Quiz 1 Exam 3 Flashcards
(229 cards)
1
Q
What is a muscarinic agonist?
A
This is a drug that activates the parasympathetic nervous system as this system uses Ach that binds to muscarinic receptors on effector organs. It can also act on sweat glands controlled by the sympathetic system as they have muscarinic receptors.
2
Q
What are the main sites that can be affected by muscarinic drugs?
A
- Parasympathetic innervated effectors organs
- Sweat glands innervated by sympathetic system
- Endothelial cells that contain muscarinic receptors but are not innervated by the parasympathetic system
3
Q
What are the two categories of muscarinic drugs?
A
Choline esters and Natural Alkaloids
4
Q
What are the 4 main muscarinic agonists categorized as choline esters?
A
Acetylcholine, Methacholine, Carbachol, and Bethanechol
5
Q
What are the 3 main muscarinic agonists categorized as natural alkaloids?
A
Muscarine (don’t need to know this)
Cevimeline, Arecoline, and Pilocarpine
CAP!
6
Q
Can choline esters, a category of muscarinic agonist, pass the BBB?
A
No because they are hydrophilic/charged.
7
Q
Do natural alkaloids, like Pilocarpine, enter to BBB? Are they metabolised by acetycholinesterases?
A
Yes they go enter the BBB and they are not metabolized by acetylcholinesterase enzyme for breakdown.
8
Q
What would be some effects to the body of a muscarinic agonist?
A
SLUDD and the 3Ds. Overall, it would depend on affinity for different receptors but in a general sense.
Salivation, Lacrimation, Urination, Digestion, Defecation, decrease heart rate, decrease bronchodilation, and decrease pupil size.
9
Q
What are the effects of the cardiovascular system with a muscarinic agonist?
A
- Reduction in heart rate via M2 receptor
- Reduction in peripheral resistance via M3 receptor presence mediated by nitric oxide
10
Q
What would be the response to LOW doses of acetylcholine (muscarinic agonist)?
A
Vasodilation and reflexive arc trigger to increase heart rate due to baroreceptors sensing decreased blood pressure.
11
Q
What would be the response to HIGH doses of acetylcholine?
A
Bradycardia and hypotension (remember, parasympathetic does NOT innervate the vessels but muscarinic receptors are present)
12
Q
What would be the effects to the respiratory system with a muscarinic agonist?
A
Bronchoconstriction and increased secretion via the M3. No clincial use for this.
13
Q
Why is the ciliary epithelium of the eye clinically relevant?
A
It secretes the aqueous humor in the eye which increases with glaucoma.
14
Q
What happens in the eye when a muscarinic agonist is given?
A
- Sphincter muscle constricts causing miosis/pupil constriction via M3
- Ciliary muscles constricts allowing for near vision and outflow of aqueous humor liquid reducing intraocular pressure via M3
15
Q
The internal sphincter of the bladder is primarily controlled by which ANS route?
A
Sympathetic and overall functions to relax the bladder muscle (detrusor) and close sphincter to inhibit urination.
16
Q
The external sphincter of the bladder is primarily controlled by which ANS route?
A
Parasympathetic and overall functions to constrict bladder muscle (detrusor) and open sphincter to promote urination.
17
Q
What would a muscarinic agonist due to urination?
A
It would promote urination via M3 receptors by contracting the bladder muscle (detrusor) and opening up the external sphincter.
18
Q
What would a muscarinic agonist due to secretory glands?
A
It would promote secretions by sweat glands, lacrimal glands, salivary glands, gastric glands, and nasopharyngeal glands.
19
Q
What would a muscarinic agonist due to the GIT?
A
It would stimulate increased secretions and motor activity as well as relax sphincters of the GIT via M3.
20
Q
What are the 6 main clinical uses of muscarinic agonists?
A
- Post-op urinary retention and bowl paralysis
- Xerostomia (dry mouth) for radiation to head and neck or Sjogren’s syndrome
- Glaucoma to enhance aqueous humor drainage
- Miotic agent to help with near vision
- Diagnostic tool for bronchial airway hyperactivity (methacholine inhalation)
- Antimuscarinic drug intoxication due to overdose of atropine (muscarinic antagonist) or tricyclic antidepressants
21
Q
What is the drug methacoline?
A
This is muscarinic agonist categorized as a choline ester.
22
Q
What is methacholine used for?
A
This muscarinic agonist is used for diagnostic testing of bronchial airway hyperreactivity.
23
Q
What is the drug bethanechol?
A
This is a muscarinic agonist categorized as a choline ester. It is selective to the GIT and urinary tract.
24
Q
What is bethanechol used for?
A
Bethanechol is used for post-op urinary retention and abdominal distention.
25
What is the drug pilocarpine?
This is a muscarinic agonist categorized as a natural alkaloid. It is selective.
26
What is pilocarpine used for?
Pilocarpine is used for xerostomia (dry mouth) and in Sjogren's syndrome with reduced secretions, as well as a miotic agent and glaucoma for the eyes.
27
What is the drug cevimeline?
This is a synthetic muscarinic agonist. It is similar to pilocarpine and is approved for Sjogren's syndrome.
28
What are the symptoms of muscarinic agonist toxicity?
Overactivation of SLUDD and the 3Ds. Include nausea, vomiting, salivation, sweating, and bronchial constriction. Reversed with a muscarinic antagonist.
29
Are acetylcholinesterase inhibitors direct or indirect muscarinic agonist?
AChEase inhibitors are indirect muscarinic agonists as they stop the breakdown of acetylcholine increasing its concentration.
30
What are the main 3 pharmacological actions of acetylcholinesterase inhibitors?
1. Stimulates muscarinic receptors are effector organs
2. Stimulates muscarinic receptors after depression or paralysis of autonomic ganglion (nicotinic receptors)
3. Stimulation of cholinergic sites in the CNS
31
What are the differences among acetylcholinesterase inhibitor drugs?
They have differences in chemical and pharmacokinetics but NOT pharmacodynamics.
32
What are the 3 classes of acetylcholinesterase inhibitor drugs?
