Autonomic Nervous System - Week 10

Question 1

Define adrenergic receptor antagonists.

Answer 1

Drugs that inhibit the interaction of NE, EPI, and other sympathomimetics with α- and β- adrenergic receptors are termed

Question 2

Antagonism of ___________ __________ receptors is of little clinical relevance in veterinary medicine

Answer 2

peripheral dopaminergic

Question 3

1. Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):

Prazosin, terazosin, doxazosin

2. State which type of antagonist these drugs are.

Answer 3

1. a1&raquo_space;» a2
2. alpha-antagonists

Question 4

1. Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):

Phenoxybenzamine

2. State which type of antagonist these drugs are.

Answer 4

1. a1>a2
2. alpha-antagonists

Question 5

1. Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):

Phenotolamine

2. State which type of antagonist these drugs are.

Answer 5

1. a1=a2
2. alpha-antagonist

Question 6

1. Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):

Atipamezole, Yohimbine, Tolazoline

2. State which type of antagonist these drugs are.

Answer 6

1. a2»a1
2. alpha-antagonist

Question 7

1. Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):

Carvedilol

2. State which type of antagonist these drugs are.

Answer 7

1. B1 = B2 >/= to a1 > a2
2. mixed alpha and beta antagonist

Question 8

1. Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):

Propranolol, Timolol

2. State which type of antagonist these drugs are.

Answer 8

1. B1 = B2
2. beta antagonist

Question 9

1. Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):

Metoprolol, Atenolol, Esmolol, Betaxolol

2. State which type of antagonist these drugs are.

Answer 9

1. B1&raquo_space;> B2
2. beta antagonist

Question 10

Adrenoceptor antagonists are a chemically _________ and _______ diverse group

Answer 10

heterogenous, structurally

Question 11

These drugs are predominantly…

Answer 11

Competitive antagonists

Question 12

Phenoxybenzamine is what type of pharmaceutical agent?

Answer 12

Beta-haloethylamine alkylating agent

Question 13

Phenoxybenzamine is an __________ antagonist, meaning you can not get the receptor free again; they are occupied and won’t be free again.

Answer 13

irreversible

Question 14

Phentolamine and Tolazoline are analogs of?

Answer 14

Imidazoline

Question 15

Prazosin is a?

Answer 15

Piperazinyl quinozoline

Question 16

Phenothiazine tranquilizers are potent ____________ (e.g., ____________) and demonstrate substantial __________ __-receptor blocking effects (side effects). The ________ in peripheral vascular resistance secondary to ___________ of these receptors is clinically significant.

Answer 16

antagonists, Acepromazine, nonselective, α, decrease, antagonism

Question 17

Describe the cardiovascular effects of α-Adrenergic Receptor Antagonists.

α1-adrenergic receptor antagonists produces ________ of both _______ and ________ vessels
Following pretreatment with an α1-adrenergic receptor antagonists, increases in ___________
vascular resistance to _____-_______ administration are eliminated.

Answer 17

dilation, arterial, venous, peripheral, NE

Question 18

Describe the EPI reversal effect.

Answer 18

Following pretreatment with an α1-adrenergic receptor antagonists, administration of EPI may induce a reduction in peripheral vascular resitance and marked vasodilation mediated by activation of β2 –adrenergic receptors ↓ arterial blood pressure

Question 19

α1-adrenergic receptor antagonists decrease ?

Answer 19

resistance to urine flow

Question 20

a2B-adrenergic receptor antagonists have a role as ____________ in platelets

Answer 20

antiaggregant

Question 21

α2-adrenergic receptor antagonists may stimulate ________ release from pancreatic _____ cells

Answer 21

insulin release from pancreatic islet cells

Question 22

α-adrenergic receptor antagonists produce ________ of the third eyelid, _____, and nasal ________.

Answer 22

protrusion, miosis, stuffiness

Question 23

α2-adrenergic receptor antagonists can reverse the ___________ mediated by α2-adrenergic receptor _______.

Answer 23

sedation, agonists

Question 24

Nonselective α1-α2 -antagonists
Phenoxybenzamine (α1___ α2 )
* Phenoxybenzamine binds _________ to α-adrenergic receptor and produces an _________ block. Once bound, it inhibits the __________ of NE at presynaptic nerve terminals. Additionally, Phenoxybenzamine acts to various degrees as an antagonist at ____________, ____________, and ___________
receptors.

Answer 24

> , covalently, irreversible, reuptake, histamine, acetylcholine, and serotonine

pheochromocytoma = tumor in? –> high amount of nor epi in blood. to revert effect of high Norepi, we need to use antagonist

Question 25

The predominant use of phenoxybenzamine in veterinary medicine is to ?

