine any effects on cell 
reproduction, and to identify potential carcinogens. Any signs of carcinogenicity would prevent the drug being taken any further.
The drug is also tested for acute toxicity by administering sufficiently large doses in vivo to produce a toxic effect or death over a short period of time. Different animal species are used in the study and the animals are dissected to test whether particular organs are affected.

Further studies on acute toxicity then take place over a period of months, where the drug is administered to 
laboratory animals at a dose level expected to cause toxicity but not death. Blood and urine samples are analysed over that period, and then the animals are killed such that tissues can be analysed by pathologists for any sign of cell damage or cancer.
Finally, long-term toxicology tests are carried out over a period of years at lower dose levels to test the drug for chronic toxic effects, carcinogenicity, special toxicology, mutagenicity, and reproduction abnormalities.
It should also be borne in mind that it is rare for a drug to be 100% pure. There are bound to be minor impurities present arising from the synthetic route used, and these may well have an influence on the toxicity of the drug.

The toxicity results of a drug prepared by one synthetic route may not be the same for the same drug 
synthesized by a different route, and so it is important to  establish the manufacturing synthesis as quickly as possible
Drug metabolism studies
The body has an arsenal of metabolic enzymes that can modify foreign chemicals, in such a way that they are
rapidly excreted.
The structure and stereochemistry of each metabolite has to be determined and the metabolite tested to see what sort of biological activity it might have. This is a safety issue, since some metabolites might prove toxic and others may have side effects that will affect the dose levels that can be used in clinical trials. Ideally, any metabolites that are formed should be inactive and
quickly excreted. However, it is quite likely that they will have some form of biological activity.
In order to carry out such studies, it is necessary to synthesize the drug, labeled with an isotope such as 
deuterium (2H or D), carbon-13 (13C), tritium (3H or T), or carbon-14 (14C). This makes it easier to detect any metabolites that might be formed.

Once a labelled drug has been synthesized, a variety of in vitro and in vivo tests can be carried out. In vivo tests are carried out by administering the labeled drug to a test animal in the normal way, then taking blood and urine samples for analysis to see if any metabolites have been formed.
For radiolabeled drugs, this can be done by using high-performance liquid chromatography (HPLC) with a
radioactivity detector. It is important to choose the  correct animal for these studies, since there are significant metabolic differences across different species. In vivo drug metabolism tests are also carried out as part of phase I clinical trials to see whether the drug is metabolized differently in humans from any of the test animals.

In vitro drug metabolism studies can also be carried out using perfused liver systems, liver microsomal fractions or pure enzymes. Many of the individual cytochrome P450 enzymes that are so important in drug metabolism are now commercially available.
Clinical trials
Usually, this will happen if the drug has the desired effect in animal tests, demonstrates a distinct
advantage over established therapies, and has acceptable pharmacokinetics, few metabolites, a reasonable half-life, and no serious side effects.

Clinical trials involve testing the drug on volunteers and patients, so the procedures involved must be ethical and beyond reproach. These  trials can take 5-7 years to carry out, involve hundreds to thousands of patients, and be extremely expensive.
There are four phases of clinical trials.
Phase I studies
Phase I studies take about a year and involve 100-200 volunteers. They are carried out on healthy human 
volunteers to provide a preliminary evaluation of the drug's safety, its pharmacokinetics and the dose levels that can be administered, but they are not intended to demonstrate whether the drug is effective or not.
Phase II studies
Phase II studies generally last about 2 years and may start before phase I studies are complete. They are carried out on patients to establish whether the drug has the therapeutic property claimed, to study the pharmacokinetics and short-term safety of the drug, and to define the best dose regimen.

Phase II trials can be divided into early and late studies (IIa and IIb respectively). Initial trials (phase IIa) involve a limited number of patients to see if the drug has any therapeutic value at all and to see if there are any obvious side effects. If the results are disappointing, clinical trials may be  terminated at this stage.

