Intranasal administration of medications

Experiments investigating the effects of medication administration via the nose are becoming increasingly common in scientific literature. Direct olfactory transport to the brain and the consequent lack of systemic side effects make nasal administration of neuroactive drugs a very attractive option for doctors and patients alike.

Neuropeptides such as insulin and melanocortins are known to play a role in central nervous control of energy homestasis, which in turn affects body weight regulation. Insulin receptors are also found in high concentration in the hippocampus, and insulin is known to influence memory consolidation. A recent paper by Hallschmid et al. studied the efficacy of intranasal neuropeptide administration in modulating both metabolic and cognitive disorders in humans, finding that administration of MSH/ACTH (i.e., melanocortins) induced weight loss in normal-weight humans, and that insulin administration “reduced body fat and improved memory functions in the absence of adverse peripheral side effects.”

Such results indicate a promising future for directed therapies in patients with central nervous system dysfunctions, and the potential of intranasal administration of medications in cryonics should not be ignored. As discussed in a previous post, intranasal administration of vasoactive medications could be a beneficial method to maintain blood pressure during stabilization. Similarly, intranasal administration of neuroprotective agents to the brain represents another time-saving means of reducing brain injury during cryonics procedures.

Intranasal administration of vasoactive agents

Stabilization in cryonics requires immediate administration of vasoactive medications to maintain blood pressure, thereby assisting and enabling adequate perfusion during cardiopulmonary support. Traditionally, vasopressors such as epinephrine have been administered intravenously, requiring skilled technicians to establish an IV line as quickly as possible. Unfortunately, even the best technicians often encounter difficulties in obtaining an IV access site, thus delaying critical intervention.

Alternatively, the intranasal (IN) route is a rapidly obtainable and feasible route of administration in an emergency situation. A growing number of studies have indicated that the nasal mucosa is a suitable substrate for quick absorption of vasoactive agents into the systemic circulation. IN epinephrine has been shown to reach peak plasma concentrations in only 15 seconds, with peak systolic pressure at 200% of control value after 60 seconds (Yamada, 2004). Similarly, a comparison of IN vs. IV administration of epinephrine in a canine model of cardiac arrest and CPR demonstrated improved coronary perfusion pressure in both groups, with similar rates of successful resuscitation (Bleske, 1992).

Several factors affect successful nasal absorption of vasopressors and other drugs, including molecular weight, pH, and lipophilicity. However, absorption can be greatly improved with the use of permeation enhancers and careful modulation of dose. Bleske et al. (1996) also investigated the effect of various doses of phentolamine and epinephrine in combination on the nasal aborption of ephinephrine during CPR, and found that 0.25 mg/kg/nostril significantly enhanced absorption of ephinephrine in a canine model. Whether administration of such permeation enhancers is necessary for intranasal administration of vasopressors in cryonics remains unknown. A more detailed review of intranasal administration of therapeutic agents and its feasibility for cryonics stabilization will appear in the upcoming issue (3rd quarter 2007) of Cryonics.