SNS Antagonists Flashcards
The function of the a1 adrenoceptor subtype
Vasoconstriction, relaxation of the GIT
(Inhibitory effect of on the gut during fight or flight - divert function to other areas)
The function of the a2 adrenoceptor subtype
Inhibition of transmitter release, contraction of vascular smooth muscle, CNS action
(inhibit sympathetic activity)
The function of the b1 adrenoceptor subtype
Increased cardiac rate and force, relaxation of the GIT and renin release from the kidney
The function of the b2 adrenoceptor subtype
Bronchodilation, vasodilation, relaxation of the visceral smooth muscle and hepatic glycogenolysis
The function of the b3 adrenoceptor subtype
Lipolysis
Other than uptake 1 receptors, how are the actions of transmitters modulated
A2 receptor on the presynaptic neuron
Switches off the effect of the NA being released, this means that the effect of NA on the postsynaptic neurone is fast and not prolonged
Example of a non-selective (a1 +b1) antagonist
Carvedilol
Example of a non-selective alpha antagonist (a1 +a2)
Phentolamine
Example of a selective a1 antagonist
Prazosin
Example of a non-selective beta antagonist (b1 +b2)
Propranolol
Example of a selective b1 antagonist
atenolol
What are some of the clinical uses of adrenoceptor antagonists
Treatment of hypertension, arrhythmias, angina and glaucoma
Describe the pathophysiology of hypertension (BP, RISK )
> Consistently being over 140/90mmHg
Important risk factor for:
stroke (50% of ischaemic stroke)
25% of heart failure (70% in elderly)
MI and chronic kidney disease
What is the ultimate goal of hypertension therapy
Reduce the mortality from cardiovascular or renal events
What are the target tissues for antihypertensive drugs
Heart = affect CO
Kidney = blood volume/ vasoconstriction (renin and aldosterone)
Arterioles = peripheral resistance
What tissues can beta blockers target in relation to hypertension
B1 = heart, kidney
B1/2 = sympathetic nerves releasing vasoconstrictor NA, CNS (blood pressure control)
Describe the mechanisms of beta-blockers
Decrease heart rate and force of contraction = decrease CO = Decrease BP
Block b1 in the kidneys (activated via sympathetic activation) = Decrease renin = Less Angiotensin 2 (a potent vasoconstrictor) and aldosterone (decrease BP and volume)
Actions of Nebivolol
Targets b1 receptors
Potentiates the action of NO (Relax)
Actions of Sotalol
Targets both b1 and b2 receptors
Inhibits K+ channels (interferes with ell hyperpolarisation)
Groups of people who should be cautious with beta-blockers (5)
Asthma/COPD = causes bronchoconstriction
Cardiac failure = Need sympathetic drive in order to match blood/tissue demand
Hypoglycemia = bb block the symptoms of hypoglycaemia (sweating, palpitations, tremors) non-selective beta-blockers can affect the b2 receptors which are involved in glucose release from the liver
Fatigue = decrease in CO and muscle perfusion
Cold extremities = loss of b2 receptor-mediated vasodilation in cutaneous vessels
What is the advantage of atenolol over propranolol
Propranolol = non-selective beta-blocker
Atenolol = selective b1 blocker
Atenolol (cardio-selective drug) antagonises the effect of NA on the heart but will affect other areas such as the kidney with b1 receptors.
Less effect on airways than non-selective drugs but still not safe for asthmatics (liver/bronchioles)
What advantage does carvedilol have over atenolol and propranolol
Dual acting b1 and a1 antagonist (4:1)
> Lowers BP by reducing peripheral resistance
> Induces a change in heart rate/CO but wanes with chronic use
Compare the blockade of a1 and a2 receptors
a1 receptors = Gq-linked = postsynaptic receptor is on vascular smooth muscle
a2 receptors = Gi-linked = presynaptic autoreceptors inhibit NE release
