UNIT 48

Drug Tolerance
The failure of the individual to react to the ordinary dose of a drug is known as tolerance. Certain species of animals tolerate quantities of drugs which would be fetal to others of the same size. In fact, so frequently is this the case that it is impossible to determine the fatal dose of any drug on an animal from experiments performed upon others of a different species, even though it be nearly related. One of the most remarkable examples of this form of tolerance is met with in the hedgehog, which resists large doses of many very active poisons. Another well-known example is the tolerance of the rabbit to large quantities of atropine. A form of tolerance which is a matter of everyday observations is that induced by the prolonged use of a drug, which has been called acquired tolerance, or mithridatism, from the tradition that Mithridates protected himself in this way from the danger of poisoning. The most familiar example of this form of tolerance is that acquired for tobacco (nicotine); the first cigar often induces violent poisoning, but if a habit be formed, considerable amounts of nicotine may be absorbed without apparent harm, because the tissues become accustomed to the presence of small quantities of nicotine, and thus fail to react to it. This tolerance is entirely different from the immunity induced by toxins. An important form of tolerance is the resistance developed by pathogenic organisms for certain drugs. Thus by subjecting susceptible organisms to inadequate doses of a drug it is possible to render them "drug fast", that is, resistant to the drug even when used in what would originally have been an adequate dpsage. This form of tolerance can be acquired by organisms cultivated in vitro as well as in vivo. Very often while some tissues acquire tolerance for a poison, others fail to do so, and either react in the same way as before or may suffer from the prolonged use of excessive quantities: for example, although after prolonged use morphine loses its action on the brain so that large doses have to be given to relieve pain, tolerance is less developed in the bowel, so that constipation continues to be induced by smaller amounts; similarly in a dog tolerant to morphine, the cardiac inhibitory centre retains its sensitiveness to it. Some animals fail to develop tolerance for certain drugs; for example the rabbit remains sensitive to morphine after prolonged treatment. It is to be noted that tolerance is soon lost if the drug be discontinued for some time. This is of great importance in cases of opium-eating, for a person who has taken opium for a long time acquires a tolerance for the drug, so that sometimes enormous quantities are required in order to induce the ordinary effects; but if to habit be discontinued for some time, the tolerance is lost, and a dose which would formerly have had little effect may now induce dangerous poisoning. The prolonged use of one drug my establish tolerance for others of the same class. Thus chronic drunkards become less sensitive to large quantities of alcohol, and are also more resistant to the action of other ordinary persons, this being due to the fact that ether and alcohol act on the same a nerve cells in the same direction, and probably induce the same changes in the

protoplasm.

246

ENGLISH IN MEDICINE

Pronunciation
tolerance I ['totems] dose [dous] poisoning jj ['poizanii)] immunity [i'mjurniti]

Words and Phrases

i n f a c t i s m e t w i t h t o l a r g e q u a n t i t i e s a c q u i r e d t o l e r a n c e d r u g f a s t t

h a t i s oth ers fail to do so eith er rea ct... or ma y suff er in ord er to due to de fapt s e n t l n e t e I a l a

c a n t i t i m a r i t o l e r a n c t i g a t r e z i s t e n t l

a m e d i c a m e n t a d i c

altele nu reues c sau reaci oneaz ... sau pot s sufere n scopu l de a cauza t (dator it)

Explanatory Notes I
hedgehog = a small insecteating animal covered with spines. It defends itself by rolling up into a ball with the spines pointing outwards, rabbit = a small animal of the hare family; in its wild state it is usually of a light brown colour, but domestic varieties are white, black, and bluish-grey, atropine = an alkaloid obtained from Atropa be l lado na. Mithridates = king of Pontus (132-63 B.C.), who is said to have acquired immunity to poison by the prolonged use of drug, and to have succeeded so well that he failed later in an attempt at suicide, mithridatism = immunity against the

action of a poison produced by small and gradually increasing doses of the same drug, cigar = a roll of tobacco leaves for smoking. ether '= a substance resulting from the action of an acid on an alcohol. 1. When very large doses large, big, great sunt sinonime. Se traduc In limba romn: mare. large este n general folosit pentru dimensiuni (suprafa), capacitate, cantitate ji se traduce; a)mare;
a large man a large building a large tree
b)spaios

