Autonomic Pharmacology Flashcards
What neurotransmitters do Sympathetic neurones release?
ACh preganglioninc
NA post ganglionic
What neurotransmitters do parasympathetic neurones release?
ACh pregangioninc acts on neruonal nAChR’s
ACh postganglionic acts on muscarinic AChR’s
What are nAChR’s?
How do they work?
What is the dfference between those found the somatic NS and those used in the ANS?
5 subunit ligand gated ion channels
binding of ligand results in a conformational change rotation of hydrophobic R groups to inside of membrane allowing Na+ ions to flow through causing depolarisation
Neuronal nAChR’s have different protein subunits making the receptor compared to those found on SK muscle in the somatic NS
What is hexamethonium? What class it it?
Was a drug that had been used that targeted only neuronal nAChR’s
Non-Competitive antagonist
blocked all autonomic transmission
Why are muscarinic receptors important?
Modulate postganglioninc PNS transmission
What are muscarinic receptors
GPCR’s
5 subtypes M1-M3 are the most important in the ANS
Where are msucarinic receptors found?
On smooth muscle
cardiac muscle
glands
What is the effect of activation of muscarinic receptors bu ACh or muscarinic agonists on smooth muscle?
Causes contraction of smooth muscle in the Gi tract
Causes vasodilation in some blood vessels that have PNS innervation e.g those of the head and neck due to release of endothelium derived relaxing factor (NO) on receptor activation
What is the effect on activation of muscarinic receptors on glands and cardiac muscle?
Glands increased secretion
Cardiac muscle decreased heart rate and cardiac output
Give two examples of muscarinic agonists
muscarine
pilocarpine
what are muscarinic agonists also referred to as?
Parasympathomimetics
as they mimic the effects of PNS innervation
What is muscarine poising what are the symptoms
how is it treated?
muscarine found in may mushrooms
high doses activation of muscarinic R’s
bradycardia resulting in a fall in blood pressure
Increased gut motility
Bronchoconstriction pupillary constriction
Treatment is a muscarinic antagonist e.g. atropine (competitive antagonist)
What is pilocarpine when is it used?
How is this drug given?
How does it work?
Muscarinic agonist
Used to treat glaucoma
Applied to the eye (topical)
Acts on M3 causes contraction of the ciliary muscles which opens drainage pore allowing the aqueous humour to drain decreasing IOP
Give two examples of a muscarinic antagonists
Atropine
Ipatropium
What are the uses of muscarinic antagonists in treatment of Asthma?
Ipratropium inhaled
binds to muscarinic receptors preventing bronchoconstriction and bronchosecretion that is a PNS action
How can msucarinic antagonists be used in the treatment of Bradycardia?
Binds to muscarinic R’s on cardiac muscle preventing activation thus preventing the slowing of heart rate
Leads to an increase in Cardiac output and contractility
How can muscarinic antagonists be used in relation to the eye?
used to dilate pupils
opposes papillary constriction when light hits the eye allowing optometrists to look at the back of the eye
tropicamide (topical antagonist)
Where are alpha 1 adrenoceptors found
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?
Smooth muscle
Decreases Gi motility
Cause vasoconstriction
Gq GPCR acts on phospholipase C
Where are Alpha 2 adreoceptors found?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?
CNS including the brainstem midbrain spinal cord cerebral cortex
Activation causes an increase in blood pressure blocks NA release from PNS
Gs acts of adenyl cyclase
Where are beta 1 adrenoceptors located?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?
Cardiac muscle
Increased contractility and cardiac output
Gs
Where are B2 adrenoceptors located?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?
Lots of places notably on bronchi causing relaxation of smooth muscle allowing for vasodilation and on smooth muscle of blood vessels supplying the heart and blood vessels –> Dilation in sympathetic activity
Gs
Where are B3 adrenoceptors located?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?
Urinary bladder
cause relaxation of smooth muscle
Gs
Give the name of an alpha adrenoceptor agonist? How does it work (hint is nasal decongestion)
Phenylephrine (Agonist)
Used as a nasal decongestant
causes vasoconstriction of blood vessels supplying nasal mucosa therefore less mucus produced
What is used when local anaesthetics are adminstered?
Adrenaline or NA
act agonists causing local vasoconstriction and therefore localisation of LA
Give an example of a alpha adrenoceptor antagonist and its use?
Tamsulosin
used in Benign prostatic hyperplasia
Antagonsit therefore causes relaxation of smooth muscle of prostrate and urinary sphincter making urination easier
Give an example of an B adrenoceptor agonist and its use?
Salbutamol
used in treatment of asthma as it results in bronchodilation?
How can beta agonists be used in the treatment of cardiogenic shock
Increase heart rate and contractility rising blood pressure
Give an example fo a B adrenoceptor antagonist?
When is it used clinically and how?
Metoprolol (most things ending with olol)
Used to treat hypertension, arrhythmias
targets B1 decreasing cardiac output
How is postgaglioninc sympathetic neruotranmission terminated?
Usign Noradrneline transporters that transport NA back into the postganglionic neurone
Give an examples of NAT inhibitors?
Cocaine and tricyclic antidepressants
how do NATi work?
Prevent the transport of NA back into postganglionic neurone
NA inhibitor signal is not terminated causing constant sympathetic stimulation
What are the effects, and side effects of NATi inhibitors like cocaine?
Effects prolonged sympathetic stimulation
Euphoria and excitement as dopamine and serotonin neurotransmitters also prevented of being transported back into neurones in CNS
Taccycardia increased blood pressure
What are mono amine oxidase inhibitors
Block monamine oxidase enzymes that usually break down NA intracellularly
What is the use of MAOi?
And how do they work?
Antidepressants
Increase the presence of NA dopamine and serotonin (5HT) in brain
What are the side effects of MAOi’s?
Postural hypotension weight gain restlessness insomnia cheese reaction
What are indirectly acting sympathetic amines?
Enter sympathetic postganglionicn nerones via NAT and then displace NA intracellulary resutling thorough the reversal of the NAT
Causes long lasting effects of NA
bronchodillation vasoconstriction increased blood pressure
what is the cheese reaction?
Interaction between MAOi’s
and indirectly acting sympathetic amines?
amine cause an increase in amount of NA in cytosol and then the MAOi’s prevent breakdown of this NA therefore more is displaced
causes sever hypertension episodes
