Chemicals [endogenous/exogenous], Memory and Breathing.


Overview of Memory-impairing Drugs

A wide variety of drugs [exogenous chemicals] impair memory. These include the benzodiazepines, anticholinergic agents, alcohol, anesthetics, barbiturates, cannabis derivatives, β-adrenergic blockers, and others. The benzodiazepines and the anticholinergics have been investigated more than the others. These drugs have a wide diversity of chemical structures, which vary from the monoatomic xenon and the biatomic nitrous oxide to the more complex structure of a benzodiazepine, a barbiturate, or a halogenated volatile anesthetic. Benzodiazepines, barbiturates, and volatile anesthetics act at the γ-aminobutyric acid type A (GABAA) receptors potentiating chloride currents. Xenon, nitrous oxide, and ketamine seem to have their major effects at the N -methyl-d-aspartate receptors. Cholinergic antagonists act at muscarinic receptors. βBlockers act at β-adrenergic receptors. Marijuana acts on cannabinoid receptors. Drugs such as ethanol act on receptors for serotonin, acetylcholine, GABA, glutamate, glycine, and dopamine. Differentiating which receptor is mediating amnesia, subjective experience (sedation, hypnosis, anxiolysis), or other behavioral effects is difficult to assess. However, despite the disparity in molecular structure, selective targets, chemical transmitters, and specific binding areas in the brain, these diverse agents seem to produce similar profiles of memory impairment. It seems that there are multiple pathways to the final effects on memory. This kind of commonality agrees with the current view that memory is a distributed property of cortical systems rather than exclusive to specific areas. 204,205Thus, one brain region may be part of more than one neural network subserving different memory abilities. The general characteristics of drug impairments are displayed in table 10. Review Article| May 2004 Drugs and Human Memory (Part 2): Clinical, Theoretical, and Methodologic Issues  Mohamed M. Ghoneim, M.D.;  David O. Warner, M.D.Anesthesiology May 2004, Vol. 100, 1277–1297.

Table 10. General Characteristics of Amnesic Drugs
Review Article| May 2004
Drugs and Human Memory (Part 2): Clinical, Theoretical, and Methodologic Issues 
Mohamed M. Ghoneim, M.D.David O. Warner, M.D.
Anesthesiology May 2004, Vol. 100, 1277–1297.

Drugs can impair memory, including long term retrograde memory. We do not understand exactly how drugs impair memory but it might be because of drug effects on the respiratory nerve/muscle pump system. This is a testable hypothesis.

We know that alcohol and benzodiazepines and barbiturates slow down breathing rate and thus change control of breathing and most likely PC02 and pH in the brain and the blood. Stimulants, like cocaine raise the respiratory rate, also possibly affecting PC02 and pH in the brain and the blood. During the time that the drug is in effect , the normal corrective actions of the respiratory pump system are impaired – in a dose related manner. Breathing stays depressed [too slow] or stays excited [too fast] and does not correct in order to control acid base conditions as usual. All physiological systems are affected, including systems involving the heart and the skeletal muscles and the smooth muscles. It is not so surprising that brain function and our conscious experience of mind is affected as well.

And we know that acute respiratory failure is a common complication of drug abuse.

Acute respiratory failure from abused substances

Acute respiratory failure is a common complication of drug abuse. It is more likely to develop in the setting of chronic lung disease or debility in those with limited respiratory reserve. Drugs may acutely precipitate respiratory failure by compromising respiratory pump function and/or by causing pulmonary pathology. Polysubstance overdoses are common, and clinicians should anticipate complications related to multiple drugs. Impairment of respiratory pump function may develop from central nervous system (CNS) depression (suppression of the medulla oblongata, stroke or seizures) or respiratory muscle fatigue (increased respiratory workload, metabolic acidosis). Drug-related respiratory pathology may result from parenchymal (aspiration-related events, pulmonary edema, hemorrhage, pneumothorax, infectious and non-infectious pneumonitides), airway (bronchospasm and hemorrhage), or pulmonary vascular insults (endovascular infections, hemorrhage, and vasoconstrictive events). Alcohol, cocaine, amphetamines, opiates, and benzodiazepines are the most commonly abused drugs that may induce events leading to acute respiratory failure. While decontamination and aggressive supportive measures are indicated, specific therapies to correct seizures, metabolic acidosis, pneumothorax, infections, bronchospasm, and agitation should be considered. Drug-related respiratory failure when due to CNS depression alone may portend well, but in patients with drug-related significant pulmonary pathology, a protracted course of illness may be anticipated. J Intensive Care Med Jul-Aug 2004;19(4):183-93.doi: 10.1177/0885066604263918. Acute respiratory failure from abused substances Kevin C Wilson 1Jussi J Saukkonen PMID: 15296619

We also know that people can have problems with “Control of Breathing ” and/or have problems with the Respiratory Muscle Pump System without the use of drugs. This suggests that , for them, the normal corrective actions of the respiratory pump system are permanently impaired. Breathing stays depressed [too slow] or stays excited [too fast] and does not correct in order to control acid base conditions. When compensatory mechanisms of the rest of the body are overwhelmed, then PC02 will shift, and most likely create a dose related respiratory and/or metabolic acidosis, creating challenges for all organs and systems of the body, including brain function and our conscious experience of mind. …..exactly like the effect of taking drugs BUT without taking any exogenous drugs.

Acute respiratory failure can also result in these people.

Acute respiratory pump failure will definitely affect memory, thinking and locomotor activity. and speed. It can cause periods of amnesia, confusion, changes in consciousness, psychomotor retardation and psychomotor excitement. Respiratory pump failure can be insidious and slow to increase and unconscious and hidden and unknown to the person experiencing its effects. And the effects can be drug-like, dysphoric/euphoric , with different patterns of mental confusion and different levels of change to locomotor activity and speed .

Perhaps both abnormal baseline breathing with drugs and abnormal baseline breathing without drugs result in the abnormal patterns of vital signs and abnormal mental status effects. This might explain the dysphoric/euphoric mental effects seen in people under the influence of drugs and in people during attacks of manic- depressive insanity. Impairment with mechanisms to correct for acidosis/alkalosis may be the underlying factor in both conditions. This is a hypothesis worth exploring I think.

C02 is a normal and useful product of metabolism, a necessary part of physiological function, and like most things- toxic in excess. Sufficient breathing and exhaling is the only way to control C02 in the blood and in the body tissues. Reversibly altered mood, mental status, and memory are the dose related result,

.sometimes it takes us a few days to complete a blog post … we edit and think some more…..

to be continued…..

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