Lecture 8: Autonomic Pharmacology Flashcards
What is the NT and receptors for the Parasympathetics?
NT: ACh
Receptors: nAChR and mAChR
What is the NT and receptors for the Sympathetics?
NT: NE>Epi (DA); ACh
Receptors: α,β, (D), nAChR, mAChR
Dopamine is the precursor to NE and Epi, where does it exert its actions?
Acts on the CNS and renal vascular smooth muscle
All preganglionic autonomic fibers use what NT?
ACh (cholinergic)
All post-ganglionic parasympathetics utilize what NT?
ACh
What are the 3 cholinergic receptors that are GPCR, Gq/11; what cascade results from activation of these receptors?
- M1
- M3
- M5
* All activate PLC; IP3; DAG cascase
What are the 2 cholinergic receptors that are GPCR, Gi/o; what is the cascade that occurs upon activation of these receptors?
- M2
- M4
* Inhibition of adenylyl cyclase (AC); decreased cAMP, activation of K+ channels
What is the location of M1-M5 cholinergic receptors?
M1: CNS, ganglia
M2: Heart, nerves, smooth muscle
M3: Glands, smooth muscle, endothelium
M4: CNS
M5: CNS
What kind of receptor is the Alpha 1 and what are its agonists?
- Gq; increased PLC; IP3; DAG; Ca2+
- Epi ≥ NE
Activation of the β3 receptor primarily causes what and where are they found; which agonist preferentially acts on this receptor?
- Found in adipose tissue
- Activation results in lipolysis
- NE is the agonist
The β2 receptor responds best to what agonist and where are these receptors found?
- Epi >> NE
- Smooth muscle (vascular, bronchial, GI, GU), skeletal muscle
- Relaxaton and Glycogenolysis; uptake of K+
What does stimulation of the alpha-1 receptor do to smooth muscle, vascular smooth muscle, and glandular smooth muscle (rules to live by)?
- Stimulate contraction of all smooth muscle
- Vascular smooth muscle - vasoconstriction
- Glandular smooth muscle - secretion
What does stimulation of the beta-2 receptor do to smooth muscle (rules to live by)?
Relax smooth muscle - vasodilation
What does stimulation of the Muscarinic receptors do to smooth muscle (rules to live by)?
- Contract smooth muscle
- ACh and muscarinic agonists given IV cause vasodilation due to release of nitric oxide (NO)
ACh and muscarinic agonists given IV will cause what?
- You get contraction of smooth muscle
- BUT, also get vasodilation due to the release of nitric oxide (NO)
What are 5 effects of the parasympathetics?
1) Salivation, lacrimation
2) Pupil constriction (myosis)
3) Decrease in HR
4) Urination, defecation
5) Increased secretion and motility
*Cholinergic
What are 5 effects of the sympathetics?
1) Cutaneous vasodilation
2) Pupil dilation (mydriasis)
3) Increase in HR
4) Reduction/elimination of the desire to urinate
5) Decreased secretion and motility
*Adrenergic
In general activation of alpha-2 receptors results in what?
- Vascular smooth muscle contraction
- Decreased insulin secretion
- Decreased release of NE (pre-synaptic α2 receptors)
β1 receptors are mainly found where and activation causes?
- Mainly found in the myocardium
- Increased force and rate of heart contraction and AV nodal conduction velocity
β2 receptors are mainly found where and activation causes?
- Mainly found on smooth muscle and most other sites
- Activation causes: vascular, bronchial, genitourinary, and GI smooth muscle RELAXATION
In a patient with an overactive parasympathetic NS presenting with worsening urinary incontinence what is the drug of choice?
- mAChR antagonist
- Will cause relaxation and inhibit bladder contraction
How is activation of the mAChR’s able to cause trigone and sphincter relaxation?
- Normally associated with contraction of smooth muscle
- BUT, also leads to vasodilation due to release of nitric oxide (NO)
What are adverse effects that may be seen after treatment with a non-selective mAChR antagonist?
Constipation, dry mouth/eyes, dizziness, and blurred vision
Why does the administration of non-selective mAChR antagonists lead to blurred vision?
- Contraction of the ciliary muscle of eye is PNS mediated (cholinergic)
- Loss of contraction of ciliary muscle = lens stays flat = decreased abillity to focus and loss of near vision
A patient presents with worsening COPD, what type of drug is best in this situation?
- A mAChR antagonist
- Will block the contraction of the bronchial smooth muscle
Tiotropium is an inhaled (mAChR antagonist), what is a common side effect of this drug?
- Decreased mucus production
- You are blocking a parasympathetic receptor, remember, the PNS is responsible for rest and digest!
A patient has a positive fractionated free metanephrine test and a 24-hour urine specimen supports this dx; what is the patients condition?
