Alpha-1 adrenergic agonists
Alpha-1 adrenergic agonists stimulate alpha-1 receptors coupled to G proteins and phospholipase C. They can be classified in two groups: those which do not cross the blood-brain barrier and have peripheral effects and those which penetrate into the brain and have mainly central effects.
Alpha-1 agonists with peripheral effects
Drugs activating alpha-1 adrenergic receptors cause vasoconstriction, uterine contractions, mydriasis.
Vasoconstriction
The vasoconstrictive effect leads to a certain number of therapeutic uses:
- Treatment of postural hypotension:
The principal products used for their vasoconstrictive effect in the treatment of postural hypotension are phenylephrine, etilefrine and midodrine.
Phenylephrine, also known as neosynephrine, has been used by oral and parenteral routes.
Etilefrine, isomer of phenylephrine, has similar properties and is also proposed in the treatment of postural hypotension.
Midodrine (which is written sometimes mitodrine) is used orally in the treatment of severe orthostatic hypotensions occurring in degenerative diseases.
In injectable form, mitodrine has a particular therapeutic use: to transform a retrograde ejaculation into an anterograde ejaculation by reinforcement of vesical sphincter tone. The danger of mitodrine injection is to elicit vasoconstriction and arterial hypertension especially in lying position.
These products can give palpitations, tachycardia, headache.
Midodrine |
PROAMATINE* Tablets |
- Treatment of migraine:
Ergotamine, an ergot derivative, is used only for the curative treatment of migraine attacks but not for its prevention. Because of its powerful and sustained vasoconstrictive activity, ergotamine can induce important adverse effects like arterial hypertension or cardiac ischemia. Outbreak of coldness of the extremities and paresthesia in patients taking ergotamine must attract attention and lead to discontinuation of the drug. In the event of indisputable vasoconstriction, a vasodilator treatment must be started.
Dihydroergotamine has an alpha-1-mimetic effect less marked than that of ergotamine and which is exerted in particular on veins. It has also serotonergic effects. It is used in preventive and curative treatment of migraine and is proposed in the treatment of postural hypotension.
- Inhibition of local anesthetics diffusion :
By their vasoconstrictive effect, alpha-1 agonists reduce the diffusion of local anesthetics simultaneously administered. The vasoconstrictive compound generally used is adrenaline.
- N asal congestion treatment:
In local use, as nasal aqueous solution for example, alpha-1-adrenergic agonists relieve congestion of mucous membranes of higher air routes by vasoconstriction . The agonists alpha-1 used, phenylephrine, naphazoline and tymazoline, give only a momentary improvement, which leads the patients to renew administrations.
Uterine contraction
Alpha-1 agonists induce uterine contractions explaining their use in obstetrics.
In practice, the agonist alpha-1 used as a drug to induce uterine contractions after postpartum is methylergometrine, also called methylergonovine, an ergot derivative which has also a vasoconstrictive effect.
Mydriasis
The mydriatic effect leads to their use in ophthalmology.
Phenylephrine, also called neosynephrine, is used by local route, in the form of ophthalmic solution, as a mydriatic for optic fundus examination and during certain ocular surgical operations. It also elicits a vasoconstriction of conjunctiva vessels and decreases conjunctival hyperemia, in particular of allergic origin. In the case of systemic diffusion it can give arterial hypertension.
Dipivefrin, also called dipivalyladrenaline, is a precursor of adrenaline.
Naphazoline, another alpha-1 agonist, is present in certain ophthalmic solutions for the treatment of conjunctival irritations.
The principal adverse effects of a lpha-1 agonists are linked to their vasoconstrictive effect which, when it is not sought or exceeds the desired aim, is an unquestionable disadvantage. They can also hamper bladder evacuation.
Alpha-1 agonists with central effects
Stimulation of alpha-1adrenergic receptors of the central nervous system has a psychostimulant effect, increases vigilance, decreases the requirement of sleep. Two drugs acting by this mechanism are adrafinil and modafinil.
- Adrafinil
Adrafinil is a central stimulant used in the elderly for the treatment of vigilance and attention disorders. Its most frequent adverse effects are agitation, excitation or aggressiveness.
- Modafinil
Modafinil whose chemical structure is close to that of adrafinil is a more potent CNS stimulant than adrafinil. It is used in the treatment of idiopathic hypersomnia and narcolepsy.
Among its adverse effects one can quote nervousness, anxiety, anorexia, tremor, headache…
Modafinil |
PROVIGIL* Tablets |
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