Answer 25

manage the symptoms of catecholamine excess in the treatment of patients with a pheochromocytoma.
Phenothiazine tranquilizers and tetracyclic antidepressant trazodone

Question 26

α-Adrenergic Receptor Antagonists
Selective α1-antagonists
Prazosin (____) has been used:
1. For the treatment of __________. Prazosin _______ arterial and venous _______ muscle
2. To decrease _________ to ______ flow in dogs with functional urethral ___________,
prostatic _________, idiopathic ___________ reflex _________.

Answer 26

α1
1. hypertension, relaxes, smooth
2. resistance, urine, obstruction, hyperplasia, vesicourethral, dyssynergia

Question 27

___________ ________ is thought to play a role in urethral obstruction recurrence. The ___-receptor blockade is a useful component of post-obstruction therapy.

Answer 27

Urethral spasm, α1

Question 28

Prazosin is a ____________ ___-antagonist. It has a higher ___–adrenergic receptor affinity than _______________. The administration of prazosin to dogs results in a greater reduction of __________ pressure than _______________. The efficacy of this drug in the treatment of urethral obstruction in cats is debated due to their ?

Answer 28

selectiv a1, α1, phenoxybenzamine, urethral, phenoxybenzamine, anatomy (distal urethra)

Question 29

List the Important limitation to using α1–adrenergic receptor antagonists for urethral relaxation.

Lead to ______________ effects:
* Reduces vascular _______ muscle _____
* Decreases in ________, ________, and ______ arterial blood pressure

Answer 29

Lead to cardiovascular effects:
* Reduces vascular smooth muscle tone
* Decreases in systolic, diastolic, and mean arterial blood pressure

Question 30

Tamsulosin and silodosin are _____________ __-antagonists
1. Tamsulosin is a _________-generation ___-adrenergic receptor ________.
2. Tamsulosin has a higher affinity for _____ subtype (found in the urethra and prostate of humans and dogs) than for the
______ subtype (in vascular smooth muscle)

3. Silodosin is a _____-generation, highly selective ____-receptor ________.
4. Dogs with or without prostatic _________ demonstrated a similar response to silodosin or tamsulosin on decreasing ___________ pressure.

Answer 30

selective, a1, second, α1, antagonist, α1A, α1B, third, α1, antagonist, hyperplasia, intraurethral

Question 31

Yohimbine, tolazoline, and atipamezole are _____________ ___-antagonists and are used to ______ the sedative effects of α2-adrenergic agonists such as ?

Answer 31

Selective, a2, reverse, xylazine,
medetomidine, dexmedetomidine, detomidine, and romifidine

Question 32

α-Adrenergic Receptor Antagonists
Selective α2-antagonists
1. Yohimbine is an _________ alkaloid found in the bark of the tree ____________ ______ and in ___________ ______. It can cause CNS __________, _______ heart rate, and _________ blood pressure by increasing _____ release from adrenergic nerves.
2. Yohimbine can increase GI ______ by increasing ____________ tone
3. Yohimbine also demonstrates a degree of _________ activity at serotonin receptors
4. It is less used in ____ animals patients (atipamezole). The efficacy for reversal of xylazine in cattle is variable

Answer 32

1. indolealkylamine, Pausinystalia yohimbe, Rauwolfia root, stimulation, increased, increased, NE
2. motility, parasympathetic
3. antagonistic
4. small

Question 33

Tolazoline is a ________, _______ ____ –and ____ adrenergic antagonist (___________ derivatives)
* Tolazoline injection is approved for reversing ________ in horses
* Tolazoline is also used off-label to reverse other ____-_________ agonists in equids such as
detomidine. Its effect is _______ and _________.
* Tolazoline can be an alternative to __________ in reversing sedation in large animals and wildlife animals (less _________).

Answer 33

mixed, synthetic, α2, α1, imidazoline, xylazine, α2, adrenergic, transient, incomplete, atipamezole, expensive

Question 34

Atipamezole was originally approved to reverse the sedative and analgesic effect of _______________ _____________. Atipamezole is more potent than _________: reverses sedation induced by ___-_______, at ____-_____ the
dose required for yohimbine.
* It has been used off-label in dogs to treat __________ by __________ decongestants (e.g., ?)
* It has been used off-label to treat intoxication from the ________/______, ____ (α2-receptor agonist)
* It is effective in ____ species, including _____.

