Cholinergic Agents 3 Flashcards
Describe the major pharmacologic manipulations of the cholinergic system.
Examine the structure of a direct acting cholinergic agonist and identify the major structural features responsible for the drug’s activity.
Explain the molecular basis for the interactions of acetylcholine
and related drugs with muscarinic receptors with particular
emphasis on stereochemical requirements of the drugs.
Given a chemical modification to the structure of a direct acting cholinergic agonist, predict the effect on the molecule’s activity and sensitivity to acetylcholinesterase.
Given a clinical condition, choose an appropriate cholinergic
agonist to treat that condition
Explain why parasympathomimetic drugs should not be used asthma, peptic ulcer, or bowel and urinary obstructions.
Explain the molecular basis for the interactions of acetylcholine
and related drugs with nicotinic receptors.
What is parasympathomimetic action?
It is an agonists that through activation is to mimic parasympathetic activation.
What does a direct agonist do to acetylcholine receptors?
It activates cholinoceptors.
What does an indirect agonist do to acetylcholine receptors?
It will stimulate acetylcholine release and inhibit acetylcholinesterase (AChE)
What is parasympatholytic action?
It is an antagonists to the cholinergic receptor and can act through direct or indirect action.
Out of the muscarinic and nicotinic receptor, which one does acetylcholine have higher affinity for?
The muscarinic receptor.
Where are nicotinic receptors found? What is their response to acetylcholine?
The only nicotinic receptors are found in muscle are in skeletal muscle. Their response is motor end-plate depolarization contraction and the mechanism is through ligand-gated opening of Na+/K+.
The 2 neural tissues where nicotinic receptors are is postganglionic and the adrenal medulla. In the postganglionic tissue the response is depolarization. In the adrenal medulla the response is catecholamine secretion. The mechanism is based on the ligand-gated opening of Na+/K+.
Where are M1 muscarinic receptors located, their function and how they do it?
M1 receptors are located in postganglionic tissue and they function in depolarization. This happens through the GPCR mechanism of Gq (excitatory) which increases PLC, IP3, DAG and Ca2+.
Where are M2 muscarinic receptors located, their function and how they do it?
M2 receptors are located in the heart and they function in inhibition. This happens through the GPCR mechanism of Gi (inhibitory) by inhibiting adenylyl cyclase and the activation of K+ channels.
Where are M3 muscarinic receptors located, their function and how they do it?
M3 receptors are located in smooth muscles, exocrine glands and the endothelium. In the smooth muscle their function is contraction, in exocrine glands their function is secrtetion and in the endothelium their function is relaxation. This happens through the GPCR mechanism of Gq (excitatory) by increasing PLC, IP3, DAG and Ca2+. Additionally there is the releases of NO and increase in GC.
Where are M4 muscarinic receptors located, their function and how they do it?
M4 receptors are found in the CNS and function in hyperpolarization. This happens through the GPCR mechanism of Gi (inhibitory) by inhibiting adenylyl cyclase.
Where are M5 muscarinic receptors located, their function and how they do it?
M5 receptors are found in the CNS and function in depolarization. This happens through the GPCR mechanism of Gq (excitatory) by increasing PLC, IP3, DAG and Ca2+.
How does choline made it into the presynaptic neuron?
Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT).
Once inside the presynaptic neuron, how does choline become acetylcholine?
The enzyme choline acetyltransferase (ChAT) combines choline and acetyl-CoA to make acetylcholine.
Where does acetylcholine bind on the postsynaptic cell?
Cholinoreceptors.
How is the action of acetylcholine terminated?
The enzyme acetylcholinesterase (AChE) will hydrolyze acetylcholine into acetate and choline.
What are the muscarinic agonist effects of the heart?
The M2 receptors found on the heart when activated leads to DECREASE in HR, conduction and force also known as BRADYCARDIA.
What are the muscarinic agonist effects of the exocrine glands?
The M3 receptors found on these glands INCREASE in SECRETION.
This can be lacrimal (tear) glands, tracheobronchial (mucus) glands, salivary (saliva) glands, digestive glands and sweat glands.
What are the muscarinic agonist effects of the smooth muscles?
The M3 receptors found on the smooth muscles INCREASES in CONTRACTION.