Factors Modifying The Dose and Actions of Drugs

Factors Modifying The Dose and Actions of Drugs

The nature of the systemic effects of drugs depend on the amount of drug, route of its administration and amount of its absorption and the following other factors.


Posology:

The study of the dose is known as Posology. The dose is the amount of a drug which gives the desired therapeutic effect in average number i.e., 50% of patients (ED50) - The minimal dose is the smallest amount which has therapeutic effect in 50% patient and maximal dose is the largest tolerated does in average patients without toxic symptoms. The therapeutic dose lies between these two doses. The median lethal dote (LD50) is the amount of drug which is fatal in the 50% of experimental animals. The Therapeutic Index (TI) is found by dividing the (LD50 ) by the therapeutic dose ((ED50) .The British Pharmacopoeia gives average dose for the adult person between eighteen to sixty years of age. The children below 18 and persons above 60 should be given a dose below the adult dose to avoid adverse effect .There are a few formulae for calculation of dose of the children under 12 years.

  1. Clark's Rule= (Weight of the child in pounds /150) X Adult dose
  2. Dilling's Formula= ( Age/20) X Adult dose
  3. Young's Rule= (Age X Adult dose) / Age+12

Thus the does of sodium bicarbonate for a child of 6 years = Adult dose of sodium bicarbonate is 1—4 Gram.
Hence, the required dose will be = 6 / (6+12) X 1 Gram =1/3 Gram i.e. 1/3 to 1 X 1/3

The dose required for the age between 12 to 16 years will be from ½ to 2/3 of the adult dose.

The children can tolerate iron, belladonna, and chloral preparations relatively better than adult but they can not tolerate opium and morphine preparations except in very small doses.
The dose for infant be calculated from their body surface and must not be calculated from the above formulae.

Sex:

Women usually, require a relatively smaller dose than man. Drugs should he avoided as far as possible during pre­gnancy and lactation to prevent harmful effect on the fetus and the baby.

Time and route of administration—

The action of drugs taken by mouth is greatly modified due to the presence or absence of food, in the stomach and intestine. The irritant drugs, like iron is better tolerated and absorbed when given after food. Adrenaline, Insulin, etc. should be given by Injection for they are destroyed by the digestive enzymes when given by mouth. Magnesium sulphate acts as purgative when given by mouth but acts as sedative when given by I. V. Sleeping pills acts better when given at bed time than during day time.

Tolerance & Addiction—

Body has the capacity to handle certain drugs even when given repeatedly. .As a result, their doses should be gradually increased to keep the action constant. This condition is called tolerance. Morphine, alcohol etc . . . . show remarkable degree of tolerance in man. When taken for some time these drugs not only show tolerance but also produce a mental and physical condition of intense urge to continue to take them. This is called addiction. If the drug is stopped the addicted people show withdrawal sickness and may even die.

Intolerance or Susceptibility —

In this condition, some patients may develop the usual symptoms of overdose even when a thera­peutic dose is given to them. In other words, its means a greater response than normal expected response to the ordinary dose.

Idiosyncrasy—

This is an inherent peculiarity of the persons in responding to certain drugs in a way completely abnormal from the usual actions of that drug. Thus morphine may produce excitation instead of sedation. This reaction occurs usually from the very first dose of the drug. Some of these actions have been found to be due to genetic abnormality.

Drug allergy or Hypersensitivity—

In this condition, the abnormal reaction occurs usually from the second or subsequent doses. The first dose (antigen) generally stimulates the body to produce some reactive substance (antibody), which sensitizes the tissues of the body. When a second dose of that drug is given the reaction {antigen—antibody reaction 1 occurs in the tissue called allergic reaction. The reactions may be immediate (anaphylactic) or a delayed one (hypersensitivity). The anaphylactic reactions are—fall of blood pressure, shock, collapse, bronchospasm, cyanosis and even death. The hypersensitivity reactions are—urticaria, skin rash, asthma, drug fever, dermatitis, hepatitis, hay fever etc.
Antihistaminics, adrenaline and cortisone preparations are used to treat these reactions.

Synergism or Potentiation:

When two similar drugs but not having action on the same site or do not cause same qua­lity of action; are combined together, then one may enhance the response of the other. In that case, the combined effect of the two will produce response which is far greater than that of the either drug given alone in much larger dose and also greater than that could be expected from simple addition of their individual effects. This type of synergism is particularly found in antibiotic combinations, such as penicillin and streptomycin, cloxacillin and penicillin and sulphonamide and trimethoprim. Adrenaline and cocaine and Mersalyl and ammonium chloride combinations show the other examples of potentiation.

Pathological Condition:

Pathological conditions of the body also modify the drug action. Digitalis glycosides improve the cardiac functions and cause diuresis only in the patient with congestive heart failure. Aspirin and other antipyretic reduce body temperature only when there is fever.

Genetic factor:

It also affects drug action due to genetic differences among the races and certain persons in the same popul­ation. Isoniazid may be acetylated either rapidly or slowly according to genetic difference in the person. In American black and white population 50% are rapid and 50% are slow acetylates and in Latin Americans 35% slow acetylates and hence more toxicity in them. Primaquine causes hemolytic anemia in those persons whose R.B.C, lacks the enzyme glucose 6-phosphate dehydrogenase.

Antagonism:

The combined effect of the two drugs may be less than that of the effect of their individual dose, as one may oppose the action of the other. This condition is called antagonism. The important examples are the acetylcholine to atropine, histamine to antihistamine, morphine to nalorphine etc. This phenomenon of drug antagonism is utilized in the treatment of poisoning or overdose of the drugs by giving the appropriate antagonist called antidote. Nalorphine & Naloxone are the antidotes in morphine poisoning.

Cumulative action:

Some drugs are excreted so slowly from the body such that therapeutic dose taken in 24 hours is not fully excreted by that time and if their daily administration is continued even in therapeutic doses for some time, the drug concentration in the body is gradually increased and suddenly the toxic symptoms develop. Emetine and glycosides of digitalis are important examples to produce this phenomenon.

Plasma half life:

The falling of plasma concentration of a drug to its half of the initial level takes a constant or fixed time called half life. Longer the half life; the drug requires less frequent administration.

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