Later studies (IIb) involve a larger numbers of patients. They are usually carried out as double-blind placebo- controlled studies. This means that the patients are split into two groups where one group receives the drug, and the other group receives a placebo. In a double-blind study neither the doctor nor the patient knows whether a placebo or drug is administered. Most phase II trials require 20-80 patients per dose group to demonstrate efficacy.
Phase III studies
Phase III studies normally take about 3 years and can be divided into phases IlIa and Illb.
These studies may begin before phase II studies are completed. The drug is tested in the same way as in phase II, using double-blind procedures, but on a much larger sample of patients. Patients taking the drug are compared with patients taking a placebo or another available treatment. Comparative studies of this sort must be carried out without bias and this is achieved by randomly selecting the patients—those who will receive the new drug and those who will receive the alternative treatment or placebo.
Nevertheless, there is always the possibility of a mismatch between the two groups with respect to factors such as age, race, sex, and disease severity, and so the greater the number of patients in the trial the better.
Phase IIIa studies establish whether the drug is really effective or whether any beneficial effects are 
psychological. Any side effects not  previously detected may be picked up with this larger  sample of patients. If the drug succeeds in passing phase IIIa, it can be registered. Phase IIIb studies are carried out after registration, but before approval.
They involve a comparison of the drug with those drugs that are already established in the field.  
Phase IV studies
The drug is now placed on the market and can be prescribed, but it is still monitored for effectiveness and for any rare or unexpected side effects. In a sense, this phase is a never-ending process as unexpected side effects may crop up many years after the introduction of the drug. For example, the beta-blocker practolol had to be withdrawn after several years of use because some patients suffered blindness and even death. The toxic effects were unpredictable and are still not understood, and so it has not been possible to develop a test for this effect.
Ethical issues
In phases I—III of clinical trials, the permission of the patient is mandatory. However, ethical problems can
still arise. For example, unconscious patients and  mentally ill patients cannot give consent, but might benefit from the improved therapy. Should one include them or not? The ethical problem of including children in  clinical trials is also a thorny issue, and so most clinical trials exclude them. This means that most licensed drugs have been licensed for adults, and that around 40% of  medicines given to children have never actually been tested on children. When it comes to prescribing for children, clinicians are left with the problem of deciding what dose levels to use, and simple arithmetic mistakes made by tired health staff can have tragic consequences. 
Furthermore, children are not small adults. It is not a simple matter of modifying dose levels based purely on the relative body weight of an adult and a child. The  pharmacodynamic and pharmacokinetic properties of a drug are significantly different in a child compared with an adult. For example, drug metabolism varies considerably with the age and development of a child. Adverse side effects also differ.

Read more »

Posted in: Pharmaceutical Marketing

Principles of Anti-microbial Therapy

I. Overview
-Antimicrobial therapy takes advantage of the biochemical differences that exist between microorganisms and human beings.
-Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity; that is, they have the ability to injure or kill an invading microorganism without harming the cells of the host.
-In most instances, the selective toxicity is relative rather than absolute, requiring that the concentration of the drug be carefully controlled to attack the microorganism while still being tolerated by the host.

II. Selection of Antimicrobial Agents
Selection of the most appropriate antimicrobial agent requires knowledge of: 
    1) the organism's identity,
    2) the organism's susceptibility to a particular agent,
    3) the site of the infection,
    4) patient factors,
    5) the safety of the agent, and
    6) the cost of therapy.

II. Selection of Antimicrobial Agents
However, some critically ill patients require empiric therapy- that is, immediate administration of drug(s) prior to bacterial identification and susceptibility testing.
A. Identification of the infecting organism
-Characterization of the organism is central to selection of the proper drug.
Cultivation and identification
-It is generally necessary to culture the infective organism to arrive at a conclusive diagnosis and to determine the susceptibility of the bacteria to antimicrobial agents.
Gram stain
A rapid assessment of the nature of the pathogen
Useful in identifying the presence and morphologic features of microorganisms
Body fluids that are normally sterile (cerebrospinal fluid [CSF], pleural fluid, synovial fluid, peritoneal fluid, and urine) are used
Definite identification (Others)
Definitive identification of the infecting organism may require other laboratory techniques, such as detection of microbial antigens, microbial DNA or RNA, or detection of an inflammatory or host immune response to the microorganism.

