Clonidine interaction

Buccafusco, J.J. (1992) Neuropharmacologic and behavioral actions of clonidine interactions with central neurotransmitters. Int Rev Neurobiol 33 55—107. 

Receptor interactions clonidine interacts at the G protein-coupled alpha receptors with a greater affinity for the alpha-2 receptors. The activation of the alpha-2 receptors results in decreased cAMP, K efflux as well as Ca entry into the nerve terminals. Activation of receptors in the sympathetic nerve endings and in the noradrenergic neurons in the CNS inhibits release of norepinephrine and may release acetylcholine. The locus coeruleus is an important modulator of alertness and may be the major site for the hypnotic effects of clonidine. Additionally, the G protein pathway has a similar transduction pathway to the opioids, explaining some of the cross-tolerance and synergy between the two classes of drugs. 

Pharmacodynamic interaction clonidine acts as an agonist at a2-receptors, and these TCAs block this receptor to varying degrees the result is an increase in blood pressure either avoid this interaction by choosing another antidepressant or increase the dose of clonidine. 

This interaction is the same as the one when clonidine is combined with TCAs however, mirtazapine is a more potent a2-receptor blocker than the TCAs avoid this interaction and choose an alternative antidepressant without a2-blocking effects. 

Figure 11. Appropriate structures of clonidine and noradrenaline for interaction with the postulated a-adrenergic receptors (on the basis of data from (43) and...

The most common side effects of clonidine are constipation, dizziness, drowsiness, dryness of mouth, and unusual tiredness or weakness. However, there are more severe side effects that clinicians and patients should be aware of, such as allergic reaction, decreased heart rate, or unusually elevated or decreased blood pressure, as well as contraindications and drug interactions that should be evaluated prior to prescription. 

Drugs that may interact with clonidine include beta-adrenergic blocking agents and tricyclic antidepressants. 

Drugs that interact may include beta blockers, indomethacin, verapamil, and clonidine. 

Uses Endogenous depression Action TCA T synaptic CNS levels of serotonin /or norepinephrine Dose Adults. 25 mg PO tid-qid >150 mg/d not OK Elderly. 10-25 mg hs Peds. 6-7 y 10 mg/d 8-11 y 10-20 mg/d >11 y 25-35 mg/d, 4- w/ hepatic insuff Caution [D, +/-] NAG, CV Dz Contra TCA allergy, use w/ MAOI Disp Caps, soln SE Anticholinergic (blurred vision, retention, xerostomia) Interactions T Effects W/ antihistamines, CNS depressants, cimetidine, fluoxetine, OCP, phenothiazine, quinidine, EtOH T effects OF anticoagulants T risk of HTN W/clonidine, levodopa, sympathomimetics T effects W/barbiturates, carbamazepine, rifampin EMS Concurrent use w/ MAOIs have resulted in HTN,... 

Numerous drug-drug interactions have been reported with the antipsychotic agents. These may be mediated through pharmacodynamic effects. For example, antipsychotics that block aj-adrenergic receptors may potentiate the antihypertensive effects of prazosin, labetalol, and some other antihypertensive agents. Conversely, antipsychotics associated with a2-adrenergic receptor blockade may interfere with the antihypertensive effects of clonidine and methyldopa (Richelson, 1999). 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Pemoline (Cylert), (112.5 to 185.5 mg) was assessed in a 3-week open trial in 15 adolescents with CD, ADHD, and SUD (Riggs et ah, 1996). Three of the subjects were receiving other psychotropic medications (clonidine (Catapres) and paroxetine [Paxil]). All subjects had a significant improvement in ADHD symptoms (p <0.002) while 10/13 reported that the pemoline (Cylert) assisted in their substance rehabilitation. No subjects developed a significant elevation in their liver function tests, nor did any subjects test positive for substances of abuse for the duration of the study. No interactions between pemoline (Cylert) and any substances of abuse were reported. 

A rather simpler compound includes both a benzodioxan nucleus and the imidazoline function associated with a-adrenergic agonists such as clonidine. As in the standard approach for preparing imidazolines, the treatment of nitrile (60-1) with alcoholic hydrogen chloride leads to the iminoether (60-2). Reaction of that intermediate with ethylenediamine then affords idazoxin (60-3) [70], a compound that interacts with a-adrenergic receptors. 

Clonidine Inhibits adenylyl cyclase and interacts with other intracellular pathways Vasoconstriction is masked by central sympatholytic effect, which lowers BP Hypertension Oral transdermal peak effect 1-3 h half-life of oral drug 12 h produces dry mouth and sedation... 

Caution [C, ] CrCl <30 Contra Component sensitivity, asthma, severe COPD, sinus bradycardia Disp Soln SE Irritation, bitter taste, superficial keratitis, ocular allergic Rxn EMS Drug is absorbed systemically OD May cause electrolyte disturbances (K), acidosis and bradycardia monitor ECG Doxazosin (Cardura, Cardura XL) [Antihypertensive/Alpha Blocker] Uses HTN symptomatic BPH Action < [-Adrenergic blocker relaxes bladder neck smooth muscle Dose HTN Initial 1 mg/d PO may be T to 16 mg/d PO BPH Initial 1 mg/d PO, may T to 8 mg/d XR 2-8mg qAM Caution [B, ] Use w/ PDE5 inhibitor (eg, sildenafil) can cause 1 BP Contra Component sensitivity Disp Tabs SE Dizziness, HA, drowsiness, sexual dysfxn, doses >4 mg T postural BP risk Interactions T Effects W/ nitrates, antihypertensives, EtOH i effects W/ NSAEDs, butcher s broom -t effects OF clonidine EMS Concurrent EtOH use can T drowsiness syncope may occur w/in 90 min of initial dose OD May cause profound hypotension place pt in supine position, give IV fluids, use pressors if needed... 

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