Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIG6XE58R)
Drug Name			Clonidine		Drug Info		Thiothixene		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Antipsychotic Agents
Structure

Mechanism of Clonidine-Thiothixene Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Clonidine				Thiothixene
Mechanism		Hypotensive effects Alpha-2 adrenergic receptor Agonist				Hypotensive effects Alpha-1 adrenergic receptor Antagonist
Key Mechanism Factor 1
		Factor Name		Adrenergic receptor alpha-2				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Adrenergic receptor alpha-1				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Clonidine and Thiothixene

Recommended Action
Management		Close clinical monitoring for development of hypotension is recommended if phenothiazines or neuroleptic agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine or neuroleptic may be appropriate, especially in the elderly. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery.

References
1	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
2	Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274. [PMID: 2857531]
3	Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9. [PMID: 7663034]
4	Product Information. Abilify (aripiprazole). Bristol-Myers Squibb, Princeton, NJ.
5	Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
6	Product Information. Geodon (ziprasidone). Pfizer US Pharmaceuticals, New York, NY.
7	Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
8	Product Information. Risperdal (risperidone). Janssen Pharmaceutica, Titusville, NJ.
9	Product Information. Seroquel (quetiapine). Zeneca Pharmaceuticals, Wilmington, DE.
10	Product Information. Zyprexa (olanzapine). Lilly, Eli and Company, Indianapolis, IN.
11	White WB "Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril." Arch Intern Med 146 (1986): 1833-4. [PMID: 3530167]