Drugs lethal combinations

A 58-year-old man with a history of angina for which he occasionally takes isosorbide dinitrate is having erectile dysfunction. He confides in a colleague who suggests that sildenafil might help and gives him three tablets from his own prescription. The potentially lethal combination of these drugs relates to... 

Ripple MG, Pestaner JP, Levine BS, Smialek JE. Lethal combination of tramadol and multiple drugs affecting serotonin. Am J Forensic Med Pathol 2000 21(4) 370-4. 

Drug interactions also may cause problems with different nonprescribed drugs or combinations of prescribed and nonprescribed drugs. The most common examples are mixing drugs that depress the central nervous system. For example, as we said earlier, alcohol and the barbiturates may be lethal in enhancing the sedative effects of each. This drug combination has caused many intentional and accidental deaths. 

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

Drug combinations I II, III, NDA 2 species up to 3 months Lethality by appropriate route, compared to components run concu rently in 1 species... 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

All of the psychological and physical effects of Rohypnol are dramatically increased when the drug is taken in combination with alcohol. In some instances, the combination can be lethal. 

Rohypnol is especially dangerous and potentially lethal when used in combination with other drugs such as alcohol. In 1994, the number of emergency room reports that mentioned Rohypnol was only 13, but this number grew to over 500 by the late 1990s many of these instances also involved the use of alcohol. 

Several pharmacological issues pertain to most CNS depressant drugs (Hobbs et al. 1996 Julien 1997). Depending on their pharmacological mechanisms, combinations of CNS depressants can produce additive or synergistic effects, when the total effect is equal to or greater than the sum of their individual effects, respectively. For example, in doses that would be safe individually, combinations of alcohol and barbiturates can be lethal. 

Talwin Nx Talwin Nx is intended for oral use only. Severe, potentially lethal reactions (eg, pulmonary emboli, vascular occlusion, ulceration and abscesses, withdrawal symptoms in narcotic-dependent individuals) may result from misuse of this drug by injection or in combination with other substances. 

The combined use of sulfonamides or sulfones with dihydrofolate reductase inhibitors, such as trimethoprim Bactrim, Septra) or pyrimethamine Fansidar), s, a good example of the synergistic possibilities that exist in multiple-drug chemotherapy. This type of impairment of the parasite s metabolism is termed sequential blockade. Using drugs that inhibit at two different points in the same biochemical pathway produces parasite lethality at lower drug concentrations than are possible when either drug is used alone. 

Alcohol has a triphasic effect on the elimination rates of drugs that require extensive biotransformation (21). For example, acute alcohol ingestion in combination with a TCA in a teetotaler who attempts suicide will significantly block the first-pass metabolism of the TCA. This chemical inhibition can triple the peak concentration of a TCA by increasing its bioavailability. This is why the consumption of alcohol in association with a TCA overdose increases lethality. 

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