Quotations from medical references I - K


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Ingram IM, Timbury GC.
Side-Effects of Librium.
Lancet 1960; ii: 766.
" Side-effects were seen in over half the patients. 2 felt drowsy on the smaller dose, 5 on the larger. 2 felt fatigued and apathetic, and dizziness and constipation were reported. 1 patient felt more energetic and 2 complained of severe irritability. After taking the drug for a week a schoolteacher struck his wife for the first time of the twenty years of their marriage. (---)

Although the number treated is small and the findings uncontrolled, the results are disappointing enough and the side-effects sufficiently troublesome to deserve attention. Other side-effects reported in trials in the United States have included dissociative reactions, hyperactivity, and ataxia.

We feel justified in suggesting that the drug should be used with circumspection and scepticism until the results of controlled trials are available. "
[Key words; aggression, disinhibition, paradoxical effects]

Jeffrey DI, Whitfield MF.
Lorazepam Poisoning.
BMJ 1974; 4: 719.
[regarding the overdosage of lorazepam in a 6-year-old boy]
" We report the case of a child with moderate overdosage of this drug which produced surprisingly severe effects. "

" Hallucinations are a recognized complication of ovedosage with diazepam, a more widely used member of the benzodiazepine group. On a body weight basis the fatal dose for a child would be between 500 and 600 mg. It was therefore surprising to find severe toxic signs with marked hallucinations in an otherwise healthy child at a fraction of that dosage. Clinicians should therefore be alert to the potential central toxicity of this drug in children with even mild to moderate degrees of overdosage. " [p. 719]
[Key words; Ativan, lorazepam, hallucinations, poisoning, children]

Karch FE.
Rage Reaction Associated with Clorazepate Dipotassium.
Annals of Internal Medicine 1979; 91: 61-62.
" Although paradoxical rage reactions associated with clorazepate have been rare, patients and physicians should be aware of possible paradoxical reactions with the use of clorazepate, and appropriate caution should be taken when prescribing this drug. " [p. 62]
[Key words; Tranxene, clorazepate, aggression, paradoxical reactions]

Karkos J.
[ Neurotoxicity of Benzodiazepines.]
Fortschr Neurol Psychiat 1991; 59: 498-520.
" The experimental data obtained after prenatal application indicate that BDZs can cause malformations, functional deficits and long-lasting behavioural anomalies. (---) The consequences of prenatal exposition to BDZs in m an, particularly their behavioural aspects, have not been sufficiently investigated as yet. Postnatal BDZs application can bring about behavioural disturbances and neurological deficits in animals and man. " [p. 498]
[Key words; teratogenic effects]

Katz RL.
Sedatives and Tranquilizers.
New England Journal of Medicine 1972; 286: 757-760.
" These agents ( i.e. the benzodiazepines), which were introduced after meprobamate, are widely used in the treatment of anxiety. As with meprobamate, the reasons for their tremendous popularity are not fully clear, but some of the same reasons may apply. " [p. 758]

" The use of drugs to alleviate the stress and strains of daily living may be harmful in many ways. In addition to the side effects and abuse of drugs, dependence on drugs to solve all problems may prevent personal growth. As Ban has stated, "It is reassur ing and supportive to self esteem for most patients to find an acute anxiety state can be alleviated without the use of medication. Sinc e most acute anxiety states remit promptly pharmacological conservatism is desireable." In addition, one cannot help wondering how much of the drug problem of contemporary children is due to the pill popping that they have observed in their parents. " [p. 760]

" Another harmful effect of drugs is that they may prevent the patient from getting to the source of the problem and taking appropriate action. "

" What can be recommended is that every time a physician reaches for his prescription pad, he ask himself if he is prescribing a sedative or tranquilizer because he has a roomful of patients waiting and is in a hurry to get on to the next patient... or whether he has carefully considered all the evidence, has found that sympathy, understanding, suggestion and reassurance are not sufficient, and has decided to prescribe a sedative or tranquilizer for positive reasons rather than as an easy way out." [p. 670]
[Key words; addiction, dependence]

Kellett JM.
The Benzodiazepine Bonzanza.
Lancet 1974; ii: 964.
" Dr Tyrer is certainly right to draw attention to the multiplicity of benzodiazepines (---). Not only are there to many, but one suspects that they are too often prescribed in ways which cause harm to the patient.

