Clinical Application Of Agonists

(1) Acute attack of bronchial asthma: the aerosol takes effect within 2-5 minutes after inhalation and lasts for 0.5-2 hours; the effect takes effect within 15-30 minutes after sublingual administration and lasts for about 1 hour.

(2) Atrioventricular block: sublingual administration or intravenous drip to treat degree II and III atrioventricular block.

(3) Cardiac arrest: It is applicable to cardiac arrest caused by slow ventricular rhythm, high atrioventricular block or sinus node failure. In order to prevent coronary perfusion pressure from decreasing due to diastolic pressure, it is often used with NA or m-hydroxylamine for intracardiac injection.

(4) Shock: on the basis of replenishing blood volume, it can be used for the treatment of septic shock with high central venous pressure and low cardiac output. However, the effect of improving microcirculation is not good. At the same time, the effect of isoproterenol on increasing myocardial oxygen consumption and heart rate is adverse to shock, which has been rarely used in clinical practice.

[Adverse reactions and precautions] Common adverse reactions include palpitation, dizziness and headache; High dose of isoproterenol inhalation in patients with hypoxia is easy to cause arrhythmia, induce and increase barycentric colic due to the increase of myocardial oxygen consumption; Long term abuse of isoproterenol in asthmatic patients may cause sudden death. Heart rate should be controlled during medication.

[Contraindication] It is forbidden to use in patients with coronary heart disease, myocarditis and hyperthyroidism.

M-receptor agonist

Pilocarpine

The drug, also known as pilocarpine, is an alkaloid derived from Rutacia.

[Pharmacological effect] It can directly act on the M-choline receptor of the effector organs innervated by the parasympathetic postganglionic fibers (including the sympathetic nerve innervating the sweat gland), especially on the eyes and glands.

(1) Eye: after eye drops, it can cause contraction, reduce intraocular pressure and regulate convulsions. Constriction: There are two kinds of smooth muscle in the iris. One is the pupil sphincter, which is dominated by the parasympathetic cholinergic nerve of the oculomotor nerve. When excited, the pupil sphincter contracts and the pupil shrinks; The other is the pupil dilated muscle, which is dominated by noradrenergic nerve. When excited, the pupil dilated due to the peripheral contraction of the pupil dilated muscle. This product can activate the M-cholinergic receptor of the pupil sphincter, showing that the pupil shrinks, and the effect can last for several hours to one day after local administration. Lowering intraocular pressure: aqueous humor is produced through secretion of ciliary body epithelial cells and vascular exudation, and flows into the anterior chamber through the pupil to reach the anterior chamber corner space, mainly through the filter curtain to the scleral sinus, and finally into the blood circulation. This product can make the iris pull toward the center through the effect of pupil contraction, and the iris root becomes thinner, so that the anterior chamber angle space around the iris is expanded, and the aqueous humor is easy to enter the scleral sinus through the filter curtain, reducing the intraocular pressure. Regulation convulsion: when the eye is near the object, the concavity and convexity can be changed through the lens, so that the object can be imaged on the optic nerve omentum, so as to see the object clearly, which is called the accommodation effect. The accommodation of the eye mainly depends on the change of lens curvature. The lens capsule is elastic, which makes the lens slightly spherical. However, due to the outward traction of the suspension ligament, the lens can be kept in a relatively flat state. The suspensory ligament is also controlled by the ciliary muscle, which is composed of circular and radial smooth muscle fibers, of which the circular muscle fibers dominated by the oculomotor nerve are the main. When the oculomotor nerve is excited or after the action of pilocarpine, the annular muscle contracts toward the center of the pupil, causing the suspension ligament to relax. Because the lens itself becomes elastic and convex, its luminosity increases, at this time it is only suitable for near objects, but difficult to see far objects. This effect of the drug is called regulating convulsion, which can disappear within 2 hours. The ciliary muscle is also innervated by noradrenergic nerve, but it does not play an important role in the regulation of the eye, so adrenergic drugs generally do not affect the regulation of the eye.

(2) Glands: large doses of pilocarpine (10-15mg subcutaneous injection) can significantly increase the secretion of sweat glands and salivary glands, as well as the secretion of lacrimal glands, gastric glands, pancreas, small intestine glands and respiratory tract mucosa.

(3) Smooth muscle: In addition to the intraocular smooth muscle mentioned above, pilocarpine can also excite intestinal smooth muscle, increasing its tension and peristalsis; Bronchial smooth muscle is excited (inducing asthma), and it can also excite smooth muscle of uterus, bladder, gallbladder and biliary tract.

(4) Cardiovascular system: When pilocarpine 0.1mg/kg is injected intravenously, heart rate and blood pressure can be decreased temporarily. If N receptor blockers are used first, it can produce obvious pressor effect. The above two effects can be cancelled by atropine, but the mechanism of its antagonism against pilocarpine induced pressor effect is still unclear, which may be related to the excitation of ganglia and adrenal medulla.

[Clinical Application]

(1) Glaucoma: Glaucoma is a common ophthalmic disease in clinical practice. The patients are mainly characterized by progressive depression of the optic nerve nipple and vision loss, accompanied by elevated intraocular pressure. In severe cases, blindness may occur. Low concentration pilocarpine (less than 2%) eye drops can be used to treat angle closure glaucoma (also known as congestive glaucoma). After medication, the pupil of the patient will shrink, the space between anterior chamber corners will expand, and the intraocular pressure will decrease. However, high concentration drugs can aggravate the symptoms of patients, so they should not be used. This product also has a certain effect on the early stage of open angle glaucoma, also known as simple glaucoma. The drug is easy to enter the eye chamber through the cornea. After a few minutes of medication, the intraocular pressure can be reduced, and it can last for 4-8 hours. The mechanism is unknown. 1% - 2% solution is commonly used for eye drops. The inner canthus should be pressed during eye drops to avoid side effects after absorption of the solution.

(2) Iritis: used alternately with mydriasis drugs to prevent iris from adhering to the lens.

(3) Others: The oral administration of this drug can be used to dry the mouth after neck radiation. However, while increasing saliva secretion, sweat secretion also increases significantly. It can also be used for the rescue of atropine poisoning.

[Adverse reaction] If the drug is overdosed, it may have symptoms similar to muscarinic poisoning, which may be manifested as excessive excitement of M-choline receptor. Atropine can be used for symptomatic treatment, maintenance of blood pressure, artificial respiration, etc