Lecture 8 Flashcards
What is a ganglionic transmission?
Autonomic ganglia lie outside the CNS and they contain the nerve endings of pre- ganglionic fibres and the cell body of post-ganglionic fibres.
What can be replicated by nicotine?
The effect of the transmitter ACh at receptors on the ganglionic neuronal membrane can be replicated by nicotine, i.e. it involves nicotinic cholinoceptors.
What are the two types of drugs acting on the ganglionic transmission?
- Ganglionic stimulants
- Ganglionic blockers
What are Ganglionic stimulants?
Drugs that stimulate both sympathetic and parasympathetic ganglia. Drugs directly affect the ganglionic nACH-receptors.
What do ganglion-stimulating agents include?
- Nicotine (low concentration)
- Lobeline
- Dimethylphenylpiperazinium (DMPP)
What are the effects of stimulation occurring at both sympathetic and parasympathetic ganglia?
- Tachycardia
- Increase in blood pressure
- Increased bronchial, salivary and sweat secretions
- Variable effects on GI-tract motility
What are Ganglionic blockers?
Drugs that block all autonomic ganglia and enteric ganglia
How can ganglionic block be achieved by?
- Prolonged depolarization
- Interference with the release of ACh
- Interference with the postsynaptic action of ACh
(examples in slide 5)
What are Ganglion-blocking agents? and what are their effects?
- Nicotine (high concentration)
- Hexamethonium
- Trimethaphan
- Tubocurarine
Effects:
- Hypotension
- Inhibition of secretions
- Paralysis of GI-tract
What is trimetaphan?
It is a short-acting drug given as an i.v. Infusion to produce hypotension during anaesthetic procedures to minimize bleeding during certain kinds of surgery, such as neurosurgery.
What is nicotine?
Nicotine is a highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors, where it dramatically stimulates neurons and ultimately blocks synaptic transmission.
What are the central effects of nicotine?
- Nicotine dependence
- Withdrawal
- De-sensitization symptoms
- Stimulation of the release of various neurotransmitters in CNS (dopamine, serotonin, GABA, glutamate)
What is the toxic dose of nicotine?
Low nicotine levels in traditional tobacco products:
- Cigarette nicotine; only 1 mg uptake in the body
- Lethal dose: LD = 500 mg nicotine
However, the danger of excess nicotine exposure due to:
- Vaping E-cigarettes
- Pure liquid nicotine
- Concentrated nicotine as a pesticide
What does nicotine cause?
- Ganglionic stimulant nicotine causes complex peripheral responses associated with generalized stimulation of the autonomic ganglia.
- Excitation by low levels of nicotine causes Ganglionic excitation.
- Blockade by high levels of nicotine causes
Ganglionic blockade.
What are the effects of nicotine on the body?
- In tobacco smoke, nicotine is present as a constituent of small tar particles
- Nicotine is rapidly absorbed through bronchi and lung alveoli
- Smoking of a single cigarette swiftly yields peak plasma levels of 25-50 ng/ml nicotine
- Such low concentrations of nicotine act as
Ganglionic Stimulant of both branches of the ANS
How much nicotine does tobacco contain?
0.2 - 5% nicotine
What is anti-AChE? and what groups do they fall into?
- They are drugs that inhibit cholinesterase
- Peripherally acting anticholinesterase drugs fall into three groups based on their duration of action:
- Short-acting anti-AChE
- Medium-acting anti-AChE
- Long-acting anti-AChE
Example of Short-acting anti-AChE
Edrophonium
Example of Medium-acting anti-AChE
- Neostigmine
- Physostigmine
- Pyridostigmine
Example of Long-acting anti-AChE
- Dyflos
- Ecothiophate
- Parathion
What is edrophonium?
- Only important short-acting anti-AChE
- Quaternary ammonium compound
- Binding to the anionic site of the AChE enzyme
- An ionic bond formed with AChE is reversible
- Pharmacological effect is very brief
- Main usage as a diagnostic tool
What is the diagnosis of acquired Myasthenia Gravis?
MG is the most common primary muscle disease due to disturbances of neuromuscular transmission. It is an acquired autoimmune disorder of neuromuscular transmission associated with AChR deficiency at the NMJ.
What is the Edrophonium test?
Improvement of muscle strength by the short-acting anti-AChE is characteristic of MG but does not occur when muscle weakness is due to other causes.
Medium-acting anticholinesterases
Neostigmine
- Oral drug application for treatment of autoimmune MG
- Reversal of competitive neuromuscular block
Pyridostigmine
- Oral drug application for treatment of autoimmune MG
Physostigmine (Eserine)
- Treatment of glaucoma
Long-acting irreversible anticholinesterases
Irreversible anticholinesterase:
- Penta-valent phosphorus compounds
- Organophosphate compounds are highly toxic:
- War gases
- Pesticides
- Limited clinical usage - Dyflos: contains a labile fluoride group
- Parathion: contains a labile organic group
- Ecothiophatean: contains a labile organic group
- Inhibitory action: Labile group is released that causes the serine hydroxyl group of AChE to be phosphorylated