1. Alcohols (edrophonium)
2. Carbamic esters of alcohols (neostigmine)
3. Organophosphates/insecticides (malathion)
33
What are the reversible cholinesterase inhibitors?
Physostigmine, Neostigmine, Pyridostigmine,
Rivastigmine, Tacrine, Donepezil, Galantamine (alzheimer's)
Edrophonium
34
Out of these 3 reversible cholinesterase inhibitors, which one can pass the BBB and enter the brain?
Physostigmine, Neostigmine, Pyridostigmine
Physostigmine because it is not charged.
35
What are the two drug that are irreversible cholinesterase inhibitors?
Insecticides and nerve gases like malathion
36
Most of the effects between direct acting muscarinic agonists and indirect acting acetylcholinesterase inhibitors are the same. What is the effect on the cardiovascular system that is different between these two drug types?
AChEase inhibitors increase BOTH sympathetic and parasympathetic ganglia supply the heart (Ach binds at ganglion sites for both system so this makes sense). The parasympathetic effect dominantes so the heart rate and cardiac output decrease.
Additionally, AChease inhibitors no direct effect on blood vessels compared to muscarinic agonists which have receptors on blood vessels. However, moderate doses of AChease inhibitors increase vascular resistance due to activity at ganglion for sympathetic.
OVERALL, modest bradycardia, decreased cardiac output, and increases in vascular resistance causing increase in blood pressure.
37
Why do AChease inhibitors need to be monitored in Alzheimer's patient with hypertension?
AChease inhibitors increased blood pressure through its actions on the ganglion at the sympathetic system.
38
What are the 4 main conditions that acetylcholinesterase inhibitors are used for?
1. Atony of bladder and GIT
2. Glaucoma
3. Myasthenia gravis
4. Alzheimer's disease
39
What is the RX for myasthenia gravis, the autoimmune disorder causing degradation of the nicotinic m receptors at the neuromuscular junction?
Acetylcholinesterase inhibitor. This would increase the concentration of acetylcholine therefore increasing the likelihood that ACh could still bind to produce an effect.
39
What is the main hypothesis surrounding Alzheimer's disease that leads to the use of what 4 AChease inhibitor drugs?
The hypothesis states that there is a loss or cholinergic transmission in the brain which can be halted with anticholinesterase inhibitors to increase the amount of ACh in the synapse. These drugs include Tacrine, Donepezil, Rivastigmine, and Galantamine
39
What are the symptoms of pesticide organophosphate toxicity like malathion?
Organophosphates have similar effects to muscarinic agonist as they inhibit AChEase resulting in a higher concentration of acetylcholine. Therefore the effects would include overexxageration of SLUDD +3D responses. Includes miosis, salivation, sweating, bronchoconstriction, vomiting, and diarrhea.
40
How is insecticide organophosphate toxicity treated?
Treated with a muscarinic agonist like atropine.
40
A nerve gas like sarin is also an irreversible AChEase inhibitor. How is toxicity of this drug treated?
Pralidoxime. This is an AChEase reactivator. Specifically, it prevents aging which is the formation of the covalent bond between AChEase and the nerve gas.
41
What drug would be used prophylactically for nerve gas exposure?
Pyridostigmine. It would prevent the actions of nerve gas if exposed but would require atropine if exposure occured.
42
Woman undergoes abdominal surgery and develops an absence of bowel motility, severe bloating, and difficulty urinating. Mild cholinomimetic stimulation with bethanechol or neostigmine is often effective at relieving these complications. Bethanechol or neostigmine in moderate doses have significantly different effects on which of the following?
A. Gastric secretory cells
B. Vascular Endothelium
C. Salivary glands
D. Sweat glands
E. Ureteral tubes
B. Vascular Endothelium. Bethanechol is a muscarinic agonist and therefore can bind to muscarinic receptors present on vascular endothelium and induce dilation leading to hypotension. Neostigmine has little direct effect on blood pressure itselg but it is an AChEase inhibitor that works at all sites where acetylcholine is present include the sympathetic ganglion. This means at moderate doses, it will increase vascular resistance via sympathetic activation causing vasocontriction leading to hypertension.
43
A crop duster pilot has been accidently exposed to high concentrations of a highly toxic organophosphate insecticide. It untreated, the cause of death due to exposure would probably be...
A. Cardiac arrythmia
B. GIT bleeding
C. Heart failure
D. Hypotension
E. Respiratory failure
E. Respiratory failure. A nicotinic sites like in the ganglion, high doses initially stimulate then and then lead to depression and paralysis at autonomic ganglion. This would include both sympathetic and parasympathetic ganglion. Since the parasypathetic is the primary control of the lungs, that effector organ would eventually shut down if not treated.
44
A man has been diagnosed with dysautonomis (chronic idopathic autonomic insuffiencey). You are considering different therapies for his disease. Pyridostigmine and neostigmine may cause which of the following in this patient?
A. Bronchodilation
B. Cycloplegia
C. Diarrhea
D. Irreversible inhibition of acetylcholinesterase
E. Reduced gastric acid secretion
C. Diarrhea. Since pyridostigmine and neostigmine and AChEase inhibitors, they mostly act similar to muscarinic agonist as they increase the concentration of acetylcholine. Therefore it would induce the SLUDD + 3D responses like defecation which would include diarrhea. It would not induce bronchodilation it would induce bronchoconstriction. These are reversible inhibitors of AChEase and they also would increase GIT secretions.
45
Parasympathetic nerve stimulation and a low infusion of bethanechol will each...
A. Cause ganglion cell depolarization
B. Cause skeletal muscle end plate depolarization
C. Cause vasodilation
D. Increase bladder tone
E. Increase heart rate
D. Increase bladder tone. This also means to contract the bladder (detrusor) muscle. Bethanechol is a muscarinic agonist and the parasympathetic system is controls release of urine. It is possible for bethanechol to cause vasodilation but parasympathetic nerve stimulation would not do this as it does not actually innervate that vascular endothelium as it is under full control by the sympathetic system.
46
Actions and clincial uses of muscarinic cholinoceptor agonists include which one of the following?
