Pharmacology - Autonomic Drugs Part 1 Flashcards
From which regions of the central nervous system do parasympathetic nerves originate?
Cranial and sacral regions
From which regions of the central nervous system do sympathetic nerves originate?
Thoracic and lumbar regions
What types of nerves arise from the spinal cord and innervate skeletal muscle directly?
Somatic nerves
How many neurons are involved in parasympathetic transmission from the spinal cord to the target organ?
2
True or False? Craniosacral parasympathetic axons synapse on neurons in the peripheral ganglia.
True
What neurotransmitter mediates parasympathetic nervous system function?
Acetylcholine
What neurotransmitter receptor mediates parasympathetic nervous system function at the peripheral ganglia?
Nicotinic acetylcholine receptors
What neurotransmitter receptor mediates parasympathetic tone in the cardiac muscle?
Muscarinic acetylcholine receptors (specifically, M2)
What neurotransmitter receptor mediates parasympathetic tone in the smooth muscle?
Muscarinic acetylcholine receptors (specifically, M3)
What neurotransmitter receptor mediates parasympathetic tone in the glandular cells?
Muscarinic acetylcholine receptors (specifically, M1 and M3)
Somatic nerves that arise from the spine innervate skeletal muscle. What neurotransmitter receptor, which is located on skeletal muscle, receives this input?
Nicotinic acetylcholine receptors
How many neurons are involved in sympathetic transmission from the spinal cord to the target organ?
2
Where is the first synapse after the spinal cord in sympathetic innervation of an organ?
Preganglionic sympathetic axons synapse on neurons in the paravertebral ganglia
True or False? Preganglionic sympathetic axons synapse on neurons in the peripheral ganglia.
False; preganglionic sympathetic axons synapse on neurons in the paravertebral ganglia
At the paravertebral ganglia, the neurotransmitter _____ acts on _____ receptors to mediate sympathetic nervous system function.
Acetylcholine; nicotinic acetylcholine
What neurotransmitter mediates sympathetic nervous system function at the sweat glands?
Acetylcholine
What neurotransmitter receptor mediates sympathetic nervous system function at the sweat glands?
Muscarinic acetylcholine receptors
What neurotransmitter mediates sympathetic tone in the cardiac muscle, smooth muscle, and glandular cells?
Norepinephrine
What are four cell types in which α- and β-adrenergic receptors mediate sympathetic tone?
Cardiac muscle, smooth muscle, glandular cells, and terminal ends of neurons
What neurotransmitter mediates sympathetic tone in the renal vascular smooth muscle?
Dopamine
What neurotransmitter receptor mediates sympathetic tone in the renal vascular smooth muscle?
D1 receptors
What two substances are released into the blood from the adrenal medulla after the activation of the sympathetic nervous system?
Epinephrine and norepinephrine
How many synapses are involved in activation of the adrenal medulla?
One; the adrenal medulla releases epinephrine and norepinephrine into the blood
Are nicotinic acetylcholine receptors ligand-gated sodium-potassium channels or G-protein coupled receptors?
Nicotinic receptors are ligand gated sodium-potassium channels
Are muscarinic acetylcholine receptors ligand-gated sodium-potassium channels or G-protein-coupled receptors?
Muscarinic acetylcholine receptors are G-protein-coupled receptors that act through second messengers
To what class of G-proteins are α1-receptors linked?
q
To what class of G-proteins are α2-receptors linked?
i
To what class of G-proteins are β1-receptors linked?
s
To what class of G-proteins are β2-receptors linked?
s
To what class of G-proteins are M1-receptors linked?
q
To what class of G-proteins are M2-receptors linked?
i
To what class of G-proteins are M3-receptors linked?
q
To what class of G-proteins are D1-receptors linked?
s
To what class of G-proteins are D2-receptors linked?
i
To what class of G-proteins are H1-receptors linked?
q
To what class of G-proteins are H2-receptors linked?
s
To what class of G-proteins are V1-receptors linked?
q
To what class of G-proteins are V2-receptors linked?
s
What are the major effects of α1-receptor activation?
It increases vascular smooth muscle contraction, and increases pupillary dilator muscle contraction (mydriasis)
What are the major functions of α2-receptor activation?
It decreases sympathetic outflow and decreases insulin release
What are the major functions of β1-receptor activation?
It increases heart rate and contractility, increases renin release from the kidneys, and increases lipolysis of adipose tissue
What is the major function of β2-receptor activation on the body’s vasculature?
Vasodilation
What is the major function of β2-receptor activation on the respiratory system?
Bronchodilation
What effect does β2-receptor activation have on glucagon release?
It increases glucagon release
Where are M1-receptors located?
The central nervous system
What effect does M2-receptor activation have on cardiac function?
It decreases heart rate and contractility
What are the effects of M3-receptor activation?
