Phenylephrine Guanethidine

Patients taking certain systemic medications are also more sensitive to the pressor effects of phenylephrine. In individuals taking atropine, the pressor effect of phenylephrine is augmented, and tachycardia can occur. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors also potentiate the cardiovascular effects of topical phenylephrine. The concomitant use of phenylephrine is contraindicated with these agents, even up to 21 days after cessation of MAO inhibitor therapy. Similarly, patients taking reserpine, guanethidine, or methyldopa are at increased risk for adverse pressor effects from topical phenylephrine because of denervation hypersensitivity accompanying the chemical sympathectomy. 

Contraindications to the topical use of hydroxyamphetamine for routine mydriasis are similar to those to phenylephrine. Because of its tachyphylaxis and ineffectiveness in postganglionic denervation, however, hydroxyamphetamine may be a safer mydriatic for use in patients with insulin-dependent diabetes, idiopathic orthostatic hypotension, or chemical sympathectomy produced by therapy with systemic guanethidine, reserpine, or methyl-dopa. Thus hydroxyamphetamine seems to be less strongly contraindicated than phenylephrine for certain high-risk patients. 

Patients taking monoamine oxidase inhibitors, anticholinergic drugs (such as tricyclic antidepressants), propranolol, reserpine, guanethidine, and methyldopa should be monitored closely if phenylephrine is used (SEDA-16, 542) (16). 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

The pressor effects of noradrenaline (norepinephrine), phenylephrine, and metaraminol can be increased in the presence of guanethidine. These drugs can also be used as eye drops, and in this situation their mydriatic effects are similarly enhanced and prolonged by guanethidine. 

The mydriasis due to phenylephrine given as a 10% eye drop solution was prolonged for up to 10 hours in a patient taking guanethidine for hypertension. This enhanced mydriatic response has been described in another study using guanethidine eye drops with adrenaline (epinephrine), phenylephrine or methoxamine eye drops. ... 

By preventing the release of noradrenaline from adrenergic neurones, guanethidine and other adrenergic neurone blockers cause a temporary drug-induced sympathectomy , which is also accompanied by hypersensitivity of the receptors. This results in the increased response to the stimulation of the receptors by directly-acting sympathomimetics such as noradrenaline and phenylephrine. 

D-amphetamine, methamphetamine, ephedrine, phenylephrine, phenteramine, mephenteramine, methylphenidate and diethylpropion all work antagonistically by displacing guanethidine from the binding site. In addition to this the combination with any of these substances carries an increased risk of cardiac arrhythmia (3, 7", 12 , 13, 26 ). 

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