Wk 12: Antihypertensives and Vasodilators Flashcards by Ashley Campbell

Metoprolol mechanism

Beta 1 antagonist

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Labetalol mechanism

alpha1 antagonist
beta1 antagonist
beta2 antagonist

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Esmolol mechansim

beta 1 antagonist

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Nicardipine mechanism

Dihydropyridine Ca blocker

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Clevidipine mechanism

Dihydropyridine Ca blocker

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Hydralazine mechanism

Arteriolar dilator

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Fenoldopam mechanism

Dopamine type 1 agonist

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Nitroprusside mechanism

NO donor

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Nitroglycerin mechanism

NO donor

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How do calcium channel blocking drugs used as antihypertensives work?

Inhibit calcium influx through the voltage-sensitive L-type calcium channels in vascular smooth muscle

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Calcium channel blockers are _________ specific, with little effect on _________ circulation

arterial
venous

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Nicardipine metabolism

Hepatic

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Nicardipine

Bolus:
Infusion:

100-400 mcg
5-15 mg/h

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Nicardipine

Onset:
t1/2:
Clinical mins:

2-10 min
2-4h
30-60 min

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Clevidipine

Metabolism

Plasma esterases to inactive metabolites

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Clevidipine

Bolus:
Infusion:

N/A
1-16mg/h

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Clevidipine

Onset:
t1/2:
Clinical mins:

Onset: 2-4 min
t1/2: 1 min (why infusion necessary)
Clinical mins: 5-15 min

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Hydralazine

metabolism

Hepatic

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Hydralazine

Bolus:
Infusion:

Bolus: 5-20mg
Infusion: N/A

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Hydralazine

Onset:
t1/2:
Clinical hours:

Onset: 5-20 min
t1/2: 2-8 h
Clinical hours: 1-8 h

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Fenoldopam

metabolism

Hepatic

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Fenoldopam

Bolus:
Infusion:

Bolus: N/A
Infusion: 0.05-1.6mcg/kg/min

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Fenoldopam

Onset:
t1/2:
Clinical min:

Onset: 5-10 min
t1/2: 5 min (why infusion necessary)
Clinical min: 30-60 min

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Fenoldopam increases _____ blood flow and increases ______ _____ and _______ blood flow

renal
urine output
splanchnic

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Some view _________ as the new "renal dopamine" (evidence is weak)

Fenoldopam

Fenoldopam Baroreflex-mediated increase in ______ _____ and ______ ________ level associated with its use

heart rate plasma catecholamine (caution in patients where tachycardia could be an issue)

Fenoldopam Adverse effects are limited to an increase in _________ __________, making this drug unsuitable for patients with ___________

intraocular pressure glaucoma

Nitrovasodilators work through the generation of NO, which then augments _______ in vascular smooth muscle, both _______ and ______, leading to vasodilation

cGMP arteries and veins

Sodium nitroprusside Nitroglycerin drug type

Nitrovasodilators

The more recent availability of intravenous __________ and other _______-specific dilators such as _________ and _________ has to some degree replaced the use of nitrodilators, especially nitroprusside

nicardipine arterial clevidipine fenoldopam

Nitroprusside Metabolism

Erythrocytes and hepatic

Nitroprusside Bolus: Infusion:

Bolus: N/A Infusion: 0.25-4mcg/kg/min

Nitroprusside Onset: t1/2: Clinical minutes:

Onset: 1-2 min t1/2: <10 min Clinical minutes: 1-10 mins

Nitroprusside ___________-mediated reflex responses

Baroreceptor

Nitroprusside may increase the area of damage associated with a myocardial infarction through a phenomenon called _______ _______

coronary steal

Clinical evidence of _______ __________ may occur when the rate of IV Nitroprusside infusion is greater than ____mcg/kg/min or when _______ donors and ___________ are exhausted, thus allowing cyanide radicals to accumulate

cyanide toxicity 2 sulfur methemoglobin

Nitroprusside Mixed venous PO2 is__________ in the presence of cyanide toxicity, indicating paralysis of ______ _________ and inability of tissues to use oxygen

