Autonomic Nervous System

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The Autonomic Nervous System consists of which two sub components?

Sympathetic Nervous System and the Parasympathetic Nervous System

List the neurotransmitter found in the Parasympathetic Nervous System

Acetylcholine

List the neurotransmitters found in the Sympathetic Nervous System

Acetylcholine, Norepinephrine, Epinephrine

List the neurotransmitters found in the Somatic Nervous System

Acetylcholine

What neurotransmitter is found in both the Sympathetic Nervous System and the Parasympathetic Nervous System?

Acetylcholine

The ANS uses what 3 neurotransmitters?

Acetylcholine, Norepinephrine, Epinephrine

Explain the somatic (motor) nervous system in terms of neurotransmitters made and released by the nerves?

Motor neurons release ACh to excite and cause skeletal muscle fibers to contract (voluntary control; note that baroreceptor reflexes are controlled by the ANS)

Where is Acetylcholine released?

- All PNS preganglionic and postganglionic neurons
- All SNS preganglionic neurons and most SNS postganglionic neurons to sweat glands
-All motor neurons to skeletal muscles

Where is Norepinephrine released?

Released by most postganglionic neurons of the Sympathetic Nervous System (except those that innervate sweat glands)

Where is Epinephrine released?

Released by Adrenal Medulla (when stimulated by ACh released by Sympathetic Nervous System pre-ganglionic neurons)

List 3 clinical uses of anticholinesterase drugs? Name drugs with clinical use.

Myasthenia Gravis therapy (with Neostigmine [Prostigmin] or Edrophonium [Tensilon])

Alzheimer's disease therapy (with Donepezil [Aricept])

Glaucoma therapy with Echothiophate (phospholine iodide)

Do anticholinesterase drugs increase or decrease the amount of acetlycholine at the synapse?

Include MOA in answer

They increase the amount of acetylcholine at the synapse
MOA: Inhibit AchE (acetylcholinestrase), the enzyme that degrades acetylcholine

List non clinical uses for anticholinesterase drugs

Malathion (insecticide), sarin (nerve gas)

Discuss clinical uses of antimuscarinic drugs and list common clinical uses

MOA: block muscarinic receptors

Mneumonic - AAAMIBO

Asthma
Anti-parkinson
Antispasmodic
Motion Sickness
Incontinence (OAB)
Bradyarrhythmias
Opthalmology

What receptor selectivity is most useful for treatment of overactive bladder?

M3 (Muscarinic subtype)

What is Tolterodine [Detrol] used for?

MOA: non-selectively blocks M2 and M3 receptors
Clinical Use: Overactive Bladder Therapy (OAB)

What is Oxybutynin [Ditropan] and Darifenacin [Enablex] used for?

MOA: selectively blocks M3 receptors (highly selective) .
Clinical Use: Overactive Bladder Therapy (OAB)

What is the MOA of nicotine, include where they can be found?

MOA: Depending on the dosage: activate nicotine receptors (low dosage) or inhibits (high doses) them at several sites (autonomic ganglia and adrenal medulla; carotid body; aortic arch and CNS)

Nicotine receptors can also be found in the somatic motor system; neuromuscular junctions

Mneumonic - AAACC

What effect does nicotine have on the CNS?

•CNS stimulant
- Multiple psychological effects: facilitate memory, suppress appetite
- Moderate can cause tremor, and high doses can cause convulsions

What effect does nicotine have on the Cardiovascular system?

•Results from the activation of nicotine receptors in ganglia of SNS and adrenal medulla
-Elicits discharge of epinephrine from the adrenal medulla
-Vasoconstriction = Increase in BP and HR
-These effects underlie cardiovascular
death

What effect does nicotine have on the GI system?

•Results from the activation of nicotinic receptors in ganglia
- Increase GI tone and can promote vomiting

MOA of botulinum toxin (botox)

What produces it?

Produced by Clostridium botulinum
MOA: Act pre-synaptically --> inhibit Ach release at the NMJ --> cause temporary local paralysis of injected muscle (Effects last weeks to several months)

Clinical uses of botulinum toxin (botox)

1) Strabismus (disorder of vision due to a deviation from normal orientation of one or both eyes so that both cannot be directed at the same object at the same time; squint; crossed eyes)
2) Severe primary axillary hyperhidrosis (excessive sweating)
3) Cervical dystonia (abnormal tone of tissue)
4) Prevention of chronic migraines,
5) OAB associated with a neurological condition

Under FDA investigation for several disorders: Limb muscle pain, Back pain

Cosmetic Use: Treat frown lines between the brows

The Central Nervous System consists of what two sub components?

Brain and the Spinal Cord

The Peripheral Nervous System consists of what two sub components?

Somatic (Motor) Nervous System and the Autonomic Nervous System

Name 3 Reversible Anticholinesterase Drugs

Neostigmine [Prostigmin], Edrophonium [Tensilon], Donepezil [Aricept]

Name 1 Irreversible Anticholinesterase Drug

Echothiophate (phospholine iodide)

Catecholamines Drugs are also called?

