Clonidine

Structural formula
General
Non-proprietary name	Clonidine
other names	2 - [(2,6-dichlorophenyl) imino] imidazoline ( IUPAC )
Molecular formula	C 9 H 9 Cl 2 N 3
Brief description	white to almost white, crystalline powder (hydrochloride)
External identifiers / databases
CAS number 4205-90-7 4205-91-8 (clonidine hydrochloride ) PubChem 2803 DrugBank DB00575 Wikidata Q412221
Drug information
ATC code	C02 AC01 N02 CX02 S01 EA04
Drug class	Antihypertensive drugs
Mechanism of action	Agonist at pre- and postsynaptic α 2 -receptors Agonist at imidazoline receptors
properties
Molar mass	230.09 g · mol -1
Physical state	firmly
Melting point	130 ° C
pK s value	8.05 (25 ° C)
solubility	soluble in water and absolute ethanol (clonidine hydrochloride)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 301-330 P: 260-284-301 + 310-310
Toxicological data	108 mg kg −1 ( LD 50 ,  mouse ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Clonidine is a chemical compound belonging to the imidazoline group . It is used as a medicinal substance for the treatment of arterial hypertension (high blood pressure), as a support during anesthesia and to dampen withdrawal symptoms. Clonidine is a α ₂ -adrenoceptor - agonist . Clonidine can be administered orally - as a tablet or capsule - or intravenously , intramuscularly or subcutaneously .

history

The original main field of application of clonidine (treatment of arterial hypertension ) was developed rather accidentally in the 1960s: In tests of various substances to decongest the nasal mucous membrane, the strong reduction in heart rate ( bradycardia ) and blood pressure ( hypotension ) were found with clonidine . Later, in animal experiments, pain-relieving and calming active components were also found.

pharmacology

Effects

Overall, the following effects result

• Lowering blood pressure
• Decrease in heart rate
• Lowering of sympathetic tone in withdrawal
• Sedation (mild)
• Pain relief

Mechanism of action

Although clonidine belongs to the group of the sympathomimetics , but has by excitation of the α ₂ -adrenoceptors the presynapse an inhibitory effect on the efferent sympathetic fibers. At the baroreceptors of the carotid artery , when the arterial blood pressure rises, the sympathetic tone is inhibited and the parasympathetic nervous system is stimulated, resulting in a decrease in blood pressure. The signal transduction takes place essentially GPCR -mediated (predominantly inhibitory G protein) via presynaptic α ₂ receptors. Those α ₂ -receptors are located in various places in the central nervous system ( hypothalamus , thalamus , medulla oblongata , formatio reticularis , locus caeruleus , nucleus tractus solitarii, etc.), their stimulation causes a reduced release of noradrenaline from the nerve endings (physiologically a negative feedback mechanism ) Reduction of the sympathetic tone and thus a sympatholytic effect. Further mechanisms are the stimulation of imidazoline receptors (including the ventrolateral medulla oblongata ) and the stimulation of postsynaptic α ₂ -adrenoceptors of the nucleus tractus solitarii, a main switching point in blood pressure regulation. All of the mechanisms mentioned have sympatholytic effects. However, clonidine interacts not only with the above-mentioned α ₂ -adrenoceptors, but also with the α ₁ -adrenoceptors because of its non-100% specificity (relative specificity / selectivity) . For this reason, rapid intravenous administration can also lead to an initial increase in blood pressure ; a paradoxical sympathomimetic effect that is most likely due to a stimulation of postsynaptic α-adrenoceptors on the smooth vascular muscles. Clonidine causes the release of growth hormone by stimulating the pituitary gland.

application areas

• Treatment of hypertension
• supportive in the treatment of drug withdrawal syndromes ( alcohol , opioids , γ-butyrolactone, etc.)
• Use in the context of the clonidine inhibition test
• Use in the context of anesthesia to dampen the vegetative part and to avoid postoperative shivering
• Sedation in intensive care medicine
• In pain therapy to reduce the opioid dosage
• Treatment of intrusion and hyperexcitability in PTSD patients
• Clonidine test for suspected growth hormone deficiency
• Treatment of glaucoma to reduce aqueous humor production and increase aqueous humor outflow

For the prevention of migraine attacks, clonidine is now considered ineffective.

Side effects

• Anticholinergic symptoms that are due to the agonistic effect of clonidine on imidazoline receptors , such as
  • Dry mouth
  • constipation
  • decreased saliva and gastric juice production
• fatigue
• Depressive mood
• Drowsiness
• orthostatic hypotension (= during the transition from lying / sitting to standing)
• Sleep disorders also include insomnia.

Interactions

The effect is increased by diuretics , vasodilators, neuroleptics , alcohol and hypnotics , the effect is weakened by tricyclic antidepressants and sometimes also neuroleptics.

Contraindication

Relative contraindications are 2nd degree AV block and severe arterial occlusive disease, while 3rd degree AV block (if no pacemaker is available), Raynaud's syndrome, or depression are absolute contraindications.

Pharmacokinetics

• Bioavailability: 75%
• Volume of distribution: 2 l kg ⁻¹
• Plasma protein binding: 30-40%
• Metabolism: Only slight (20%) hepatic metabolism, especially to p -hydroxyclonidine
• Plasma half-life: 5–13 h after oral administration, 7–11 h after iv administration
• Elimination: predominantly (65%) renally, at most 10% via the faeces, clearance 182 ± 0.3 ml / min / kg.

Clonidine crosses the blood-brain barrier and is excreted in breast milk .

Trade names

Catapresan (A, D, CH), Haemiton (D), Isoglaucon (A, D), Paracefan (D)

Web links

Commons : Clonidine  - collection of pictures, videos and audio files

Individual evidence

1. ↑ ^{a b} European Pharmacopoeia Commission (Ed.): EUROPEAN PHARMACOPOE 6TH EDITION . tape 6.0-6.2 , 2008.
2. ↑ Mutschler, Geisslinger, Kroemer, Ruth, Schäfer-Korting: Mutschler drug effects. 9th edition, 2008, ISBN 978-3-8047-1952-1 .
3. ↑ ^{a b c} Entry on clonidine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
4. ↑ ^{a b} Entry on clonidine hydrochloride in the GESTIS substance database of the IFA , accessed on February 10, 2017(JavaScript required) .
5. ^ Post-traumatic stress disorder (PTSD) and other consequences of trauma . psychiatriegespraech.de. Retrieved July 5, 2012.
6. ↑ E. Mutschler, M. Schäfer-Korting: drug effects - textbook of pharmacology and toxicology. 7th edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 1996, ISBN 3-8047-1377-7 ; P. 294.
7. ↑ Guidelines for Diagnostics and Therapy in Neurology - Migraine Therapy ( Memento of the original from April 5, 2018 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , As of August 21, 2015. 
8. ↑ Lexicon of Neuroscience: Clonidine (accessed on: Sept. 7, 2016).
9. ↑ Pharmaceutical product information Catapresan: [1] (accessed on: Sept. 7, 2016).

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !