Barbiturates Opioids

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

The estimated sensitivity of skin tests for muscle relaxants is approximately 94-97%. Sensitivity for other substances varies. It is good for synthetic gelatins, (3-lactams, but poor for barbiturates, opioids and benzodiazepines dyes, and chlorhexidine. 

Depressants alcohol, barbiturates Opioids heroin, morphine, methadone... 

II. Toxic dose. In general, the toxic therapeutic ratio for benzodiazepines is very high. For example, oral overdoses of diazepam have been reported in excess of 15-20 times the therapeutic dose without serious depression of consciousness. On the other hand, respiratory arrest has been report after ingestion of 5 mg of triazolam and after rapid Intravenous injection of diazepam, midazolam, and many other benzodiazepines. Also, ingestion of another drug with CNS-depres-sant properties (eg, ethanol, barbiturates, opioids, etc) will likely produce additive effects. 

Opiates produce more discreet inhibitory effects since they bind to and activate inhibitory opioid receptors which, due to their restricted distribution, cause less widespread effects than those of the barbiturates and alcohol. Activation of the opioid receptors leads to a decrease in release of other neurotransmitters (glutamate, NA, DA, 5-HT, ACh, many peptides, etc.) and direct hyperpolarisation of cells by opening of K+ channels and decreasing Ca + channel activity via predominant actions on the mu opiate receptor (see Chapter 12). 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

Behaviorai effects Opioids produce sedation, but not as profoundly as CNS depressants like barbiturates or general anesthetics. A person administered an opioid is generally lethargic but arousable. 

Deaths, cardiac and resp have been reported during initiation and conversion of pain pts to methadone Tx from Tx w/ other opioids Uses Severe pain detox w/ maint of narcotic addiction Action Narcotic analgesic Dose Adults. 2.5-10 mg IM q3-8h or 5-15 mg PO q8h titrate as needed Feds. 0.7 mg/kg/24 h PO or IM -s- q8h T slowly to avoid resp depression X in renal impair Caution [B/D (prolonged use/high doses at term), + (w/ doses =/> 20 mg/24 h)], severe liver Dz Disp Tabs, inj SE Resp depression, sedation, constipation, urinary retention, T QT interval, arrhythmias Interactions T Effects W/ cimetidine, CNS depressants, protease inhibitors EtOH T effects OF anticoagulants, antihistamines, barbiturates, glutethimide, methocarbamol ... 

Drug withdrawal reactions - tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, barbiturates, alcohol, opioids. 

The MAC requirement also is reduced by the coadministration of other CNS depressants, such as barbiturates or opioid analgesics. CNS stimulants, such as amphetamine, may elevate the partial pressure needed for anesthesia. 

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

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