Sanctuary sites and compartments: deciphering the enigma

It has been a common observation that many drugs get accumulated in the body at certain sites labelled as anatomical or physiological compartments where they are not expected to exert their desired effect. While the field of pharmacology considers these so-called sites or imaginary compartments as “sanctuary compartments” which could comprise of specialised tissue system where drugs could bind to tissue proteins or nucleoproteins, adipose cells serving as reservoir for extensively lipid soluble drugs, aqueous humour, cerebrospinal fluid, bones, and even plasma proteins, the reach and impact of the sanctuary compartments or sanctuary sites (which is the more preferred and broader term) has grown beyond that and spread extensively. Now, it is not just about certain drugs finding safe haven in these sanctuary compartments but also about certain disease conditions like HIV infection and cancer doing the same. Evidence has been accumulating regarding the fact that human immunodeficiency virus and various type of cancer cells have been using these compartments or sites to avoid being exposed to drugs which cannot penetrate well into such sanctuary sites. This phenomenon over the period of time has culminated in the development of resistance towards anti-retroviral and anti-neoplastic drugs to name a few. This means of acquired resistance is proving to be a major barrier to providing effective treatment to the patients. This review focusses on sanctuary compartments, their basic idea, the benefits associated with them, the challenges it poses to modern day medicine and finally, the possible methods of overcoming those challenges by attempting to un-sanctify the sanctuary compartments.

Drugs affecting sleep and wakefulness: a review

It was in the second half of the twentieth century that Sleep Medicine was recognized as an immensely respected field of clinical research. As a result, past few decades have seen this field making some giant strides towards a better understanding of the neurochemical mechanisms that regulate the state of sleep and wakefulness. This involves a complex interplay of neuronal systems, neurotransmitters and some special nuclei located in the brain. Major wakefulness promoting nuclei being the orexinergic neurons in the lateral hypothalamic region and the tuberomammillary nucleus (TMN) while the sleep-promoting nucleus being ventrolateral preoptic nucleus (VLPO). Sleep-related complaints are one of the common complaints encountered by the physicians and the psychiatrists. As, long-standing sleep disturbances can have far-reaching implications on an individual’s physical, mental and social wellbeing, the importance of drugs affecting sleep and wakefulness could not be stressed upon anymore. Broadly, the sleep disorders are classified as insomnia, hypersomnia, and parasomnia and the presently available drugs work either by acting on the sleep-promoting GABAergic system like benzodiazepines, barbiturates etc. or by interacting with wakefulness promoting system like histaminergic system, 5- hydroxtryptaminergic system, orexinergic system etc. There are drugs which interact with other mechanisms which modulate arousal, like melatonin receptor agonists which promote sleep and adenosine receptor antagonists which promote wakefulness. This review article tries to have an overview of the available drugs for use in pathological states of sleep and wakefulness with a special emphasis on the commonly prescribed drugs and the recently approved one’s.