It is intcrfStiiig to note that tho al>ovo iiu'iitioiu'd coni'lusidiis 

 did not apply in tlie case of aiitlu'lniintie efficacy of the com- 

 pounds asainst To.vocara caiii.s and Tuxuscari.s Iroiiina. 



In critical tests on doRS with nionolironi hydrocarbons, 

 Wright, Schaffer, Bozicevicli and Underwood (li)37) fovuid that 

 an increase in the hydrocarbon chain was associated Avith a 

 ]irogressive decrease in water solubility from one member to 

 the next without a progressive change in anthelmintic cfti 

 cacy against JnciiluKtoiiia canhiKin. The jieak of anthelmintic 

 efficacy against hookworms was reached with n butyl bromide, 

 the efticacy thereafter declining. This compound was the only 

 member of the series possessing a water solubility lying within 

 the optimum solubility range of chlorinated hydrocarbons. It 

 appeared probable that an optimum solnbilit.v range similar 

 to that for chlorinated hydrocarbons exists among lironiinated 

 hydrocarbons so far as anthelmintic efficacy against hookworms 

 is concerned. These authors concluded that water solubility 

 api'earcd to be the factor most definitely correlated with an- 

 thelmintic efficacy of bromiuated hydrocarbons for hookworms, 

 as it is with chlorinated hydrocarbons. Wright and Schaffer 

 (lil.31) came to similar conclusions in connections with mono- 

 iodated compounds. 



l.amson and his associates (1934, 1935) studied extensively 

 the anthelmintic value of a large number of phenolic coni- 

 jionnds, most of the comparalde tests having been carried out 

 on AKcaris Uimhricoidfs in I'itro. These compounds included 

 (1) alkyl resorcinols, (2) alkyl phenols, (3) alkyl eresols, (4) 

 polyalkyl phenols, and (5) phenols with other than normal 

 alkyl side chains. The authors concuded that the ascaricidal ac- 

 tivity of phenolic compounds is related to the local irritating 

 action although all phenols exhibiting such action are not 

 necessarily active ascaricides. To be effective as an asearicide, 

 it was found that a phenol should lie a liquid or a substance 

 which will lifjuify or emulsify in the intestinal tract. Such 

 substances were found to have a melting ])oint of not over 7.5° 

 C. The solubility range of ascaricidal phenols was found to 

 lie between 1:1,000 to 1:35,000, although the most effective 

 anthelmintic of this type in the large number of compounds 

 studied was hexylresorcinol with a water solubility of 1:2,000. 



It was found that the ascaricidal properties of phenols and 

 resorcinols are increased by the introduction of alkyl radicals. 

 Such properties become more marked with the lengthening of 

 the alkyl chain and reach a maximum which differs in differ- 

 ent series, thereafter declining rapidly. The ascaricidal value 

 of dihydroxybenzenes was not strikingly different from that 

 of mouohydroxybenzenes. No significant differences were 

 found between ortho and para alkyl phenols. The introduction 

 of single normal chains into the nucleus was more effective 

 than the introduction of multiple chains with the same total 

 number of carbon atoms. Normal chains in general were more 

 effective than branched chains, although exceptions were noted, 

 such as the increased efficacy of thymol over that of n-propyl 

 meta cresol. Some of the differences in activity were thought 

 to be accounted for by the higher melting point of the branched 

 chain compounds over that of normal compounds. Cyclic side 

 chains behaved similarly to forked chains. 



From the evidence at hand it may be concluded that little 

 or no correlation can be drawn between the anthelmintic effi- 

 cacy and the chemical constitution of compounds differing 

 widely in their chemical structure. When closely allied com 

 pounds have been tested against a single species of parasite, 

 the results have indicated generally that there is a rise and fall 

 in anthelmintic activity within the homologous series, the ac- 

 tivity reaching a peak and then declining. In the case of 

 liquids, the anthelmintic efficacy is definitely linked with the 

 water solubility and in the case of solid compounds with the 

 water solubility and the melting point. In general, in homolo- 

 gous series compounds with normal chains are usually more 

 effective than those with branched chains. Finally, the evi 

 denee, meager as it is, emphasizes almost dramatically the 

 extreme specificity of anthelmintics. 



