Ephedrine interactions

Interactions with caffeine and aspirin can increase the effects of ephedrine. Norepinephrine works in part by increasing the levels of cyclic aminomethyl propanol (AMP) in cells. Caffeine inhibits the enzyme that breaks down cyclic AMP. Together, ephedrine makes more cyclic AMP, and caffeine prevents it from breaking down. Aspirin inhibits the receptors that turn off release of norepinephrine. 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

From calculations of the preferred conformation of the ephedrine and pseudo ephedrine molecules the topography of the adrenergic receptor as a flat surface has been deduced (26). This view, however, does not explain the decisive effect of the additional methyl group its relative position should not influence the interaction with the proposed receptor to a large extent (Fig. 7a). However, as the differences in activities are especially high for the ephedrine and pseudo ephedrine isomers, we believe that the receptor must have an intercalated structure similar as projected for the "binding sites" of the silicones (Fig. 7b). ... 

Only in this case the relative position of the additional methyl groups can exert such profound differences in the interaction with the receptor, as it is observed for these drugs in the biological system and similarly with the synthetic model. The energy-niveau of the rotamer of D-ephedrine in b) is energetically only slightly higher than of the rotamer in a)... 

Other conditions in which ephedra is contraindicated are anxiety disorders, angle-closure glaucoma, prostate adenoma with residual urine volume, pheochromocytoma, and thyrotoxicosis (Gruenwald et al. 1998). Known medications that may interact adversely with ephedrine include heart glycosides, halothane, guanethidine, MAO inhibitors, secale alkaloids, and oxytocin. 

The main limitation to the clinical use of the MAOIs is due to their interaction with amine-containing foods such as cheeses, red wine, beers (including non-alcoholic beers), fermented and processed meat products, yeast products, soya and some vegetables. Some proprietary medicines such as cold cures contain phenylpropanolamine, ephedrine, etc. and will also interact with MAOIs. Such an interaction (termed the "cheese effect"), is attributed to the dramatic rise in blood pressure due to the sudden release of noradrenaline from peripheral sympathetic terminals, an event due to the displacement of noradrenaline from its mtraneuronal vesicles by the primary amine (usually tyramine). Under normal circumstances, any dietary amines would be metabolized by MAO in the wall of the gastrointestinal tract, in the liver, platelets, etc. The occurrence of hypertensive crises, and occasionally strokes, therefore limited the use of the MAOIs, despite their proven clinical efficacy, to the treatment of atypical depression and occasionally panic disorder. 

Figure 4.8 shows the UV absorption spectrum of a 100 mg/100 ml solution of ephedrine. Ephedrine has the simplest type of benzene ring chromophore, which has a spectrum similar to that of benzene with a weak symmetry forbidden band ca 260 nm with anA (1%, 1 cm) value of 12. Like benzene its most intense absorption maximum is below 200 nm. There are no polar groups attached to or involved in the chromophore so that its vibrational fine structure is preserved because the chromophore does not interact strongly with the solvent. 

From the 13C-NMR spectra of a series of 2-methylamino-l-phenyl-1 -propanol ephedrine analogs, it was established that the chemical shifts of C-l and C-3 are always 3-4 ppm smaller in the anti-than in the jvn-diastereomers363,364. This was explained by a greater number of gauche interactions in the energetically preferred anti conformation leading to a shielding of these two carbons. 

Ephedra (ma huang) is a popular botanical incorporated into a variety of formulations for weight loss, energy or performance enhancement, and symptomatic control of asthma. A pharmacodynamic interaction leading to a fatality has been reported with concurrent use of caffeine and ephedra (62), possibly as a result of additive adrenergic agonist effect of the ephedrine alkaloids and caffeine on the cardiovascular system and the CNS (63). Ephedra was recently withdrawn from the market (64). 

Thus, ephedrine can apparently interact with other health factors that may increase the hazards of using it as a stimulant. Despite this, Bechler s widow has filed a 600 million lawsuit against the manufacturers of Xenadrine. 

Methyldopa [Aldomet) [Antihypertensive/Centrally Acting Antiadrenergic] Uses HTN Action Centrally acting antihypertensive Dose Adults. 250-500 mg PO bid-dd (max 2-3 g/d) or 250 mg-1 g IV q6-8h Peds. 10 mg/kg/24 h PO in 2-3 + doses (max 40 mg/kg/24 h - q6-l2h) or 5-10 mg/kg/dose IV q6-8h to total dose of 20—40 mg/kg/24 h i in renal insuff/elderly Caution [B (PO), C (IV), +] Contra Liver Dz MAOIs Disp Tabs, inj SE Discolors urine inidal transient sedadon/drowsiness frequent, edema, hemolydc anemia, hepadc disorders Interactions T Effects W/ anesthetics, diuredcs, levodopa, Li, methotrimeprazine, thioxanthenes, vasodilators, verapamil T effects OF haloperidol, Li, tolbutamide 1 effects W7amphetamines, Fe, phenothiazine, TCAs 1 effects OF ephedrine EMS Use diuredcs, verapamil, and sympathomimedcs w/ caudon may T risk hypotension, arrhythmias and pressors effects OD May cause profound hypotension, drowsiness, and impaired myocardial conduction activated charcoal may be effective... 

CNS, smooth muscle T diuresis X- pit aggregation Available forms Daily t doses w/ max 3 g PO daily Contra Avoid in PRG lactation, CAD, hyperthyroidism, anxiety disorders d/t high, caffeine content Notes/SE Insomnia, tach, anxiety, N/V, HA, HTN, Sz Interactions T Effects OF anticoagulants, anti-pits, BBs, bron-choclilators T risk of hypertensive crisis W/ MAOIs T effects W/ cimetidine, ciprofloxacin, ephedrine, hormonal contraceptives, dieophylline, cola, coffee X-effects OF adenosine, antihypertensives, benzodiazepines, Fe, X- effects W/ smoking EMS Tinctures contain EtOH may exacerbate GI disorders HTN T effects of anticoagulants and BBs... 

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