- Pheochromocytoma
- An endocrine tumor that secretes catecholamines
The patient with a pheochromocytoma presents with headache, increased perspiration, palpitations, and a significantly increased BP, what drug should be used to decrease the BP?
Alpha-1 antagonist
The patient with a pheochromocytoma presents with headache, increased perspiration, palpitations, and a significantly increased BP, an antagonist of which receptor will most likely reduce her HR?
Beta-1 receptor antagonist
The patient with a pheochromocytoma presents with headache, increased perspiration, palpitations, and a significantly increased BP,after administration of a beta-receptor selective antagonist (propranolol) what do you expect to happen and why?
- Worsening of HTN
- This is known as unopposed alpha stimulation
- Since the pheochromocytoma is secreting catecholamines, you must block both the alpha and beta receptors.
- Only blocking the beta receptor will slow down the heart rate, but the BP will likely increase due to catecholamines acting on the alpha-1 receptor.
How does Clonodine work and what are the affects in a patient with a pheochromocytoma?
- A centrally-acting alpha-2 receptor agonist
- Activates central pre-synaptic alpha-2 receptors and suppresses the release of catecholamines
- Has NO EFFECT on patient with pheochromocytoma
A patient who presents with symptoms of an overactive sympathetic nervous system (i.e., pupils fixed/dilated, increased HR, delirium, cutaneous vasodilation, and high fever), how can you account for the high fever?
- Inhibition of mAChR’s
- The sympathetic NS uses ACh to induce sweating in an attempt to decrease body temperature
- If this receptor is inhibited you will see an increase in body temperature
A patient who presents with symptoms of an overactive sympathetic nervous system (i.e., pupils fixed/dilated, increased HR, delirium, cutaneous vasodilation, and high fever), marked cutaneous vasodilation is noted upon PE, which agent is most appropriate to use in this situation?
- Acetylcholinesterae inhibitor
- We want to block the enzyme that breaks down ACh since we need more ACh in this patient
What drugs would be used in a patient with Atony of the Bladder (AKA inability to urinate due to lack of muscle tone)?
- Direct-acting cholinergic agonist
- Indirect-acting cholinergic agonist
*Will lead to smooth muscle contraction, by acting on the mAChR’s
What is the receptor for the parasympathetics found on cardiac muscle?
mAChR M2
If a patient is exhibitng CNS symptoms and you want to give a drug to correct this, what is an important characteristic of the drug that needs to be considered?
The drug needs to be uncharged, so that it can cross the BBB
What is Myasthenia Gravis and what drug is given to treat?
- Autoimmune disease where antibodies are made that affect nAChR’s in skeletal muscle
- We give an AChE inhibitor, which increases ACh, and helps to activate the reduced number of receptors!
A 29 yo male presents to the ED unconcious w/ nonreactive, pinpoint-sized pupils, massive oral foaming, and muscle fasciculation. His pants are wet with urine and feces. What receptor family is most likely involved in his presenting symptoms?
A. Adrenergic
B. Cholinergic
C. GABA
D. Glutamate
E. Opioid
B) Cholinergic
*These presenting symptoms are clearly parasympathetic mediated
A 29 yo male presents to the ED unconcious w/ nonreactive, pinpoint-sized pupils, massive oral foaming, and muscle fasciculation. His pants are wet with urine and feces. An agent from which drug class was most likely ingested?
A) AChE inhibitor
B) Beta-blocker
C) Centrally acting alpha-2 receptor agonist
D) mAChR agonist
E) mAChR antagonist
A) AChE inhibitor
*The muscle fasciculations are the key symptom here. There are no mAChR’s on skeletal muscle
If a patient presents with symptoms indicative of overactive parasympathetic NS with muscle fasciculations, you need to think about an overdose of what; what kind of drug is given in this situation?
- Need to think about ingestion of an AChE inhibitor
- We give mAChR antagonists (atropine) to these patients, which will help manage all the sx’s, except for the muscle fasciulations.
- We don’t give a drug that is a nAChR antagonist
A 46 yo female presents complaining of dry eyes and a dry mouth. Her sx’s have been present for the past 6 months and have progressively worsened. She saw an opthamologist 3 months ago and has been using artifical tears with little relief. She often has to wake up in the night to drink water and frequenly has to drink to help her swallow food. She experiences the feeling of grit or sand in her eyes on a daily basis?
Which agent is most appropriate in this situation?
A) AChE inhibitor
B) AChE regenerator
C) Charged mAChR antagonist
D) mAChR agonist
E) Uncharged mAChR antagonist
D) mAChR agonist
- A pure mAChR will be more selective towards the effects we want in this patient
- An AChE inhibitor would help too, but would also be producing unwanted side effects since it acts at the nAChR’s as well.
