5/22/18

Vicki, I have never stopped loving you, I just didn’t want to duplicate our Garden Grove experience.  I wouldn’t have visited you repeatedly if the dream we had died in me.  I had prepared an email yesterday to send you but put it off so I could read it again.  Things are complex, since humans are part animal and a bit rational.  The rational side acts as a guard occasionally.  It also helps in figuring out how to be master or events for a few people who aren’t part of the common herd.    

Still as Michael S. Gazzaniga wrote:  The brain rules.”    I think that the relationship with Janice is over, the quality keeps getting lower.  I will explain more in the next email. 

And as for gods, they are a guiding light.  As the Greek philosophers held, a god most act god like.  And the poets wrote monstrous lies about them (they didn’t have priests).  I hold that when someone tells me about the god they know that they lie.  I hold that a god would promote the greatest good for the greatest number.  Why that hasn’t occurred is a mystery.  I hold that the gods want us to follow that maxim.  Thus it is our godly duty not just to radiate goodness (fellow-feeling for our brethren), but to seek to promote their wellbeing.

Elderly people are more likely than younger patients to develop cognitive impairment as a result of taking medications. This reflects age- and disease-associated changes in brain neurochemistry and drug handling. Delirium (acute confusional state) is the cognitive disturbance most clearly associated with drug toxicity, but dementia has also been reported. The aetiology of cognitive impairment is commonly multifactorial, and it may be difficult to firmly establish a causal role for an individual medication.

In studies of elderly hospital patients, drugs have been reported as the cause of delirium in 11 to 30% of cases. Medication toxicity occurs in 2 to 12% of patients presenting with suspected dementia. In some cases CNS toxicity occurs in a dose-dependent manner, often as a result of interference with neurotransmitter function. Drug-induced delirium can also occur as an idiosyncratic complication. Finally, delirium may occur secondary to iatrogenic complications of drug use.

Almost any drug can cause delirium, especially in a vulnerable patient. Impaired cholinergic neurotransmission has been implicated in the pathogenesis of delirium and of Alzheimer’s disease. Anticholinergic medications are important causes of acute and chronic confusional states. Nevertheless, polypharmacy with anticholinergic compounds is common, especially in nursing home residents. Recent studies have suggested that the total burden of anticholinergic drugs may determine development of delirium rather than any single agent. Also, anticholinergic effects have been identified in many drugs other than those classically thought of as having major anticholinergic effects.

Psychoactive drugs are important causes of delirium. Narcotic agents are among the most important causes of delirium in postoperative patients. Long-acting benzodiazepines are the commonest drugs to cause or exacerbate dementia. Delirium was a major complication of treatment with tricyclic antidepressants but seems less common with newer agents. Anticonvulsants can cause delirium and dementia.

Drug-induced confusion with nonpsychoactive drugs is often idiosyncratic in nature, and the diagnosis is easily missed unless clinicians maintain a high index of suspicion. Histamine H₂receptor antagonists, cardiac medications such as digoxin and β-blockers, corticosteroids, non-steroidal anti-inflammatory agents and antibiotics can all cause acute, and, less commonly, chronic confusion.

Drug-induced confusion can be prevented by avoiding polypharmacy and adhering to the saying ‘start low and go slow’. Special care is needed when prescribing for people with cognitive impairment. Early diagnosis of drug-induced confusion, and withdrawal of the offending agent or agents is essential.

Keywords

Dementia   Adis International Limited   Nursing Home Resident  Oxybutynin   Neuroleptic Malignant Syndrome 

Selected from full text JK:

1.1.3 Clinical Significance The prevalence of delirium in older people on admission to hospital ranges from 10 to 24%, and delirium develops in a further 5 to 32% of older patients after admission.[9-11] Advanced age, dementia and severe illness are important predisposing factors for delirium.[12] Delirium is associated with a high mortality rate, prolonged duration of hospital stay and a high rate of discharge to institutional care.[9,10] Many patients subsequently develop dementia, although it is unclear whether delirium itself contributes to chronic cognitive impairment or is just a marker of a subclinical dementing process.[13]. . .

Drug-induced confusion is among a number of potentially treatable causes of dementia.

Table I. Drugs associated with delirium in prospective medical studies Study Drug No. of patients

O’Keeffe and Lavan[5] Tricyclic antidepressants 6 Levodopa 2 Oxybutynin 2 Benzatropine 1 Pethidine 1 Phenytoin 1 Digoxin 1

 Francis et al.[11] Narcotics 9 Benzodiazepines 7 Anticholinergics 7 Methyldopa 3 NSAIDs 3

Medication toxicity accounts for between 2 and 12% of cases of dementia in a number of studies.[19-21] For example, Larson et al.[19] found drug induced confusion in 35 of 308 patients with suspected dementia. Furthermore, the relative odds of developing drug-induced confusion increased from 1.0 when 0 to 1 drugs were used to 9.3 when 4 to 5 drugs were used.  [That is a 9 fold increase].

