Ganglionic Blockers Flashcards
What are ganglionic blockers (GB’s)?
Antagonists of cholinergic nicotinic (Nn) receptors found in autonomic ganglia (synapses b/t preganglionic and posganglionic neurons).
On what locations do drugs acting on sympathetic ganglia have an impact?
They can have an impact not only on blood vessels (the tone of the vasculature) but also upon nerves innervating the heart, giving them action on cardiac function itself.
What are the two ganglionic blocker clinical agents?
- Mecamylamine
2. Trimethaphan
Why have these GB agents been replaced in the Rx of HTN?
The GB have global effects on the ANS (widespread effects on the whole body). These agents have been replaced in the Rx of HTN by more specific drugs that have less global effects upon the ANS.
What is significant about clinical use of Mecamylamine?
It has been designated and ORPHAN drug for the Rx of Tourette’s Syndrome, a nicotinic-responsive psychiatric disorder
What is the nt of autonomic ganglia? What does it do in these synapses?
ACh is the nt of both SNS and PSNS ganglia b/t preganglionic and postganglionic neurons. The ACh is released from the preganglionic terminal and binds to and interacts w/ Cholinergic Nicotinic receptors (Nn-R’s) on the postganglionic membrane. This occurs not only in the paravertebral/sympathetic chain which serves multiple organs, but also in the more discrete PS innervation.
What is the main general problem with the administration of GB’s? What has this resulted in?
The administration of a GB can potentially have global effects thruout the body b/c there is very little way in which you can address specific action upon some ganglia but not others. This is the main reason GB’s have fallen from clinical use.
What are Nn-R’s? What mechanism do they work thru?
Cholinergic Nn-R’s are ionotropic receptors, as they are LIGAND-GATED NONSPECIFIC ION CHANNELS in the postsynaptic membrane. When activated, the postsynaptic membrane becomes depolarized as ions (primarily Na+ and CA2+ (and K+???)) can move thru freely.
How is the postsynaptic signal regulated/modulated in the autonomic ganglia? Why?
The postganglionic neuron’s membrane often has other receptors such as cholinergic M-R’s, peptidergic R’s, catecholaminergic R’s, and peptidergic R’s that influence how quickly the responsiveness of the postsynaptic membrane will be restored.
This serves to prevent the hyper-stimulation of the postsynaptic membrane by the arrival of multiple signals w/in a short period of time.
Explain the concept of the prevailing tone of an organ in relation to GB’s?
The various organs of the body are innervated by sympathetic and PS nerves. These nerves exert a tone upon that end organ. Whether or not the tone is Symp of PS, when the GB is administered that tone is diminished/ablated, leading to a change in function of that organ system. This change is dependent upon which of the 2 branches of the ANS holds the predominant/prevailing tone in that organ under normal circumstances.
What is the predominant/prevailing tone in arterioles? What is the result of ganglionic blockade? What about for veins?
The arterioles have a predominant sympathetic (adrenergic) tone. When a GB is administered, this will cause a net effect of loss of symp tone, leading to vasodilation, increased peripheral blood flow and hypotension (reduced BP).
What is the predominant/prevailing tone in the heart? What is the result of ganglionic blockade?
In the heart, the predominant tone is a PS (cholinergic) tone. Therefore, loss of PS tone on the heart due to a GB leads to an increased HR and under some circumstances leads to Tachycardia.
What is the mechanism of action of the GBs trimethaphan and macamylamine? What is the mech of action of the GB hexamethonium (an ancient GB no longer in use? What is the net effect of GB’s?
Mecamylamine and Trimethaphan are COMPETITIVE ANTAGONISTS that compete with ACh for binding to Nn-R receptor binding sites.
In contrast, the GB Hexamethonium appears to block the Nn-R channel AFTER it opens, shortening the duration of current flow.
Both mechanisms block the initial EPSP, resulting in inhibition of ganglionic transmission.
Why do GB’s have a wide range of adverse effects?
The lack of specificity of effect for GB’s means a potential loss of PS or Symp tone thruout the innervated organs, leading to a wide range of adverse effects.
What are the main adverse effects of GB’s?
- Postural Hypotension (get up too quickly and fall over due to loss of Symp tone of vessels)
- Tachycardia (due to loss of PS tone on the heart)
- Arrhythmias (often accompany tachycardia)
