Lecture 8 Flashcards
Describe autonomic ganglia
Autonomic ganglia lie outside the CNS and they contain the nerve endings of preganglionic fibres and the cell body of post-ganglionic fibres.
The effect of the transmitter ACh at receptors on the ganglionic neuronal membrane can be replicated by….
nicotine, i.e. it involves nicotinic cholinoceptors.
Two types of drugs acting on ganglionic transmission
- Ganglionic stimulants
- Ganglionic blockers
Ganglionic Stimulants
Drugs that stimulate both sympathetic and parasympathetic ganglia
Ganglion-stimulating agents include:
- Nicotine (low concentration)
- Lobeline
- Dimethylphenylpiperazinium (DMPP)
Stimulation occurs at both sympathetic and parasympathetic ganglia causing what complex effects
- Tachycardia
- Increase of blood pressure
- Increased bronchial, salivary and sweat secretions - Variable effects on GI-tract motility
Ganglionic Blockers
Drugs that block all autonomic ganglia and enteric ganglia
In general, ganglionic block may be achieved by:
(A) Prolonged depolarization:
Example: Continuous action of the postsynaptic membrane due to anti-AChE drugs.
(B) Interference with the release of ACh:
Example: Inhibition of vesicle excocytosis by botulinum toxin.
(C) Interference with the postsynaptic action of ACh:
Example: Pharmacological block of the ionic channel associated with the receptor.
Ganglion-blocking agents include:
- Nicotine (high concentration)
- Hexamethonium
- Trimethaphan
- Tubocurarine
effects of Ganglion-blocking agents include:
- Hypotension
- Inhibition of secretions
- Paralysis of GI-tract
Trimethaphan usage:
Short-acting drug given as an i.v. infusion to produce hypotension during anesthetic procedures to minimize bleeding during certain kinds of surgery, such as neurosurgery, thereby decreasing the need for blood transfusion.
nicotine properties
- Half-life in human body: t1/2 = 2 hours; relatively fast degradation
- Non-smoker: 2-3 times more sensitive to nicotine than smokers
- Rapid uptake of nicotine in smoke via oral mucosa and lung alveoli, followed by fast transportation to heart and brain (omitting initial liver metabolism)
- Fast wave-like receptor occupation after inhalation of nicotine-containing smoke
Central effects of nicotine
- Nicotine dependence/withdrawal/de-sensitization symptoms.
- Stimulation of release of various neurotransmitters in CNS (dopamine, serotonin, GABA, glutamate)
Toxic dose of nicotine
Low nicotine levels in traditional tobacco products:
- Cigarette nicotine; only 1 mg uptake in body
- Lethal dose: LD = 500 mg nicotine
Peripherally acting anticholinesterase drugs fall into what 3 groups based on their duration of action
- Short-acting anti-AChE
- Medium-acting anti-AChE
- Long-acting anti-AChE
Short-acting anti-AChE
- Edrophonium: Diagnostic drug for MG
Medium-acting anti-AChE
- Neostigmine: Reversal of competitive NM block, Oral drug application for treatment of autoimmune MG
- Physostigmine: Glaucoma treatment
- Pyridostigmine: Oral drug application for treatment of autoimmune MG
Long-acting anti-AChE (Toxic agents)
- Dyflos
- Ecothiophate: Glaucoma treatment
- Parathion: Insecticides
Edrophonium
- Quaternary ammonium compound
- Binding to the anionic site of AChE enzyme
- Ionic bond formed with AChE is reversible
- Main usage as diagnostic tool
Diagnosis of acquired Myasthenia Gravis
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.
Long-acting 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 of Irreversible anticholinesterase:
Labile group is released that causes serine hydroxyl group of AChE being phosphorylated
