Pharmacology - Autonomic Drugs Part 2 Flashcards
According to the mnemonic DUMBBELSS, what four major physiologic processes are blocked by atropine?
Diarrhea, Urination, Miosis,Bronchospasm, Bradycardia, Excitation of skeletal muscle, Lacrimation, Sweating, and Salivation
True or False? Increased body temperature is a sign of atropine toxicity.
True (ie, “hot as a hare”)
True or False? Slower heart rate is a sign of atropine toxicity.
False; heart rate would be increased
True or False? Dry mouth is a sign of atropine toxicity.
True (ie, “dry as a bone”)
True or False? Dry, flushed skin is a sign of atropine toxicity.
True (ie, “dry as a bone, red as a beet”)
True or False? Cycloplegia is a sign of atropine toxicity.
True (ie, “blind as a bat”)
True or False? Diarrhea is a sign of atropine toxicity.
False; constipation is a sign of atropine toxicity
True or False? Disorientation is a sign of atropine toxicity.
True (ie, “mad as a hatter”)
Which two adverse effects of atropine are more common in elderly patients?
Urinary retention and acute angle closure glaucoma
True or False? Atropine toxicity can cause urinary incontinence.
False; atropine toxicity can cause urinary retention in men with prostatic hypertrophy
True or False? Atropine toxicity can cause fecal incontinence.
False; atropine toxicity causes constipation, not fecal incontinence
What type of acetylcholine receptors does hexamethonium antagonize?
Nicotinic acetylcholine receptors
What effect does hexamethonium have on heart rate?
It can prevent bradycardia in response to increased blood pressure when pressors are given
Name four toxicities of hexamethonium.
Severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction
Name 11 drugs that act as direct sympathomimetics.
Isoproterenol, dobutamine, phenylephrine, epinephrine, norepinephrine, dopamine, albuterol, terbutaline, ritodrine, metaproterenol, and salmeterol
Which types of receptors are activated by epinephrine?
α1-, α2-, β1-, and β2-receptors
Low doses of epinephrine are selective for _____ (α1, α2, β1, β2) adrenergic receptors.
β1
Which types of receptors are activated by norepinephrine?
α1- and α2-; β1-receptors (with lower affinity)
Does norepinephrine have greater affinity for α-adrenergic receptors or β1-receptors?
α-Adrenergic receptors
Isoproterenol is an agonist for which receptors?
β1- and β2-receptors equally
Which types of receptors does dopamine activate, and how strongly does it activate them relative to one another?
D1 = D2 receptors > β-receptors > α-receptors
Dopamine is an agonist for which receptors?
β1- and β2-receptors
Dopamine is _____ (ionotropic/not ionotropic) and _____ (chronotropic/not chronotropic), while dobutamine is _____ (ionotropic/not ionotropic) and _____ (chronotropic/not chronotropic).
Ionotropic; chronotropic; ionotropic; not chronotropic
Phenylephrine is an agonist for which receptors?
α1-receptors > α2-receptors
Metaproterenol, albuterol, salmeterol, and terbutaline are agonists for which receptors?
β2-receptors > β1-receptors
Ritodrine acts on _____ (α1, α2, β1, β2)-adrenergic receptors.
β2
What are the clinical applications of epinephrine?
Anaphylaxis, open-angle glaucoma, asthma, hypotension
What effect does norepinephrine have on renal perfusion?
It decreases renal perfusion
What is the clinical application for isoproterenol?
Atrioventricular block
What role does dopamine have in treating shock?
Increases blood pressure while maintaining renal perfusion
True or False? Dopamine can be used to treat heart failure.
True
What are the clinical applications for dobutamine?
Shock, heart failure, cardiac stress testing
What are the clinical applications of phenylephrine?
Treats nasal decongestion; causes vasoconstriction; dilates pupils
What is the clinical application for albuterol?
Acute asthma
Which sympathomimetics can be used to reduce premature uterine contractions?
Terbutaline, salmeterol
Amphetamine, ephedrine, and cocaine are (direct/indirect) sympathomimetics.
Indirect
By what mechanism does amphetamine exert its sympathomimetic effect?
It stimulates the release of stored catecholamines
By what mechanism does ephedrine exert its sympathomimetic effect?