increased cytochrome oxidase

Nitroprusside In cyanide toxicity, ________ _______ develops as a reflection of anaerobic metabolism in the tissues

metabolic acidosis

Nitroprusside Adverse effects from methemoglobinemia produced by Nitroprusside are _______ even in patients with a congenital inability to convert methemoglobin to hemoglobin (methemoglobin reductase deficiency)

unlikely

The clinical use of Nitroprusside has significantly _________ with the introduction of more selective ________ agents which have a greater margin of safety and much less or absent toxicity

declined arterial

Before the availability of newer drugs, Nitroprusside was used widely in the settings of controlled_____________, __________ emergencies, ______ and _____ surgery, and ____________

Controlled hypotension Hypertensive emergencies Aortic and cardiac surgery Heart failure

Nitroglycerin Metabolism

Hepatic Erythrocytes Vascular walls

Nitroglycerin Bolus: Infusion:

Bolus: 20-400mcg Infusion: 10-400mcg/min

Nitroglycerin Onset: t1/2: Clinical mins:

Onset: 1-2 min t1/2: 1-3 min Clinical mins: 5-10 mins

Nitroglycerin The nitrite metabolite of nitroglycerin is capable of oxidizing the ________ ion in hemoglobin to the ________ state with the production of ______________

ferrous ferric methemoglobin

________ doses of nitroglycerin may produce methemoglobinemia, especially in patients with ________ dysfunction

High hepatic

The most common clinical use of nitroglycerin is ____ or ___ administration for the treatment of _______ __________

sublingual IV angina pectoris

Nitroglycerin is used for _________ ischemia

myocardial

Nitroglycerin is used for controlled __________, however _________ is a problem

hypotension tolerance

Nitroglycerin is NOT RECOMMENDED in patients with ____________ ____________ ___________ or in the presence of ________ _________ ___________

hypertrophic obstructive cardiomyopathy severe aortic stenosis

Cardiac arrhythmias occur most commonly in the _____________ period, most of which are relatively ________ and are due to transient changes in ___________, _________, ________

perioperative benign physiology, surgical stimuli, the effect of anesthetic agents

Drugs administered for the ___________ suppression of cardiac arrhythmias pose little threat to the uneventful course of anesthesia and should be_________ up to the time of induction of anesthesia

chronic continued

_________ __________ still has an important role in arrhythmia management

Medication management

Catheter ablation techniques are preferred treatments for many ____________ arrhythmias including ______ and certain types of ______ _______

supraventricular atrial atrial fibrillation

Pharmacologic treatment of cardiac arrhythmias is principally used to suppress _____ ______ and _____ _______ that is not responsive to catheter ablation treatments and for patients with __________ _______- __________ devices who are receiving frequent indicated electrical shocks

atrial fibrillation atrial flutter implantable cardioverter- defibrillator

The two major physiologic mechanisms that cause ectopic cardiac arrhythmias are _______ and _______ _________

reentry enhanced automaticity

Factors encountered in the perioperative period that facilitate cardiac arrhythmias due to both mechanisms (reentry and enhanced automaticity) include: (6)

Hypoxemia Electrolyte and acid-base abnormalities Myocardial ischemia Altered sympathetic nervous system activity Bradycardia Administration of certain drugs (ex: ondansetron, droperidol)

Antiarrhythmic drugs produce pharmacologic effects by blocking passage of ____ across _____ ______ present in the heart ______ ion ______ ion ______ ion

ions ion channels sodium potassium calcium

The effects of cardiac antiarrhythmic drugs on the _______ ________and ________ ________ _______ of the cardiac action potential determine the clinical effects of these drugs

action potential effective refractory period

Phase 0

Depolarization Na+ IN

Phase 1

Initial repolarization K+ OUT Cl- IN

Phase 2

Plateau Ca+ IN K+ OUT

Phase 3

Final repolarization K+ OUT

Phase 4

Resting phase Na+ OUT

Time during which cells cannot be depolarized again

Effective refractory period

Cardiac arrhythmic drugs are most commonly classified into four groups based primarily on the ability of the drug to: -Control arrhythmias by blocking specific ____ channels and ______ during the cardiac action potential