A. Bronchodilation (treatment of asthma)
B. Miosis (treatment of glaucoma)
C. Decreased GIT motility (treatment of diarrhea)
D. Decreased neuromuscular transmission and relaxation of skeletal muscle (during surgical anesthesia)
E. Vasoconstriction
B. Miosis (treatment of glaucoma). Muscarinic agonist cause vasodilation via binding to M3 receptors on vascular endothelium.
47
What are the 4 main ganglionic blocker drugs?
1. **Mecamylamine**
2. Trimethaphan
3. D**- Tubocucarine**
4. **Succinylcholine**
5. Hexamethonium
48
What are ganglionic blocking drugs?
These are nicotinic antagonist as at the ganglion there are nicotinic n receptors. If we block the ganglion, we are blocking the nicotinic n receptors there.
49
What areas are effected by ganglionic blocking drugs?
As ganglionic blocking drugs are nicotinic antagonists, these would effect the parasympathetic system at the ganglion, it would effect the sympathetic system at the ganglion, and it would effect the neuromuscular junction where nicotinic m receptors are present.
50
What is the MOA of mecamylamine?
This is a ganglion blocker (nicotinic antagonist) that is a nondepolarizing, noncompetitive antagonist of ACh receptors in the brain and muscles.
51
What is the MOA of trimethophan?
This is a ganglion blocker (nicotinic antagonist) that is a nondepolarizing, competitive antagonist of the nicotinic acetylcholine receptors.
52
What is the MOA of hexamethonium?
This a long-acting ganglion blocker (nicotinic antagonist) that is nondepolarizing, mixed action antagonist of Ach receptors.
53
What are the two types of MOAs for ganglionic blockers?
1. Depolarizing blockade
2. Non-depolarizing blockade includes competitive, non-competitive, and mixed antagonists.
54
Which ganglionic blocker discussed is the only one that can cross the BBB?
Mecamylamine
55
What is the effect to the eye when a ganglion blocker is introduced?
Ganglion blockers are nicotinic antagonists. The predominant tone of the eye is parasympathetic. Blocking this results in the sympathetic taking over resulting in loss of near vision (cycloplegia) therefore far vision is induced. However, pupil size is not really effected but could result in moderate dilation (mydriasis).
56
# **
What is the effect on the genitourinary tract with a ganglionic blocker?
The predominant tone of the bladder is controlled by the parasympathic system. When inhibited, this would result in difficulty urinating due to sympathetic takeover. Additionally, both erection and ejaculation would be impacted and impaired as an erection is controlled by the parasympathetic and ejaculation is controlled by the sympathetic.
57
What happens in the cardiovascular system, both blood vessels and the heart, when a ganglionic blocker is introduced?
Ganglionic blockers are nicotinic antagonists. The blood vessels are dominated by the sympathetic system. Therefore addition of a ganglionic blocker would result in loss of tone resultin in vasodilation leading to hypotension. The heart is dominated by the parasympathetic so loss of this would result in tachycardia.
57
What is the effect of a ganglionic blocker on the GIT?
As the GIT is dominated by the parasympathetic system, blocking this would result in decreased tone, motility, and secretions.
58
What is the main effect to skeletal muscle neuromuscular junctions with the use of neuromuscular blocking agents like succinylcholine and d-tubocurarine?
Even though succinylcholine is a depolarizing non-competitive agent and d-tubocurarine is a non-depolarizing competitive agent at Nm receptors, they both block the action of acetylcholine at the nicotinic m receptors at the neuromuscular junctions causing **paralysis.**
58
What are the two clinically used ganglionic blocker drugs and what are they used for?
1. Mecamylamine- Blocks central nicotinic receptors as it can cross BBB and may be an adjuct therapy with transdermal nicotine patches for smoking cessation
2. Trimethaphan- Treatment of hypertensive crises and dissecting aortic aneurism as it procudes controlled hypotension
58
What is the treatment for toxicities of non-depolarizing competitive ganglion blockers (nicotinic antagonist) like trimethaphan and D-tubocurariene?
AChEase inhibitor like neostigmine. This would increase ACh concentrations to displace the blocker. It would be given with atropine (muscarinic antagonist) to reduce excess acetylcholine on muscarinic receptors producing intense SLUDD + 3D response.
58
What is the one non-depolarizing competitive nueromuscular blocking agent (nicotinic m receptor antagonist)?
D-tubocurarine
59
# **
What would be the effects to salivary and sweat glands with a ganglionic blocker?
Ganglionic blockers are nicotinic antagonists. Salivary glands are controlled by the parasympathetic while sweat glands are controlled by sympathetic. When these ganglion are blocked, salivary glands stop secreting and it results in xerostomia (dry mouth). It also results in decreased sweat secretions which results in anhidrosis (no sweat secretions).
59
What is the prototype antinicotinic (nictonic antagonist) agent?
Curare
60
What is the one depolarizing, non-competitive neuromuscular blocking agent (nicotinic m receptor antagonist)?
Succinylcholine
61
What enzyme is succinylcholine metabolized by ?
Pseudocholinesterase as it is more resistant to degradation by acetylcholinesterase.
62
What were the main 3 non-selective alpha adrenergic agonists discussed?
Oxymetazoline, Epi, and NE
(Note: Epi and NE also act on Beta but we will get to that later)
63
What were the main 2 alpha-1 agonists discussed?
Phenylephrine and Midodrine
64
What were the 3 alpha-2 agonists discussed in class?
Apraclonidine, Brimonidine, and clonidine
65
We know that alpha-1 receptors are located in the vasculature, but what receptor controls the blood vessels in the eyes?
a2A
66
What adrenergic receptors can be targeted in the eye for glaucoma?
a2
B1 and B2
67
What adrenergic receptor in the nose can be acted on to induce nasal decongestion?
a1
68
It is known that most alpha-2 receptors act as those presynaptic receptors in the nerve terminals. However, some can act on blood vessels in the _______ to induce blood vessel __________.
Eye
Contraction
69
What is the difference between direct and indirect adrenergic agonists?
