83 - Drugs in ANS Adrenergic drugs Flashcards
Where are the sites of actions for adrenergic drugs?
- Sympathetic postganglionic synapse >release NA to alpha and beta receptors
- Sympathetic nicotinic receptors at adrenal medulla > release adrenaline to alpha and beta receptors
What are the principle pathways and actions of a1 adrenoceptors?
Gq protein
Phospholipase C > IP3
increase intracellular Ca2+ release
Vasoconstriction
What are the principle pathways and actions of a2 adrenoceptors?
Gi/o protein reduce cAMP reduce PKA reduce intracellular Ca2+ release reduce intracellular K+
Inhibit transmitter release
What are the principle pathways and actions of b1 adrenoceptors?
Gs protein
increase cAMP
increase PKA
Increase cardiac rate and force
What are the principle pathways and actions of b2 adrenoceptors?
Gs protein
increase cAMP
increase PKA
vasodilation
bronchodilation
What are the principle pathways and actions of b3 adrenoceptors?
Gs protein
increase cAMP
increase PKA
Lipolysis
_______ are examples of adrenergic drugs.
________ is able to activate a1,a2 and b1 receptors.
________ is able to activate all a1,a2,b1 and b2 receptors.
_______ is able to activate only beta receptors.
Catecholamines;
noradrenaline;
adrenaline (one more methyl group);
Isoprenaline
NA, Adr and Iso activate which common receptor?
What is the effect upon the activation of this receptor?
Beta 1 receptors
Increase chronotropic effect (increase heart rate) and iontropic effect (increase force of contraction) > increase cardiac output
Na and Adr activates _______ receptors that causes vasoconstriction.
Adr and Iso activates ____receptors to cause vasodilation.
a1 ;
b2
Name the adrenoceptor agonist for a1 receptors.
Phenylephrine
Name the adrenoceptor agonist for a2 receptors.
Clonidine (“close” > Gi protein)
Name the adrenoceptor agonist for b1 receptors.
Dobutamine
Name 2 adrenoceptor agonists for b2 receptors.
Salbutamol
Terbutaline
Ritodrine
Name the adrenoceptor agonist for b3 receptors.
BRL 3744
What are the 4 a1 antagonists?
- Phentolamine (拉麵)
- competitive reversible - Phenoxybenzamine (惡死benz)
- irreversible - Terazosin (Terror 祖先)
- long-acting - Tamsulosin
- selective on a1A receptors
Name an a2 antagonist.
Yohimbine
yo 人叫人 not to close
What are the 1st, 2nd and 3rd generation beta blockers?
1st: Propranolol (b1,b2)
2nd: Metoprolol + atenolol
(b1>b2, cardioselective)
3rd: Celiprolol (b1 blocker, weak b2 agonist)
Carvedilol (b1/2 blocker, a1 blocking activity)
How is catecholamines produced?
flow chart
Tyrosine > DOPA > Dopamine (DA) > noradrenaline > adrenaline
How is NA at the synaptic cleft be removed except binding to a/b receptors? (2 ways)
- taken up by noradrenaline transporter (NET)
> Monoamine oxidase (MAO) to become metabolites
//> VMAT (such that NA is stored rather than metabolised by MAO)
- bind to a2 receptors at presynpatic cell > produce negative feedback
_________ inhibits the vesicular monoamine transporter (VMAT) for noradrenaline.
Reserpine
> NA in cytoplasm is metabolised by MAO > depletes the storage granules of NA with high or repeated doses
Adrenergic neuron blocking drugs like _________ are concentrated in the cytoplasm via ________.
What are their function?
Guanethidine
NET (Noradrenaline transporter)
Functions:
- inhibit exocytosis of NA
- uptaken into synaptic vesicles to displace NA
- weak local anaesthetic activity
Repeated
Which drug can be used as a selective a2 receptor agonist to inhibit the release of NA at the presynaptic cell?
Clonidine
___________enters the NA biosynthetic pathway to
form a false transmitter __________that replaces NA.
It has a more potent agonist than NA for the negative feedback but
is a less potent agonist than NA on the end-organ.
a-methyl-DOPA;
a-methyl-NA
Indirect acting sympathomimetics like _______ can be used to displace NA from vesicles, allowing it to be released.
This reduces NA re-uptake , which has a weak adrenoceptor agonist action.
- Competitive inhibition on MAO too.
Tyramine
inhibits MAO and release NA from vesicles
