Phenylpropanolamine Caffeine

Many diet pills that work by increasing the number of calories burned have been developed. Most of these contain one or more of the three ingredients caffeine, phenylpropanolamine (PPA), and ephedrine. In the United States, PPA and ephedrine have been withdrawn from the market because they produce serious side effects, including heart attack and stroke. Caffeine, which is still found in many diet pills, will be further discussed in Chapter 6. 

Doxapram Nikethamide Pentylenetetrazol Strychnine Picrotoxin Bicuculline Amphetamine Methamphetamine Methylphenidate Pemoline Ephedrine Phentermine Fenfluramine Phenylpropanolamine Caffeine Theophylline Theobromine... 

V-101 Flame ionization Simultaneous analysis of salicylamide, phenylpropanolamine HC1, caffeine, chlorpheniramine maleate phenylephrine HC1 and pyrilamine maleate, the sample should be treated with l+-(dimethylamino)-pyridine in pyridine-acetic anhydride 1 1. (62)... 

Look-alikes contain caffeine, ephedrine, or phenylpropanolamine, either singly or in combination. Ephedrine is a natural stimulant with a chemical structure resembling adrenaline that produces more anxiety and less euphoria than amphetamines. It... 

We mentioned these oral forms of stimulants at the end of Chapter 6. They usually contain phenylpropanolamine, sometimes combined with caffeine, and are packaged and named to look like amphetamines. 

Phenylpropanolamine, which is available over the counter for weight loss, inhibits caffeine metabolism, leading to excessive stimulation for example, manic psychosis (SEDA-17,1). 

Pharmacokinetic and pharmacodynamic interactions between caffeine 250 mg and phenylpropanolamine 25 mg have been investigated in six healthy subjects in a double-blind, placebo-controlled study. Coadministration of caffeine and phenylpropanolamine produced an additive increase in blood pressure, not attributable to a pharmacokinetic interaction and despite the fact that phenylpropanolamine attenuated the responses of adrenaline and renin to caffeine (17). 

However, in another study in 16 healthy subjects who took caffeine 400 mg plus phenylpropanolamine 75 mg, the peak plasma-caffeine concentration was significantly higher than after caffeine alone. There were greater increases in both systolic and diastolic blood pressures, and adverse effects were more frequent after the combination than after either drug alone or after placebo (18). 

Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991 50(4) 363-71. 

Lake CR, Rosenberg DB, Gallant S, Zaloga G, Chernow B. Phenylpropanolamine increases plasma caffeine levels. Chn Pharmacol Ther 1990 47(6) 675-85. 

Ephedra was also sold in combination with many other herbs in obscure combinations. Labels frequently listed 10 or 15 different herbs, but, analysis usually disclosed only the ephedra alkaloids and caffeine as present in sufficient quantities to be physiologically active. After several well-publicized accidental deaths, products clearly intended for abuse, such as herbal ecstasy, and other look-alike drugs (products usually containing ephedrine or phenylpropanolamine designed to look like illicit methamphetamine, but in concentrations higher than recommended by industry or the FDA) were withdrawn from the market. Labels on these products were frequently misleading. For example, one might suppose that a product called Ephedrine 60 contained 60 mg of ephedrine when, in fact, the actual ephedrine content was 25 mg. 

Lake CR, Zaloga G, Bray J, Rosenberg D, Chernow B. Transient hypertension after two phenylpropanolamine diet aids and the effects of caffeine a placebo-controlled follow-up study. Am J Med 1989 86(4) 427 132. 

Phenylpropanolamine also increases caffeine plasma levels. Whether there is also an effect on theophylline distribution kinetics is a matter of some debate (Lake et al., 1990 Upton, 1991). Even if such an effect does exist, however, it is not known whether such an effect would be of any clinical significance in the case of ma huang, which contains only very small amounts of pure phenylpropanolamine. Reduced metabolism of pseudoephedrine is... 

Lake C, Rosenberg D, et al. Phenylpropanolamine increases plasma caffeine levels. Clin Pharmacol Ther 1990a 47 675-85. 

