Diagnosis, evaluation and treatment of coronary artery disease by exercise simulation using closed loop drug delivery of an exercise simulating agent beta agonist

A transdermal iontophoretic device for closed loop delivery of a drug to a mammal comprising:

• at least one cardiovascular sensing device being operatively connected to said mammal;
• said device simultaneously being operatively connected to a device for receiving and processing a signal from said sensing device;
• said receiving and processing device simultaneously being operatively connected to a power source;
• said power source simultaneously being operatively connected to a transdermal iontophoretic drug delivery device;
• and
• said drug delivery device simultaneously being operatively connected to said mammal;
• wherein said drug has the chemical structure:
• ##STR9## wherein X.sub.1 and X.sub.2 ar independently hydrogen, hydroxy, methoxy or carbamoyl, provided that X.sub.1 and X.sub.2 are not both hydrogen or carbamoyl;
• one of Y.sub.1 and Y.sub.2 is hydrogen and the other is hydrogen or methyl, provided that if Y.sub.1 is methyl, then X.sub.1 is not carbamoyl;
• Z is hydrogen or hydroxy;
• and n is 2 or 3;
• or a pharmaceutically acceptable acid addition salt thereof.

A closed loop transdermal iontophoretic delivery system for controlling the delivery of a drug to a mammal comprising:

• means for monitoring at least one cardiovascular variable of said mammal, and means for producing a signal from said monitoring means;
• means for receiving and processing said signal;
• and
• means for controlling delivery of a drug to said mammal through a transdermal iontophoretic delivery device in response to said signal, wherein said drug is an ionized catecholamine and wherein said drug has the chemical structure:
• ##STR10## wherein X.sub.1 and X.sub.2 ar independently hydrogen, hydroxy, methoxy or carbamoyl, provided that X.sub.1 and X.sub.2 are not both hydrogen or carbamoyl;
• one of Y.sub.1 and Y.sub.2 is hydrogen and the other is hydrogen or methyl, provided that if Y.sub.1 is methyl, then X.sub.1 is not carbamoyl;
• Z is hydrogen or hydroxy;
• and n is 2 or 3;
• or a pharmaceutically acceptable acid addition salt thereof.

A closed loop transdermal iontophoretic delivery system for controlling the delivery of a drug to a mammal comprising:

• means for monitoring at least one cardiovascular variable of said mammal, and means for producing a signal from said monitoring means;
• means for receiving and processing said signal;
• means for controlling delivery of a drug to said mammal through a transdermal iontophoretic delivery device in response to said signal;
• and
• an air activated tourniquet operatively connected to said receiving and processing means and said mammal.

A device for eliciting cardiovascular responses in a mammal similar to cardiovascular responses elicited by aerobic exercise which comprises:

• (a) a drug delivery system for administering an exercise simulating agent into said mammals blood stream;
• (b) an infusion control system for controlling infusion of said exercise simulating agent into the blood stream of said mammal which is operatively connected to said delivery system, said infusion control system including a discontinuing system for discontinuing infusion of exercise simulating agent into said mammal's blood stream when a preselected time period has expired or when said cardiovascular responses are outside said preselected range and which is operatively connected to said drug delivery system, said control system further including a second drug delivery system for administering a .beta.-adrenergic blocking agent controlled by said discontinuing system which is activated simultaneously with the discontinuing system and which administers said blocking agent when said discontinuing system is activated;
• and
• (c) a monitoring system connected to said mammal to measure response levels of said mammal to said exercise simulating agent which is operatively connected to said drug delivery system and infusion control system such that infusion of exercise simulating agent may be feedback-controlled to obtain and maintain a preselected range of responses of said mammal to said exercise simulating agent.

A device for eliciting cardiovascular responses in a mammal similar to cardiovascular responses elicited by aerobic exercise which comprises:

• (a) a drug delivery system for administering an exercise simulating agent into said mammal's blood stream;
• (b) an infusion control system for controlling infusion of said exercise simulating agent into the blood stream of said mammal which is operatively connected to said delivery system, said infusion control system including a discontinuing system for discontinuing infusion of exercise simulating agent into said mammal's blood stream when a preselected time period has expired or when said cardiovascular responses are outside said preselected range and which is operatively connected to said drug delivery system, said control system further including an air activated tourniquet for terminating absorption of said exercise simulating agent into said mammal's blood stream when said discontinuing system is activated;
• and
• (c) a monitoring system connected to said mammal to measure response levels of said mammal to said exercise simulating agent which is operatively connected to said drug delivery system and infusion control system such that infusion of exercise simulating agent may be feedback-controlled to obtain and maintain a preselected range of responses of said mammal to said exercise simulating agent.