Renate Coetzee

34378553

Blog #2.5

Give a short and critical explanation of the rationale of using fluvoxamine (a selective serotonin re-uptake inhibitor (SSRI) in the treatment of Covid patients. Your answer must be properly and appropriately referenced (in-text references as well).

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is approved by the FDA for the treatment of obsessive-compulsive disorder and is used for other conditions, including depression but not for the treatment of any infection.

In a murine sepsis model, fluvoxamine was found to bind to the sigma-1 receptor in immune cells thst reduced production of inflammatory cytokines. An in vitro study of human endothelial cells and macrophages, fluvoxamine reduced the expression of inflammatory genes. More studies are needed to establish whether the anti-inflammatory effects of fluvoxamine observed in nonclinical studies also occur in humans beings and are clinically relevant in the setting of COVID-19.

Thus, there is insufficient evidence to recommend either for or against the use of fluvoxamine for the treatment of COVID-19. Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of fluvoxamine for the treatment of COVID-19. (NIH, 2021).

NIH (National institute of health). 2021. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/fluvoxamine/ Date of access: 25 Oct. 2021

Renate Coetzee

34378553

Blog #2.4

What do you understand by the term “endothelium-dependent” vasodilation?

Endothelium-dependent vasodilation is the concept that the endothelium controls vascular tone in a paracrine fashion (i.e., by secreting diffusible soluble mediators able to act on physically contiguous cells in order to induce vasodilation of vessels such as endothelium derived relaxing factor (EDRF).

When we talk about the NOS enzyme, what is meant by “constitutive” and “inducible” enzymes and what are the pathological and physiological implications thereof?

Constitutive enzymes are always present in the organism in constant amounts regardless of its metabolic state. In the NOS system that is nNOS (neuronal) and eNOS (endothelium). Inducible enzymes are thus enzymes that are induced in the body during certain metabolic states. In the NOS system that is iNOS (inducible).

These enzymes act during different metabolic states to exert their effect in the body (i.e. to casue vasodilation of the body by synthesising nitric oxide).

Explain how NO contributes to the fatal pathology of septic shock:

Endotoxins from the bacterial wall induce the synthesis of iNOS in macrophages, neutrophils, T cells, hepatocytes, smooth muscle, endothelial cells and fibroblasts. This widespread synthesis of nitric oxide results in exaggerated hypotension, shock and in certain cases death. This can be reduced or reversed by means of NOS inhibitors in humans.

Which autacoids’ mechanism of action depends on effects on the guanylyl cyclase-cGMP system?

Nitric oxide.

NO may be toxic to the cell. Which mechanisms are available to the body to counter this detrimental effect of NO?

The use of nitric oxide inhibitors can counter the toxic effects of NO on the body.

Name a way in which NO can act pro-inflammatory. Give examples of where it will have advantages or disadvantages:

NO can have pro-inflammatory effects by recruiting certain leukocytes and releasing inflammatory mediators. This increases iNOS activity. The NO produced acts as an microbicide (advantage) and plays important role in the body via immune cell function.

NO can however exacerbate tissue injury if released for a prolonged time in the body (disadvantage). May then contribute to disease pathogenesis.

In which possible neurological and psychiatric diseases is NO involved?

Parkinson disease.