ion currents

Quinidine Procainamide Disopyramide Moricizine Class

Class IA antiarrhythmic

Lidocaine Tocainide Mexiletine class

Class IB antiarhythmic

Flecainide Propafenone class

Class IC antiarrhythmic

Esmolol Propranolol Acebutolol class

Class II

Amiodarone Sotalol Ibutilide Dofetilide Bretylium class

Class III

Verapamil Diltiazem class

Class IV

Class I MOA

Inhibit fast sodium ion channels

Class II MOA

Decrease rate of depolarization

Class III MOA

Inhibit potassium ion channels

Class IV MOA

Inhibit slow calcium channels

Antiarrhythmic drugs also differ in their pharmacokinetics and efficacy in treating _______ types of arrhythmias

specific

Although used in the past, _________ is no longer recommended as prophylactic treatment for patients in the early stages of acute myocardial infarction and without malignant ventricular ectopy

lidocaine

________ __________ after heart surgery is a common complication that has been associated with prolonged hospitalization and cardiovascular morbidity

atrial fibrillation

Prophylactic therapy with _____, ______, _______, and ______ has been effective in reducing the occurrence of atrial fibrillation, length of hospital stay, cost of hospital treatment, possibly reduces the risk of stroke

amiodarone beta blockers sotalol magnesium

Drug treatment of cardiac arrhythmias is not uniformly effective and frequently causes _____ ______

side effects

The benefit of antiarrhythmic drugs is clearest when it results in the _________ termination of a sustained ________ ex: termination of ________ _________ by lidocaine or __________ _________ by adenosine or verapamil

immediate tachycardia ventricular tachycardia supraventricular tachycardia

Quinidine is a class ___ drug that is effective in the treatment of acute and chronic ___________ ___________

IA supraventricular arrhythmia

Quinidine is rarely used because of its ______ ________

side effects

Supraventricular tachyarrhythmias associated with ______ _______ ________syndrome are effectively suppressed by quinidine

Wolff-Parkinson-White

Quinidine MOA Decreases the slope of phase ____ depolarization, which explains its effectiveness in suppressing arrhythmias caused by _________ _______

4 enhanced automaticity

Quinidine is ________ in the ______ to inactive metabolites, which are excreted in the ________

hydroxylated liver urine

The concurrent administration with ______ or ________ may lower blood levels of quinidine by enhancing ______ clearance

phenytoin rifampin liver

Quinidine has a _____ therapeutic ratio, with side effects including (3)

low Heart block Hypotension Proarrhythmia effects

Procainamide is as effective as quinidine for the treatment of ________ ________ but less effective in abolishing __________ _________

ventricular tachyarrhythmias atrial tachyarrhythmias

Procainamide Premature _____ ______ and paroxysmal ______ _______ are suppressed in most patients within a few minutes after IV, which is better tolerated than IV quinidine May still cause _________

Premature ventricular contractions Paroxysmal ventricular tachycardia Hypotension

Procainamide undergoes ________ metabolism and ________ elimination Dose must be decreased when _____ function is abnormal

hepatic renal renal

The activity of the N-acetyltransferase enzyme response for the acetylation of procainamide is genetically determined Patients who are rapid acetylators, the elimination half-time of procainamide is ____ hours compared with ____ hours in slow acetylators

2.5 5

Similar to quinidine, use of procainamide has dramatically ________ due to its side effect profile and availability of newer agents

decreased

Hypotension that results from procainamide is more likely to be caused by ________ ________ _______ than _______ ________

direct myocardial depression peripheral vasodilation

Chronic administration of procainamide may be associated with a syndrome that resembled ________ __________ _________

systemic lupus erythematosus

Lidocaine is used principally for suppression of _________ ________, having minimal if any effect on _________ ___________

ventricular arrhythmias supraventricular tachyarrhythmias

Advantages of lidocaine over quinidine or procainamide: (4)

