Cocaine Interactions
Antihypertensive Agents
Beta-blockers
Cardiac glycosides
Cholinesterase Inhibitors
- Cyclophosphamide
- Disulfiram
- Dronabinol, THC
- Duloxetine
- Furazolidone
Halogenated anesthetics
Monoamine oxidase inhibitors (MAOIs)
Nitrates
Radiopaque Contrast Agents
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-Receptor Agonists
Sulfonamides
Sympathomimetics
Thyroid hormones
Tricyclic antidepressants
Cocaine Interactions
With regular use of cocaine, dopamine concentrations in the brain decrease, eventually leading to dopamine-receptor supersensitivity. This change in receptor sensitivity at postsynaptic receptor sites is believed to be the basis for the sensations of withdrawal. Bromocriptine, a dopamine-receptor (D2) agonist, has been shown to significantly reduce symptoms of cocaine withdrawal , further supporting the role of dopamine in cocaine’s mechanism of action. Pimozide, a dopamine-receptor antagonist, may block cocaine-induced stimulation.
Additive effects and increased toxicity may be observed when using cocaine in combination with other sympathomimetics. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as CNS stimulation, hypertensive crisis, cardiac arrhythmias or ischemia (angina). The addition of epinephrine (vasoconstrictor) to cocaine preparations (i.e. extemporaneous compounding of cocaine with epinephrine to produce formulations for application to the nasal mucosa or to prepare wounds for suturing) is unnecessary and may increase the likelihood of cardiac arrhythmias, ventricular fibrillation, and hypertensive episodes. Cocaine and other drugs that have the potential for abuse should not be consumed while taking ephedra, Ma huang. Many case reports have cited adverse cardiovascular reactions in patients taking stimulant type drugs in combination with ephedra.
Concomitant use of cardiac glycosides with sympathomimetics, including cocaine, can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity.
Concomitant use of cocaine with levodopa can result in an increase in the risk of developing cardiac arrhythmias. Levodopa should be used cautiously in patients who are known users of cocaine. Conversely, electrocardiographic monitoring should be considered when using cocaine in patients receiving levodopa.
Use of cocaine with antihypertensive agents, especially postganglionic blocking agents such as guanadrel or guanethidine, may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation. Concomitant use of cocaine and beta-adrenergic blocking agents, including ophthalmic preparations, can cause unopposed alpha-adrenergic activity, resulting in heart block, excessive bradycardia, or hypertension. Beta-blockers are indicated, however, to reduce cocaine-induced tachycardia, myocardial ischemia, and arrhythmias. In theory, the use of alpha-blocker and beta-blocker combinations or selective beta-blockers in low doses may not cause unopposed alpha stimulation in this situation. Labetalol, a beta-blocker with some alpha-blocking activity, has been used successfully to treat cocaine-induced hypertension. Because cocaine stimulates a generalized adrenergic response, it can reduce the antianginal effects of nitrates.
Concurrent use of dronabinol, THC with cocaine may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 - 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm.
Halogenated anesthetics (especially chloroform, cyclopropane, halothane, or trichloroethylene and, to a lesser extent, enflurane, isoflurane, or methoxyflurane) may sensitize the myocardium to the effects of sympathomimetics , including cocaine.
Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Dosage adjustment of the cholinesterase inhibitor may be necessary to control the symptoms of myasthenia gravis. Additionally, cholinesterase inhibitors reduce the metabolism of cocaine, therefore, prolonging cocaine’s effects or increasing the risk of toxicity. It should be taken into consideration that the cholinesterase inhibition caused by echothiophate, demecarium, or isoflurophate may persist for weeks or months after the medication has been discontinued.
Cyclophosphamide is believed to reduce the levels of endogenous pseudocholinesterases, which may explain an increased risk of toxicity from cocaine when cocaine is administered to patients receiving cyclophosphamide. If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, the anesthesiologist should be alerted.
