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Clinical Toxicology of Snakebite In Africa and The Middle East / Arabian Peninsula
Published in Jürg Meier, Julian White, Handbook of: Clinical Toxicology of Animal Venoms and Poisons, 2017
Dendroaspis: Five commercial antivenoms are available, for which activity is claimed against the venoms of all four species (87 nos 6, 9, 119, 122 and 128). These include SAIMR “polyvalent antivenom" and “Dendroaspis antivenom”, Pasteur-Mérieux “IPSER Afrique”, Behringwerke “Central Africa" and Pasteur-Mérieux “Dendroaspis”. The main therapeutic problem is the prevention or treatment of rapidly developing respiratory paralysis. Pressure immobilisation is recommended as first aid. The initial dose of antivenom should be not less than 50 ml, which should be repeated in 30–60 minutes if there has been a deterioration in neurotoxic signs. There is at least one anecdotal report of a response to anticholinesterase in a victim of D. viridis envenoming in Sierra Leone. Assisted ventilation may be needed in severe cases.
Neurotransmission at Parasympathetic Nerve Endings
Published in Kenneth J. Broadley, Autonomic Pharmacology, 2017
The principles of receptor classification have been discussed thoroughly in Chapter 3 with special emphasis on adrenoceptors. In the case of muscarinic receptors, however, agonists have only played a minor role in receptor subclassification since, with the exception of McN-A-343 (see Table 8.3), selective agonists are only recently becoming available. Even so, these still do not display the marked selectivity for muscarinic receptor subtypes that occurs with adrenoceptors. McN-A-343 was shown to selectively stimulate autonomic ganglia and induce a depolarization of the postganglionic neurone. This response, however, was not mediated as expected via nicotinic receptors but via a muscarinic receptor since it was blocked by atropine. This receptor mediates the slow excitatory postsynaptic potential (s-EPSP) involved in ganglionic transmission (see Chapter 11) and is defined as the M1 receptor (Figure 7.7). The M1 receptor is selectively stimulated by McN-A-343 and preferentially blocked by pirenzepine in ganglia (eg the rat superior cervical ganglion). As a result of these observations, two subtypes of muscarinic receptor were initially proposed: M1 and M2 receptors. The M1 receptor was located to certain brain regions (cerebral cortex and hippocampus) and autonomic ganglia. More recently, the M1 receptor has also been identified as the muscarinic receptor subtype mediating inhibition of noradrenaline release and of the twitch response to electrical stimulation of the rabbit vas deferens (Grimm et al. 1994). Two toxins from the venom of the Eastern green mamba (Dendroaspis angusticeps), MTx1 and MTx2, display selective agonist activity at M1 receptors and inhibit twitch responses of the rabbit vas deferens. A further toxin, m1-toxin, binds irreversibly and selectively to M1 receptors and behaves as an allosteric antagonist (Jerusalinsky & Harvey 1994).
Ethnomedicinal plants used for treatment of snakebites in Tanzania – a systematic review
Published in Pharmaceutical Biology, 2022
Neema Gideon Mogha, Olivia John Kalokora, Halima Mvungi Amir, David Sylvester Kacholi
Venomous snakes are found in most parts of the world, in all climatic conditions except in frozen environments and at higher altitudes (WHO 2007; Kasturiratne et al. 2008). Africa alone is a home of 400 different snake types, whereby nearly 50% are found in East Africa. Some of them are black mamba (Dendroaspis polylepis Günther (Elapidae)), spitting cobra (Naja nigricollis Hallowell (Elapidae)), Rufous-beaked snake (Ramphiophis rostratus Peters (Psammophiidae)), puff adder (Bitis arietans Parker (Viperidae)) and green mamba (Dendroaspis jamesoni Traill (Elapidae)) (Kipanyula and Kimaro 2015; Omara 2020). Snakebites are life-threatening due to the scarcity of proven medication. Although antivenom serum has been developed as a lifesaving option, it is associated with the development of immediate or delayed hypersensitivity (anaphylaxis or serum sickness) and does not avert local tissue damage (Maya Devi et al. 2002). For example, an antidote such as immunoglobulin G produced in horses could react to serum and cause sickness, renal failure and anaphylaxis (Cannon et al. 2008; Giovannini and Howes 2017). Still, antivenom administration is considered chiefly a definitive treatment for snakebites. Other treatments include respiratory support therapy, surgical of affected necrosis tissues or even amputation (Cannon et al. 2008; de Moura et al. 2015).
Snake venomics – from low-resolution toxin-pattern recognition to toxin-resolved venom proteomes with absolute quantification
Published in Expert Review of Proteomics, 2018
Mamba venoms, dominated by dendrotoxins (Kunitz-type inhibitor fold) and 3FTxs, represent a striking deviation from the 3FTx/PLA2 dichotomic general trend across elapid venoms (Figure 5(a)). Genus-wide top-down venomics analysis of the five species and subspecies within genus Dendroaspis revealed their proteoform-resolved venom proteomes (Figure 5(b)). This detailed information laid the foundations for rationalizing the notably different potency and pharmacological profiles of Dendroaspis venoms at locus resolution, and suggested a plausible causal dietary correlation between the divergent KUN-predominant venom of terrestrial mammals specialist D. polylepis and the 3FTx-rich venoms shared by the other four, mainly arboreal, mamba species, whose diet is dominated by arboreal taxa, mainly birds. Deploying highly toxic venom in conjunction with a strike-release predatory strategy, thereby reducing potential risk of injury posed by mammalian prey, has also evolved in other mammal-specialist snakes [97].
The clinical course and treatment of black mamba (Dendroaspis polylepis) envenomations: a narrative review
Published in Clinical Toxicology, 2021
Mark Aalten, Carsten F. J. Bakhuis, Ilias Asaggau, Maaike Wulfse, Maurits F. van Binsbergen, Eran R. A. N. Arntz, Max F. Troenokarso, Jashvin L. R. Oediet Doebe, Ubah Mahamuud, Leila Belbachir, Myrthe Meurs, Nastya A. Kovalenko, Marcel A. G. van der Heyden
Dendroaspis polylepis venom contains five different types of toxins: neurotoxins, myotoxins, coagulotoxins, nephrotoxins, and necrotoxins [42]. D. polylepis venom is known to be especially neurotoxic. A recent study by Laustsen et al., investigating the immunoprofile of D. polylepis toxins, revealed alfa-neurotoxins to be the most lethal component in acute toxicity [43]. These neurotoxins are antagonists for the nicotinic acetylcholine receptors (nAChRs) in skeletal muscles. As alfa-neurotoxins inhibit binding to the nAChRs, administration of D. polylepis venom will result in impeded muscle contractions and a higher concentration of ACh in the neuromuscular junction [44].