Clonidine is a sympathomimetic drug in the imidazoline group. It is mainly used to treat arterial hypertension (high blood pressure). Because of severe side effects, it is considered a reserve therapeutic agent.
What is clonidine?
The drug clonidine is a sympathomimetic that belongs to the group of imidazolines. It can be used to treat hypertension, to aid in drug withdrawal, as part of the so-called clonidine inhibition test, in hypertensive crisis, against chronic open-angle glaucoma, and for sedation. To a limited extent, it can also be used in sedation and analgesia. However, because of relatively severe side effects, it is now used only as a reserve therapeutic agent in the treatment of hypertension and in drug withdrawal.
Pharmacologic Action
In clonidine, several mechanisms of action can be distinguished by which the substance acts. One is activation of presynaptic α2-adrenoreceptors, and in addition, activation of postsynaptic α2-adrenoreceptors, as well as inhibition of adrenaline release in the adrenal medulla. Clonidine binds to presynaptic α2-adrenoreceptors both in the central nervous system and in the periphery. This binding results in decreased release of norepinephrine via the G-protein coupled signaling cascade. This decreased release of norepinephrine results in a decrease in sympathetic tone. Furthermore, clonidine also activates postsynaptic α2-adrenoreceptors. This occurs particularly in the region of the nucleus tractus solitarii, the switching site of the baroreceptor reflex (response to the change in blood pressure triggered by the baroreceptors). The aforementioned inhibition of adrenaline release in the adrenal medulla, together with stimulation of central imidazoline receptors, leads to further enhancement of the symphaticolytic effect. Clonidine exerts an effect even at very low doses of a few micrograms. The plasma half-life is approximately nine to eleven hours, and the LD50 dose is 108 mg-kg^-1 when administered orally to mice. It is partially metabolized in the liver; however, 65% of the drug is excreted unchanged by the kidney. Clonidine can be administered perorally in the form of a tablet, or intravenously. Clonidine crosses the blood–brain barrier and passes into breast milk. The bioavailability is approximately 75%. The volume of distribution is 2 l-kg^-1.
Medicinal use and application
Clonidine may be used to treat the following conditions: arterial hypertension; refractory gestational hypertension; hypertensive crisis; chronic open-angle glaucoma; migraine; opioid withdrawal syndrome; alcohol withdrawal syndrome; and postoperative shivering. Due to high side effects, clonidine is mainly used as a reserve therapeutic agent in combination therapy for the treatment of arterial hypertension, as well as for supportive treatment of withdrawal syndromes. Overall, the following effects are present: Reduction of blood pressure, reduction of heart rate, reduction of sympathetic tone in withdrawal, sedation (mild), and pain relief. The main application of clonidine – therapy of arterial hypertension – dates back to a rather accidental discovery in the 1960s. Various substances, including clonidine, were tested for their ability to decongest the nasal mucosa. In the course of these tests, the sharp reduction in heart rate and lowering of blood pressure stood out. These effects were subsequently exploited therapeutically by the medical community. Clonidine thus became mainly a therapeutic agent for arterial hypertension. Later, sedative and analgesic effects were also observed in animal experiments. However, it should be noted that clonidine has relatively strong side effects, and for this reason, other agents with fewer side effects should be preferred.
Risks and Side Effects
The severe side effects already mentioned take the form of dry mouth, constipation, decreased saliva and gastric juice production, fatigue, depressed mood, sedation, and impotence. Clonidine should not be used concomitantly with diuretics, hypnotics, vasodilators, or alcohol, as these substances lead to an increase in the effect of clonidine. Also, when taking neuroleptics, clonidine should not be used. After intravenous application, an initial increase in blood pressure is possible.Clondin should not be used if hypersensitivity (allergy) to clonidine is known. Other contraindications include sinus node syndrome, bradycardia (heart rate below 50/minute), endogenous depression, certain cardiac arrhythmias, coronary artery disease, acute myocardial infarction, advanced arterial occlusive disease (CAD), Raynaud’s syndrome, thrombangiitis obliterans, cerebrovascular insufficiency, renal insufficiency and constipation. Clonidine is also contraindicated during pregnancy and lactation.