Increased exocrine gland secretions, gut peristalsis, bladder contraction, bronchoconstriction, miosis, and accommodation
What effect does D1-receptor activation have on renal vasculature?
It relaxes renal vascular smooth muscle
What are the effects of H1-receptor activation?
Pruritis, pain, nasal and bronchial mucus production, contraction of bronchioles
What is the effect of H2-receptor activation?
It increases gastric acid secretion
What effect does V1-receptor activation have on vascular smooth muscle?
It increases vascular smooth muscle contraction
The activation of what two types of G-protein-coupled receptors can increase vascular smooth muscle contraction? Which receptors mediate vascular relaxation?
α1- and V1-receptors increase contraction; relaxation is mediated by β2, and D1 (renal only)
What is the effect of V2-receptor activation? Where are they located?
It increases water permeability and reabsorption in the collecting tubules of the kidney
What five types of receptors are coupled with Gqproteins?
α1, M1, M3, H1, and V1
What five types of receptors are coupled with Gsproteins?
β1, β2, D1, H2, and V2
What three types of receptors are coupled with Giproteins?
a2, M2, and D2
What enzyme is activated directly downstream of Gq-coupled receptors?
Phospholipase C
What enzyme is activated directly downstream of Gs-coupled receptors?
Adenyl cyclase
What enzyme is inhibited directly downstream of Gi-coupled receptors?
Adenyl cyclase
Adenyl cyclase catalyzes the conversion of adenosine triphosphate into what molecule?
cAMP
What final effector enzyme is activated by receptors that are coupled with Gsproteins?
Protein kinase A
What final effector enzyme is inhibited by receptors that are coupled with Giproteins?
Protein kinase A
Phospholipase C catalyzes the cleavage of membrane lipids into what molecules?
Inositol trisphosphate3 and diacylglycerol
What is the effect of increased inositol triphosphate on the intracellular concentration of calcium?
It increases the intracellular calcium concentration
What enzyme is activated by diacylglycerol?
Protein kinase C
What pharmacologic agent blocks the uptake of choline into cholinergic nerve terminals?
Hemicholinium
What enzyme is responsible for the formation of acetylcholine? What are its two substrates?
Choline acetyltransferase; Acetyl-CoA and choline
What pharmacologic agent blocks the transport of acetylcholine into the presynaptic vesicles in nerve terminals?
Vesamicol
The entry of what ion into the nerve terminal induces the release of acetylcholine into the synaptic cleft?
Calcium
What toxin inhibits the calcium-induced release of acetylcholine from the cholinergic nerve terminals?
Botulinum
What enzyme breaks down acetylcholine in the synaptic cleft? What two products result from this reaction?
Acetylcholinesterase; choline and acetate
Tyrosine transporters are located in the nerve terminals of what type of cells?
Noradrenergic cells; tyrosine is the precursor of norepinephrine
Tyrosine is a precursor to the formation of which neurotransmitters? What is the order of their synthesis?
Tyrosine, DOPA, dopamine, norepinephrine, epinephrine
What pharmacologic agent blocks the conversion of tyrosine to DOPA?
Metyrosine
Tyrosine is converted into dopamine via what intermediate precursor?
DOPA; DOPA can be used as a pharmacologic agent to increase central nervous system dopamine
What pharmacologic agent blocks the transport of dopamine into the presynaptic vesicles in nerve terminals?
Reserpine
Dopamine is converted into norepinephrine in the ______ (cytoplasm/presynaptic vesicle).
Presynaptic vesicles
The entry of what ion into the nerve terminal induces the release of norepinephrine into the synaptic cleft?
Calcium
What pharmacologic agent inhibits the calcium-induced release of norepinephrine from the noradrenergic nerve terminals?
Guanethidine
What pharmacologic agent stimulates the release of norepinephrine from the noradrenergic nerve terminals?
Amphetamine
How is norepinephrine cleared form the synaptic cleft?
Diffusion, metabolism (monoamine oxidase A), and reuptake
What pharmacologic agents inhibit the reuptake of norepinephrine into the nerve terminals?
Cocaine, amphetamine, and tricyclic antidepressants
What three receptor types modulate the presynaptic release of norepinephrine from the noradrenergic nerve terminals?
M2-receptors, angiotensin II receptors, and α2-receptors
What effect does the activation of α2-receptors in presynaptic sympathetic nerve terminals have on norepinephrine release?
It inhibits norepinephrine release
What effect does the activation of angiotensin II receptors in presynaptic sympathetic nerve terminals have on norepinephrine release?
It stimulates norepinephrine release
What effect does the activation of M2-receptors in presynaptic sympathetic nerve terminals have on norepinephrine release?
It inhibits norepinephrine release
The norepinephrine-mediated activation of α2-receptors on presynaptic sympathetic nerve terminals is an example of a mechanism of what type of feedback?
