3 L4 Sympathetic Nervous System Drugs Flashcards
Describe noradrenaline
NT of sympathetic system - Active even when individual is at rest
Describe adrenaline
Hormone released from adrenal gland in response to sympathetic activation
a 1 short
Vasoconstriction
a 2 short
Modulate sympathetic activity - Cognition - Arousal - Wakefulness
B 1 short
Increase HR and force of contraction
B 2 short
Vasodilation - Bronchodilation - Gluconeogenesis
a 1 adrenergic receptors mechanism
a1 mediates smooth muscle contraction in skin - Gq coupled GPCR increases Ca- contraction - Vasoconstriction in skin and GIT
a1 agonists
Phenylephrine - Adrenaline - Noradrenaline
Describe congestion and decongestion
Congestion- Vasodilation of nasal blood vessels- Narrow nasal passage
Decongestion- Vasoconstriction of nasal blood vessels- Broadens nasal passage
B1 effects in heart
B1 activation activates PKA which phosphorylates troponin 1 (speeds up Ca dissociation of Ca from myofilaments) - PKA also phosphorylates PLB which speeds up Ca uptake into SR - Increases HR and force of contraction
Where is NA released from
Locus Coerulus (LC) in brain
Describe NA activity throughout day
Higher activity during day and during stress - LC (Locus Coerulus) activity is very low during sleep
What can a2R activation cause in the brain
Enhances the strength of relative sensory input to the PFC
Describe the relationship between levels of NA and cognition in brain
Moderate levels of NA- Increase cognition by binding to a2 receptors
High levels of NA- Decrease cognition by binding to a1 receptors
4 main treatments for ADHD
Inhibit reuptake of NA AND dopamine (methylphenidate) - Inhibit reuptake of NA only (atomoxetine) - Facilitate release of NA and dopamine (amphetamine) - a2 NA receptor agonists (guanfacine)
Describe neuromodulation of a2 receptors (what kind of G-protein is it coupled to)
Coupled to Gi leading to activation hyperpolarisation- Decreases neurotransmission of irrelevant stimuli (noise)
Neuromodulation of D1R and what G protein they’re coupled with
Coupled to Gs so D1R activation enhances neurotransmission of relevant stimuli
What do NET and DAT stand for and what class of drugs are they
Norepinephrine transporters - Dopamine transporters- NDRIs
Most common NDRI drug name
Methylphenidate
NET NDRI method of action
NET removes NA from synapse - Inhibiton of NET increases NA in the synapse and binding to a2 receptors
DAT NDRI method of action
Inhibition of DAT increases dopamine binding to D1 receptors
What is the requirement for NRDIs
Require natural release of NA in synapse, otherwise there is nothing to activate the receptors
Selective NET inhibitor name
Atomoxetine
Amoxetine (Selective NET inhibitor) method of action
Increases NA binding to a2 receptors - Also leads to increased dopamine in PFC (limited dopamine transporters in PFC so dopamine can share NET transporter)
