10.18 NS drugs Flashcards
M1 receptor (G protein):
Gq
M2 receptor (G protein):
Gi
M3 receptor (G protein):
Gq
α1 receptor (G protein):
Gq
α2 receptor (G protein):
Gi
β1 receptor (G protein):
Gs
β2 receptor (G protein):
Gs
Gq signaling involves (cAMP and PKA / PLC and calcium)
Gq signaling involves PLC –> Ca2+ (activation)
Gs signaling involves (cAMP and PKA / PLC and calcium)
Gs signaling involves AC –> cAMP –> PKA (activation)
Gi signaling involves (cAMP and PKA / PLC and calcium)
Gi signaling involves inhibition of AC –> decreased cAMP
Most organs are innervated by both the sympathetic and parasympathetic divisions; the exception is vascular smooth muscle which is only controlled by _
Most organs are innervated by both the sympathetic and parasympathetic divisions; the exception is vascular smooth muscle which is only controlled by sympathetic nervous system
Sympathetic receptor in the pupil
Sympathetic receptor in the pupil:
α1
Sympathetic receptor in the salivary glands
Sympathetic receptor in the salivary glands:
β2
Sympathetic receptor in the bronchioles
Sympathetic receptor in the bronchioles:
β2
Sympathetic receptor in the heart
Sympathetic receptor in the heart:
β1
Sympathetic receptor in the vascular SM
Sympathetic receptor in the vascular SM:
α1, β2
Sympathetic receptor in the GI tract
Sympathetic receptor in the GI tract:
β2
Sympathetic receptor in the uterus
Sympathetic receptor in the uterus:
β2
Sympathetic receptor in the urethra
Sympathetic receptor in the urethra:
α1
Sympathetic receptor in the bladder
Sympathetic receptor in the bladder:
β2
Parasympathetic receptor in the pupil
Parasympathetic receptor in the pupil:
M3
Parasympathetic receptor in the salivary glands
Parasympathetic receptor in the salivary glands:
M3
Parasympathetic receptor in the heart
Parasympathetic receptor in the heart
M2
Parasympathetic receptor in the bronchioles
Parasympathetic receptor in the bronchioles:
M3
Parasympathetic receptor in the GI tract
Parasympathetic receptor in the GI tract:
M3
Parasympathetic receptor in the bladder
Parasympathetic receptor in the bladder:
M3
Parasympathetic receptor in the urethra:
Parasympathetic receptor in the urethra:
none
What is the general rule for selectivity of parasympathetic drugs for the M receptors?
Most parasympathetic drugs tend to affect both M2 and M3 equally
* Why we see toxicity
α2 receptors are located _
α2 receptors are located on the presynaptic neuron and functions as a regulator; inhibits the release of too much NE/E
What are three synonyms for drug classes that stimulate the parasympathetic NS?
Stimulate parasympathetic:
Parasympathomimetic =
Cholinomimetic =
Muscarinic receptor agonist
Direct parasympathetic agonists work by _
Direct parasympathetic agonists work by activating the receptor just like Ach does
Indirect parasympathetic agonists work by _
Indirect parasympathetic agonists work by inhibiting acetylcholinesterase (breakdown of Ach)
Drugs (2) that can reverse bradycardia
To reverse bradycardia we need to inhibit M2
Atropine
Glycopyrrolate
What are the effects of an M2 antagonist like atropine/ glycopyrrolate?
M2 agonist: decreases depolarization at the SA/AV node –> decreases heart rate –> decreases cardiac output
M2 antagonist: reverses the bradycardia; increases SA/AV node firing to increase HR
What do M3 agonists do in the bronchioles?