Direct agonists will bind directly to receptors and induce transmitter release while indirect agonists block the reuptake of NE or Epi.
70
Alpha adrenergic receptors have the highest affinity for what?
Epi then NE then isoproterenol (b1, b2, b3 agonist)
71
If Isoproterenol binds, it is a _______ receptor.
Beta
71
Beta adrenergic receptors have the highest affinity for what?
Isoproterenol then EPI then NE
71
What often happens to receptors after taking a drug for a period of time?
Desensitization occurs in part to phosphorylation and internalization of receptors. The receptors are out of homeostasis due to overstimulation and internalize those receptors to stop being activated.
71
It is know that a2 is the big presynaptic receptor. However, drugs can act on the presynaptic brake to reduce blood pressure. Which drug does this?
Clonidine
71
How does clonidine reduce blood pressure even though it is an a2 receptor agonist?
Clonidine activates presynaptic a2 receptors which acts like a break to inhibit the release of NE in the synapse. This inhibition of NE release stops it from reaching circulation to produce hypertension.
71
It appears that increasing substituents on the amine group for sympathomimetic drugs increases it affinity for the _______ receptor.
Beta. Example of this is isoproterenol as it has a fairly large group attached to the amine.
71
It appears the removing hydroxyl (OH) groups from the ring structure of sympathomimetic drugs increases the selectivity for _______ receptors.
Alpha. It also decreases potency but makes it no longer a substrate for metabolism by COMT.
72
What are the effects of an a1 agonist like phenylephrine or midodrine on the cardiovascular system?
Phenylephrine and midodrine will cause vasoconstriction in the vasculature leading to hypertension. In response with the reflex arc, the heart rate will decrease. These drugs have no direct action on the heart. The decrease in heart rate is solely due to the body noticing the hypertension.
72
What is the one exception to a1 agonist induced hypertension not inducing the reflex arc to decrease heart rate?
Heart transplant
72
How do beta receptor agonists influence the cardiovascular system?
1. B1 (only in heart) agonists increase pacemaker activity (chronotropic), dromotropic (conduction velocity), and contractility (inotropic) to overall INCREASE HEART RATE
2. B2 (vasculature of skeletal muscle) agonists cause vasodilation leading to decrease in mean arterial pressure. DECREASE BLOOD PRESSURE
72
What happens to the cardiovascular system when a non-selective adrenergic agonist is given that acts on both beta and alpha receptors like EPI?
Both the heart rate will increase via beta1 and blood pressure will increase via alpha1 receptors.
72
If an a1 agonist like phenylephrine or midodrine is added as well as a ganglionic blocker like mecamylamine or trimethaphan, what would be the cardiovascular response?
The phenylephrine and midodrine would still act on the a1 receptor to induce vasoconstriction however, because the ganglionic blockers like mecamylamine and trimethaphan block the reflex arc between the spinal cord and parasympathetic (sympathetic too but parasympathetic decreases HR), there would be no changes in the heart rate.
73
What would be the result of adding phenylephrine to the eyes?
Phenylephrine is an alpha-1 agonist and pupil size is controlled by the alpha-1 receptor. This would result in pupil dilation (mydriasis).
73
What type of drug would be used for nasal decongestion?
An alpha agonist should be used. Oxymetazoline is the typical drug used in Afrin and that is non-selective for a1 and a2. The main receptors in the nose are a1.
73
What are the two mixed-acting sympathomimetics?
1. Ephedrine
2. Pseudoephedrine
73
What are the clinical uses for ephedrine?
Anti-asthmatic via B2 and decongestant via a1. It was banned by the FDA though.
74
What are the clinical uses for pseudoephedrine?
Decongestion via a1 and stress-induced incontinence via B3
74
What are the 2 very similar sounding drugs that act on both a1 and a2A that reduce eye redness by constricting blood vessels in the eye via a2A?
Oxymetazoline and Xylometazoline
74
What is the one non-selective beta agonist?
Isoproteronol
75
What receptor in the eye is activated to reduce redness via vascoconstriction?
a2A
76
What are the two beta-1 agonist?
**Dobutamine** and Prenalterol
77
What are the three beta-2 agonists?
**Albuterol**, salmeterol, and terbutaline
78
What is the one beta-3 agonist?
Mirabegron
79
What are the clinical functions of beta-2 selective agonists like albuterol, salmeterol, and terbutaline?
They vasodilate the bronchioles for treatment of asthma and relax the uterus in premature labor.
80
What structure/drug do bath salts look like?
Bath salts have a similar structure to amphetamines. Amphetamines stimulate NE release from the synapse.
81
What are the desired effects of bath salts seen?
Increased concentration, sexual performance, sociability, energy, and euphoria, with mild empathogenic effects.
82
What are the toxic/adverse effects of bath salts?
Loss of appetite
Trismus/ Bruxism (lock jaw/ teeth grinding)
Nausea
Muscle Aches
Ataxia
Sweating
Tachycardia
Insomnia
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
83
Does albuterol or salmeterol have a longer duration of action?
Salmeterol has a longer duration of action greater than 12 hours while albuterol lasts between 3-4 hours.
84
Why is epinephrine used for an anaphylactic reaction and not albuterol?
Epinephrine is a very non-selective adrenergic agonists meaning it will act on all those receptors to induce bronchodilation, vasoconstriction, increase cardiac output, and stimulate release of inflammatory mediators. Albuterol is beta-2 selective meaning it only bronchodilates and in cases of anaphylaxis, the body needs more help than that. It works well as an anti-asthmatic
85
What are some symptoms of an anaphylatic reaction?
Wheezing, SOB, swollen mouth, weak pulse. The allergic reactions leads to release of mediators from mast and basophils which cause this.
86
What are the beta-agonists that can be used as anti-asthmatics?
The non-selective beta agonists that can be used include isoproterenol and epinephrine. The beta-2 selective agonists include albuterol and terbutaline.
87
T or F: Beta agonists cannot be used as heart stimulants.
False. Non-selective or beta-1 agonists could be used to increase heart rate.
