Autonomic Pharmacology Flashcards
At which points can drugs target autonomic transmission
Synapse
Along axon - not specific
At target organ
Where are Muscarinic receptors present?
At effector organs of parasympathetic ns
Where are nicotinic receptors present in sympathetic and para ns
In ganglion
Structure of nicotinic cholinergic receptor
Transmembrane
5 subunits
2 ACh molecules need to bind
What is hexamethonium
A methonium derivative
Selective antagonist for neuronal sub type of nicotinic receptor
Not competitive
Blocks all the effects of autonomic stimulation (all preganglionic fibres are cholinergic)
Why is hexamethonium not used anymore
Not specific enough
Has too many side effects
What NT is released on to muscarinic receptors
ACh
How many transmembrane segments do muscarinic receptors have
7
How many subtypes of muscarinic receptors
5
First 3 (M1-3) are important in the periphery
Why are muscarinic drugs described as “parasympathomimetic drugs”
Mimic the effects of parasympathetic NS activation
Where were muscarinic drugs found
In family of fungi
General Effects of parasympathomimetics
Cardiovascular - decreased HR
Smooth muscle - contracts
Exocrine glands - secrete eg. Sweat, salivation, bronchial secretion
Source of muscarinic poisoning
Muscarinic agonists in Many mushrooms
Adverse effects of poisoning by muscarinic agonists
Bradycardia so decreased BP
Increased gut motility
Bronchoconstriction
Pupillary constriction
Salivation
Lacrimation
Treatment of muscarinic poisoning
Muscarinic antagonist (atropine)
Example of muscarinic agonist tht treats glaucoma and how it works
Pilocarpine
Route of administration: Topical to the eye
Action: on M3 receptors on ciliary muscles, improving aqueous humour drainag, dropping intraocular pressure
Types of muscarinic antagonists and where they act
Antagonists specific to muscarinic receptor they act on
M1 - stomach and salivary glands
M2 - cardiac
M3 - smooth muscle
Less specific antagonists like are used more widely
Atropine
Hyoscine
Cyclopentolate
Clinical uses of antimuscarinic drugs
Stop parasympathetic NS
- Asthma (ipratropium)
- Treat bradycardia (atropine)
- During operations (atropine)
- Dilate pupils (tropicamide)
- Urinary incontinence (oxybutynin)
- Motion sickness
Why is atropin used in operations
Skeletal NMJ blocking agent given to cause paralysis
Stop cholinergic transmission
After operation need to reverse paralysis with acetylcholinesterase inhibitor
This increases ACh at NMJ
Excessive ACh in the lungs and heart
Atropine used to block muscarinic receptors in airways
5 main subtypes of adrenoceptors (sympathetic) and their role
Alpha 1 - contract smooth muscle
Alpha 2 - presynaptic auto inhibition, direct vasoconstriction, central inhibition of sympathetic outflow
Beta 1 - increases heart rate and contractility
Beta 2 - relax smooth muscle (bronchodilation, vasodilation)
Beta 3 - relax smooth muscle (bladder), lipolysis
Main uses of alpha adrenoceptor receptor agonists
- Vasoconstrictors (adrenaline/ noradrenaline) with local anaesthetic (keeps LA at target tissue). Alpha 1.
- Nasal decongestants (phenylephrine). Alpha 1
- Hypertension. Central alpha 2.
- Facial erythema in rosacea (brimonidine). Alpha 2.
How adrenoceptors produce intrinsic cascade
Receptor stimulated
Gq protein activated
Stimulates phospholipase C
Releases Ca from Intracellular stores
DAG activates and causes Intracellular cascade
Signal transduction mechanisms for alpha 1 adrenoceptor
G protein: Gq
Target: phospholipase C
Transduction effect: increase IP3/ DAG
