Ketamine drug interactions

In addition to pharmacokinetic drug-drug interactions, pharmacodynamic effects have been reported as well. Halothane increases the susceptibility to ventricular arrhythmias under theophylline therapy as a result of increased sensitivity of the myocardium to endogenous catecholamine release by theophylUne. Ketamine lowers the theophyUine seizure threshold. Benzodiazepines Uke midazolam, diazepam, lorazepam, and Uurazepam increase the central nervous system concentration of adenosine, a potent central nervous system depressant. As theophyUine also blocks adenosine receptors, it counteracts benzodiazepine-induced sedation, resulting in increased dosage requirements for these compounds. ... 

Drug-drug interactions A randomised controlled trial (n = 135) showed significant synergism in pain control between morphine and ketamine in a prehospital setting [58 ]. 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

The mechanisms of action of phencyclidine and ketamine are complex (Gorelick Balster, 1995). The drugs are non-competitive antagonists at NMDA receptors, and also bind to associated phencyclidine/sigma opioid receptors. They also have agonist actions at dopamine receptors, complex interactions with both nicotinic and muscarinic acetylcholine receptors and poorly understood interactions with noradrenergic and serotonergic systems. These multiple actions may combine to produce delirium and psychotic reactions. 

The more active enantiomer at one type of receptor site may not be more active at another receptor type, eg, a type that may be responsible for some other effect. For example, carvedilol, a drug that interacts with adrenoceptors, has a single chiral center and thus two enantiomers (Figure 1-2, Table 1-1). One of these enantiomers, the (S) -) isomer, is a potent B-receptor blocker. The (R)(+) isomer is 100-fold weaker at the receptor. However, the isomers are approximately equipotent as -receptor blockers. Ketamine is an intravenous anesthetic. The (+) enantiomer is a more potent anesthetic and is less toxic than the (-) enantiomer. Unfortunately, the drug is still used as the racemic mixture. 

Among the drugs which are known to interact with barium, the barbiturates sodium pentobarbital and phenobarbital were found to have an increased depressive effect on the hearts of rats exposed to barium (Kopp et al. 1985 Perry et al. 1983, 1989). This hypersensitivity of the cardiovascular system to anesthesia was not observed in similarly treated animals that were anesthetized with xylazine plus ketamine. Results of the study indicated that the hypersensitivity was specific to the barbiturates and not a generalized effect of anesthesia (Kopp et al. 1985). 

Currently there is a trend toward the synthesis and large-scale production of a single active enantiomer in the pharmaceutical industry [61-63]. In addition, in some cases a racemic drug formulation may contain an enantiomer that will be more potent (pharmacologically active) than the other enantiomer(s). For example, carvedilol, a drug that interacts with adrenoceptors, has one chiral center yielding two enantiomers. The (-)-enantiomer is a potent beta-receptor blocker while the (-i-)-enantiomer is about 100-fold weaker at the beta-receptor. Ketamine is an intravenous anesthetic where the (+)-enantiomer is more potent and less toxic than the (-)-enantiomer. Furthermore, the possibility of in vivo chiral inversion—that is, prochiral chiral, chiral nonchiral, chiral diastereoisomer, and chiral chiral transformations—could create critical issues in the interpretation of the metabolism and pharmacokinetics of the drug. Therefore, selective analytical methods for separations of enantionmers and diastereomers, where applicable, are inherently important. 

Drugs that make the urine alkaline (e.g. sodium bicarbonate, carbonic anhydrase inhibitors) will reduce the elimination of memantine. Memantine should be used with caution with other NMDA antagonists, such as amantadine, ketamine and dextromethorphan, or concurrent use should be avoided, because of the theoretical increased risk of adverse effects. Memantine is predicted to interact with other drugs eliminated by the same renal secretion mechanism, but no important interaction was seen with glibenclamide, hydrochlorothiazide, metformin or triamterene. 

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