88
What receptor controls constricts the internal sphincter of the bladder
The a1 receptor constricts and inhibits urination in the bladder.
89
What receptor relaxes the detrusor muscle of the bladder to inhibit urination?
B3
90
What is the only FDA approved drug that aids in urinary incontinence?
Mirabegron. This is a beta-3 receptor agonist that relaxes the detrusor muscle to inhibit urination.
91
What adrenergic receptor is located on the liver? If activated, what would occur?
B2 is located in the liver. If activated, this would induce gluconeogenesis and glycogenolysis as we want to utilize energy for E type situations.
92
What are the main 3 clinical applications of alpha-1 agonists like phenylephrine and midodrine?
1. Orthostatic hypotension
2. Severe hemorrhage
3. Nasal decongestion
93
What are the main 2 clinical applications of alpha-2 agonists like clonidine, brimonidine, and apraclonidine?
1. Hypertension (via CNS)
1. Glaucoma
94
What adrenergic agonists is used primarily for nasal decongestion and red eyes?
Oxymetazoline which is a non-selective alpha agonist and therefore can also act on a2A
95
What is the main clinical application dobutamine?
This is a beta-1 agonist and is used for acute heart failure (increases HR to prevent further failure)
96
What drug acts on a1, a2, and b1?
Norepinephrine!
97
What drug acts on a1, a2, b1, b2, and b3?
Epinephrine
98
Which of the following are probable signs of the anaphylactic reaction to a bee sting?
A. Bronchodilation, tachycardia, hypertension, vomiting, and diarrhea
B. Bronchospasms, tachycardia, hypotension, and laryngeal edema
C. Diarrhea, bradycardia, and vomiting
D. Laryngeal edema, bradycardia, hypotension, and diarrhea
E. Miosis, tachycardia, vomiting, and diarrhea
B. Bronchospasms, tachycardia, hypotension, and laryngeal edema
Tachycardia may be due to histamine direct response on the heart.
99
A woman with impaired renal function and necrotic ulcer admitted to ER. She has long-standing T2D and you examine her retinas for possible vascular changes. Which of the following drugs is a good choice when pupillary dilation, but not cycloplegia, is desired?
A. Isoproterenol
B. Norepinephrine
C. Phenylephrine
D. Pilocarpine
E. Tropicamide
C. Phenylephrine. Use an a1 selective agonist because dilation of eye is mediated by the constriction of the radial muscle in the eye resulting in mydriasis done through a1 activation.
a2 agonist is the blood vessels of the eye. Do not get confused.
100
Man had a heart transplant. His current blood pressure is normal and his heart rate is fairly normal. Which of the following drugs would have the least effect on his heart rate?
A. Albuterol
B. Epinephrine
C. Isoproterenol
D. Norepinephrine
E. Phenylephrine
E. Phenylephrine. This drug targets the a1 receptors and would increase blood pressure and normally decrease heart rate in response through the reflex arc. However, this does not happen in those with a heart transplant.
Epinephrine acts on all adrenergic receptors so not this one. Isoproterenol acts on all beta receptors so not that. NE acts on a1, a2, and b1 so not that. Maybe albuterol since it is selective for beta2 but at high enough concentrations it could act on beta1 and increase heart rate.
101
Review Question.
A. Atropine
B. Epinephrine
C. Isoproterenol
D. Phenylephrine
E. Physostigmine
B. Epinephrine. It causes increases to blood pressure through a1 activation and increase heart rate and output via beta1.
102
What are the two naturally occurring muscarinic receptor antagonists?
Atropine and scopalamine
103
Muscarinic antagonists usually produce anti-SLUDD responses and 'E' type responses. What are some of those responses?
Mydriasis of the eyes, tachycardia, bronchodilation, secretion inhibition with sweat and saliva
104
What is the main non-selective muscarinic antagonist?
Atropine
105
What is the main M3 receptor antagonist?
Solifenacin (VESIcare) and Oxybutynin (Dithopan)
(Darifenacin too)
106
How are dually innervated organs (eyes, heart, lungs, GIT, etc) affected by muscarinic antagonists?
Those with parasympathetic dominance will show sympathetic dominance through cholinergic effects like mydriasis, tachycardia, bronchodilation, reduced GIT motility and secretions.
107
How are organs only express muscarinic receptors (ie: sweat and salivary glands) effected by a muscarinic antagonist?
All effects to that organ will be blocked. For sweat and salivary glands, specifically with atropine, all secretions will stop as those are innervated by M3 receptors.
108
How are organs that are only innervated by the sympathetics effected by muscarinic antagonists?
There is little to no effect as they do not have muscarinic receptors.
109
What are the main effects of atropine?
Atropine is a non-selective muscarinic antagonist. It induces mydriasis, blurring vision, constipation via reduced secretions and motility of GIT, urinary retention through detrusor relaxation and sphincter constriction, tachycardia, and anhidrosis. Interestingly, it produces CNS effects like increased hallucination and delirium through modulation of dopamine and glutamate.
110
Atropine typically acts as a competitive non-selective muscarinic antagonist. What is another unique method of action this drug has?
It can also act as a inverse agonist on muscarinic receptors.
111
What are the unique CNS side effects of atoprine?
It can increase hallucinations and delirium through modulation of dopamine and glutamate. However this does not occur at typical doses.
112
At small doses, what is the first noticed effect produced by muscarinic antagonist?
Reduced salivary and bronchial secretions
113
For ophthalmic cases like producing mydriasis and reduce tear secretion, is a longer or shorter acting muscarinic antagonist (mydriatic eye drops) used?
Shorter acting agents are preferred. Something that tropicamide
114
What is the net effect on the cardiovascular system with the use of a muscarinic antagonist?
Blocking M2 on the heart will result in tachycardia. Blocking M3 receptors located on the blood vessels while prevent vasodilation via nitric oxide but overall there is no significant change in blood pressure.
115
With what drug is hyperactive bronchoconstrictor reflex in asthmatic patients and COPD treated with?
Antimuscarinic agent like tiotropium (Spiriva) or **ipratropium (Atrovent)**
116
What is the brand name for Ipratropium?
