What is the NT and receptors for the Parasympathetics?
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?
All post-ganglionic parasympathetics utilize what NT?
What are the 3 cholinergic receptors that are GPCR, Gq/11; what cascade results from activation of these receptors?
* 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?
* 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
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
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
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?
- 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?
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.