Answer 34

medetomidine, hydrochloride, yohimbine, α2, agonists, one-tenth, intoxication, imidazoline, oxymetazoline, tetrahydrozoline, xylometazoline, insecticide, acaricide, amitraz, all, ruminants

Question 35

β-Adrenergic Receptor Antagonists
β-adrenergic receptor antagonists are structurally similar to ____________
* Most of the available drugs are pure _________
* Some β-adrenergic antagonists exhibit ___________-___________ activity (similar to local anesthetics)
* There are β-adrenoceptor blockers classified as _______ ________ (they favor the ______ conformation).
* There are several that are partial β-adrenergic receptor agonists:
a) They cause a _____ activation (not as a full agonist such as EPI)
b) They ______ the activation of β-Adrenergic receptor in the presence of high levels of ?

Intrinsic sympathetic activity (ISA)?

Answer 35

catecholamines, antagonists, membrane, stabilizing, inverse, agonists, inactive, partial, inhibit, EPI and NE

Question 36

Question 37

Antagonism of cardiac β-adrenergic receptors slows __________ conduction and
produces negative _______, ________ effects

both decrease?

Answer 37

atrioventricular, inotropic chronotropic, cardiac output

Question 38

β-blocking drugs when administered chronically may ____ _________ __________ in hypertensive patients.
___________ peripheral vascular resistance is often an acute effect observed.

Answer 38

↓blood pressure, Increased

Question 39

List the Pulmonary effects of administering B-blocking drugs.

Nonselective β-adrenergic receptor antagonists will ______ β2-receptors in bronquial ________ muscle –> ___________ and ________ airway resistance ?

Answer 39

Nonselective β-adrenergic receptor antagonists will block β2-receptors in bronquial
smooth muscle
Bronchoconstriction and increased airway resistance

Question 40

β-Adrenergic Receptor Antagonists

Effects on the eye
Topical administration of β-adrenergic receptors antagonists:
* Reduce intraocular ______ by blocking ___ released from ________ nerve endings
* ________ in aqueous humor production

Metabolic and endocrine effects
* β-adrenergic receptors antagonists inhibit the activation of ______ and ________
* Nonselective β-adrenergic antagonists may delay recovery from ___________ (type-1 ___ type-2 diabetes mellitus

Answer 40

pressure, NE, sympathetic, Decreases, lipolysis, glycogenolysis, hypoglycemia, >

Question 41

β-Adrenergic Receptor Antagonists
β-adrenergic receptor antagonists are classified as:

Answer 41

1. Nonselective β-adrenergic receptor antagonists → first generation
2. β1-selective receptor antagonists → second generation
3. Nonselective (or subtype selective) β-adrenergic receptor antagonists with additional
   cardiovascular actions unrelated to β-adrenergic receptor blockade → third generation
   Most frequently used drugs in veterinary patients include:
   Propranolol, atenolol, esmolol, metoprolol, and carvedilol

Question 42

β-Adrenergic Receptor Antagonists
1. Nonselective β-adrenergic receptor antagonists → _____ generation

Propranolol
* Competitive ________ with no intrinsic ________ activity (ISA)
* Blocks both __ and ___ receptors
* Recent evidence indicates propranolol is an _____ agonist of β-receptors
* It has membrane- _________ activity
* Today, with the development of more selective β-adrenergic receptor antagonists its use is ____ frequent
Pharmacological effects:
* Propanolol decreases the _____ heart rate and depresses __-__ conduction
* It decreases cardiac ______
* It decreases myocardial ______ demand
* It increases airway ________

Answer 42

first, antagonist, sympathetic, β1, β2, inverse, stabilizing, less, sinus, A-V , output, oxygen, resistance

Question 43

β-Adrenergic Receptor Antagonists
Propranolol
It has been administered IV, IM, SC, or orally in the treatment of: ??
* ______arrhythmias
* _______tension
* _____throphic and __________ cardiomyopathies
* Cardiovascular consequences of _________ or ____________

Side effects:
* Upregulation of β-adrenergic receptors occurs with long-______ therapy
* _______ cessation of therapy leads to excessive stimulation of β-adrenergic receptors
* Propanolol may cause ________ and is contraindicated in asthmatic animals

Answer 43

Tachy, Hyper, Hyper, obstructive, thyrotoxicosis, pheochromocytoma

term, Abrupt, bronchospasm

Question 44

β-Adrenergic Receptor Antagonists
2. β1-selective receptor antagonists → ________ generation

Metoprolol
* It does not exhibit intrinsic ________ activity (ISA)
* At ____ doses it blocks β2 receptors
* Metoprolol does not possess membrane- _________ activity
Pharmacological effects:
* Decreased ____ heart rate and slowed ___–___ conduction
* ________ cardiac output
* Decreased myocardial _____ demand
* ______ blood pressure
* ___________ of the β-agonist-induced tachycardia