Rapid onset Prompt disappearance of effects when continuous infusion is terminated Greater therapeutic index Reduced side effect profile

Lidocaine MOA The effectiveness of lidocaine in suppressing premature ventricular contractions reflects its ability to decrease rate of spontaneous phase ____ depolarization The ineffectiveness of lidocaine against supraventricular tachyarrhythmias presumably reflects its inability to alter the rate of spontaneous phase 4 depolarization in ______ cardiac cells

4 atrial

Lidocaine is metabolized in the _____, and resulting metabolites may possess ______ __________ activity

liver cardiac antiarrhythmic

Phenytoin is particularly effective in suppression of __________ _________ associated with _______ toxicity and may be useful in the treatment of __________ _________ __________ or ________ __ ______

ventricular arrhythmias digitalis paradoxical ventricular tachycardia torsades de pointes

Phenytoin IV dose is ____ mg (____mg/kg) every ___ mins until the cardiac arrhythmia is controlled or ___ to ___mg/kg (max _____mg) has been administered

100mg 1.5mg/kg 5 mins 10 to 15mg/kg (max 1000mg)

Phenytoin MOA Phenytoin exerts a greater effect on the electrocardiographic ____ interval than does _________ and shortens the ___ interval more than any of the other antiarrhythmic drugs

QTc Lidocaine QTc

The ability of some volatile anesthetics to depress the ________ node is a consideration if administration of phenytoin during general anesthesia is planned

sinoatrial node

Phenytoin is ________ in the liver and then _______ with glucuronic acid for excretion in the __________

hydroxylated conjugated urine

Impaired _______ function may result in higher than normal blood levels of phenytoin

hepatic

_______, _________, and _________ may inhibit metabolism and increase phenytoin blood levels

warfarin phenylbutazone isoniazid

Phenytoin toxicity most commonly manifests as _____ disturbances, especially ________ disturbances (6)

CNS Cerebellar Ataxia, nystagmus, vertigo, slurred speech, sedation, mental confusion

Phenytoin partially inhibits _______ secretion

insulin

In phenytoin, _______, _______, and ________ may occur as a manifestation of drug-induced bone marrow depression

leukopenia granulocytopenia thrombocytopenia

Flecainide is a fluorinated local anesthetic analogue of _________- that is more effective in suppressing _________ __________ beats and __________ _________ than quinidine and disopyramide

procainamide premature ventricular ventricular tachycardia

Flecainide is effective for treatment of __________ and ________ tachyarrhythmias

ventricular and atrial

Oral absorption of flecainide is ________, and a prolonged elimination half-time (about ____ hours) makes twice daily dose of ____ to ____mg acceptable

excellent 20 hours 100-200mg

Elimination of flecainide is decreased in patients with __________, ___________, or decreased __________

congestive heart failure renal failure left ventricular function

Flecainide Proarrhythmic effects occur in a _______ number of treated patients especially in presence of ______________

significant left ventricular dysfunction

Flecainide prolongs the _______ complex and may depress ______ function, as do beta-adrenergic antagonists and calcium channel blockers Do not administer in patients with ____ and ____ degree AV heart block

QRS sinoatrial node second and third

The most common noncardiac adverse effect of flecainide is dose-related ______ _______

blurred vision

Flecainide increases the _______ _______ of pacemakers

capture thresholds

Propafenone, like flecainide, is an effective oral antiarrhythmic drug for suppression of ________ and ______ tachyarrhythmias

ventricular atrial

The rate of metabolism is genetically determined with about ____% of patients able to metabolize propafenone efficiently in the liver Availability of propafenone increases significantly in the presence of _____ disease

