Adrenergic pharmacology Flashcards
Describe neurons in the sympathetic NS.
Short preganglionic axons, long postganglionic axons.
Where are beta-adrenoceptors innervated?
Heart, juxtaglomerular apparatus, brown adipose tissue
Where are beta-adrenoceptors non innervated?
Bronchial smooth muscle, uterine smooth muscle, skeletal muscle vasculature
What neurotransmitter is released at postganglionic sympathetic nerve terminals?
Noradrenaline
Sweat glands have acetylcholine from muscarinic receptors.
What are full and partial agonists acting at beta2 adrenoceptors?
full: adrenaline, isoprenaline
partial: prenalterol
What are full and partial agonists acting at alpha2 adrenoceptors?
full: noradrenaline
partial: clonidine
How are catecholamines synthesised?
Phenylalanine -> tyrosine.
Tyrosine is transported into cell. L Tyrosine -(tyrosine hydroxylase)-> L DOPA -(L amino acid decarboxylase)-> dopamine (transported into vesicle by vmat) -(dopamine beta dehydroxylase)-> noradrenaline -> (in periphery) adrenaline
What are some effects of alpha 1 activation?
Constriction of blood vessels Decrease in GI motility Contraction of bladder and eye minor glycogenolysis in liver Contraction of smooth muscle except in gut
What are some effects of alpha 2 activation?
Constriction of blood vessels
Decrease in GI motility
Aggregation of platelets
Decreased NA release
What are some effects of beta 1 activation?
Increase in force and rate of heart
Renin release from kidney
What are some effects of beta 2 activation?
Dilation of blood vessels and bronchi Decrease in GI motility Relaxation of uterine smooth muscle Tremor of skeletal muscle Glycogenolysis in liver
What are some effects of beta 3 activation?
Relaxation of bladder detrusor
Lipolysis of fat cells
What is propranolol?
A beta blocker - a non-cardioselective beta-adrenergic antagonist.
It binds reversibly to β1 and β2 receptors, reduces heart rate, bp, cardiac output, peripheral vasoconstriction so less NA/A binds β1 and β2 causing Gs activation.
Name a β2 adrenergic agonist and its use.
Salbutamol is used to treat asthmatic symptoms by causing dilation of bronchial smooth muscle, opening the airways. This prolongs the QT interval of an ECG.
A side effect of Salbutamol may be increased heart rate due to reduced blood pressure.
Name a drug that can treat hypertension, Raynauds and frostbite.
Phentolamine, non selective α agonist.
What is Timolol used for?
It is prescribed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent.
It is a non-selective β-adrenergic antagonist (β blocker)
What does sympatholytic mean?
a drug antagonistic to or inhibiting the transmission of nerve impulses in the sympathetic nervous system
eg β blockers and α antagonists
What is the dominant β receptor in the heart?
β1 receptors
Which receptor does clonidine act on?
α1 receptors.
Treats ADHD, high blood pressure, anxiety and migraines.
What is ‘adrenaline reversal’?
The fall in blood pressure observed when given adrenaline following blockage of α-adrenergic receptors by an antagonist eg phenoxybenzamine
What is the effect of isoprenaline?
Vasodilation of skeletal muscle and other vascular beds causing decrease in blood pressure and reflex tachycardia. Isoprenaline is a very selective agonist for β receptors.
What is phenoxybenzamine?
An irreversible non-competitive antagonist binds covalently to α adrenoceptors.
(log-dose response curve would have a reduced slope, and decreased max response to agonist)
Which drug can treat nasal stuffiness and why?
Phenylephrine is a selective α1-adrenergic receptor agonist.
Causes activation of postjunctional alpha-adrenergic receptors found on precapillary and postcapillary blood vessels of the nasal mucos, causing vasoconstriction, and shrinkage of nasal tissue.
It also dilates the pupil and increases blood pressure.
On which receptors are NA and A more potent?
NA is more potent on α than β, and most on α1.
A is more potent on β receptors.
How does reserpine act?
Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic.
What is Tetrabenazine?
Tetrabenazine is a short acting noradrenaline and dopamine depletory, which is reversible and is used to treat hyperkinetic movement disorders, such as Huntington’s disease (monoamine depletor)
what is another name for the norepeniphrine transporter?
Solute carrier family 6 member 2 (SLC6A2)
sodium:neurotransmitter symport