Denervation hypersensitivity

Phenylephrine can also be used as a diagnostic test for Horner s syndrome (see Chapter 22). Phenylephrine in the 1% concentration can markedly dilate the pupil with postganglionic sympathetic denervation. It causes minimal or no dilation in the normal eye. If the lesion is central or preganglionic, the affected pupil responds in a manner similar to the normal eye because denervation hypersensitivity is minimal or absent. 

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. 

Pharmacologic Evaluation. The denervated iris sphincter in Adie s pupil shows cholinergic hypersensitivity. This response is expected according to the principle of denervation hypersensitivity. The hypersensitivity does not seem to correlate with either the amount of sphincter denervation, the duration of the Adie s pupil, or the amount of light-near dissociation. Occasionally, an acute Adie s pupil shows very little hypersensitivity during the first few weeks after onset but gradually becomes increasingly hypersensitive several months after the initial episode. 

The effects of adenosine are potentiated in patients receiving dipyridamole, an adenosine-uptake inhibitor, and in patients with cardiac transplants owing to denervation hypersensitivity. Methylxanthines, such as theophylline and caffeine, block adenosine receptors therefore, larger than usual doses are required to produce an antiarrhythmic effect in patients who have consumed these agents in beverages or as therapy. 

Nervous system Cervical cord injuries effectively inactivate most of the sympathetic nervous system, leading to denervation hypersensitivity to exogenous catecholamines. The potential consequences of this have been demonstrated in two cases [70 ]. 

The authors pointed out the difference in outcomes in these two cases and suggested that the standard dose of adrenaline given to the first patient was in effect excessive, because of denervation hypersensitivity, while the low dose given in the second case was effective and safe. 

Adenosine Negative chronotropic effect Hypersensitivity Effect on sinus node of denervated heart Life-threatening asystole (>0.5 min) may occur if used to treat supraventricular arrhythmia or stress testing... 

Acetylcholine Negative chronotropic effect Hypersensitivity Effect on sinus node of denervated heart ... 

The denervation-receptor hypersensitivity develops after a nigrostriatal cell reduction of 90% and more (Riederer et al., 1989b Agid, 1991 Montastruc, 1991). A positive correlation between decline of D2 receptor density and duration of disease, age and duration of l-DOPA therapy cannot be found (Guttman and Seeman, 1986). 

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