II

a large dog

roomy;

spacious,

a large room a large house

c)mare, ntins, vast (ntindere, sumS, numr) etc.;

UNIT 49

Epinephrine
Mechanism of Action. Epinephrine induces its effect by combining with receptors in the end-organs. After ergotoxine, an alkaloid which antagonizes the action of epinephrine in some organs, the end-organ remains active though the receptor on which epinephrine acts is paralyzed. Epinephrine also does not act on the anatomical nerve ends, for.after these have degenerated and disappeared, the usual effects of epinephrine are elicited by the injection. It is obvious that the action is exercised on some substance intermediate between the nerve and the end-organ. Epinephrine and other catecholamines promote the accumulation of cyclic 3,5-adenosine phosphate and active phosphorylase and it has been suggested that they induce their effects through this reaction. Their action is terminated by amine oxidase and O-methyl transferase. Epinephrine injected intravenously acts in very small quantities, 0.001 mg often sufficing to raise the blood-pressure in the dog. The effect is of very short duration, but it may be repeated indefinitely by fresh injections. Epinephrine applied locally induces such vasoconstriction that it is only slowly absorbed. Injected hypodermically it causes local ischemia so that comparatively large doses (0.5 to 1 mg) compared with those necessary by intravenous injection are required to give a distinct rise of blood-pressure and dilatation of the bronchi; injected intramuscularly it induces stronger general effects. Epinephrine is inneffective when administered orally unless used in large doses (4 mg), being converted in the gastro-intestinal tract to toxic oxidation products. The massage of the skin over the area in which a hypodermic injection has been made-enhances the effect of the drug, the action of which may be elicited in this way even an hour after its injection. Toxicology. Animals are poisoned by large amounts injected hypodermically, with pros&tion, collapse and paralysis of the central nervous system. Large doses induce pulmonary edema as a result of an increase in pulmonary venous pressure and congestion of the capillaries. Some protection against this lethal action is afforded by morphins and chloral hydrate with a more complete protection by papaverine. The minimal lethal dose of epinephrine administered subcutaneously to man is about 10 mg per kilo of body weight, but alarming symptoms may follow the intravenous injection of as little as 0.3 mg.

Pronunciation
epinephrine - [epi'nefrin] adrenaline - [a'drenalin] paralyze - f'paeralaiz] catecholamine - [kaeti'kobmin] massage - [msesa^] toxicology [.tdksi'^IM^i] papaverine [pa'peivarin]

i
* I9 1 I*

I
I

I r

fis; {J m9 9 1 if t

tl %

f11 if 12
1

Ii

I : .

