Before using Alupent Beta-2, you must know all about the risks and complications associated with it.
The actions of a particular beta-2 adrenergic agonist in most tissues have been clearly differentiated depending on its relative activity at the predominant receptor type present in a given tissue.
The overall actions are:
Adrenaline increases heart rate by increasing the slope of slow diastolic depolarization of cells in the SA node. It also activates latent pacemakers in A-V node and Purkinje fibres; arrhythmia can occur with high doses that raise blood pressure (BP) markedly. Raised BP reflexly depresses the SA node and unmasks the latent pacemakers.
Certain anesthetics (chloroform, halothane) sensitize the heart to arrhythmic action of adrenaline. Idioventricular rate is increased in patients with complete heart block.
Force of cardiac contraction is increased. In addition, development of tension as well as relaxation is accelerated. Thus, systole is shortened more than diastole. Cardiac output (CO) and oxygen consumption of the heart are markedly enhanced.
Conduction velocity through AV node, bundle of His, atrial and ventricular fibres is increased; partial A-V block may be overcome. Refractory period (RP) of all types of cardiac cells is reduced. All cardiac actions are predominantly beta-1 receptor mediated.
When BP rises markedly, reflex bradycardia occurs due to stimulation of vagus – this is the usual response seen when NA is injected intravenously.
Both vasoconstriction (alpha) and vasodilatation (beta-2) can occur depending on the drug, its dose and vascular bed. Constriction predominates in cutaneous, mucous membrane and renal beds.
Vasoconstriction occurs through alpha-1 and alpha-2 receptors. On the contrary, dilatation predominates in skeletal muscles, liver and coronaries.
The direct effect on cerebral vessels is not prominent – blood flow through this bed parallels change in BP.
The action is most marked on arterioles and precapillary sphincters; large arteries and veins are affected at higher doses.
The effect depends on the amine, its dose and rate of administration.
- Noradrenaline causes rise in systolic, diastolic and mean BP; it does not cause vasodilatation (no beta-2 action), peripheral resistance increases consistently due to alpha action.
- Isoprenaline causes rise in systolic but marked fall in diastolic BP (beta-1: cardiac stimulation, beta-2: vasodilation). The mean BP generally falls.
- Adrenaline given by slow IV infusion or s.c. injection causes rise in systolic but fall in diastolic BP; peripheral resistance decreases because vascular beta-2 receptors are more sensitive than alpha receptors. Mean BP generally rises and pulse pressure is increased.
- Rapid IV injection of adrenaline produces a marked increase in both systolic as well as diastolic BP. The BP returns to normal within a few minutes and a secondary fall in mean BP follows.
Adrenaline and Isoprenaline, but not noradrenaline are potent bronchodilators (beta-2).This action is more marked when the bronchi are constricted. Adrenaline given by aerosol additionally decongests bronchial mucosa by alpha action.
Adrenaline can directly stimulate respiratory center (RC) but this action is seldom manifest at clinically used doses.
Rapid IV injection causes transient apnea due to reflex inhibition of RC. Toxic doses of adrenaline cause pulmonary edema by shifting blood from systemic to pulmonary circulation.
The direct effect on muscle fibers is exerted through beta-2 receptors and differs according to the type of fibre. The active state is abbreviated and less tension is developed in the slow contracting red fibers.
There is incomplete fusion of individual responses. This along with enhanced firing of muscle spindles is responsible for the tremors produced by beta-2 agonists.
Adrenaline causes glycogenolysis resulting in hyperglycemia, hyperlactaciademia (beta-2); lipolysis resulting in a rise in plasma free fatty acid and calorigenesis (beta-2 + beta-3). These are due to direct action on liver, muscle and adipose tissue cells.
In addition, metabolic effects result from reduction of insulin (alpha-2) and augmentation of glucagon (beta-2) secretion.
Transient hyperkalemia followed by hypokalemia occurs due to initial release of potassium from liver, and latter its enhanced uptake into skeletal muscles as well as in liver.