M3 agonists: found throughout the body besides the heart (pupil, salivary gland, bronchioles, GIT, bladder, uterus)
* In bronchioles: Induce bronchoconstriction
* Ex: methacholine
Name 3 types of M3 antagonists that can act in the bronchioles:
Ipratropium
Tiotropium
Aclidinium
These M3 antagonists will trigger bronchodilation to treat things like COPD
Drugs to treat gastrointestinal motility include _ and _ which target _ receptor in the GIT
Drugs to treat gastrointestinal motility include dicyclomine and hyoscyamine which target M3 receptor in the GIT
* They will inhibit smooth muscle contraction in the gut to decrease peristalsis rate
* Used in IBS
M3 receptors can be found in the glands (regulate secretions);
Agonists include:
Antagonists include:
M3 receptors can be found in the glands (regulate secretions);
Agonists include: pilocarpine
Antagonists include: glycopyrrolate
To treat urinary retention we can either activate _ parasympathetic receptor in the detrusor muscle of the bladder (squeezes the bladder)
Or we can cause urethral smooth muscle to relax which means we want _ sympathetic receptor to be inhibited
To treat urinary retention we can either activate M3 parasympathetic receptor in the detrusor muscle of the bladder (squeezes the bladder)
* Agonist: bethanechol
Or we can cause urethral smooth muscle to relax which means we want alpha1 sympathetic receptor to be inhibited
* alpha1 antagonists: alfuzosin, silodosin, tamsulosin
What is the effect of an M3 antagonist in the bladder?
M3 antagonist in the bladder would cause urinary retention
* Ex: use oxybutynin and tolterodine to treat an overactive bladder
_ is a M3 agonist that causes the pupils to constrict
Carbachol is a M3 agonist that causes the pupils to constrict
_ is an M3 antagonist that causes the pupils to dilate
Atropine is an M3 antagonist that causes the pupils to dilate
Miosis means _
Miosis means pupil constriction
Mydriasis means _
Mydriasis means dilation
β1 agonists do what?
β1 agonists: stimulate AV/SA node –> increase HR –> increase CO
β1 antagonists are indicated for treatment of _ and _
β1 antagonists are indicated for treatment of hypertension and angina
β2 agonists do what?
β2 agonists: bronchodilation
* ex: albuterol, salmeterol, formoterol
What does antagonizing the alpha1 receptor in the urethra do?
alpha1 antagonists: alfuzosin, silodosin, tamsulosin
Normally sympathetic NS will lead to retention of urine –> so normally SM of urethra is contracted –> if we add alpha 1 antagonist is causes relaxation and allows urination
_ drug is an alpha1 agonist that leads to pupil dilation
Phenylephrine drug is an alpha1 agonist that leads to pupil dilation
Ritodrine and terbutaline are drugs used to stop preterm labor; they work by _
Ritodrine and terbutaline are drugs used to stop preterm labor; they work by agonizing B2 receptors in the uterus
* Uterine relaxation
Vascular smooth muscle contains both α1 and β2 but the effect of _ usually dominates
Vascular smooth muscle contains both α1 and β2 but the effect of α1 usually dominates
* Meaning we see constriction of vessels when sympathetic system is active
* α1 agonists will cause vasoconstriction and increase in BP
Clonidine is an α2 agonist which is used to treat _
Clonidine is an α2 agonist which is used to treat hypertension
Side effects of pilocarpine:
Intended to increase salivation
* Side effects: pupil constriction, diarrhea
* All are M3 targets
Side effects of atropine:
Intended to target M2 to increase heart rate
* Side effects: pupil dilation, dry mouth, constipation
* Not very selective so it inhibits M3 and M2
Toxicities of parasympathomimetics:
DUMBBELS:
Diarrhea
Urination
Miosis
Bradycardia
Bronchoconstriction
Emesis
Lacrimation
Salivation
Side effects of tamsulosin:
Tamsulosin is intended to inhibit alpha1 in the bladder to relax the urethra
* Side effects: inhibits alpha1 in the eyes and vascular smooth muscle –> miosis, hypotension
Side effects of nadolol:
Nadolol is a beta blocker that is intended to block beta1 to decrease BP
* Side effects: blocks B2 as well and can cause bronchoconstriction