It stimulates the release of stored catecholamines
By what mechanism does cocaine exert its sympathomimetic effect?
It inhibits catecholamine uptake in the nerve terminal
What are the clinical indications for use of amphetamines?
Narcolepsy, obesity, attention deficit hyperactivity disorder
What are three clinical applications of ephedrine?
To treat nasal congestion, urinary incontinence, and hypotension
True or False? Phenylephrine can be used to treat nasal congestion.
True
What are the effects of cocaine when used topically?
Vasoconstriction and local anesthesia
Is the effect of epinephrine on β-receptors greater than, equal to, or less than its effect on α-receptors?
Equal to, except at low doses, at which epinephrine is selective for β1
Is the effect of isoproterenol on β-receptors greater than, equal to, or less than its effect on α-receptors?
Greater than
What are the effects of norepinephrine on heart rate, systolic and diastolic blood pressure, and pulse pressure?
It increases systolic and diastolic blood pressure, slightly increases pulse pressure (systolic increases more than diastolic), and reduces heart rate by causing reflex bradycardia
What are the effects of epinephrine on heart rate, systolic and diastolic blood pressure, and pulse pressure?
It increases systolic blood pressure, decreases diastolic blood pressure, greatly increases pulse pressure, and increases heart rate
Why does norepinephrine administration result in reflex bradycardia?
Norepinephrine raises blood pressure, causing a vagal response that leads to reflex bradycardia via increased parasympathetic input to the heart
Epinephrine causes an increase in heart rate via which receptor subtype?
β1 receptors; although epinephrine exhibits affinity for both β subtypes, it is selective for β1 at low doses, leading to tachycardia
What effect does isoproterenol have on pulse pressure and heart rate?
Increases pulse pressure and heart rate
What is the effect of clonidine on central adrenergic outflow? Which receptor does it act on?
It is an α2-agonist and decreases central adrenergic outflow; remember that the α2-receptor is responsible for negative feedback
What are the clinical applications of clonidine?
Hypertension, especially with renal disease, because it does not decrease blood flow to the kidneys
What is the effect of α-methyldopa on central adrenergic outflow? Which receptor does it act on?
It is an α2-agonist and decreases central adrenergic outflow
What are the clinical applications of α-methyldopa?
Hypertension, especially with renal disease, because it does not decrease blood flow to the kidneys
What are two patient populations for which α-methyldopa is indicated (as an antihypertensive)?
Renal failure patients, pregnant patients
What is the clinical application and mechanism of action of phenoxybenzamine?
Phenoxybenzamine is a nonselective α-blocker that is used to treat pheochromocytoma
Would you use phenoxybenzamine or phentolamine before removal of a pheochromocytoma? Why?
Phenoxybenzamine, because it is irreversible. Phentolamine is reversible, so the high levels of catecholamines released during surgery would overcome the α-block
What is the clinical application and mechanism of action of phentolamine?
Phentolamine is a nonselective α-blocker that is used to treat pheochromocytoma
What are two adverse effects of nonselective α-blockers?
Orthostatic hypotension and reflex tachycardia
What are the clinical applications and mechanisms of action of prazosin, doxazosin, and terazosin?
They are each an α1-selective blocker used to treat hypertension and urinary retention in benign prostatic hyperplasia
What are three effects of α1-selective blocker toxicity?
Orthostatic hypotension (first dose only), dizziness, headache
What is the clinical application and mechanism of action of mirtazapine?
Mirtazapine is an α2-selective blocker used to treat depression
What are three effects of α2-selective blocker toxicity?
Sedation, increased serum cholesterol, increased appetite
What is the net effect of epinephrine on blood pressure before and after nonselective α-blockade? Why?
Before α-blockade, epinephrine increases blood pressure; after α-blockade, it decreases blood pressure. This is because epinephrine also activates β2, which lowers blood pressure and is not blocked
What is the net effect of phenylephrine on blood pressure before and after nonselective α-blockade? Why?
Before α-blockade, phenylephrine increases blood pressure; after α-blockade, it has little effect on blood pressure. This is because phenylephrine is specific for α and does not activate ß2, so it is completely negated by α-blockade
Why does epinephrine, a pressor, cause hypotension if a patient is pretreated with an α-blocker?