As with delirium, there are a number of difficulties in establishing a causal relationship between dementia and drugs [Yes when a physician sees over 1,000 patients a year, with 15 minute window of which 2.3^rd of time spent is on the computer.]

Polypharmacy with anticholinergic compounds is common in nursing home residents, a population which has a high prevalence of Alzheimer’s disease. For example, Blazer et al.[24] noted that 60% of almost 6000 nursing home residents (and 23% of ambulant elderly controls) received drugs with anticholinergic properties, while up to 32% of nursing home residents and 13% of controls were taking 2 or more anticholinergic drugs simultaneously

3.2 Clinical Features of Anticholinergic Toxicity The CNS effects of anticholinergic medications include subtle neuropsychological deficits, especially involving memory and attention, and delirium. Anticholinergic delirium is characteristically associated with agitated behaviour and florid visual hallucinations.[25] Signs of peripheral autonomic anticholinergic toxicity may or may not be present. Anticholinergic medications may also cause chronic cognitive deficits and mimic Alzheimer’s disease.[26]

Anticholinergic drugs used in PD, such as trihexyphenidyl or benzatropine, often cause cognitive impairment or hallucinations in elderly patients.[32] The high prevalence of dementia in elderly patients with PD adds to the risk of anticholinergic induced confusion. De Smet et al.[33] reported that delirium developed in 93% of patients with dementia and PD compared with 46% of patients with dementia on drug regimens which did not include anticholinergic agents. Oxybutynin is used to reduce uninhibited bladder contractions in patients with increased urinary frequency or urinary incontinence. It has recently been shown that oxybutynin can cause cognitive deficits in elderly people,[34] and delirium has also been reported.[35]

Tune et al.[40] studied the antimuscarinic effects of the 25 most commonly prescribed drugs for elderly patients in the radio-receptor assay. Fourteen drugs produced detectable anticholinergic effects, and 10 produced levels of anticholinergic activity, expressed as atropine equivalents, that have been shown to produce significant cognitive impairment in elderly people.

4. Cognitive Impairment Due to Psychoactive Drugs Psychoactive drugs are the commonest causes of drug-induced cognitive impairment.[11,19,41,42] CNS toxicity with these agents is usually dose-related, although it also depends greatly on the vulnerability of the individual patient.

5. Cognitive Impairment Due to Nonpsychoactive Drugs Drug-induced confusion with the agents discussed in the following sections is often idiosyncratic in nature, and the diagnosis is easily missed unless clinicians maintain a high index of suspicion.

Table II. Drugs associated with cognitive impairment Drug Class Examples Risk Comment Anticholinergics Atropine Scopolamine High Glycopyrronium bromide is a safer agent for anaesthetic premedication Benzodiazepines Nitrazepam, Flurazepa, Diazepam Temazepam High Medium Cognitive impairment is more common with long-acting agents. Withdrawal delirium also occurs Opioid analgesics Pethidine (meperidine) High Risk may be highest with pethidine Antipsychotics Thioridazine Chlorpromazine Risperidone Medium Low Although often used in the treatment of delirium, antipsychotics with significant anticholinergic activity can worsen confusion Antiparkinsonian drugs Trihexyphenidyl Benzatropine Bromocriptine Levodopa Selegiline (deprenyl) High Medium Risk is highest in drugs with anticholinergic activity Antidepressants Amitriptyline Imipramine Nortriptyline Desipramine SSRIs High Medium Low Risk is highest in drugs with anticholinergic activity Anticonvulsants Primidone Phenytoin Medium Low Risk may be lowest with valproic acid and newer anticonvulsants H2 Antagonistsa Cimetidine Ranitidine Low Proton pump inhibitors may be less likely to cause delirium H1 Antagonistsa Chlorphenamine Low Antihistamines are available in many over-the-counter preparations Cardiovascular drugs Quinidine Digoxin Methydopa β-Blockers Diuretics ACE inhibitors Medium Low Digoxin toxicity is dose-related, but in elderly people confusion may occur with normal serum concentrations Corticosteroids Prednisolone Medium Risk is dose-related NSAIDs Indomethacin Ibuprofen Medium Low Paracetamol is a safer alternative for short term use Antibiotics Cephalosporins Penicillin Quinolones Low Although delirium has been reported with many antibiotics, this may be more related to the effect of the underlying infection