OPIUM AND MORPHINE 271 



sion, while large doses give rise to spinal reflex excitability in the lower 

 animals — especially in the horse, ass, cattle and cats. 



Medulla. — Large medicinal doses stimulate the vagus and vasocon- 

 strictor centres, and pupillary centre in man, and usually in dogs, while 

 the respiratory and cough centres are depressed. 



On the Spinal Cord. — Small medicinal doses depress the motor 

 cells, but large and toxic amounts stimulate the motor cells indirectly 

 and cause convulsions — probably — as in strychnine poisoning — by in- 

 creasing the activity of the receptive and transmitting cells of the cord. 



Convulsions, caused by spinal and cerebral motor stimulation, rarely 

 occur in man or dogs, but are common after toxic amounts in horses, 

 cattle or cats. The result of a fatal dose is paralysis of the central 

 nervous system, including the respiratory and, to much less degree, the 

 vagus centres. 



The unique and inestimable value of opium depends upon its ano- 

 dyne action. Relief from suflEering is often induced without the produc- 

 tion of sleep. 



Muscular weakness is present in man and dogs, but even this evi- 

 dence of depression may be absent in horses and ruminants, yet pain 

 be effectually relieved. 



Initial stimulation of the vomiting centre may cause emesis; but, 

 as depression of the centre rapidly ensues, the act becomes later im- 

 probable. The excitability of the motor and sensory nerves is slightly 

 increased, but otherwise the nerves are not affected except in poisoning, 

 when the sensory, and later the motor nerves are paralyzed. The mus- 

 cles remain uninfluenced. 



Respiration. — ^After large doses of opium respiration becomes slow 

 and feeble. Death occurs from failure of the respiratory centres — ■ 

 partly due to their insensitiveness to CO2 stimulation. Thus exagger- 

 ated breathing, due to COj accumulation, alternates with temporary arrest 

 of respiration (Cheyne-Stokes breathing). 



Circulation. — Medicinal doses commonly produce little effect upon 

 the heart. Large doses slow the heart's action, while toxic quantities 

 depress the organ. The cardiac muscle may be slightly stimulated, with 

 acceleration of the pulse, but depression soon follows more or less syn- 

 chronously with stimulation of the vagus centre, so that the pulse be- 

 comes infrequent. Toxic doses of morphine directly depress the rhythm, 

 conductivity, and contractibility of the heart muscle, so that irregular- 

 ity, and heart block occur in poisoning. Finally, before death, depres- 

 sion of the inhibitory apparatus occurs, and this, coexisting with depres- 

 sion of the heart itself, produces a feeble, rapid pulse, characteristic of 

 the last stage of opium poisoning. Death occurs with diastolic arrest of 

 the heart owing to failure of the cardiac muscle, although fatality is 

 mainly due to the more powerful effect of the drug upon the respiratory 

 centre. 



The action of opium upon the vasomotor system is unimportant. 

 Immediately after the administration of large doses there is a primary 

 stimulation, followed in the toxic stage by some depression of the vaso- 

 motor centres in the W^kS^^^Mcm^^' 



