Drug dependence barbiturates

The various barbiturates differ m the time required for the onset of sleep and m the duration of their effects All the barbiturates must be used only m strict accordance with instructions to avoid potentially lethal overdoses Drug dependence m some mdi viduals IS also a problem... 

Ibrahim RB, Wilson JG, Thorsby ME, et al Effect of buprenorphine on CYP3Aactivity in rat and human liver microsomes. Life Sci 66 1293—1298, 2000 Iguchi MY, Handelsman L, Bickel WK, et al Benzodiazepine and sedative use/abuse by methadone maintenance clients. Drug Alcohol Depend 32 257—266, 1993 Isbell H Manifestations and treatment of addiction to narcotic drugs and barbiturates. Med Clin North Am 34 423 38, 1950... 

Wilder A Diagnosis and treatment of drug dependence of the barbiturate type. Am J Psychiatry 125 758-765, 1968... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

German chemists knew in the 1900s that barbiturates could be addictive. However, people who took barbiturates did not always exhibit symptoms of drug dependence or withdrawal. By the 1940s, the addictive nature of barbiturates alarmed groups ranging from the American Medical Association (AMA) to the United States Food and Drug Administration (FDA). 

Older adults and pregnant women should consider the risks associated with barbiturate use. When a person ages, the metabolization rate for drugs decreases. As a result, people over age 65 are at higher risk of the harmful effects of barbiturates. There is also greater risk for drug dependence. 

Schedule II drags have a high potential for abuse. They are accepted for medical use with restrictions. These drugs may lead to severe psychological or physical dependence. Barbiturates in this category are amo-barbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal, Tuinal). 

So even if the tired patient is able to get to sleep without drugs during barbiturate withdrawal, he or she may awaken early in the morning and not be able to get back to sleep. Other factors may be involved, but it is clear that once dependence on sleeping pills has developed, considerable time must pass before normal sleep patterns return (Mendelson, 1980). All of these factors make it ea.sy to understand why dependence on drugs such as barbiturates for sleeping so often develops. Dependence certainly limits the usefulness of these and other depressants as a treatment of sleep disorders. 

HYPNOTICS are agents that induce sleep. They are used mainly to treat short-term insomnia, for instance in shiftwork, to cope with Jet-lag or in sleep disturbances due to emotional problems or in serious illness. The best-known and most-used hypnotics in current use are the benzodiazepines - and this class of drug is also used, at a lower dose, as ANXIOLYTICS. Examples from the class that are of relatively long-lasting action and may cause drowsiness the next day include diazepam, flunitrazepam, flurazepam and nitrazepam. Examples with a shorter duration include loprazolam, lormetazepam and temazepam. All can cause drug dependence on continued usage. Examples of hypnotics that are now much less used include chloral hydrate, chlormethiazole and triclofos. The barbiturates (e.g. amylobarbitone) are now very little used, as they are prone to cause serious dependence and are dangerous in overdose. 

Benzodiazepines show less tendency to tolerance and dependency than other older sedative-hypnotic drugs, especially barbiturates. Also, benzodiazepines produce less abuse potential. 

The barbiturates also cause a physical dependence different from the opioid narcotics. In an individual addicted to barbiturates, the barbiturates should not be withdrawn abruptly but, rather, tapered slowly. Sudden withdrawal of the barbiturates can precipitate extreme agitation and grand mal seizures. This can lead to a spasm of the respiratory musculature, producing impaired respiration, cyanosis, and possibly, death (42). As a rule, drug dependence is followed by tolerance, in which increasing doses are required to obtain the same pharmacological effect. Because barbiturates cause tolerance and, often, dependence, their use as a hypnotic rarely is justified. 

Acute and chronic administration of alcohol can inhibit the biotransformation or detoxification of many drugs, such as barbiturates, meprobamate, and amphetamines by liver enzymes. The effect can occur in two opposite ways. Alcohol and cannabinoids effects are additive. Both are CNS depressants. Animal studies indicate that simultaneous administration of alcohol and tetrahydrocannabinol (THC), the psychoactive component of marijuana, increased the tolerance and physical dependence to alcohol. Human studies show that alcohol and THC combination enhanced the impairment of physical and mental performance only, and there is no evidence of any interaction between both drugs. With barbiturates. 

Chronic use of barbiturates for insomnia or anxiety can lead to drug dependence, which can go unnoticed for months or years. The symptoms are slurred speech... 

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