MAOIs, or drugs that possess MAO-inhibiting activity (e.g., furazolidone, linezolid, or procarbazine), can prolong and intensify the cardiac stimulation and vasopressor effects of sympathomimetics, such as cocaine. Phenelzine and tranylcypromine appear to pose the greatest risk since these 2 MAOIs also have intrinsic amphetamine-like activity. In the presence of MAOIs, cocaine and other drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. It is unclear if selegiline, an inhibitor of MAO type B, can also predispose to this reaction. Cocaine should not be administered during or within 14 days following the use of MAOIs or drugs with MAO-inhibiting activity.
Sympathomimetic amines, including cocaine, should be used with caution in patients with thyrotoxicosis since these patients who are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
Although not a major metabolite associated with cocaine, ester-type local anesthetics such as cocaine are metabolized to PABA. Para-aminobenzoic acid, PABA, in turn, antagonizes the effects of sulfonamides. Although this interaction may be more theoretical than real, whenever possible, ester-type local anesthetics should be avoided in patients receiving sulfonamides.
Cocaine use has been associated with precipitating seizures. Since tramadol decreases the seizure threshold, an increased risk of seizures may be seen with concomitant use of these two drugs.
Disulfiram has been reported to increase the Cmax and the AUC of cocaine by 2 - 3 fold and 3 - 6 fold, respectively, in one study of volunteers with cocaine-abuse histories who received intranasal cocaine after disulfiram pre-treatment. Disulfiram increased the heart rate response to cocaine compared to placebo pretreatment. After administration of a 2 mg/kg intranasal cocaine dosage, the disulfiram pretreated group also experienced increased diastolic and systolic blood pressures. Disulfiram treatment should proceed with caution in those patients with a history of active cocaine abuse.
Use of disinfectant solutions containing heavy metals are not recommended for chemical disinfection, and preventative measures are required if heavy metal disinfectants are used for skin or mucous membrane disinfection, prior to local anesthetic administration. Local anesthetics may cause the release of heavy metal ions from disinfectant solutions, which if injected with the anesthetic, may cause severe local irritation, swelling and edema.
Concomitant use of cocaine with drugs that have CNS serotonergic properties (e.g., duloxetine, serotonin-receptor agonists, SSRIs, nefazodone or venlafaxine) could potentiate serotonin neurotransmission, and result in the serotonin syndrome (symptoms may include mental status changes, diaphoresis, tremor, myoclonus, hyperreflexia or fever).
Cocaine-induced toxicities on the cardiovascular and nervous system appear to be mediated by serotonin and dopamine neurotransmission. The tricyclic antidepressants target these monoamine systems and may thus amplify the cardiovascular or convulsive effects of cocaine, particularly during cocaine abuse. In the medical use of cocaine as a local anesthetic, interactions with tricyclic antidepressants are not common, but special care must be taken since there may be an increased risk of cardiac arrhythmia. Administer cocaine with caution and in conjunction with close clinical monitoring, especially when injecting cocaine combined with a vasoconstrictor (e.g., epinephrine) in patients receiving tricyclic antidepressants.
Cocaine is primarily metabolized via plasma esterases. Cocaine is partially metabolized by N-demethylation in the liver as a minor route of elimination, which may potentially include microsomal oxidative metabolism via CYP3A4 as a pathway of cocaine bioactivation. CYP3A4 metabolism appears to result in a metabolite that may be hepatotoxic per in vitro studies. Some CYP3A4 inhibitors have been reported to attenuate cocaine hepatotoxicity in vitro, but more data are needed. No clinically significant positive or negative interactions between cocaine and inhibitors of CYP3A4 have been reported in vivo.
Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Cocaine is a CNS stimulant and has been associated with precipitating seizures; cocaine should be avoided for at least 48 hours before myelography and should not be used for at least 24 hours postprocedure.
[ Last revised: 2/16/2005 5:52:00 PM ]
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