AFLATOXINS

Aflatoxins are the toxic metabolities of toxigenic fungi Aspergillus flavus and A. parasiticus. These moulds invade and grow on all sorts of stored feed ingredients and organic matters and produce mycotoxins under favourable aerobic conditions when sufficient moisture (>15%) and relative humidity (90-95%) and ambient temperature (24-25oC) are available, through toxin production to some extent can take place at lower or higher temperatures as well.  

Aflatoxins are produced in varying quantities in a variety of grains and nuts, pea nut is the most important one. Cotton see meal, cotton seed cake, maize corns, com-meals, silages, wheat, barley, oats, rice and other grains or cereal products are invaded by these fungal toxins.

            Several aflatoxin fractions have been isolated and differentiated from one another by their fluorescence under ultraviolet, RF values on thin layer chromatography and structural identification and synthesis. Aflatoxins which fluoresce blue under ultraviolet light are termed as BI and B2 while others which are dihydroderivatives of B₁ and B₂ and fluoresce green are designated as G₁ and G₂ Hydroxylated metabolites of B, and B2 aflatoxins are excreted in milk and are termed as MI and M₂. Human exposure occurs on consumption of aflatoxins from the mycotoxins- infested feed stuffs as well as meat and milk of animals consuming toxigenic fungi contaminated feeds.

            Out of the four main aflatoxins, aflatoxin B₁ (AFB₁) is most important because of its toxicity and high concentration in the contaminated feeds. B₂ and G₂ are present in very less concentrations. The order of toxicity is: B₁ > G₁ > B₂ > G₂. These toxins are relatively heat resistant and not soluble in water. The melting points for B_I, B2 ' G_I and G₂ aflatoxins are 269°, 238°, 245° and 239°C, respectively. Even the toxigenic fungi or toxins are not destroyed by milling of the grains.

            Aflatoxins are a group of polycyclic, unsaturated, substituted coumarin derivatives with highly reactive bifuran nucleus on one side and a pentenone (B toxin) or a six membered lactone (G - toxin) ring on the other side as shown in Fig. 8.1.

Presence of additional oxygen in the AFG compounds results in reduction of their activity by a factor of 2 while unsaturated compounds are 4-5 times more potent compared to dihydro derivatives. The structure of B toxin resembles closely with the structure of pyrrozolidone which has got basic carcinogenic activity. Aflatoxins are potent mutagens, carcinogens, teratogens and liver damaging agents.

Mechanism of toxicity: Majority of the aflatoxins ingested in feed are physically bound to ruminal contents and as little as 2-5% reach the intestines. Aflatoxin BI in excess of 100  mg/kg of feed is considered to be toxic to cattle. Aflatoxins are rapidly absorbed from the intestine and bound to blood proteins. Liver removes most of the toxins from the blood stream. AFB₁ is primarily metabolized by a microsomal cytochrome P-450 dependent mixed function oxidase system in the liver and other organs to AFB₁ -2,3 epoxide mainly, which is a highly reactive intermediate. Other metabolites of AFB₁ are Q₁, P₁, B₂ and aflatoxicol. Epoxides are chiefly detoxified by glutathione

PRESCRIPTION WRITING

The prescription is one of the most important therapeutic transactions between physician and patient. The art of prescription writing is an ancient inheritance. The ancients started their prescription with an appeal to the gods for its success. The ancient symbol, Rx, signifying the appeal, was established centuries ago and has been carried down to the present time.

Many ancient prescriptions were noted for their multiple ingredients and complexity of preparation. The importance of the prescription and the need for complete understanding and accuracy made it imperative that a universal and standard language be employed. Thus, Latin was adopted, and its use was continued until approximately a generation ago. Present-day prescription practices lead, for the most part, to prescriptions containing a single ingredient, written in English, with doses given in the metric system. The ancient "Rx" and the Latin "Signatura," abbreviated as "Sig.," are all that remain of the ancient art of the prescription.

Drug use is a complex process and there are many drug related challenges at various levels, involving prescriber, pharmacists and patients. While medication misadventure can occur any where in the health care system from prescriber to dispenser to administration and finally to patient use, To avoid undesirable and/or serious effects on the patient, both physician and pharmacist must render the highest of professional services. Accurate diagnosis; proper selection of medication, dosage form and route of administration; proper size and timing of dose; precise dispensing; accurate labeling; and correct packaging all must be provided.

Types of Drugs

Prescriptioned/Legend Drugs: These drugs may not be dispensed by a pharmacist without a prescription from a physician, osteopath, dentist, etc. Federal and State drugs are "legend." Labels on these medications carries the legend: "Caution! Federal law prohibits dispensing without a prescription."

Controlled Drugs: In addition to requiring a prescription, these drugs require additional safeguards for storage. Refills are also limited. Both State and Federal government agencies promulgate regulations regarding these drugs. The Federal agency is the Drug Enforcement Administration and the State agency is the Division of Narcotics and Dangerous Drugs of DHHR.

Over-the-Counter (OTC) Drugs: These drugs do not require a prescription.

Form of the Written Prescription

A prescription consists of the superscription, the inscription, the subscription, the signa, and the name of the prescriber.

Superscription

The date when the prescription order is written; the name, address and age of the patient; and the symbol Rx (an abbreviation for "recipe," the Latin for "take thou."

Inscription

The body of the prescription, containing the name and amount or strength of each ingredient.

Subscription

The directions to the pharmacist, usually consisting of a short sentence such as: "make a solution," "mix and place into 10 capsules," or "dispense 10 tablets."

Signatura

From the Latin "signa," meaning "write," "make," or "label," this sections contains the directions to the patient. These should always be written in English; however, physicians continue to insert Latin abbreviations, e.g. "1 cap t.i.d. pc," which the pharmacist translates into English, "take one capsule three times daily after meals." Since the pharmacist always writes the label in English, the use of such abbreviations or symbols should be discouraged.

The instruction, "take as directed," is not satisfactory and should be avoided. The directions to the patient should include a reminder of the intended purpose of the medication by including such phrases as "for pain," "for relief of headache," or "to relieve itching".

Labeling

When the physician wants his patient to know the name of the drug, the box on the prescription form marked "label" should be checked.

Refills

The physician should designate the number of refills he wishes the patient to have.

Proprietary vs. Non-Proprietary ("Generic") Prescriptions

In recent years, some hospitals and private physicians are indicating on the prescription their willingness or desire that the pharmacist dispense a non-proprietary or "generic-named" preparation instead of the trade name item written on the prescription. Some have a box on the prescription designated "N.P.P." In this way, the pharmacist can use a form of the drug which may be less expensive to the patient.

The amount to be dispensed should be clearly stated and should be that needed by the patient. Excessive amounts should never be dispensed, as it is not only expensive to the patient, but may lead to accumulation of medicines in the home, which later can cause harm to the patient or members of his family. It is far better to have several refills of a prescription than to have an excessive amount prescribed at one time.