Lecture 2 | Anti-cachectic drugs Flashcards
Targets of pharmacological interventions in cachexia
Stimulate appetite, reduce GI problems, reduce inflammation and stimulate anabolism/reduce catabolism.
Drugs that stimulate appetite
Corticosteroids, progestins, cannabinoids and ghrelin
Corticosteroids
Hormone derived from glucocorticosteroids
Types differ in efficacy/potency and kinetics
Reduce (protective) innate and adaptive immune response and temporarily (4 weeks) stimulate appetite and mood.
Significant side-effects.
Progestins
Hormone derived from progesterone
Stimulate appetite, increase body weight (fluid retention) and improve QoL.
Cannabinoids
Cannabidiol (CBD): non-hallucinogenic, improve sleep and GI function.
Tetrahydrocannabinol (THC): hallucinogenic, anti-inflammatory, painkiller, improve appetite and mood.
Ghrelin
Hormone that stimulates appetite (rises before meal)
Anamorelin = ghrelin analogue -> stimulate normal appetite response
Eicosanoid pathway
Starts with arachidonic acid = omega-6 PUFA which is stored in cell membranes.
Transformation into:
- Prostaglandins by COX-1 & COX-2
- Leukotriens by 5-lipoxygenase
NSAIDs mechanism
Inhibit COX-1 and/or COX-2 and therefore reduces the formation of prostaglandins that normally stimulate NFkB (inflammatory pathways).
Drugs that reduce inflammation
NSAIDs, N-3 fatty acids, anti-cytokines (corticosteroids, THC)
N-3 fatty acids mechanism
Omega-3 PUFAs compete with omega-6 PUFAs for the COX enzymes. Leads to the production of more anti-inflammatory (lipoxins, resolvins, maresins, protectins) instead of pro-inflammatory mediators.
Anabolic androgenic steroids mechanism
Derived from testosterone, which is lower in cachexia. Increase muscle mass but side-effects (male hormone).
Selective androgen receptor modulators (SARMs)
Result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. E.g. Enobosarm
