Lidocaine Verapamil

A growing number of other diverse compounds have also been shown to bind to an allosteric site on the muscarinic receptors. Among them are pirenzepine (highly selective for Mi receptor), lidocaine and verapamil (ion channel blockers), tacrine (anticholinesterase compound), batrachotoxin, and strychnine (glycine receptor antagonist) [25,31-35],... 

The answer is e. (Hardman, pp 858-874.) Because verapamil, a Ca channel blocker, has a selective depressing action on AV nodal tissue, it is an ideal drug for both immediate and prophylactic therapy of supraventricular tachycardia (SVT). Nifedipine, another Ca channel blocker, has little effect on SAT Lidocaine and adenosine are parenteral drugs with short ha If-lives and, thus, are not suitable for prophylactic therapy. Procainamide is more suitable for ventricular arrhythmias and has the potential for serious adverse reactions with long-term use. 

The enzyme is the principal participant in N-demethylation reactions where the substrate is a tertiary amine. The list of substrates includes erythromycin, ethylmor-phine, lidocaine, diltiazem, tamoxifen, toremifene, verapamil, cocaine, amiodarone, alfentanil and terfenadine. Carbon atoms in the allylic and benzylic positions, such as those present in quinidine, steroids and cyclosporin A, are also particularly prone to oxidation by CYP3A4, a range of substrates is illustrated in Figure 7.10. 

Verapamil Itraconazole Ketoconazole Lidocaine Maprotiline Midazolam Progesterone Propanolol Quinidine Trim ipra mine ... 

Cimetidine Lidocaine, propranolol, verapamil, imipramine Increased absorption... 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

Drugs metabolized by CYP that interact with cimetidine include, but are not limited to, the following lidocaine, quinidine, midazolam, triazolam, nifedipine, verapamil, and fentanyl (4). In each instance, inhibition of CYP by cimetidine results in reduced metabolic clearance and increases in serum concentrations of the other drug, which can lead to the expected toxicity and adverse experiences characteristic of the other drug. 

When the interaction of the modifiers was studied on DPPS liposomes rather than DPPC liposomes, a major difference was the observed change in AH. This is exemplified in Figure 5.18. At lipid to drug molar ratios ranging from 1 0.01 to 1 0.1, the change in AH was observed for all studied compounds with the exception of verapamil and lidocaine. The decrease in AH of DPPS, indicating a new type of phospholipid organization, was paralleled by the formation of a new endothermic peak at... 

As noted above, the antiarrhythmic drugs can modify impulse generation and conduction. More than a dozen such drugs that are potentially useful in treating arrhythmias are currently available. However, only a limited number of these agents are clinically beneficial in the treatment of selected arrhythmias. For example, the acute termination of ventricular tachycardia by lidocaine or supraventricular tachycardia by adenosine or verapamil are examples in which antiarrhythmic therapy results in decreased morbidity. In contrast, many of the antiarrhythmic agents are now known to have lethal proarrhythmic actions, that is, to cause arrhythmias. 

The most used and validated probe drugs for C YP3 A phenotyping are midazolam and 14C-erythromycin (Watkins 1994). Alfentanyl, alprazolam, dapsone, dextromethorphan, lidocaine. nifedipine, omeprazole, quinine, verapamil have also been used but less frequently, and CYP3A specificity for some of them has been questioned. The endogenous 6(->-hydroxycortisol test (measurement of 6 3-hydroxycortisol cortisol ratio in urine) is only useful for detecting CYP3A induction, and may be influenced by renal CYP3 A activity. 

Patients should be advised to rest and to avoid extreme heat. They should be warned that symptoms may be aggravated by illness, stress, malnutrition, pain, or surgery. Various drugs have been shown to worsen symptoms of myasthenia gravis. These include the aminoglycoside antibiotics such as tobramycin, gentamicin, and neomycin tetracyclines such as doxycycline and minocycline class 1 antiarrhythmics such as lidocaine, quinidine, and procainamide magnesium in calcium and multivitamin supplements beta-blockers such as timolol and propranolol calcium channel blockers such as verapamil and penicillamine. 

Single Phase I metabolic pathway CYP3A Alprazolam, midazolam, triazolam, verapamil, diltiazem, dihydro pyridine calcium channel blockers, lidocaine... 

The use of vacutainer tubes and heparin was shown to alter the determination of protein binding. Heparin was shown to decrease the plasma binding of certain drugs including phenytoin, propranolol, lidocaine, diazepam, quinidine, and verapamil. This is also an in vitro artifact attributable to continued ex vivo activity of the lipoprotein lipase enzyme and accumulation of fatty acids in the blood collection tube. 

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