If α-receptors are blocked, the β-agonist properties of epinephrine predominate and lower blood pressure
Name six clinical applications for β-blockers.
Hypertension, angina pectoris, myocardial infarction, supraventricular tachycardia, congestive heart failure, glaucoma
Which two β-blockers are used to treat supraventricular tachycardia?
Propranolol, esmolol
What β-blocker is frequently used to treat glaucoma?
Timolol
How do β-blockers work in the setting of angina pectoris?
Decrease heart rate and contractility; decrease myocardial oxygen consumption
A 63-year-old patient is referred to you from the emergency room for long-term care after his first myocardial infarction. Is a β-blocker suggested or contraindicated for this patient?
Suggested; after myocardial infarction, patients should receive β-blockers to decrease risk of mortality
What is the mechanism of β-blockers in the treatment of supraventricular tachycardia?
They decrease atrioventricular conduction velocity
To which class of antiarrhythmic agents do β-blockers belong?
Class II; drugs that slow atrioventricular conduction
How does the use of β-blockers affect the progression of congestive heart failure?
Slows progression of heart failure; β-blockers reduce cardiac output but have proven benefit in congestive heart failure
What is the mechanism of β-blockers in the treatment of glaucoma?
They reduce the secretion of aqueous humor, reducing intraocular pressure
Why should β-blockers be used with caution in diabetic patients?
β-Blockers should be used with caution in diabetic patients because they can block initial warning signs of hypoglycemia such as increased heart rate and diaphoresis
Name five nonselective β-blockers.
Propranolol, timolol, nadolol, pindolol, and labetalol
Name five β1-selective antagonists.
Acebutolol, Betaxolol, Esmolol, Atenolol, Metoprolol (remember: A BEAM of β1-blockers)
Which β-blocker is the shortest acting?
Esmolol
What β-blockers have partial agonist activity?
Pindolol, Acebutolol (remember: Partial Agonist)
What are two nonselective α- and β-antagonists?
Carvedilol, labetalol
A patient with a history of Graves’ disease (hyperthyroidism) presents with chest pain. Her resting heart rate is 128 beats per minute, her blood pressure is 120/80 mmHg, and her respiratory rate is 18 breaths per minute. You order thyroid-stimulating hormone and thyroxine tests. What class of drugs would address her cardiac problems while you await the lab results?
ß-Blockers, such as propranolol, will reduce heart rate and consequently reduce angina
What is the mechanism of β-blockers in treatment of hypertension?
Decreasing cardiac output and decreasing renin secretion
What are some effects of β-blocker toxicity?
Bradycardia, atrioventricular block, congestive heart failure (reduced cardiac output), sedation, sleep alteration, impotence, exacerbation of asthma
What symptoms indicate cholinesterase inhibitor poisoning?
DUMBBELSS: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of the skeletal muscle and the central nervous system, Lacrimation, Sweating, and Salivation
What mechanism underlies the symptoms of acetylcholinesterase inhibitor poisoning?
Inhibition of acetylcholinesterase leads to overactivity of the body’s cholinergic systems
The symptoms of parathion poisoning are caused by the inhibition of what enzyme?
Acetylcholinesterase
The symptoms of organophosphate poisoning are caused by the inhibition of what enzyme?
Acetylcholinesterase
A child ingests insecticide and presents with diarrhea, abdominal pain, wheezing, pinpoint pupils, and copious tears and salivation. What medication should he be given?
Atropine and pralidoxime
What antidote can be given to a patient who presents with diarrhea, urinary incontinence, miosis, bronchospasm, bradycardia, lacrimation, sweating, and salivation?
Atropine and pralidoxime
Why is it important to give pralidoxime as well as atropine in organophosphate poisoning?
Because organophosphates are irreversible inhibitors of acetylcholinesterase and pralidoxime helps to regenerate functional acetylcholinesterase
Atropine is used as an antidote for what kind of poisoning? By what mechanism does it accomplish this?
Organophosphate/anticholinesterase inhibitor poisoning; it inhibits muscarinic acetylcholine receptors
Pralidoxime is used as an antidote for what kind of poisoning? By what mechanism does it accomplish this?
Organophosphate/cholinesterase inhibitor poisoning; it regenerates active acetylcholinesterase
