Cholinergic Drugs - Kruse Flashcards
What are the neurotransmitters and receptors for parasympathetic?
NT = ACH Receptors = nAhR, mAChR
What are the neurotransmitters and receptors for sympathetic?
NT = NE >Epi (DA); Ach
receptors: a, b, (D), nAChR, mAChR
what neurotransmitters does sweat glands use?
Ach.
In general, which parasympathetic receptor has the higher affinity for the heart?
M2
In general, which sympathetic receptor has the higher affinity for the heart?
beta 1
which parasympathetic receptors are found on blood vessels?
M3.
In general, which sympathetic receptors are found on blood vessels?
a1, a2, b1, b2
Which sympathetic receptor is found on trachea and bronchi and what is the action?
beta 2, bronchodilation –> relaxation
Which parasympathetic receptor is found on tracheal and bronchial smooth muscle and what is the action?
M2 and M3 equally and they cause contraction
In the stomach explain what happens with sympathetic stimulation and parasympathetic stimulation to each of the following:
a. motility and tone
b. sphincters
c. secretion
a. symp = decrease; parasyp = increase
b. symp = constrcts; parasyp = relax
c. symp = inhibition; parasyp = stimulation
what sympathetic receptor causes a pregnant woman to contract and relax the uterus?
a1 = contraction
beta 2 = relaxation
Explain where each of the following receptor are found and which GPCR it uses M1 M2 M3 M4 M5
M1 = nerve; Gq M2 = heart, nerves, smooth muscle; Gi M3 = glands, smooth muscle, endothelium; Gq M4 = CNS; Gi M5= CNS; Gq
which muscarinic receptor is predominant in most organs (or receptor abundnace is equal)
M3
M2 predominates in which organ?
heart
Mainly which muscarinic receptors are found on smooth muscle?
M2 and M3
What is the general MOA difference between direct and indirect cholinergic agonists?
Both direct and indirect mimic the actions of Ach on nAChR and mAChRs. Direct agonists acts directly on the receptor itself to mimic the action of Ach. and indirect acts indirectly to increase Ach concentration.
in what two chemical forms do direct acting cholinergic drugs exist?
Alkaloids or Choline esters
What is the MOA, charge status, absorption and distribution capacity, and metabolism of choline ester forms of direct acting cholinergic agonists
MOA: agonists binds to cholinergic receptors
- Choline esters are permanently charged
- poorabsorption and distribution to CNS
- metabolized by AchE
What are the direct acting choline esters and rank them in terms of affinity
Ach > Methacholine > carbachol > bethanechol
Of the choline esters which one are not susceptible to cholinesterase?
Carbachol and bethanechol. Ach is the most susceptible.
List the alkaloids of direct acting cholinergic agonists
muscarine and nicotine.
How are alkaloids and choline esters different?
Alkaloids are uncharged tertiary amines and are well absorbed and thus can cross BBB to reach CNS. Example nicotine patches
What are the three groups of AchE inhibitors and how are they different?
- Alcohols, reversible
- Carbamic acids esters, reversible but longer lasting than alcohols
- Organophosphates irreversible and thus with the use of organophasphate, the body needs to make more ACh to replenish. it’s often used as insecticide and weapon. They’re uncharged and lipophilic and thus can enter CNS
List the charged AChE inhibitors and explain their PK
Charged AchE inhibitors are insoluble in lipids and does not cross BBB, poor PO absorption.
They include: edrophonium, pyridostigmine, neostigmine, echothiophate, ambenonium
