The effects of adrenaline (epinephrine), noradrenaline (norepinephrine) and other directly-acting sympathomimetics are slightlyincreased in presence of reserpine.
Pretreatment with phenylephrine 10 % eye drops caused a blood pressure increase of 30/12 mmHg in 11 patients taking reserpine,whereas no significant increase in blood pressure occurred in 176 patients who were given phenylephrine eye drops and who were not taking reserpine (See reference number 1). After 7 healthy subjects took reserpine 0.25 to 1mg daily for 2 weeks increase in blood pressure response to noradrenaline (norepinephrine) was increased by 20 to 40 % (See reference number 2). A man taking reserpine who became hypotensive while undergoing surgery failed to respond to an intravenous injection of ephedrine, but did so after 30 minutes treatment with noradrenaline, presumably because stores of noradrenaline at adrenergic neurones had become replenished (See reference number 3). The mydriatic effects of ephedrine have also been shown to be antagonised by pretreatment with reserpine (See reference number 4). However,in contrast, one report claimed that ephedrine 25mg given orally or intramuscularly, once or twice daily, proved to be an effective treatment for re-serpine-induced hypotension and bradycardia in schizophrenic patients (See reference number 5).
Studies in dogs have demonstrated that adrenaline (epinephrine),noradrenaline (norepinephrine) and phenylephrine (all sympathomimetics with direct actions) remain effective vasopressors after treatment with reserpine, and their actions are enhanced to some extent (See reference number 6-8). Metaraminol has also been successfully used to raise blood pressure in reserpine-treated patients (See reference number 9).
The rauwolfia alkaloids (e.g. reserpine) cause adrenergic neurones to lose their stores of noradrenaline (norepinephrine),so that they can no longer stimulate adrenergic receptors and transmission ceases. Indirectly-acting sympathomimetics, which work by stimulating release of stored noradrenaline, may therefore be expected to become ineffective. In contrast, effects of directly-acting sympathomimetics should remain unchanged. However, their effects may be enhanced (as described above) because when receptors are deprived of stimulation by noradrenaline for any length of time they can become supersensitive. Drugs with mixed direct and indirect actions, such as ephedrine, should fall somewhere between two, although reports cited seem to indicate that ephedrine has predominantly indirect activity (See reference number 3,4).
These are established interactions, but paucity of clinical information suggests that in practice they do not present many problems, perhaps because effects of these vasopressors are so closely monitored, and titrated to effect. If a pressor drug is required,a directly-acting drug such as noradrenaline (norepinephrine) or phenylephrine may be expected to be effective. The receptors may show some supersensitivity so that a dosage reduction may be required. table 1 below, gives a classification of sympathomimetics.
Kim JM,Stevenson CE, Mathewson HS. Hypertensive reactions to phenylephrine eyedrops inpatients with sympathetic denervation. Am J Ophthalmol (1978) 85, 862–8.
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Ziegler CH,Lovette JB. Operative complications after therapy with reserpine and reserpinecompounds. JAMA (1961) 176, 916–19.
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Noce RH,Williams DB, Rapaport W. Reserpine (Serpasil) in the management of the mentallyill. JAMA (1955) 158, 11–15.
Stone CA,Ross CA, Wenger HC, Ludden CT, Blessing JA, Totaro JA, Porter CC. Effect of :5.5pt; font-weight:normal; color:#000000″>αmethyl-3,4-dihydroxyphenylalanine (methyldopa), reserpine and related agents on some vascular responses in the dog. J Pharmacol Exp Ther (1962) 136, 80–8.
Eger EI,Hamilton WK. The effect of reserpine on the action of various vasopressors. Anesthesiology (1959) 20, 641–5.
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| Table 1 A categorisation of some sympathomimetic drugs | |
|---|---|
| Drug | Receptors stimulated |
| Direct stimulators of alpha and beta receptors | |
| Adrenaline (Epinephrine) | Beta more marked than alpha |
| Mainly direct stimulators of alpha receptors | |
| Phenylephrine | Predominantly alpha |
| Metaraminol | Predominantly alpha |
| Methoxamine | Predominantly alpha |
| Noradrenaline (Norepinephrine) | Predominantly alpha |
| Mainly direct stimulators of beta-1 receptors | |
| Dobutamine | Predominantly beta-1, some beta-2 and alpha |
| Dopamine | Predominantly beta-1, some alpha |
| Direct stimulators of beta-1 and beta-2 receptors (beta-agonist bronchodilators) | |
| Bambuterol | Predominantly beta-2 |
| Fenoterol | Predominantly beta-2 |
| Formoterol | Predominantly beta-2 |
| Isoetharine | Predominantly beta-2 |
| Isoprenaline (Isoproterenol) | Beta-1 and beta-2 |
| Orciprenaline | Predominantly beta-2 |
| Pirbuterol | Predominantly beta-2 |
| Reproterol | Predominantly beta-2 |
| Rimiterol | Predominantly beta-2 |
| Ritodrine | Predominantly beta-2 |
| Salbutamol (Albuterol) | Predominantly beta-2 |
| Salmeterol | Predominantly beta-2 |
| Terbutaline | Predominantly beta-2 |
| Tulobuterol | Predominantly beta-2 |
| Direct and indirect stimulators of alpha and beta receptors | |
| Ephedrine | Alpha and beta |
| Etefedrine | Alpha and beta |
| Phenylpropanolamine | Alpha and beta |
| Pseudoephedrine | Alpha and beta |
| Mainly indirect stimulators of alpha and beta receptors | |
| Amfetamine (Amphetamine) | Alpha and beta – also central stimulant |
| Mephentermine | Alpha and beta – also central stimulant |
| Methylphenidate | Alpha and beta – also central stimulant |
| Tyramine | Alpha and beta |