Autonomic Nervous System - Week 10 Flashcards
Define adrenergic receptor antagonists.
Drugs that inhibit the interaction of NE, EPI, and other sympathomimetics with α- and β- adrenergic receptors are termed
Antagonism of ___________ __________ receptors is of little clinical relevance in veterinary medicine
peripheral dopaminergic
- Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):
Prazosin, terazosin, doxazosin
- State which type of antagonist these drugs are.
- a1»_space;» a2
- alpha-antagonists
- Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):
Phenoxybenzamine
- State which type of antagonist these drugs are.
- a1>a2
- alpha-antagonists
- Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):
Phenotolamine
- State which type of antagonist these drugs are.
- a1=a2
- alpha-antagonist
- Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):
Atipamezole, Yohimbine, Tolazoline
- State which type of antagonist these drugs are.
- a2»a1
- alpha-antagonist
- Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):
Carvedilol
- State which type of antagonist these drugs are.
- B1 = B2 >/= to a1 > a2
- mixed alpha and beta antagonist
- Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):
Propranolol, Timolol
- State which type of antagonist these drugs are.
- B1 = B2
- beta antagonist
- Explain the receptor selectivity for alpha 1, alpha 2, beta 1, beta 2 receptors for the following antagonist(s):
Metoprolol, Atenolol, Esmolol, Betaxolol
- State which type of antagonist these drugs are.
- B1»_space;> B2
- beta antagonist
Adrenoceptor antagonists are a chemically _________ and _______ diverse group
heterogenous, structurally
These drugs are predominantly…
Competitive antagonists
Phenoxybenzamine is what type of pharmaceutical agent?
Beta-haloethylamine alkylating agent
Phenoxybenzamine is an __________ antagonist, meaning you can not get the receptor free again; they are occupied and won’t be free again.
irreversible
Phentolamine and Tolazoline are analogs of?
Imidazoline
Prazosin is a?
Piperazinyl quinozoline
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.
antagonists, Acepromazine, nonselective, α, decrease, antagonism
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.
dilation, arterial, venous, peripheral, NE
Describe the EPI reversal effect.
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
α1-adrenergic receptor antagonists decrease ?
resistance to urine flow
a2B-adrenergic receptor antagonists have a role as ____________ in platelets
antiaggregant
α2-adrenergic receptor antagonists may stimulate ________ release from pancreatic _____ cells
insulin release from pancreatic islet cells
α-adrenergic receptor antagonists produce ________ of the third eyelid, _____, and nasal ________.
protrusion, miosis, stuffiness
α2-adrenergic receptor antagonists can reverse the ___________ mediated by α2-adrenergic receptor _______.
sedation, agonists
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.
> , 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
The predominant use of phenoxybenzamine in veterinary medicine is to ?
manage the symptoms of catecholamine excess in the treatment of patients with a pheochromocytoma.
Phenothiazine tranquilizers and tetracyclic antidepressant trazodone
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 _________.
α1
1. hypertension, relaxes, smooth
2. resistance, urine, obstruction, hyperplasia, vesicourethral, dyssynergia
___________ ________ is thought to play a role in urethral obstruction recurrence. The ___-receptor blockade is a useful component of post-obstruction therapy.
Urethral spasm, α1
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 ?
selectiv a1, α1, phenoxybenzamine, urethral, phenoxybenzamine, anatomy (distal urethra)
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
Lead to cardiovascular effects:
* Reduces vascular smooth muscle tone
* Decreases in systolic, diastolic, and mean arterial blood pressure
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)
- Silodosin is a _____-generation, highly selective ____-receptor ________.
- Dogs with or without prostatic _________ demonstrated a similar response to silodosin or tamsulosin on decreasing ___________ pressure.
selective, a1, second, α1, antagonist, α1A, α1B, third, α1, antagonist, hyperplasia, intraurethral
Yohimbine, tolazoline, and atipamezole are _____________ ___-antagonists and are used to ______ the sedative effects of α2-adrenergic agonists such as ?
Selective, a2, reverse, xylazine,
medetomidine, dexmedetomidine, detomidine, and romifidine
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
- indolealkylamine, Pausinystalia yohimbe, Rauwolfia root, stimulation, increased, increased, NE
- motility, parasympathetic
- antagonistic
- small
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 _________).
mixed, synthetic, α2, α1, imidazoline, xylazine, α2, adrenergic, transient, incomplete, atipamezole, expensive
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 _____.
medetomidine, hydrochloride, yohimbine, α2, agonists, one-tenth, intoxication, imidazoline, oxymetazoline, tetrahydrozoline, xylometazoline, insecticide, acaricide, amitraz, all, ruminants
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)?
catecholamines, antagonists, membrane, stabilizing, inverse, agonists, inactive, partial, inhibit, EPI and NE
Antagonism of cardiac β-adrenergic receptors slows __________ conduction and
produces negative _______, ________ effects
both decrease?
atrioventricular, inotropic chronotropic, cardiac output
β-blocking drugs when administered chronically may ____ _________ __________ in hypertensive patients.
___________ peripheral vascular resistance is often an acute effect observed.
↓blood pressure, Increased
List the Pulmonary effects of administering B-blocking drugs.
Nonselective β-adrenergic receptor antagonists will ______ β2-receptors in bronquial ________ muscle –> ___________ and ________ airway resistance ?
Nonselective β-adrenergic receptor antagonists will block β2-receptors in bronquial
smooth muscle
Bronchoconstriction and increased airway resistance
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
pressure, NE, sympathetic, Decreases, lipolysis, glycogenolysis, hypoglycemia, >
β-Adrenergic Receptor Antagonists
β-adrenergic receptor antagonists are classified as:
- Nonselective β-adrenergic receptor antagonists → first generation
- β1-selective receptor antagonists → second generation
- 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
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 ________
first, antagonist, sympathetic, β1, β2, inverse, stabilizing, less, sinus, A-V , output, oxygen, resistance
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
Tachy, Hyper, Hyper, obstructive, thyrotoxicosis, pheochromocytoma
term, Abrupt, bronchospasm
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
second, sympathetic, high, stabilizing, sinus, A-V, Disminished, oxygen, Reduced, Inhibition
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
Supraventricular, Premature, Systemic, Hyperthrophic, Thyrotoxicosis, bronchospastic
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 ?
sympathetic, rate, output, systolic, diastolic, Supraventricular, hypertension, Hyperthrophic
asthma, bronchospams, β2, β1, congestive, renal, lethargy, hypotension, or diarrhea
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 ?
second, stabilizing, short, 20, tachyarrhythmias, cats, cardiac output
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 ?
third, α1, stabilizing, vasodilation, afterload, scavenging, antidysrhythmic, sympathetic, arrhythmic, dilated cardiomyopathy and chronic valve disease
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
β1, third, negative, hypotension, bronchspasm, reduced, Chronic mitral valvular, dilated, carvedilol
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 _______
cats, dynamic obstruction of the left ventricular outflow tract (LVOT), concentric ventricular hypertrophy
β-adrenergic receptor antagonists, particularly atenolol
congenital, LVOT, β, atenolol