Atrovent
117
What type of drug is Ipratropium?
Muscarinic antagonist used to treated COPD and hyperactive bronchconstrictor reflex.
118
First-generation antihistamines like diphenhydramine are also potent __________ agents.
antimuscarinic
119
What is the drug oxybutynin?
This is a muscarinic antagonist that acts primarily on M3 receptors in the bladder to reduce urinary incontinence.
120
What is the drug class and function of Solifenacin?
This is an M3 antagonist with the brand name VESIcare. It aids in urinary incontience.
121
What is the main condition in which muscarinic antagonists are contraindicated in?
Acute closed angle glaucoma
122
What is the medication used to treat an overdose with an anti-muscarinic?
Physostigmine (AChEase inhibitor)
123
What are the 3 alpha 1 antagonists discussed?
Prazosin, tamsulosin, siladosin
124
Why is orthostatic hypotension a side effect of using alpha antagonists?
Alpha antagonist block a1 therefore preventing endogenous molecules like Epi and NE from binding to vasoconstrict and increase blood pressure upon standing to get blood to the brain. Therefore, when a person stands the body has to work extra hard to try to get blood to the brain and it takes longer therefore blood pressure is lower upon standing.
124
What are the 2 non-selective alpha adrenergic antagonists discussed?
Phentolamine and phenoxybenzamine
124
What are the main three diseases treated by alpha adrenergic antagonists?
1. Pheochromocytoma (catecholamine secreting tumor on adrenal)
2. Primary hypertension
3. Benign prostatic hyperplasia (BPH)
125
What was the one alpha 2 antagonist discussed?
Yohimbine
125
What is the interesting effect that alpha antagonists have on epinephrine?
Typically epinephrine is a pressor meaning it increased blood pressure and heart rate by binding to all adrenergic receptors. However, in the presence of an alpha antagonist, epinephrine becomes a depressor.
125
What alpha antagonist targets a1 and is used to treat primary hypertension?
Prazosin
125
What are the two main adverse reactions of alpha antagonists?
Orthostatic hypotension and reflex tachycardia
125
What was the one IRREVERSIBLE alpha antagonist discussed?
Phenoxybenzamine. It turns off the receptor by covalently bonding to it and then the receptor is internalized.
125
Why is reflex tachycardia a side effect of alpha antagonist?
Alpha 1 receptors are blocked therefore there is no vasoconstriction and the blood pressure drops. In response to decreased blood pressure, the body increases the heart rate to respond bring blood pressure back to homeostasis.
125
What happens to blood pressure if epinephrine is administered after phentolamine has been given?
Since alpha antagonist turn epinephrine from a pressor into a depressor, the addition of EPI will bring down the blood pressure while the heart rate mildly increases due to epinephrine acting on beta-1 in the heart and via reflexes.
126
What type of drug is phentolamine?
This is a competitive reversible non-selective alpha adrenergic antagonist.
127
How is pheochromocytoma managed before surgery?
It is managed with the non-competitive irreversible non-selective alpha antagonist called phenoxybenzamine.
128
Why are some selective a1 antagonists used for difficulty urinating in benign prostatic hyperplasia?
There are a1 receptors located within the internal sphincter of the bladder. When inhibited these promote urine flow which is compressed by the enlarged prostate.
129
129
Epi produces an increase in blood pressure. In the presence of drug X, it produces a decrease in blood pressure. Drug X is most likely which of the following?
A. Phentolamine
B. Propranalol
C. Albuterol
D. Dibutamine
E. Phenylephrine
A. Phentolamine as this is the only alpha antagonist listed among the choices.
129
What are the 3 a1 antagonists used to promote urination in benign prostatic hyperplasia?
Prazosin (Minipress)
Tamsulosin (Flomax)
Silodosin (Rapaflo)
129
T or F: A person with hypotension and BPH can be given an a1 antagonist to aid in their urination ability.
False. Those with hypotension need to be given an even more selective drug for a1A like Tamsulosin or Silodosin as these drugs will not target the a1 receptors on the blood vessels.
130
Sally discontinued her use of phentolamine while on vacation. What can she expect to experience as a consequence?
A. Rapid weight gain
B. Agitation
C. Tachycardia
D. Rebound hypertension
E. A and C
D. Rebound hypertension. There is no longer a block on those alpha receptors so EPI and NE can bind and vasoconstrict causing hypertension.
130
Which of the following is a potential side effect of using an alpha blocker?
A. Orthostatic hypotension
B. Agitation
C. Tachycardia
D. Urinary Retention
E. A and C
E. Both orthostatic hypotension and tachycardia. With the tachycardia, if we block the ability of the vessels to constrict, that induces hypotension. The heart will try to compensate by increasing heart rate.
130
What is the general clinical use of beta adrenergic antagonists (beta-blockers)?
Cardiac Function
131
What were the two discussed non-selective beta blockers?
Propranolol and timolol
132
What were the two discussed beta-1 blockers?
Metoprolol and atenelol
133
What were the two discussed mixed beta blockers?
Carvedilol and labetalol
(blocks b1, b2, and a1)
134
Why are the non-selective beta-blockers problematic to use in those with asthma?
Non-selective beta-blockers like propranolol and timolol block all beta receptors meaning they will block beta-2 in the lungs therefore causing bronchoconstriction and increased secretions.
135
What is unique about the mixed beta-blockers like carvedilol and labetalol?
These also are alpha-1 antagonist that promote vasodilation.
136
Do beta-1 blockers have any effect on the heart in normal individuals? As in individuals with normal sympathetic control.
Beta-1 blockers here like atenolol and metoprolol will not reduce the heart rate much in these individuals.
137
Non-selective and beta-1 blockers antagonize the release of _________ from the kidneys caused by sympathetic system.
Renin
138
What happens to the heart and blood pressure when giving a non-selective beta blocker like propranolol in response to EPI?
Contractile force and heart rate would decrease while the blood pressure would increase in response to unopposed alpha receptor mediated vasoconstriction.