Simultaneous caffeine (UV 298), chlorpheniramine (UV 265), guaifenesin (glycerylguai-colate) (UV 284), phenylpropanolamine (UV 260)... 

Indrayanto, G. Sunarto, A. Adriani, Y. Simultaneous assay of phenylpropanolamine hydrochloride, caffeine, paracetamol, glycerylguaiacolate and chlorpheniramine in Silabat tablet using HPLC with diode array detection. J.Pharm.Biomed.Anal., 1995,13, 1555-1559... 

Ehctracted amphetamine, benzoylecgonine, caffeine, codeine, cotinine, desipramine, diazepam, diphenhydramine, ephedrine, hydrocodone, hydromorphone, lidocaine, methadone, metheimphetamine, morphine, nordiazepam, nortriptyline, oxazepam, pentazocine, phen-metrazine, phenobarbital, phentermine, phenylpropanolamine, secobarbital Interfering flurazepam, imipramine... 

Achari, R.G. Jacob, J.T. A study of the retention behavior of some basic drug substances by ion-pair HPLC. J.Liq.Chromatogr., 1980, 3, 81-92 [also N-acetylprocainamide, antazoline, caffeine, chlorpheniramine, codeine, ephedrine, epinephrine, naphazoline, papaverine, pheniramine, phenylephrine, phenylpropanolamine, procainamide, quinidine, scopolamine, xylocaine]... 

Extracted acetaminophen, amobarbital, butabarbital, chlordiazepoxide, diazepam, eth-chlorvynol, flurazepam, glutethimide, methaqualone, methypiylon, nitrazepam, pentobarbital, phenobarbital, phenytoin, primidone, salicgrlic acid, secobarbital, theophylline Simultaneous amitriptyline, caffeine, clomipramine, codeine, desipramine, ethotoin, imip-ramine, lidocaine, mesantoin, methsuximide, nirvanol, nortriptyline, oxazepam, procainamide, phenylpropanolamine, propranolol, quinidine... 

Simultaneous acetaminophen, acetophenazine, amoxapine, amphetamine, atropine, ben-peridol, buspirone, caffeine, carbamazepine, chlorpheniramine, codeine, dextromethorphan, diazepam, diphenhydramine, flupenthixol, flurazepam, heiloperidol, hydergine, hy-drocodone, hydromorphone, lidocaine, loxapine, mepazine, meperidine, mesoridazine, methaquaalude, 3,4-methylenedioxyamphetamine, 3,4-methylenedio30 ethylamphetam-ine, 3,4-methylenedioxymethamphetamine, morphine, norcocaine, oxazepam, pentobarbital, phenylpropanolamine, procainamide, procaine, propyl benzoylecgonine, quinidine, quinine, salicylic acid, secobarbital, theophylline, trazodone, 3-tropanyl-3,5-dichloroben-zoate, vancomycin, WIN 35428... 

Also analyzed 6-acetylmorphine, amiloride, amphetamine, benzocaine, benzoylecgonine, caffeine, cocaine, do o lamine, fluoxetine, glutethimide, hexobarbital, hypoxanthine, le-vorphanol, LSD, meperidine, mephobarbital, methadone, methylphenidate, methyprylon, N-norcodeine, oxazepam, oxycodone, phenylpropanolamine, prilocaine, procaine, terfena-dine... 

Noninterfering acetaminophen, aspirin, amitriptyline, huprenorphine, caffeine, carba-mazepine, chlorpromazine, desipramine, dextromethorphan, doxepin, ephedrine, fenfluramine, imipramine, lidocaine, loxapine, meperidine, methadone, methaqualone, naloxone, naltrexone, nicotine, orphenadrine, oxycodone, papaverine, pentazocine, phendimetra-zine, phenmetrazine, phentermine, phenylpropanolamine, phenytoin, primidone, procaine, promethazine, propoxyphene, propyphenazone, theobromine, theophylline, trazodone, triflupromazine, trimethoprim, trimipramine... 

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