In the past three months I have seen 3 patients who were all receiving over 50 mg. of diazepam daily and had been doing so for several months. They were all young women of unstable personalities who had shown no improvement in their behaviour while on diazepam: if anything, suicide attemps had increased."
[Key words; Valium, diazepam, addiction, abuse, dependence, depression, suicide]

Keup W.
[ Flunitrazepam (Rohypnol) Reaches the Leading Position of Abuse among Benzodiazepine Derivative. ]
Sucht 1992; 38: 3-6.
Flunitrazepam (Rohypnol) in a random access sample of 8.165 persons with substance abuse problems of the German Substance Abuse Warning System (---) has reached in the past few years the leading position of abuse among benzodiazepine derivatives. A stricter control seems urgently needed, e.g. by establishing an additional Schedule in drug related legislation, between simple prescription and narcotic prescription, to allow a more effective control of this and other similar substances. [ SUMMARY p. 3]
[Key words; Rohypnol, flunitrazepam, addiction, abuse, dependence]

Kemper N, Poser W, Poser S.
[ Addiction Potential of the Benzodiazepines Is Greater Than Previously Assumed. ]
Deutsche Medizinische Wochenschrift 1980; 105: 1707-1712.
The position of benzodiazepine dependence among addiction diseases was studied retrospectively by analysing the case reports of in-patients at the Psychiatric Clinic, G\'9attingen. Addicts constitute the largest group of patients in this clinic, a situation probably true in general of psychiatric hospitals in the Federal Republic of Germany. Isolated alcoholism is the most frequent addiction, followed by combined alcohol-drug dependence and pure drug dependence. At present, benzodiazepines are the most commonly used addictive drugs. Although most of benzodiazepine dependents have changed to to it from another drug, primary benzodiazepine dependence is increasing. Among the benzodiazepines, lorazepam seems to have a particularly high addiction potential. On withdrawal of benzodiazepines, symptoms were less marked than after stopping a combination of benzodiazepines and alcohol, and (or) barbiturates; they generally developed with some time delay. [SUMMARY p. 1707]
[Key words; addiction, abuse, dependence]

Kennebäck G, Hollstedt C, Persson A.
[ Complex Partial Seizures with Focal EEG Abnormalities During Benzodiazepine Withdrawal.] Läkartidningen 1992; 89: 2523-2525.
The clinical and electroencephalographic features of three women presenting with complex partial seizures during benzodiazepine withdrawal are presented and discussed. [SUMMARY p. 2525]
[Key words, addiction, abuse, dependence, seizures]

Khan A, Joyce P, Jones AV.
Benzodiazepine Withdrawal Syndromes.
New Zealand Medical Journal 1980; 92: 94-96.
" We report eight cases of benzodiazepine withdrawal syndromes seen in a general psychiatric hospital. These consisted of acute organic brain syndrome, grand mal convulsions and abstinence syndromes. All of the cases were using benzodiazepines in prescribed therapeutic doses. These problems appear to be more common than are generally acknowledged. " [SUMMARY p. 94]

All of the reported cases were using benzodiazepines in therapeutic doses and were documented within a short period of time in a relatively small population, alarming us regarding the true incidence of these problems. ( - - - )

Amongst the group who manifested the abstinence syndrome certain common features were discerned. These were women who had been prescribed a benzodiazepine in therapeutic doses over a minimum of three years for persisting anxiety and/or depression. On withdrawal they uniformly suffered from insomnia, panic attacks, agitation, depersonalisation and an increase in depression. Their suffering was obvious and they all described it as beeing the worst experience of their lifes. " [p. 96]
[Key words; addiction, abuse, dependence, depression, withdrawal psychosis, depersonalization]

Kielholz P.
[ A National Inquiry on the Frequency of Drug Abuse in Switzerland.] German
Schweizerische Ärztezeitung 1968; 40: 1077-1110.
" Tranquilizer werden nur in Einzelfällen als Hauptsuchtmittel angegeben, wobei es sich um Valium, Librium, Petranquil, Quaname, Oblivon und Seresta handelt. Etwas häufiger werden sie als Nebensuchtmittel benutzt. Wegen der noch zu kurzen Beobachtungszeit fur diese Medikamente kann aus diesen Befunden noch kein endgultiger Schluss gezogen werden. " [p. 1083]

" Alle Packungen suchtgefährdender Mittel sollten an gut sichtbarer Stelle eine Warnung vor missbräuchlicher und regelmässiger Verwendung enthalten. (---)

Die Bevölkerung ist laufend mit allen zur Verfugung stehenden Mitteln uber die Suchtgefahr aufzuklären. Es muss immer wieder betont werden, dass Hypnotica, Analgetica, Tranquilizer und Stimulantien keine harmlosen Medikamente sind, sondern zur Drogenabhängigkeit und Gesundheitsschädigung fuhren können. " [p. 1092]
[Key words; Librium, Valium, chlordiazepoxide, diazepam, addiction, abuse, dependence, long-term effects]

