Indirect acting agent

The amphetamine class of stimulants are potent, indirect-acting agents that cause a release of the neurotransmitters dopamine and norepinephrine from storage areas in the CNS. The mildest CNS stimulant is phenethylamine (PEA), a component of cheese and chocolate, while cocaine is considered a potent CNS stimulant. 

Metaraminol (aramine) is a mixed-acting agent an agonist at vascular a adrenergic receptors and an indirectly acting agent that stimulates the release ofNE. The drug has been used in the treatment of hypotensive states or off-label to relieve attacks of paroxysmal atrial tachycardia, particularly those associated with hypotension (see Chapter 34 for preferable treatments of this arrhythmia). 

The indirect-acting agents (cocaine and tyramine) act through catecholamines in or released from the nerve terminal clonidine acts primarily on the receptor of the presynaptic nerve terminal. The answer is (C). 

Amphetamine and related compounds are indirect acting sympathomimetic agents that are frequently abused due to their stimulant properties on the central nervous system. Amphetamines act by inducing the... 

B. Psychomotor stimulants such as amphetamine are also indirectly acting sympathomimetics that increase the release of catecholamines from sympathetic nerve terminals. While amphetamine and other congeners possess additional actions on peripheral sympathetic nerves, this is the most likely explanation for the cardiac stimulation observed following the administration of these agents. 

Anticholinesterase drugs are compounds that block AChE and inhibit the destruction of released ACh. The resultant higher neurotransmitter levels then increase the biological response. Anticholinesterases can therefore be considered as indirect cholinergic agents. Acetycholinesterase inhibitors can act by either of two mechanisms ... 

Tachyphylaxis refers to a quickly developing tolerance brought about by the rapid and repeated administration of drugs. For example, indirect-acting sympathomimetic agents such as tyramine, which exert their effects through the release of norepinephrine, are able to cause tachyphylaxis. If norepinephrine is not present, tyramine fails to act until the supply of norepinephrine in nerve terminals has been replenished (Figure 3.3). 

Indirect-acting agonists These agents, which include amphetamine and tyramine, are taken up into the presynaptic neuron and cause the release of norepinephrine from the cytoplasmic pools or vesicles of the adrenergic neuron (see Figure 6.8). As with neuronal stimulation, the norepinephrine then traverses the synapse and binds to the a or p receptors. 

Indirect-acting adrenergic agonists cause norepinephrine release from presynaptic terminals (see Figure 6.8). They potentiate the effects of norepinephrine produced endogenously, but these agents do not directly affect postsynaptic receptors. 

The clinically useful anticholinesterase agents diisopropyl fluorophosphate (DFP, Floropryl) and echothiophate iodide (Phospholine Iodide [PI]) demonstrate an indirect-acting mechanism resulting in increased levels of acetylcholine at the cholinergic receptor sites. The inhibition of acetylcholinesterase produces a relatively long-lasting and irreversible effect of maintaining active levels of acetylcholine at the parasympathetic synapses. 

Because of the structural differences, the primary mechanism of action, i.e., direct or indirect acting on ictor Xa as well as other attributes, differs with the various agents. The hictor Xa inhibitors that are in development are shown in Table TV. Only a few of these agents are currently undergoing clinical trials. 

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