Mechanisms of vascular tone regulation
The pharmacological effect of adrenergic blockers is largely determined by how specific receptors normally respond to neurotransmitters of the sympathetic nervous system.
- Postsynaptic $\alpha_1$-adrenergic receptors. Under physiological conditions, their stimulation causes vasoconstriction. Accordingly, pharmacological blockade of $\alpha_1$-receptors eliminates this predominant sympathetic tone, which naturally leads to vasodilation — widening of the vascular bed.
- Postsynaptic $\beta_2$-adrenergic receptors. Their stimulation normally ensures relaxation of the smooth musculature of the vascular wall. If $\beta_2$-receptors are blocked, this natural relaxation mechanism is completely shut down. It is important to understand that $\beta_2$-receptor blockade not only fails to promote vasodilation, but can actually provoke vasospasm because the tone of $\alpha$-receptors remains "unbalanced".
- Presynaptic $\alpha_2$-adrenergic receptors. These structures act as a braking mechanism (negative feedback). If blocked, normal control is disrupted, and an excessive amount of norepinephrine is released into the synaptic cleft. This excess neurotransmitter will prevent vasodilation unless postsynaptic receptors have been reliably blocked.
Clinical comparison: propranolol and prazosin
Differences in mechanisms of action determine completely different clinical niches for specific drugs. A classic example is the comparison between a non-selective $\beta$-blocker and a selective $\alpha_1$-blocker.
Propranolol It is a classic non-selective agent (blocks both $\beta_1$- and $\beta_2$-receptors).
- Main effects: Lowers blood pressure (antihypertensive action), exhibits antianginal and antiarrhythmic activity.
- Indications: Successfully used for stable angina pectoris, supraventricular rhythm disorders, management of thyroid storm, treatment of arterial hypertension, and even for the prophylaxis of migraine attacks.
- Limitations: The main drawback of the drug is the worsening of peripheral circulation. This occurs precisely due to the non-selective blockade of vascular $\beta_2$-receptors, which can lead to vasospasm.
Prazosin It is a selective $\alpha_1$-adrenergic receptor blocker.
- Mechanism: Causes direct vasodilation of both peripheral arteries and veins.
- Advantages: Unlike propranolol, prazosin does not cause vasospasm, but rather effectively eliminates it. Therefore, the drug is indicated for peripheral arterial diseases accompanied by ischemia (e.g., Raynaud's disease or thromboangiitis obliterans).
Drug selection in comorbid pathology: bronchial asthma
The presence of concomitant bronchial asthma cardinally changes the tactics of prescribing adrenergic blockers, especially in the treatment of arterial hypertension. The main problem is that the blockade of $\beta_2$-adrenergic receptors in the bronchi inevitably provokes severe bronchospasm.
Safety analysis of various drug groups:
- Non-selective $\beta$-blockers (propranolol, carvedilol). Block both receptor types ($\beta_1$ and $\beta_2$). In patients with asthma, they are absolutely contraindicated.
- Selective $\beta_1$-blockers (metoprolol, bisoprolol). Considered less dangerous as they predominantly act on the heart. However, their selectivity is not absolute: at high doses it is lost, and the drugs begin to block $\beta_2$-receptors. Prescribing them to such patients requires extreme caution and strict monitoring.
- Selective $\alpha_1$-blockers (doxazosin). Act exclusively on the vascular bed and have no effect on the tone of bronchial smooth muscle.
Thus, the optimal strategy for treating hypertension in a patient with asthma is to choose drugs that do not affect $\beta_2$-receptors — for example, doxazosin. If the use of $\beta$-blockers is necessary, only highly selective $\beta_1$-agents are permissible. (Tamsulosin also exists, but it has marked uroselectivity and is not typically used in cardiological practice to lower blood pressure).
Briefly: answers to topical questions
What side effects are characteristic of propranolol?
Propranolol is characterized by both common side effects of beta-blockers and specific side effects associated with its non-selectivity.
Common side effects include:
- Atrioventricular block — conduction disturbance.
- Decreased myocardial contractility — negative inotropic effect.
- Bradycardia — slowing of the heart rate.
Specific side effects include:
- Bronchospasm — occurs due to blockade of bronchial $\beta_2$-receptors.
- Peripheral vasospasm — leads to worsening of peripheral circulation.
Which drugs belong to the group of selective beta-1-adrenergic blockers?
The group of cardioselective $\beta_1$-adrenergic blockers includes:
- metoprolol;
- bisoprolol;
- nebivolol;
- atenolol;
- betaxolol;
- talinolol;
- esmolol.
Which drugs are included in the group of selective alpha-1-adrenergic blockers?
The group of selective $\alpha_1$-adrenergic blockers includes drugs that selectively block the corresponding receptors of blood vessels or the prostate gland.
The main representatives of the group include:
- Prazosin — causes direct vasodilation of peripheral arteries and veins.
- Doxazosin — a long-acting drug used for hypertension and prostate conditions.
- Terazosin — a long-acting drug for the treatment of BPH.
- Tamsulosin — a uroselective drug that selectively blocks $\alpha_{1A}$-adrenergic receptors.
- Alfuzosin — an analogue of tamsulosin used for prostate disorders.
What are the clinical indications for prescribing tamsulosin?
Clinical indications for prescribing tamsulosin include pathologies accompanied by impaired urine outflow.
The drug is used in the following cases:
- Benign prostatic hyperplasia — to relax the smooth muscles of the prostate and bladder neck.
- Multiple sclerosis — prescribed to adult patients to correct urinary disorders in detrusor-sphincter dyssynergia and difficulty emptying the bladder.
For the treatment of arterial hypertension, this uroselective drug is usually not used, as it does not have a significant effect on vascular tone and systemic blood pressure.
Alpha-1 — vessels deflated (vasodilation upon blockade). Beta-2 — bronchi constricted (asthma danger upon blockade).
Class and exam questions
Can carvedilol be prescribed to a patient with bronchial asthma?
No, carvedilol is a non-selective $\beta$-blocker. It blocks $\beta_2$-receptors in the bronchi, which is guaranteed to cause severe bronchospasm. This is an absolute contraindication.
Are selective $\beta_1$-blockers (e.g., bisoprolol) safe in asthma?
They are safer than non-selective ones, but require great caution. When dosages are exceeded, $\beta_1$-blockers lose their selectivity and can also trigger bronchospasm.
Which adrenergic blocker is best chosen to lower blood pressure in a patient with asthma?
Preference is given to drugs that do not affect $\beta_2$-receptors at all. An excellent option would be doxazosin (a selective $\alpha_1$-blocker).
What else to study on this topic
- Mechanism of loss of $\beta_1$-blocker selectivity at higher doses
- Uroselectivity of tamsulosin and its clinical use
- The role of presynaptic $\alpha_2$-receptors in norepinephrine release
- Pharmacodynamics of adrenergic blockers in the treatment of migraine
- Specifics of propranolol use in thyrotoxic crisis
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