Adrenergic Pharmacology Flashcards
What type of neurons are all preganglionic fibers in the autonomic nervous system?
Cholinergic
What neurotransmitters are primarily involved in the adrenergic synapse?
Noradrenaline and adrenaline
Where is noradrenaline produced within the sympathetic nervous system?
Adrenergic neurons and adrenal medulla
What enzyme is crucial in the first step to synthesis of noradrenaline and adrenaline?
Tyrosine hydroxylase
How is noradrenaline release regulated at adrenergic synapses?
By autoinhibitory feedback mediated by α2 receptors
What are the two important classes of adrenergic receptors?
α and β receptors
What effect does stimulation of α1 receptors have on blood vessels?
Vasoconstriction
How does the β1 receptor affect the heart?
Increases the rate and force of contraction
What is the role of β2 receptors in the lungs?
Relaxation of smooth muscles, leading to bronchodilation
What is the clinical use of α-methyl-p-tyrosine?
Alternative treatment for pheochromocytoma. It inhibits Tyrosine hydroxylase
How does reserpine affect noradrenaline storage?
Inhibits vesicular uptake of NA, leading to its depletion
What is the mechanism of action of indirect sympathomimetic drugs like amphetamine?
Taken up by NET and VMAT in exchange for NA reducing NA reuptake.
NA, is then metabolised by MAO or escapes via NET back into the synaptic cleft augmenting NA release.
Have an inhibitory effect on MAO
How does cocaine affect noradrenaline neurotransmission?
Inhibits the reuptake of noradrenaline at presynaptic terminal
What are the effects of sympathomimetics on the cardiovascular system?
Increased heart rate and force of contraction, leading to hypertension
How do α2 receptors regulate noradrenaline release?
Inhibit the release of noradrenaline via feedback inhibition
What role does clonidine, an α2 receptor agonist, play in blood pressure regulation?
It inhibits noradrenaline release, which can lower blood pressure
How do β1 receptors influence renal function?
They increase the release of renin from juxtaglomerular cells, which raises blood pressure
What is the effect of activating β2 receptors on vascular smooth muscle?
It leads to vasodilation
How does adrenaline act during anaphylaxis?
It decreases the release of mediators from mast cells, alleviates airway obstruction, and improves cardiovascular response
What is the result of α1-adrenergic agonist effects during anaphylaxis?
Increased vasoconstriction, increased peripheral vascular resistance, and decreased mucosal edema
What is the impact of β2-adrenergic agonist effects during anaphylaxis?
Increased bronchodilation and decreased release of inflammatory mediators from mast cells and basophils
What is the primary action of α1 receptors on blood vessels?
Vasoconstriction
How do α2 receptors affect insulin secretion?
They decrease insulin secretion from pancreatic islets
What is the function of β1 receptors in the kidneys?
Increase renin release from juxtaglomerular cells
What systemic effect does β2 receptor activation have?
Vasodilation, bronchodilation, and relaxation of uterine muscles
How do amphetamines influence noradrenaline levels?
They increase noradrenaline release by exchanging with VMAT and NET and reducing NA reuptake
What is the effect of cocaine on neurotransmitter levels in the synaptic cleft?
It increases levels by inhibiting the reuptake of neurotransmitters like noradrenaline
How does the action of circulating catecholamines compare to neuronally released noradrenaline?
Circulating catecholamines have a longer duration of action compared to neuronally released NA
What role does renin play in blood pressure regulation?
It catalyzes the conversion of angiotensinogen to angiotensin I, leading to an increase in blood pressure
How do β2 receptors affect airway smooth muscle?
They cause bronchodilation by relaxing the smooth muscle
What is the effect of adrenaline on α1 and β2 receptors during anaphylaxis?
It causes vasoconstriction via α1 receptors and bronchodilation via β2 receptors
How do β1 receptors affect cardiac function?
They increase the heart rate and force of contraction
What is the significance of β2 receptors in the uterus?
They relax uterine muscles
How does the β2 receptor influence blood vessel?
It causes vasodilation, reducing peripheral resistance
In the context of anaphylaxis, how does adrenaline assist?
It reduces mediator release from mast cells, alleviates respiratory tract obstruction, and enhances cardiovascular function
How does the body respond to a fight-or-flight situation via the sympathetic nervous system?
Increased heart rate, sweating, and pupil dilation.
What are the primary hormones involved in sympathetic nervous activation?
Noradrenaline and adrenaline.
In the context of sympathetic nervous system activation, which hormone is released first and which follows if the stimulus persists?
Noradrenaline is released first; adrenaline follows if the stimulus persists.
How do cholinergic and adrenergic drugs differ in their mechanism of action on the autonomic nervous system?
Cholinergic drugs act on acetylcholine receptors, while adrenergic drugs act on noradrenaline or adrenaline receptors.
In a patient with hypertension, how might an α1 receptor antagonist aid in managing their condition?
By causing vasodilation and reducing blood pressure.
Explain the role of β1 receptors in cardiovascular physiology.
They increase the rate and force of heart contractions.
How do β2 receptors influence respiratory function?
By causing bronchodilation, easing air flow.
Describe the mechanism of action of α-methyl-p-tyrosine in treating pheochromocytoma.
It inhibits tyrosine hydroxylase, reducing noradrenaline biosynthesis.
How does reserpine affect noradrenaline levels in treating hypertension?
It inhibits VMAT, preventing NA storage and leading to its depletion.
In the context of indirect sympathomimetic drugs, how does cocaine affect noradrenaline levels?
It inhibits the reuptake of noradrenaline, increasing its synaptic levels.
What is the effect of β2 receptor activation on smooth muscle?
Relaxation, leading to vasodilation and bronchodilation.
How does the duration of effects differ between neuronally released noradrenaline and circulating catecholamines?
Circulating catecholamines have prolonged effects compared to neuronally released noradrenaline.
How does adrenaline assist in managing anaphylaxis?
It decreases mediator release from mast cells, alleviates airway obstruction, and improves cardiovascular response.
What is the clinical significance of α2 receptor agonists like clonidine in hypertension?
They inhibit noradrenaline release, reducing blood pressure.
How does the effect of adrenaline on α1 and β2 receptors influence blood vessel tone?
Adrenaline causes weaker vasoconstriction by stimulating both α1 and β2 receptors.
Considering anaphylactic shock, explain how adrenaline’s action on α1-adrenergic receptors benefits the patient.
It increases vasoconstriction and peripheral vascular resistance, reducing mucosal edema.
Detail the sequence of steps leading from β1 receptor activation to increased blood pressure.
β1 activation increases renin release, leading to angiotensin II production, aldosterone release, and sodium/water retention, raising blood pressure.
How do β2-adrenergic agonist effects contribute to managing anaphylaxis?
They increase bronchodilation and decrease inflammatory mediator release.
In treating mood disorders, how might the action of reserpine on VMAT be beneficial?
Reserpine inhibits vesicular monoamine transporter (VMAT), preventing the storage of monoamines (e.g., serotonin, dopamine, norepinephrine) in synaptic vesicles. This leads to their depletion in the synaptic cleft. While this typically induces depressive effects, early observations of reserpine’s effects helped shape the monoamine hypothesis of mood disorders, guiding the development of modern antidepressants that enhance monoamine availability.
When considering drugs affecting sympathetic neurotransmission, categorize an example that impacts NA breakdown.
MAO inhibitors like moclobemiA53:C56de increase NA availability by inhibiting its breakdown.