Figure:
Some laboratory techniques that are useful in the diagnosis of microbial diseases

B. Empiric therapy prior to identification of the organism
Ideally, the antimicrobial agent used to treat an infection is selected after the organism has been identified and its drug susceptibility established.
However, in the critically ill patient, such a delay could prove fatal, and immediate empiric therapy is indicated.
1. Timing
Acutely ill patients with infections of unknown origin require immediate treatment.
A neutropenic patient (one who has a reduction in neutrophils, predisposing the patient to infections),
A patient with severe headache, a rigid neck, and sensitivity to bright lights (symptoms characteristic of meningitis)
2. Selecting a drug
The choice of drug in the absence of susceptibility data is influenced by the site of infection and the patient's history (for example, whether the infection was hospital- or community-acquired, whether the patient is immunocompromised, as well as the patient's travel record and age).
C. Determination of antimicrobial susceptibility
After a pathogen is cultured, its susceptibility to specific antibiotics serves as a guide in choosing antimicrobial therapy.
Some pathogens usually have predictable susceptibility patterns to certain antibiotics.
Such as Streptococcus pyogenes and Neisseria meningitidis
In contrast, some species often show unpredictable susceptibility patterns to various antibiotics and require susceptibility testing to determine appropriate antimicrobial therapy.
Such as most gram-negative bacilli, enterococci, and staphylococcal species
1. Bacteriostatic vs. bactericidal drugs
Bacteriostatic drugs arrest the growth and replication of bacteria
The body's immune system attacks, immobilizes, and eliminates the pathogens.
If the drug is removed before the immune system has scavenged the organisms, enough viable organisms may remain to begin a second cycle of infection.
Bactericidal drugs kill bacteria
Because of their more aggressive antimicrobial action, these agents are often the drugs of choice in seriously ill patients.

Figure
Effects of bactericidal and bacteriostatic drugs on the growth of bacteria in vitro.

2. Minimum inhibitory concentration
To determine the minimum inhibitory concentration (MIC), tubes containing serial dilutions of an antibiotic are inoculated with the organism whose susceptibility is to be tested.
The tubes are incubated and later observed to determine the MIC- that is, the lowest concentration of antibiotic that inhibits bacterial growth. (FIG)
To provide effective antimicrobial therapy, the clinically obtainable antibiotic concentration in body fluids should be greater than the MIC.
3. Minimum bactericidal concentration
This quantitative assay determines the minimum concentration of antibiotic that kills the bacteria under investigation.
The tubes that show no growth in the MIC assay are subcultured into antibiotic-free agar media.
The minimum bactericidal concentration is the lowest concentration of antimicrobial agent that results in a 99.9 percent decline in colony count after overnight broth dilution incubations.
Antimicrobials are usually regarded as bactericidal if the MBC is no more than four times the MIC.

D. Effect of the site of infection on therapy: The blood-brain barrier
Adequate levels of an antibiotic must reach the site of infection for the invading microorganisms to be effectively eradicated.
Capillaries with varying degrees of permeability carry drugs to the body tissues.
Capillary in brain: formed by the single layer of tile-like endothelial cells fused by tight junctions.

The penetration and concentration of an antibacterial agent in the CSF is particularly influenced by the following:
Lipid solubility of the drug:
The lipid solubility of a drug is a major determinant of its ability to penetrate into the brain.
For example, lipid-soluble drugs, such as the quinolones and metronidazole, have significant penetration into the CNS.
In contrast, β-lactam antibiotics, such as penicillin, are ionized at physiologic pH and have low solubility in lipids. They therefore have limited penetration through the intact blood-brain barrier under normal circumstances.




In infections such as meningitis, in which the brain becomes inflamed, the barrier does not function effectively, and local permeability is increased.
Some β-lactam antibiotics can then enter the CSF in therapeutic amounts.

Molecular weight of the drug:
A compound with a low molecular weight has an enhanced ability to cross the blood-brain barrier, whereas compounds with a high molecular weight (for example, vancomycin) penetrate poorly, even in the presence of meningeal inflammation.
Protein binding of the drug:
A high degree of protein binding of a drug in the serum restricts its entry into the CSF. Therefore, the amount of free (unbound) drug in serum, rather than the total amount of drug present, is important for CSF penetration.

Figure
Effects of bactericidal and bacteriostatic drugs on the growth of bacteria in vitro.

D. Patient factors
-Immune system
-Renal dysfunction
-Hepatic dysfunction
-Poor perfusion
-Age
-Pregnancy
-Lactation
E. Safety of the agent
Penicillins: The least toxic of all drugs, because they interfere with a site unique to the growth of microorganisms.
Chloramphenicol: Less microorganism specific and are reserved for life-threatening infections because of the drug's potential for serious toxicity to the patient.





Article Posted By: Md. Enamul Hoque Khan
Student of MPharm. Department of Pharmacy,
East West University

Read more »

Posted in: Pharmaceutical Microbiology