Chemical Classification 



The following classification showing the various chemical 

 groups to which anthelmintics belong is taken mainly from the 

 excellent summary of Lamson and Ward (1932). The listing 

 includes for the most part the compounds more commonly em- 

 ployed against nematode parasites and contains mainly those 

 drugs which have been shown by adequate test to possess 

 marked anthelmintic properties. For information concerning 

 the chemical grouping of other drugs, including those employed 

 in cestode and trematode infections, the reader is referred to 

 the more detailed classification of Lamson and Ward. 



1. Inorganic substances 

 Bismuth subcarbonate 

 Copper sulphate 



.\ntimony i)otassiuni tartrate 

 Colloidal iodine 

 Sodium arsenite 

 (^;irbon disulphide 

 Hydrogen peroxide 



2. Hiilofii nuUil Itydrocarbons 

 a. Alipathic 



(1) Saturated 

 Chloroform 

 Rromoform 

 Carbon tetrachloridi' 

 n Butyl chloride 

 n-Butylidene chloride 

 n-Butyl bromide 



(2) Unsaturated 

 Tetrachlorcthylene 



3. PItcnols 



a. Monoliydric phenols 



uHexylm cresol 

 Thymol 

 Carvacrol 

 Betanaphthol 



b. Diliydric phenols 



n Hexylresorcinol 

 n-Heiitylresorcinol 



4. Oiiionic acids and their salts or esters 

 Aluminum subacetate 



5. Orijnnic dioxides 

 Disuccinyl perovide 



(i. Organic antimomi coiiiponnds 



Sodium antimony III jiyrocatechin disulphonate of sodium 



' ' Filsol ' ' 



"Stibsol" 



7. Terpcnes 



a. Bridged ring 

 (1) Peroxides 



Ascaridol 



b. Sesquiterpenes 

 Santonin 



8. Alkaloids 

 Nicotine 

 Pyrethrine 



9. Enzymes 

 Fie in 

 Bromelin 



10. Plant products 

 Leche de higueron 

 Digenea simplex 

 Oleum chenopodii 

 Oleum eucalypti 

 Oleum terebinthinae 

 Quassia 



Tobacco 



11. Dyes and similar conij)ounds 



a. Thiaziu 

 Phenothiazine 



b. Triamino triphenyl methane 

 Gentian violet 



c. Phthalein 

 Mercurochrome 



General Principles of Anthelmintic Medication 



Elscwliere in this discussion we have emphasized the specific- 

 ity of anthelmintics, a thing which is of prime importance 

 from a medical standpoint. It is not only a waste of time and 

 effort to employ a nonspecific treatment against a given para- 

 sitic infection but it is a hazard to the safety and well being 

 of the host. Specific treatments cannot be chosen unless an 

 accurate diagnosis is made. Hence any anthelmintic medica- 

 tion should be predicated on such a diagnosis. Even today when 

 the average physician or veterinarian is far better qualified 

 than formerly in the field of parasitolog.y, we find practitioners 

 administering anthelmintic treatment on the basis of a clinical 

 diagnosis without proper laboratory checks. No parasitic in- 

 fection is characterized by pathognomonic symptoms and the 

 shifting sand of the clinical picture is not a sufficiently firm 

 foundation upon which to base treatment with drugs which at 

 best have only a small margin of safety. 



In the past, mass treatment of large population groups has 

 been a popular method of attack against a given parasite. 

 The benefits anticipated from such a procedure have not been 

 generall.v realized for all too frequently the important sub.iect 

 of prophylaxis has not been given sufficient attention. Under 

 such circumstances, the population groups involved have con- 

 tinued to indulge in the habits responsible for their parasitic 



335 



