Lecture 19 Flashcards
(26 cards)
What are the 2 receptor ACh activates in the parasymp system and where are the receptros found
Nicotinic AChR in the ganglion
Muscarinic AChR in the target tissues
What are the receptors that activate in the Sympathetic system, What activates them and where are they found
NAChR in the ganglion by ACh
Alpha and Beta receptors in the target organs by Noradrenaline/norepinephrine(NA or NE)
activating NACHr in the adrenal glands causes systematic release of NA and EPI
What are the other enzymes that can bind to NAChR and muscarinic Receptors
Nicotine for NAChR
muscarine for muscarinic receptors
What is the primary activator(NT) of the sympathetic nervous system
Noradrenaline(main) and adrenaline
Whats the difference in function for noradrenaline and adrenaline
Noradrenaline- NT of the nervous system, active even when the body is at rest. More effect in the brain
adrenaline- A hormone released from the adrenal gland in response to sympathetic activation. Stronger in physiological effect-especially for beta receptors causing inc HR. As adrenaline is a hormone it causes a response in every tissue it reaches rather than having a target area
What are some of the physiological effects carried out by Noradrenaline and adrenaline
Inc: Hr(beta 1), secretion, sewating
Inhibit: GI motility
bronchodilation, vasodilation for the muscle liver and brain
vasoconstriction for skin and GIT
enhanced neuronal activity
What receptors are activated by NA and EPI and what do they do
-Adrenergic GPCR’s
Alpha 1- Gq receptor, activates PLC path causing Ca2+ secretion for contraction
Alpha 2- moderates release of NA and stops neurotransmission. found in brain
Alpha 2 Not in the brain- Gi, stops cAMP production
Beta 1 and 2- both are Gs activating the cAMP pathway
How does Alpha one receptors work and how are they used to decongest the nose
They mediate smooth muscle contraction through the Gq-PLC pathway and also vasoconstrict the skin and GIT
nasal congestion is caused by vasodilation of the blood vessels causing a narrow nasal passage. Agonists of the alpha 1 receptor such as adrenaline, phenylephrine and noradrenaline (in this case phenylephrine) can be used to constrict the nasal blood vessels allowing for a broader nasal canal curing congestion
What are the effects of adrenaline on the heart
The Gs beta 1 receptor activates the PKA path where PKA phosphorylates troponin 1, speeding up calcium dissociation from myofilaments.
In this case PKA also phosphorylates phospholamban (PLB) which increases the speed of uptake of Ca2+ into the SR allowing the heart to beat faster and stronger
Does PKA do the same thing in every cell in every area of the body
No, different cells types have different influences from PKA
different targets-different outcome
Describe the activity of noradrenaline and where it is released from
Noradrenaline is released from the locus coerulus (LC). It is high in activity during the day, contributing to alertness.
activity is still present during sleep just in much lower levels.
Stress in life can increase the activity of noradrenaline
What are some of the roles of Noradrenaline in the brain
Inc arousal,
enhance: sensory processing, attention, formation and retrieval of all types if memory
promotes wakefulness
What does low levels of NA and dopamine in the prefrontal cortex indicate
ADHD
What are the 4 main forms of ADHD drug treatment
NDRI’s, NDRA’S, Selective NET uptake inhibitors and Alpha 2 Noradrenaline receptor agonist (this is the only option that doesnt increase anxiety and can be used to treat both conditions)
How does neuromodulation of Alpha 2 receptors help manage appropriate stimuli
activation of the receptors enhances signal to noise ratio of relevant stimuli. The process is the Alpha 2 Gi hyperpolarises the neuron resulting in less neurotransmission of irrelevant stimuli
How does neuromodulation of D1 receptors help manage appropriate stimuli
D1 are Gs meaning they increase transmission for the relevant stimuli, in this case through delay cells in the prefrontal cortex.
delay cells hold sensory information between sensory stimulus and subsequent action. They can also contribute to improvements in working memory
What are the 2 nonpharmacological treatments for ADHD
Exercise for children, cognitive behavioural therapy
What are NDRI’s and how do they work as ADHD treatment
NDRI means NET and DAT reuptake inhibitors. they work by inhibiting the mentioned transporters by forcing them to release the NT without stimulus. Allowing for more NA(noradrenaline) DA(dopamine) to stay in the synapse binding to Alpha 2 and D1 receptors
to work they require normal dopamine and noradrenaline release
The most common drug prescribed is the NDRI methylphenidate
Describe selective NET inhibitors and how they work as an ADHD treatment
inhibit the NET increasing NA binding to Alpha 2 receptors. They require regular release of NA to function.
As this form of treatment doesn’t involve dopamine, it’s dependency risk is much lower and there is no euphoric feelings associated with consumption
however inhibiting NET causes and inc in dopamine in the prefrontal cortex as there isnt enough DAT there so they would typically share with the NET
Describe Alpha 2 agonists as a ADHD treatment
Direct activation of the Alpha 2 receptors causing inhibited release of NA(when the receptors are found pre syn in the locus coeruleus) to help reduce sympathetic nervous system activity while still enhancing cognition
Alpha 2 agonists are the only ones that inhibit noradrenaline meaning it decreases anxiety symptoms too
What type of drug is Amphetamine and how is it used to treat ADHD
A NDRA, it works by binding to reuptake transporters and vesicle storage proteins causing both dopamine and noradrenaline to be released into the cytoplasm. Then a type of reverse transport happens to force the 2 NT into the synapse.
unlike the alpha 2 agonists amphetamine increases activity without activation of the locus coeruleus
as this drug contains dopamine activity changes it has a higher drug abuse potential. To prevent this a prodrug called lisdexamfetamine that must be metabolised in the liver first, has been created to reduce abuse potential
Can use of stimulants help cognition of people without a diagnosis of ADHD
It was found that non-prescription use in appropriate doses had a few different treatments improving memory, cognition etc. but the effect sizes are small meaning sometimes it just felt as if it was enhancing cognition
Describe anxiety and how you would typically treat it
Anxiety is often paired with excess sympathetic nervous system activity(too much noradrenaline). The first way to treat is non pharmacological followed by noradrenergic modulators and benzodiazepines (however has a very high drug abuse potential)
How does exercise connect to anxiety
Exercise improves symptoms with an effect size of 0.55 It works by increasing dopamine and noradrenaline to the point of tolerance happens leading to internalization of the receptors - reducing anxiety symptoms