Answer 44

second, sympathetic, high, stabilizing, sinus, A-V, Disminished, oxygen, Reduced, Inhibition

Question 45

β-Adrenergic Receptor Antagonists
Metoprolol can be used orally to treat:
* ______________ tachyarrhythmias
* _________ ventricular contractions
* ___________ hypertension
* ____________ cardiomyopathy
* _____________ in cats
Metoprolol is relatively safe to use in animals with __________ disease

Answer 45

Supraventricular, Premature, Systemic, Hyperthrophic, Thyrotoxicosis, bronchospastic

Question 46

β-Adrenergic Receptor Antagonists
Atenolol

• Atenolol does not have intrinsic _______ activity (ISA)
• It decreases heart _____, cardiac _____, and ______ and ______ pressures

Atenolol is administered orally to treat: ?
* _________ arrhythmias
* Systemic _______
* _________ cardiomyopathy in cats
Side effects:
* It should be used cautiously in animals with _______ or a history of ______. At
high doses it can block ___ receptors
* Excessive ___-blockade can greatly reduce cardiac output
* It must be used with caution in patients with ________ heart failure, in _____ failure
patients
* Atenolol can cause ?

Answer 46

sympathetic, rate, output, systolic, diastolic, Supraventricular, hypertension, Hyperthrophic

asthma, bronchospams, β2, β1, congestive, renal, lethargy, hypotension, or diarrhea

Question 47

β-Adrenergic Receptor Antagonists
2. β1-selective receptor antagonists → ______ generation
Esmolol
* It has little membrane-_________ activity
* It is an ultra-______-acting β1-selective receptor antagonist (~____ min.)
Therapeutic uses:
* Esmolol and propranolol are the first choices for IV use for _______________
* Ventricular outflow obstruction in _____
Side effects:
* Excessive β1-blockade can greatly reduce ?

Answer 47

second, stabilizing, short, 20, tachyarrhythmias, cats, cardiac output

Question 48

β-Adrenergic Receptor Antagonists
3. Nonselective β-receptor antagonists → ______ generation
Carvedilol
* Demostrates modest ____-adrenergic receptor antagonist properties
* Carvedilol demostrates membrane __________ activity but no intrinsic sympathetic activity
* As carvedilol also inhibits α1-adrenergic activity, it can cause ___________ and reduce _________.
* Carvedilol has free radical ___________ and ____________ effects
* β-adrenergic blockade, reduces effects of ________ stimulation
Therapeutic uses:
* Used as an anti- ________ drug
* In the longterm management of ?

Answer 48

third, α1, stabilizing, vasodilation, afterload, scavenging, antidysrhythmic, sympathetic, arrhythmic, dilated cardiomyopathy and chronic valve disease

Question 49

Clinical Uses of β-Adrenergic Receptor Antagonists
Acquired cardiac disease in dogs
* Studies in heart failure patients have demostrated that β-adrenoceptor antagonism with selective (_____)-
receptor antagonists or ____-generation antagonists reduce mortality and increase quality of life
* The treatment of heart failure was earlier avoided due to the ______ inotropic effects, _________, and _______. The availability of more β1-receptor selective drugs have __________ these complications
* _________ _________ _______ disease (CMVD) is the most common cause of heart disease and CHF in dogs, followed by ________ cardiomyopathy (DCM)
* Dogs with mitral valve disease that were treated with orally adm. of _________ had improvement in quality life scores and a modest reduction in systolic blood pressure

Answer 49

β1, third, negative, hypotension, bronchspasm, reduced, Chronic mitral valvular, dilated, carvedilol

Question 50

Clinical Uses of β-Adrenergic Receptor Antagonists
Hypertrophic cardiomyopathy (HCM) and ventricular outflow obstruction
* HCM is the most common cardiac disease in ____. A high percentage of affected cats will also develop ?
* HCM and hypertrophic obstruction cardiomyopathy (HOCM) are characterized by ?
* The most commonly prescribed medications used to reduce dynamic LVOT obstruction in cats with HCM are ?

• Subaortic stenosis (SAS) in dogs is a ______ cardiac abnormality that causes varying degree of _____ obstruction. Dogs with severe SAS have been treated with __-blockers, most commonly _______

Answer 50

cats, dynamic obstruction of the left ventricular outflow tract (LVOT), concentric ventricular hypertrophy

β-adrenergic receptor antagonists, particularly atenolol

congenital, LVOT, β, atenolol

Question 51