Cholinoceptor antagonists Flashcards
Describe affinity and efficacy in terms of the agonists and antagonists
Both agonists and antagonists possess affinity (they can both bind and unbind from receptors. There is constant state of agonists/antagonists binding to receptor forming agonists/antagonists-receptor complexes before unbinding)
However only agonists have efficacy - they produce a response
Important - affinity is only used when talking about drugs binding to receptors not if they are blocking channels. AFFINITY = receptors
Where are nicotinic receptors found?
Through out the ANS - see diagram
What are nicotinic receptor antagonists also called?
Ganglion blocking drugs - think about where nicotinic receptors are found in the ANS. They can influence parasympathetic and sympathetic function
These drugs can block the receptors as well as the ion channel it self
Name two nicotinic receptor antagonists?
Hexamethonium & Trimetaphan (Block and receptor)
Use-dependent block. When nicotinic channels are open these drugs work best. These drugs only have affinity when talking about it binding to receptors
Hexamethonium - more channel blocker
Trimetaphan - more receptor antagonist
Because nicotinic receptors are involved in sympathetic and parasympathetic function which effect do you see when you use nicotinic receptor antagonists?
This is dependent on which system is dominant at that moment in time. NRA block both parasympathetic and sympathetic systems (don’t discriminate) however if one system is dominant it will be the effects of that system that is lost. THINK
Draw diagram showing all the ANS effects on the body
See diagram on slides
Why do nicotinic antagonists cause hypotension?
The vascular system is innervated by the sympathetic system which causes vasoconstriction. Blockage of nicotinic receptors means loss of vasoconstrictor function so vasodilation occurs and hypotension follows.
Sympathetic system also causes renin release - decrease in renin means a decrease in the renin angiotensin system and aldosterone as well. See notes on renin angiotensin system
What are the side effects of nicotinic receptor antagonists?
There are lots of side effects go back to the diagram and think about what is effected.
Smooth muscle: Pupil dilation, decreased GI tone (constipation), bladder dysfunction, bronchodilation
Exocrine secretions
What are the clinical uses of hexamethonium and trimetaphan?
Hexamethonium - 1st antihypertensive drug. Not great though because of the many side effects of using a nicotinic receptor antagonist. NRA not really used
Trimetaphan - Short acting; reduces blood pressure during surgery. Still used today
What venom is a NRA?
a-bungarotoxin - binds irreversibly to receptors forms covalent bonds.
Effective because it targets ANS but importantly the somatic nervous system so all the skeletal muscle becomes paralysed. Can’t move.
Where are muscarinic receptors found?
More selective - found on effector organs in the parasympathetic system.
Exception - sweat glands in the sympathetic system
Give examples of muscarinic receptor antagonists?
Atropine
Hyoscine
Plant based - structurally very similar
How do muscarinic receptor antagonists affect the the CNS?
Atropine; (therapeutic) Normal dose - little effect, Toxic dose - mild restlessness –> agitation (stimulates CNS)
Hyoscine; (therapeutic) Normal dose - sedation, amnesia, Toxic dose - CNS depression or paradoxical CNS excitation (associated with pain)
Completely different CNS effects
What is the muscarinic receptor antagonist used in the examination of the retina? Describe its effects
Tropicamide binds to muscarinic receptors in the parasympathetic nervous system innervating the iris muscle. This causes a dilated pupil - parasympathetic innervation of the iris causes contraction so the pupil becomes small.
How are muscarinic receptor antagonists used in anaesthetic premedication
Parasympathetic effects:
Trachea + bronchioles = constriction –> BLOCKS
Salivary glands = copious water secretion –> BLOCKS
Heart = lowers heart rate and contractility –> BLOCKS
MRA also have sedation effects - Hyoscine
See notes and lectures
How are MRA used in a neurological way?
Motion sickness - hyoscine patch. Sensory miss-match between visual information and information from the ear about balance causing the hippocampus to activate the vomiting centre.
Hyoscine blocks the MR that induce the vomiting signal meaning you don’t get the feeling of nausea
How do MRA work in Parkinson’s Disease?
Usually there are dopaminergic neurones coming from the substantia nigra which release dopamine. The dopamine binds to D1 receptors on the striatum which allows for fine control of movement. The M4 receptor does the opposite and reduces fine control. In Parkinson’s disease there is a loss of these dopaminergic neurones so D1 stimulation decreases - there is less dopamine. So by using a MRA you block the M4 receptors reducing the inhibitory effect directed at fine movement. So the D1 receptors that are being stimulated are doing so at a maximum rate. Enhances D1 receptor function.
How are MRA used in Asthma/COPD?
Ipratropium bromide - charged so it remains in the lungs. Polar can’t diffuse like atropine
Atropine
Parasympathetic effects causes constriction of the lungs so MRA would block this effect = dilation
How are MRA used to treat IBS?
Blocks gastrointestinal function of increased motility and tone and secretions.
M3 selective receptor antagonists
What are the unwanted side effects of MRA?
Hot as hell
Dry as a bone
Blind as a bat
Mad as a hatter
See notes
What drug can be used to treat an atropine overdose and how?
Physostigmine - anticholinesterase will prevent the break down of ACh in the synapse so the levels of ACh will rise. As a result the levels of ACh will out compete the atropine.
See cholinomimetics
Describe the most deadly and potent toxin the world?
Botulinum toxin - produced from the bacteria Clostridum Botulinum. See notes; SNARE complex