King SA, Strain JJ.
Benzodiazepines and Chronic Pain.
Pain 1990; 41: 3-4.
"... their [i.e.the benzodiazepines] frequent prescription is disturbing for several reasons. The benzodiazepines are not innocuous drugs. They are addicting and their sudden discontinuation can result in serious withdrawal reactions. They can produce a variety of side effects, most notably sedation, impairments in cognition, and depression ..." [p. 3]
[Key words; addiction, abuse, dependence, withdrawal, depression, cognitive impairment]

Kornhuber HH.
[ The Benzodiazepine Risk.] German
Deutsches Ärzteblatt 1988; 85: B-405.
" Die Schwere der Benzodiazepinabh\'8angigkeit wird durch die grosse Häufigkeit von Ruckfällen nach Entziehung und die lange Dauer der Entzugssymptome (meist uber Monate) bewiesen. Leistungsversagen, beruflicher Abstieg, Unfälle, vorzeitige Berentung, Ehescheidung und Selbstmordversuche kommen bei Benzodiazepinabhängigkeit häufig vor. Der Absetzversuch fuhrt regelmässig zu jenen Symptomen, deretwegen sie ursprunglig genommen wurden: Unruhe, Angst, Schlaflosigkeit.

Ob die Kollegen, die heute noch das Benzodiazepinproblem herunterspielen, nicht einmal daruber nachdenken sollten, dass man die enormen Mittel fur Kosten und Folgekosten der Benzodiazepine zum Wohle der Patienten nutzlicher anwenden könnte - zumal in dieser Zeit harter "Kostendämpfung" im Gesundheitswesen. Daruber hinaus ist im Blick auf das Leid, das die Benzodiazepine verursachen, an den hippokratischen Eid zu erinnern. Die Pharmaindustrie aber, die grosse Leistungen vollbracht hat, ist schlecht beraten, wenn sie das verteidigt, was sie am meisten angreifbar macht: den Missbrauch von Benzodiazepinen. "
[Key words; addiction, dependence, withdrawal, depression, suicide, social decline, costs, drug manufacturers]

Krakowski AJ, Langlais LM.
Acute Psychiatric Emergencies in a Geriatric Hospital.
Psychosomatics 1974; 15: 72-75.
" Psychotropic drugs are probably overused in the senile group for the alleviation of behavior disturbances, especially anxiety and overactivity. The excessive doses and prolonged use may result in paradoxical effects and in confusional states, especially when polypharmacy is applied. ( - - - )

The polypharmacy may, however, be responsible for the reciprocal potentiation of untoward effects and be motivated less by the need of the patient than the need of the prescribing physician. " [p. 73]
[Key words; addiction, dependence, long-term effects, paradoxical effects, polypharmacy, the elderly]

Kripke DF, Garfinkel L.
Excess Nocturnal Deaths Related to Sleeping Pill and Tranquilliser Use.
Lancet 1984; i: 99.
" The group 1 subjects (who took no sleeping pills or tranquillizers) showed disproportionately fewer deaths during the usual hours of sleep, but group 2 subjects showed an excess of deaths during the same hours. The two groups differed significantly in the temporal distribution of deaths. " [p. 99]

" These results are consistent with the hypothesis that barbiturate sleeping pills and tranquillizers, in normal use, cause extra deaths during sleep. " [p. 99]
[Key word; hypnotics, the elderly]

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Key words:
abuse, accidents, addiction, adolescents, aggression, amnesia, anxiety, apnea, children, cognitive impairment, confusion, costs, dependence, depersonalization, depression, detoxific ation, driving, drug accumulation, drug manufacturers, the elderly, encephalopathy, fatigue, fractures, hallucinations, headaches, hostility, hypnotics, infants, insomnia, long-term effects, low Apgar scores, mania, memory impairment, mult iple prescribing, nightmares, OCD, oral cleft, paranoia, paradoxical effects, phobias, poisoning, polypharmacy, pregnancy, protracted withdrawal syndrome, psychomotor impairment, psychosis, rebound, respiratory depression, seizures, shop-lifting, social decline, suicide, teratogenic effects, tinnitus, tolerance, traffic, withdrawal, withdrawal psychosis.

Trade Names:
Ativan, Dalmane, Euhypnos, Halcion, Klonopin, Lexotan, Librium, Mogadon, Noctamid, Normison, Rohypnol, Serax, Serenid, Serepax, Tranxene, Valium, Versed, Xanax.

Generic Names:
alprazolam, bromazepam, chlordiazepoxide, clonazepam, clorazepate, diazepam, flunitrazepam, flurazepam, lorazepam, lormetazepam, nitrazepam, midazolam, oxazepam, temazepam, triazolam.