Negative feedback
Name four direct cholinergic agonists.
Bethanechol, carbachol, pilocarpine, methacholine
What is the clinical application of bethanechol?
Treatment of postoperative and neurogenic ileus and urinary retention (remember: Beth Anne, call (bethanechol) me if you want to activate your Bowels and Bladder)
What is the mechanism of action of bethanechol?
Bethanechol is a direct cholinergic agonist resistant to acetylcholinesterase that works on receptors in the bowel and bladder
What two direct agonist cholinomimetic drugs can be used to treat glaucoma?
Carbachol and pilocarpine
Carbachol and pilocarpine are effective for the treatment of open-angle glaucoma because they activate what muscle?
The ciliary muscle of the eye
What is a methacholine challenge test?
A test in which methacholine is inhaled to stimulate muscarinic receptors and induce bronchoconstriction to diagnose asthma
Pilocarpine is effective for the treatment of narrow-angle glaucoma because it activates what muscle?
The pupillary sphincter
True or False? Pilocarpine is susceptible to acetylcholinesterase.
False; pilocarpine is resistant to acetylcholinesterase
Name five indirect cholinergic agonists.
Neostigmine, pyridostigmine, edrophonium, physostigmine, echothiophate
What are the clinical indications for use of neostigmine?
The treatment of postoperative and neurogenic ileus
True or False? The treatment of myasthenia gravis is a clinical application of pyridostigmine.
True
Which anticholinesterase is used to diagnose myasthenia gravis? Why?
Edrophonium; the effects last for minutes and if weakness is transiently reversed it is diagnostic of myasthenia gravis
True or False? The treatment of glaucoma is a clinical application of physostigmine.
True (remember: “PHYS is for the EYES”)
Which pharmacologic agent is used to treat atropine overdose?
Physostigmine, because it crosses the blood-brain barrier and is able to reverse central nervous system as well as peripheral nervous system effects
What is the clinical indication for use of echothiophate?
The treatment of glaucoma
Indirect cholinergic agonists increase endogenous acetylcholine by inhibiting what enzyme?
Acetylcholinesterase
Why is pyridostigmine used to treat myasthenia gravis?
It increases the amount of acetylcholine in the neuromuscular synapse, thereby increasing muscle strength
What effect does neostigmine have on the central nervous system?
None; it does not penetrate the blood-brain barrier (remember: NEO CNS = NO CNS)
What is the clinical application and mechanism of action of topical atropine, homatropine, and tropicamide?
These drugs antagonize muscarinic receptors in the eye to produce mydriasis and cycloplegia
What is the mechanism and clinical application for benztropine?
It is a muscarinic antagonist used to reduce symptoms of Parkinson’s disease
What is the mechanism and clinical application for scopolamine?
It is a muscarinic antagonist used to treat motion sickness
What is the mechanism and clinical application for ipratropium?
It is a muscarinic antagonist used to treat asthma and chronic obstructive pulmonary disease (remember: I PRAY I can breathe soon!)
What is the mechanism and clinical application for methscopolamine?
It is a muscarinic antagonist used to treat peptic ulcers
What is the mechanism and clinical application for oxybutynin?
It is a muscarinic antagonist used to reduce urgency in mild cystitis and reduce bladder spasms
What is the mechanism and clinical application for glycopyrrolate?
It is a muscarinic antagonist used to reduce urgency in mild cystitis and reduce bladder spasms
What is the mechanism and clinical application for pirenzepine?
It is a muscarinic antagonist used to treat peptic ulcers
What is the mechanism and clinical application for propantheline?
It is a muscarinic antagonist used to treat peptic ulcers
Which muscarinic antagonist can be used to reduce urgency in patients with mild cystitis?
Oxybutynin (also glycopyrrolate)
Which muscarinic antagonist is most commonly used to treat motion sickness?
Scopolamine
Which muscarinic antagonist can be used to treat bladder spasms?
Oxybutynin (also glycopyrrolate)
You recently prescribed haloperidol to your patient to treat his schizophrenia, but he has since developed Parkinson’s-like motor adverse effects. What drug could you add to his regimen to treat this?
Benztropine
Atropine is used for therapeutic effect in which four organ systems?
Eyes, gastrointestinal system, respiratory system, urinary system
What are the two effects of atropine on the eye?
Pupil dilation, cycloplegia
What is the effect of atropine on the airway mucosa?
It decreases secretions
What is the effect of atropine on the stomach?
It decreases acid secretion
What is the effect of atropine on gastrointestinal motility?
It decreases motility
What is the effect of atropine on the bladder in a patient with cystitis?
It decreases urgency
A patient affected by botulinum toxin will be affected at which neurotransmitter/receptor group(s)?
Botulinum toxin affects all neurotransmitter/receptor groups that have acetylcholine as the neurotransmitter