li m
f p 1I # m i l

i1

UNIT 50

Drugs of the Carbohydrate Group

Glucose (Dextrose). The most important simple sugar in the living cell is glucose. It accumulates in many fruits, cherries, strawberries, juniper fruits (up to 4 per cent), and grapes (up to 20 to 30 per cent). Glucose is produced on an industrial scale by hydrolyzing starch with dilute acid. After hydrolysis, the acid is neutralized with sodium carbonate, and the solution is decolourized and evaporated under vaccum to a syrup (Liquid Glucose). This syrup which is widely used, contains not only glucose but also di-, tri-, and tetrasaccharides from incomplete hydrolysis of the starch. Pure glucose is obtained by crystallization. Glucose has a variety of uses in technology (crystallization inhibitors, in the fermentation industries, in tooth pastes, in the tanning industry, in silvering of mirrors, and many other things^ Fructose (Levoluse). This sugar is obtained by hydrolysis of inulin, a polysaccharide of fructose. Sources of inulin are Helianthus tuberosus and Taraxacum officinale. While glucose overflows into the urine, fructose is metabolized by diabetic individuals. The reason for this difference is not yet quite understood, but it is known that insulin counteracts the inhibitory action of the anterior pituitary on hexokinase, an enzyme which is involved in the phosphorylation of glucose, a step necessary for the further metabolism of glucose. Phosphorylation of glucose is impaired in the diabetic, while the phosphorylation of fructose is not influenced by insulin. Fructose is used in parenteral feeding and has been recommended in diabetic emergencies (acute ketoacidosis). Honey. Honey consists of a concentrated solution or semicrystalline mixture of glucose and fructose in equal amounts together with small quantities of vitamins and other compounds. It is produced in the stomach of the bee by inversion of sucrose, which the bee collects from flower nectar. Cellulose. The substance that makes up the major parts of the cell wall in plants is a polysaccharide known as cellulose. Its molecule is built up of more than a thousand glucose units attached to each other in ^-linkage to form a straight chain.

Cellulose is insoluble in all ordinary solvents. It is prepared by extracting wood and other materials with strong alkali or calcium sulfite which dissolves the lignin, a substance that commonly accompanies cellulose. Cellulose may then be dissolved in Schweitzer's reagent. Upon acidification of the solution of the copper-cellulose complex, cellulose precipitates. Cellulose is not readily hydrolyzed, but by use of elevated temperatures, high pressures, and high acid concentration hydrolysis is possible. The free alcoholic groups of cellulose ut easily acetyiated This property is utilized in the manufacture of acetyl-cellutost. which is employed extensively in the manufacture of textile fibres. The alcoholic groups cia also be estcrified with nitric and other acids. Nitrated cellulose is used in explosives

PHARMACOLOGY AND THERAPEUTICS

25 5

Cellulose a most important foodstuff for herbivorous animal,. The animal does no. Huce i en2yme' ,celluase' to for the hydrolysis of cellulose tot microbes if | rumen and ,n the intestines of herbivorous an.mals produce ellu?e"nd Z mak(: cellulose unliable as a food. Without the existence of microorga isms cellu o wlI|d accumulate and life would soon be impossible on the c " 8 earth because ofThe re ul ing shortage of carbon.

f r au frVeS as 3 flUer and thiS Contribules mechanically to the otil.ty of the intestines. Cellulose, being chemically inert and insoluble, is used in ft m Bfji SK fl <87 ! 93 per cent cellulose). Many plant fibres consisting mostly of cellulose are used in the manufacture of cloth and plastics.

Pronunciation
g l u c o s - ['glurkouz] e f r u c to s e ['frAktous] d i lu te [dai'lu:t] crystallization - ['krists'laizei/an] - [heksou'kaineisl parenteral - [pae'rentsral] insoluble - [in'soljubal]

Words and Phrases

the living cell dilute acid sodium carbonate the tanning industry the silvering of mirrors the phosphorylation of glucose parenteral feeding in /J-linkage strong alkali calcium sulfite Schweitzer's reagent
acidification of the solution

free alcoholic groups tht resulting shortage of carbon celula vie acid diluat carbonat de sodiu industria de tbcit piei argintarea oglinzilor fosforilarea glucozei alimentaie parenteral (pe cale de injecii) n caten alcali puternici sulfit de calciu reactivul Schweitzer aciduirea soluiei concentraie mare n acid grupe alcoolice libere diminuarea carbonului

high acid concentration

Explanatory Notes
fc'tlft elecampane, wild tun-flower, the root of Inula helenium. or Insulin a* I preparation made from the pancreas of the pig or ox; it is used I the treatment of diabetes; by its action the sugar content of the blood and urine is reduced to normal, the ability of the organism to reduce carbohydrate being increased. J pi I ttrn tit liquid jg flwctl which feMl Mftk(MOm