139
Why can beta-blockers be given as an anti-hypertension even though mainly alpha-1 receptors are found on the vasculature?
Well the mechanism is not completely understood. It is thought that it decreases heart rate and contractile force it may also decrease peripheral resistance. It does block beta-1 receptors in the kidneys which antagonizes renin which may also be a reason.
140
What are the 3 main heart conditions that beta-blockers are used for?
Ischemic heart disease (MI), cardiac arrhythmias, and chronic heart failure.
141
Why are beta-blockers used for ischemic heart disease (MI)?
Beta-blockers antagonize beta-1 on the heart therefore decreasing heart rate resulting in less cardiac work and less oxygen demand. It improves exercise tolerance too.
142
Beta-blockers prolong survival in patients who have had a _________________.
Heart attack
143
Why are beta-blockers used for cardiac arrhythmias?
Beta-blockers increase A/V node refractory period and therefore slow ventricular rates, atrial flutter, and fibrillation. Overall, it regularizes the heart rate and suppresses the arrhythmia.
144
Why are beta-blockers used for chronic heart failure?
Beta-blockers reduce mortality but it is not understood why. Long-term it reduces the sympathetic effects on the heart caused by cardiac output failure.
145
Can beta-blockers be used to treat glaucomas?
Yes! Beta-blockers reduce the intraocular pressure by suppressing the production of aqueous humor.
146
What type of beta-blocker is used in glaucomas?
A non-selective beta-blocker like timolol
147
Do beta-blockers treat hyperthyroidism or treat the symptoms of it?
Beta-blockers treat the symptoms of hyperthyroidism as this condition is associated with tachycardia and anxiety.
148
Why can beta-blockers be used for hyperthyroidism?
Hyperthyroidism is associated with an increase of beta receptors in many tissues therefore increases beta adrenergic tone. Blocking this tone may reduce the symptoms of hyperthyroidism.
149
What are some common adverse effects of beta-blockers?
1. Bradycardia and reduction of exercise tolerance
2. Decreased inotropy (strength of heart contraction)
3. Worsening of pre-existing asthma or COPD
4. Rebound hypertension with abrupt discontinuation
5. Sleep disturbances
6. Cold limbs
150
Why is exercise intolerance an adverse effect of beta-blockers?
Beta-blockers reduce the ability for the heart rate to increases therefore decreasing the amount of oxygen in blood that is pumped to exercising tissues.
151
Why is rebound hypertension an adverse effect of beta-blockers abrupt discontinuation?
Abrupt discontinuation results in the up-regulation of beta receptors following prolonged blockade of those receptors.
152
Why are cold limbs an adverse effect of beta-blockers?
Cold limbs is a side effect of peripheral vasoconstriction which can be a result of some beta blockers.
153
When given to a patient, phentolamine reverses which of the following?
A. Bradycardia produced by phenylephrine
B. Bronchodilation produced by epinephrine
C. Increased cardiac contractile force induced by norepinephrine
D. Miosis produced by bethanechol
E. Vasodilation produced by isoproterenol
A. Phentolamine will reverse bradycardia produced by phenylephrine.
Phenylephrine is an a1 agonist. It will vasoconstrict the vessels resulting is a reflex response of bradycardia. Phentolamine is a non-selective alpha antagonist. It will bind to alpha 1 and block it therefore producing vasodilation and responding tachycardia.
154
Man has hypertension and an enlarged prostate which is shown to be benign prostatic hyperplasia. He claims to have urinary retention. Which of the following drug would be the most appropriate initial therapy?
A. Albuterol
B. Atenolol
C.Metoprolol
D. Prazosin
E. Timolol
D. Prazosin
Beta-blockers are not used for urinary retention. We use alpha-1 blockers for urinary retention due to benign prostatic hyperplasia. We can use Prazosin. If he had hypotension though, we would need to use a selective a1A blocker like tamsulosin or silodosin.
155
Which of the following drugs would be most effective in reducing a cocaine toxicity?
A. Phenylephrine
B. Epinephrine
C. Metoprolol
D. Carvedilol
E. Silodosin
D. Carvedilol
Cocaine acts to block the reuptake of NE and dopamine in the synapse. Therefore there would be way too much NE floating around binding to a1, a2, and b1 receptors. Since carvedilol is a mixed acting beta blocker it acts on b1, b2, and a1 therefore blocking 2/3 targets that excess NE is acting on
156
A patient is set to receive epinephrine. She has previously received an adrenoceptor-blocking agent. Which of the following effects of epinephrine would be blocked by phentolamine but not metoprolol?
A. Cardiac stimulation
B. Increase of cAMP in fat
C. Mydriasis
D. Relaxation of bronchial smooth muscle
E. Relaxation of uterus
C. Mydriasis
Epi binds to all adrenergic receptors. Phentolamine is a non-selective alpha antagonist and metoprolol is beta-1 antagonist. a1 in the eye controls mydriasis so phentolamine would act block the effects of epi causing mydriasis by blocking the receptors.
157
A patient is set to receive epinephrine. She has previously received an adrenoceptor-blocking agent. Which of the following effects of epinephrine would be blocked by metoprolol but not phentolamine?
A. Vasoconstriction of blood vessels in the skin
B. Cardiac stimulation
C. Bronchodilation
D. Mydriasis
E. Vasodilation of skeletal muscle
B. Cardiac stimulation
158
A new drug was given to animals. A large dose of EPI was given before and after the agent was given for comparison. Which of the following agents does the new drug closely resemble?
A. Atenolol
B. Atropine
C. Labetalol
D. Phenoxybenzamine
E. Propranolol
C. Labetalol
Labetalol is a mixed acting beta antagonist that blockers b1, b2, and a1. It decreases blood pressure by blocking epi causing vasoconstriction leading to vasodilation. It decreases heart rate and cardiac output too.
159
Is acute closed angle glaucoma a medical emergency and progressive?
Acute closed angle glaucoma is a medical emergency that requires laser or surgical intervention.
159
What is a glaucoma?
Glaucoma is an ophthalmic disorder characterized by neuropathy of the optic nerve and vision loss that is related to increased intraocular pressure.
