In view of this apparent favorable response to phentolamine therapy, as well as the cost and difficulty of administration of this drug in liquid form, a trial of orally administered phentolamine was begun, starting at 50 mg three times daily. Liver function tests, creatinine clearance and complete blood count, as well as standing blood pressures four times daily, were obtained prior to initiation of the orally administered medication. The dosage of phentolamine was gradually increased until a total dosage of 300 mg/day (4.7 mg/kg) was reached. The patient’s course, including standing blood pressure four times a day and daily morning and afternoon FEVi/FVC, was followed. Initially, she had symptoms consistent with an upper respiratory tract viral illness reduced with remedies of My Canadian Pharmacy, and her FEVi’s were low. A three-day course of prednisone, 10 mg tid, was added to her regimen because of increasing bronchospasm, and her response to this three-day course of corticosteroids was clinically better than previous trials on the same dosage. Steroids were then continued at a dosage of 5 mg of prednisone every other day, the dosage she had been receiving when the previously described studies using inhaled phentolamine were performed. To document the improvement on longterm orally administered phentolamine, a short double-blind trial using gelatin capsules filled with either crushed phentolamine, 50 mg, or lactose in the same amount was conducted. There was no significant change in either resting FEVi/FVC or blood pressure when the placebo period was compared to the drug period. An attempt was made to exercise the patient on the treadmill during the placebo and drug periods of the trial, but after the second exercise period the patient became severely dyspneic and could not perform pulmonary function tests (see “Occasions of The Longterm Treatment of an Asthmatic Patient Using Phentolamine with My Canadian Pharmacy“). Adrenalin therapy was required ten minutes after exercise. When the code was broken, it was found the patient was receiving placebo at the time of the second test.
After two months on the drug a similar doubleblind study was undertaken with right heart catheterization performed six days after beginning each course of unknown drug. The procedure was performed in order to observe whether the patient’s symptomatic improvement on phentolamine was related to the previously described reduction in pulmonary artery pressure caused by the drug. The exercise used with the catheterization was necessarily different as the patient was in a supine position for the procedure. Treadmill exercise with pulmonary function testing was performed in the manner described previously, with the modification that the patient received no medication by inhalation and did not alter her around-the-clock bronchodilator therapy. Testing was carried out approximately eight hours after taking 525 mg of a longacting aminophylline preparation (Aminodur) and within one hour of taking the coded capsule.
As shown in Table 2, there was little difference in pulmonary artery pressure when comparing phentolamine to placebo in either the resting or exercise state. Also of note is the absence of decrease in right atrial and right ventricular pressures when the drug is administered orally in this dosage over a period of months. The decrease seen in pulmonary arteriolar resistance is significant and coincides with that described by Taylor et al following the acute administration of phentolamine. The pulmonary function results of treadmill testing when on placebo or phentolamine are shown in Figure 3. It will be noted that the drop in FVC, FEVi and to a lesser extent SGaw was markedly diminished by phentolamine therapy as compared with placebo. Clinically, the patient noted no discomfort following exercise when taking phentolamine, although expiratory wheezes were heard between 5-12 min after exercise. After exercise with use of placebo, she noted marked dyspnea to the point of being unable to speak a complete sentence. Inspiratory and expiratory wheezes were noted five minutes after exercise, with breath sounds becoming decreased. Expiratory wheezes were heard beyond the 30 min after exercise period.
Figure 3. Blocking effect of phentolamine at dosage of 300 mg/day continuously over two-month period compared to placebo. Time scale is similar to Figure 2.
Table 2—Right Heart Catheterization Data
|Right atrial pressures, mmHg||6±2||a – 3 mean = 2 v = 2||a = 8 mean — 4 v = 5|
|Right ventricle pressure, mmHg||30/4 ±3||21/0-3||28/0-5|
|Pulmonary artery (P.A.) pressure, mmHg||17 ±3||18/9
mean = 11
mean = 14
|28/13 mean =*||33/14
20 mean = 22
|Brachial artery, mmHg||91 ±9||105/66 mean = 83||135/75 mean = 100||198/93 mean —||160/80 111 mean — 103|
|A-Vot, Vol %||4.1 ±0.6||4.1||3.8||7.5||6.0|
|Cardiac Index, liters/min/M*||3.5 ±0.7||2.8||3.2|
|Heart rate, beats/min||78 ±12||80||62||120||88|
|Paoj sat, %||65-80||76||76.5||62||69|
|Brachial artery Oj sat, %||86-98||95||92.5||97||94|