Cases Of Agonists

selectivity β Receptor agonists

Dobutamine

It is a synthetic product with chemical structure similar to dopamine and optical activity. It is used as racemate in clinical practice.

[Pharmacokinetics] Similar to dopamine, it is easy to be destroyed by the intestine and liver after oral administration, and its elimination is rapid. t1/2 takes about 2 minutes, so it is generally administered by intravenous drip, and the time to reach the steady blood concentration is about 10-12 minutes.

[Pharmacological action] Dobutamine levorotatory stimulation α Receptor, Dextra Antagonist α 1 receptor, thus racemate pair α The effect of the receptor is counteracted, and both left and right rotators can be excited β And the effect of the latter is 10 times stronger than that of the former. The effect of dobutamine on vascular β 2 Receptors have little effect. Therefore, the comprehensive effect of racemic dobutamine is mainly manifested as excitement β 1 Receptor. Compared with isoproterenol, dobutamine has a more significant effect on enhancing myocardial contractility than on accelerating heart rate, and it rarely causes tachycardia. However, when the intravenous drip speed is too fast or the concentration is too high, it causes the heart rate to accelerate. The effect of accelerating atrioventricular conduction and intraventricular conduction is similar to that of isoproterenol.

[Clinical application] It is used to treat heart failure with weakened myocardial contractility caused by various reasons, such as cardiac exhaustion caused by acute myocardial infarction, dilated cardiomyopathy, heart failure caused by rheumatic valvular disease, and low output syndrome caused by open heart surgery. It is clinically used as short-term supportive treatment. It can enhance myocardial contractility, increase cardiac output and reduce pulmonary capillary wedge pressure, so that left ventricular filling pressure can be significantly reduced. At the same time, it does not speed up the heart rate, which is conducive to improving cardiac function. It can also promote sodium excretion and diuresis secondary, which is conducive to eliminating edema. When used in patients with heart failure with low output and slow heart rate, the effect of improving left ventricular function is better than that of dopamine.

[Adverse reactions and precautions] There are palpitations, nausea, headache, chest pain, shortness of breath and other symptoms. If there is an increase in systolic blood pressure (most increase 10-20mmHg, and a few increase 50mmHg or more), and the heart rate increases (most increase 5-10 times per minute on the original basis, and a few increase more than 30 times), the dosage should be reduced or the medication should be suspended. Because it can accelerate the atrioventricular conduction, patients with atrial fibrillation may have a faster ventricular rate after administration, so digoxin should be used before using this drug to avoid rapid ventricular rate reaction.

[Contraindications] Patients with obstructive hypertrophic cardiomyopathy should not use it.

Non selective β Receptor agonist

Isoprenaline

It is a synthetic product, which is made of hydrogen atom on NA amino group replaced by isopropyl group, and is used as its hydrochloride for medicine.

[Pharmacokinetics] When taken orally, intestinal mucosal cells can destroy it and lose efficacy; The sublingual drug can relax local blood vessels, and a small amount can be quickly absorbed from the sublingual venous plexus; The aerosol is inhaled and absorbed quickly. After absorption, it is mainly metabolized by COMT in liver and other tissues, less metabolized by MAO, and less absorbed by noradrenergic nerve endings, so the action time is slightly longer than adrenaline, t1/2 is about 2 hours. The prototype and its metabolites are mainly excreted through the kidney.

[Pharmacological action] Yes α Receptors have little effect on β 1、 β 2 receptors have strong excitatory effect.

(1) Heart: excited β 1 receptor, which can produce strong cardiac excitation, and enhance the myocardial contractility, cardiac output, conduction, heart rate, systolic and diastolic periods. Isoproterenol excites the heart more effectively than adrenaline, but it mainly excites the sinus node and has less influence on ectopic pacemaker points, so it rarely causes ventricular fibrillation and other arrhythmias.

(2) Blood vessels and blood pressure: stimulate blood vessels β Receptor 2 significantly relaxes skeletal muscle blood vessels, also relaxes coronary vessels, and has weak relaxations on renal and mesenteric vessels. Because the heart is excited and the peripheral blood vessels are relaxed, the systolic pressure will increase and the diastolic pressure will decrease slightly. When a large dose of intravenous injection is used, the blood pressure will decrease significantly.

(3) Bronchus: stimulates bronchial smooth muscle β 2 receptor can relax bronchial smooth muscle, inhibit the release of histamine and other allergens, relieve the spasm of bronchial smooth muscle, and dilate the bronchus, which is stronger than adrenaline. Because the metabolism of isoproterenol has β Receptor antagonistic effect, so long-term repeated use can weaken the efficacy.

(4) Metabolism: increase tissue oxygen consumption; It can promote the decomposition of liver glycogen, and the effect of increasing blood glucose is weaker than that of adrenaline; The function of promoting fat decomposition and increasing free fatty acid in blood is similar to that of adrenaline.