159
What part of the eye produces aqueous humor?
Ciliary epithelium (portion of the ciliary body)
159
Once the aqueous humor is produced, it is secreted into the ______ _________ where it flows through the pupil into the ________ ________.
Posterior chamber
Anterior chamber
159
What are the two main ways that the aqueous humor exits the eye?
Trabecular meshwork into Schlemm's canal and uveoscleral outflow
160
What are the major and minor routes of aqueous humor exit?
80% trabecular meshwork into Schlemm's canal
20% in uveoscleral outflow
160
When saying a glaucoma is closed or open angle, what is this angle between?
Iris and cornea angle
160
What is the pathophysiology in an open angle glaucoma?
It can be due to obstruction of the trabecular meshwork mainly or loss of trabecular cells or reduced diameter of Schlemm's canal.
161
What is the pathophysiology in an acute closed angle glaucoma?
It is due to a mechanical obstruction of outflow through the trabecular network.
161
What are the two main ways the medications can treat open angle glaucoma"
1. Reduce production of aqueous humor
2. Increase outflow of aqueous humor
161
What are the 3 classes of drugs that are used to decrease the production of aqueous humor in open angle glaucoma?
1. B1 and B2 antagonists
2. a2 agonists
3. Carbonic anhydrase inhibitors
161
What are the 3 classes of drugs that are used to increase the outflow of aqueous humor in open angle glaucoma?
1. Muscarinic agonists
2. AChEase inhibitors
3. Prostaglandin analogs
161
What is the 1st line of treatment for open angle glaucoma?
Beta adrenergic antagonist like Timolol and Prostaglandin Analongs.
161
Why does targeting beta adrenergic receptors in the eye work in treating open angle glaucoma?
Beta receptors are present on the ciliary epithelium where the aqueous humor is produced. By antagonizing those receptors, the production of aqueous humor decreases.
162
For those using a beta blocker like timolol for open angle glaucoma, what can occur in 20-50% of patients?
Tachyphylaxis meaning that there is a loss of drug response due to body upregulating number of beta receptors present on the ciliary epithelium.
162
Why does targeting a2 receptors in the eye work in treating open angle glaucoma?
a2 receptors are present on the blood vessels in the eye. By activating these receptors it causes vasoconstriction therefore reducing aqueous humor production.
163
What are the two typical a2 agonists used to treat open angle glaucoma?
Brimonidine and apraclonidine
164
Why are carbonic anhydrase inhibitors used to treat open angle glaucoma?
Carbonic anhydrase is the first enzyme in the production of aqueous humor in the ciliary epithelium. Blocking this enzyme blocks the production of aqueous humor.
165
What are two topical carbonic anhydrase inhibitors used to reduce aqueous humor production in the treatment of open angle glaucoma?
Brinzolamide and Dorzolamide
166
Why are carbonic anhydrase inhibitors 3rd or 4th line therapies for the treatment of open angle glaucoma?
They have many adverse effects including blood dyscrasias, renal failure, COPD, and paresthesia of extremities.
167
How do muscarinic agonists work in treating open angle glaucoma?
Muscarinic agonists bind to M3 receptors in ciliary muscle stimulating contraction causing miosis. This opens the trabecular meshwork and facilitates the drainage of aqueous humor.
168
Why are the two muscarinic agonists that can be used for open angle glaucoma in increasing the outflow of aqueous humor?
Pilocarpine and Carbachol
169
Why is the muscarinic agonist, pilocarpine, no longer a 1st line therapy for open angle glaucoma?
It can cause too much miosis resulting in myopia, loss of night vision, and accomodation spasms. If it gets into systemic circulation is also binds to muscarinic receptors stimulating activity of the parasympathetic nervous system like miosis, bradycardia, diarrhea, salivation, sweating, and vasodilation.
170
Why are acetylcholinesterase inhibitors used in the treatment of open angle glaucoma?
AChEase inhibitors indirectly activate M3 receptors on the ciliary muscle by increasing concentrations of ACh. This causes contraction of the ciliary muscle inducing miosis and opening up the trabecular meshwork to facilitate outflow of aqueous humor.
171
What are the two AChEase inhibitors used in the treatment of open angle glaucoma?
Physostigmine and Echothiophate
172
Why are prostaglandin analogs used to treat open angle glaucoma?
They increase uveoscleral outflow of aqueous humor.
173
What are the 3 common prostaglandin analogs used in the treatment of open angle glaucoma?
Latanoprost, Bimatoprost, and Travoprost
174
Why are prostaglandin analogs the 1st line treatment for open angle glaucoma?
They have superior efficacy and minimal adverse effects.
175
What are the two interesting side effects of prostaglandin analogs like Latanoprost and Bimatoprost?
They increase iris pigmentation while thickening and lengthening the eyelashes.
176
What is the surgery used for a closed angle glaucoma?
Laser iridotomy. This is when a hole is made into the iris to release intraocular pressure.
177
What pharmacotherapy can be given for closed angle glaucoma if an iridotomy can't be done right away?
Intraocular pressure can be lowered with beta antagonists (beta-blockers), prostaglandin analogs, or carbonic anhydrase inhibitors. Hyperosmotics like mannitol can also be used to draw water out of the eye in an acute closed angle glaucoma attack.
178
What types of medications can cause or exacerbate closed angle glaucomas?
Phenylephrine and pseudoephedrine.
Anticholinergic and sympathomimetic drugs like 1st generation antihistamines, TCAs, and antipsychotics.
179
Timolol should avoided in patients who have a history of which of the following?
A. Hypertension
B. Difficulty swallowing
C. Asthma/COPD
D. Urinary incontinence
C. Asthma/COPD
could also be hypertension as a non-selective beta blocker like timolol would decrease heart rate therefore the reflex arc would trigger vasoconstriction to bring back homeostasis.
180
Your patient has a history of closed angle glaucoma. What type of medication should you avoid?
A. Anticholinergics
B. Cholinergics
C. Beta blockers
D. Alpha antagonists
A. Anticholinergics as they could displace the pupil.
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