Sympathomimetic drugs

Epinephrine

1) Targeted Receptors
2) Effect on Body
3) Clinical Uses

binds to alpha1, alpha2, beta1, beta2
beta1 → cardiac stimulation (@ the heart)
beta2 → bronchodilation (@ the lungs)
alpha → constriction of arterioles

Clinical Use: Acute hypersensitivity reactions [EpiPen], cardiac stimulant, in combination w/local anesthetics (the addition of epinephrine is useful to prolong the duration of anesthesia

Norepinephrine [Levophed]

1) Targeted Receptors
2) Effect on Body
3) Clinical Uses

binds to alpha1, alpha2, beta1

alpha → vasoconstriction
beta1 → cardiac stimulation

Clinical Use: hypotensive state, cardiac arrest

Dopamine

1) Targeted Receptors
2) Effect on Body
3) Clinical Uses

binds to alpha1, beta1, dopamine receptors

MOA: stimulates dopamine receptors → vasodilation of renal and mesenteric arteries

Clinical Use: hypotension and shock

Isoproterenol

1) Targeted Receptors
2) Effect on Body
3) Clinical Uses

Beta selective
beta1 → cardiac stimulation
beta2 → brochodilation

Clinical Use: Increases contractility and cardiac output in hypotension, surgery, congestive heart failure (CHF), and cardiac arrest

Dobutamine

1) Targeted Receptors
2) Effect on Body
3) Clinical Uses

Beta selective (since it binds selectively to beta receptors, there are less AE)
beta1 - cardiac stimulation
(some alpha1)

Clinical Use: Increases contractility and cardiac output in hypotension, surgery, congestive heart failure (CHF), and cardiac arrest

Name 2 Beta Selective Adrenergic Neurotransmitters

Isoproterenol
Dobutamine

Epinephrine can activate which adrenergic receptors?

Epinephrine can activate all alpha and beta receptors, but not dopamine receptors

Norepinephrine can activate which adrenergic receptors?

Norepinephrine can activate alpha1, alpha2, and beta1 receptors, but not beta2 or dopamine receptors

Dopamine can activate which adrenergic receptors?

Dopamine can activate alpha1, beta1, and dopamine receptors

Which neurotransmitters can activate dopamine receptors?

Dopamine

Explain the pharmacodynamics of norepineprhine (slide on the powerpoint)

Tyrosine (tyrosine hydroxylase) --> DOPA (DOPA decarboxylase) --> Dopamine (dopamine beta hydroxylase) --> norepinephrine (MAO and COMT)

- Stored in storage vesicules
- Released following depolarization
- Inactivated by Monoamine oxiade (MAO) and COMT or uptake into vesicles for reuse

Alpha1 Receptors respond to which neurotransmitters?

Epinephrine, Norepinephrine, Dopamine

Alpha2 Receptors respond to which neurotransmitters?

Epinephrine, Norepinephrine

Beta1 Receptors respond to which neurotransmitters?

Epinephrine, Norepinephrine, Dopamine

Beta2 Receptors respond to which neurotransmitter?

Epinephrine

Alpha1 receptors are useful for what?

vasoconstriction of arterioles; ejaculation; bladder neck + prostate contraction

Alpha2 receptors are useful for what?

minimal clinical significance, located in presynaptic junction

Beta1 receptors are useful for what?

heart: ↑HR, ↑force of contraction, ↑ velocity of AV nodes conduction
kidney: renin release

Beta2 receptors are useful for what?

bronchial dilation; uterine muscle relaxation; vasodilation; glycogenolysis

Which Andrenergic Agonist(s) is most useful for Hypotension?

dopamine-selective
β₁-selective
α₁-selective (some)

Dobutamine
Isoproterenol
Norepinephrine[Levophed]
Dopamine

Which Andrenergic Agonist(s) is most useful for Cardiac Stimulation?

β₁-selective
α₁ -selective (some)

Epinephrine
Norepinephrine
Dobutamine
Isoproterenol

Which Andrenergic Agonist is most useful for Bronchodilation?

β₂-selective

Which Andrenergic Agonist is most useful for Uterine Relaxation?

β₂-selective

Which Andrenergic Agonist is most useful for Decongestants?

α₁-selective
Phenylephrine

What three classes of drugs are used to treat glaucoma? List drug with class!

Cholinergic Drugs - Pilocarpine
Anticholinesterase Drugs - Echothiophate (phospholine iodide)
Adrenergic Receptor Beta Antagonist (B-blockers) Drug - Timolol [Timoptic]

What classes of drugs are used to treat Hypertension? List drugs with class! Which one is an agonist?

Sympathomimetic drugs: Non-Catecholamines a. Clonidine[Catapres] *** this is the only agonist ***


Adrenergic Receptor: alpha-Antagonists → alpha1 selective antagonists
Prazosin [Minipres]
Terazosin [Hytrin]

Adrenergic Receptor beta-Antagonists: beta blockers
Nonselective beta1 and beta2 → Propanolol [Inderal]
Selective beta1 → Metoprolol [Lopressor]
Partial agonist → Pindolol
Non-selective Beta-blockade with Alpha-blockade → Labetrolol

What class of drugs are used to treat Benign Prostatic Hypertrophy? List drugs with class!

Adrenergic Receptor: alpha-Antagonists → alpha1 selective antagonists
Tamsulosin[Flomax]
Finasteride[Proscar 5mg]

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