90% liver

Propafenone depresses the myocardium and may cause conduction abnormalities such as ________, _________ , and _______

sinoatrial node slowing AV block BBB

Propafenone interferes with the metabolism of _________ and _______ resulting in increased plasma concentrations of these beta blockers Also increases the plasma concentration of ______ and may prolong __________

propranolol metoprolol warfarin prothrombin time

Beta-adrenergic antagonists are effective for treatment of cardiac arrhythmias related to enhanced activity of the _________

sympathetic nervous system

Multifocal atrial tachycardia may respond to esmolol or metoprolol but is best treated with _________

amiodarone

Beta-adrenergic antagonists, especially __________, may be effective in controlling torsades de pointes for patients with prolonged QTc intervals

propranolol

__________, ________, and _________ are approved for prevention of sudden death following ____________

Acebutolol Propranolol Metoprolol myocardial infarction

Amiodarone is a potent antiarrhythmic drug with a wide spectrum of activity against refractory___________ and ___________ tachyarrhythmias

supraventricular ventricular

Amiodarone _____ mg IV is recommended for ventricular tachycardia or fibrillation resistant to electrical defibrillation

300

Preoperative oral administration of amiodarone decreases the incidence of ______ ______ after cardiac surgery It is also effective for suppression of tachyarrhythmias associated with ______ _______ ______ syndrome

atrial fibrillation Wolff-Parkinson-White

Amiodarone MOA Prolongs the _______ ________ ______ in all cardiac tissues and also has an __________ effect (noncompetitive blockade of __ and __ receptors)

effective refractory period antiadrenergic alpha and beta

Amiodarone acts as an ________ drug by dilating _________ _______ and increasing coronary blood flow

antianginal coronary arteries

Amiodarone has a __________ elimination half time (___ days) and is minimally dependent on _____ excretion

prolonged 29 renal

Amiodarone's prinicple metabolite, __________ is pharmacologically active and has a _______ elimination half-time than the parent drug, resulting in __________ of this metabolite with chronic therapy

desethylamiodarone longer accumulation

Side effects in patients treated chronically with amiodarone are _______, especially when the daily maintenance dose exceeds _____mg

common 400mg

Screening tests recommended for chronic administration of amiodarone: (4)

chest radiographs pulmonary function tests thyroid-stimulating hormone liver function

Amiodarone side effects (7)

Neurologic toxicity Optic neuropathy Corneal microdeposits Prolong the QTc interval Heart rate often slows and is resistant to atropine Pulmonary alveolitis Transient, mild increases in plasma transaminase and fatty liver infiltration

Amiodarone inhibits hepatic _____ enzymes resulting in increased plasma concentrations of ______, _____, ______, _____, and _______

P450 digoxin, procainamide, quinidine, warfarin, cyclosporin

Amiodarone displaces ________ from protein-binding sites

digoxin

Verapamil is highly effective in terminating paroxysmal __________ __________, controls _______ tachycardia, and effectively controls the ventricular rate in most patients who develop ______ ______ or ________

supraventricular tachycardia reentrant atrial fibrillation flutter

Verapamil does not have a depressant effect on _______ _______ and will not slow the ventricular rate in patients with _______ syndrome

accessory tracts WPW

Verapamil has little efficacy in the therapy for _______ ectopic beats

ventricular

The usual dose of verapamil for suppression of paroxysmal supraventricular tacyhcardia is __ to ___mg IV (____ to ____mcg/kg) over ___ to ___ mins followed by a continuous infusion of about ____mcg/kg/minute to maintain a sustained effect

5 to 10mg IV (75-150mcg/kg) over 1 to 3 mins 5mcg/kg/min

Before administration of verapamil, the administration of _______ ______ before administration may decrease verapamil-induced hypotension without altering the drug's antiarrhythmic effects dose: ____ g IV approximately ___ mins before

calcium gluconate 1g IV 5 mins

Verapamil MOA Verapamil and the other calcium channel blockers inhibit the flux of ________ ions across the ______ channels of vascular smooth muscle and cardiac cells Manifests as a decreased rate of spontaneous phase ___ depolarization

calcium slow 4

Verapamil has a substantial depressant effect on the ___ node and a ________ _______ effect on the SA node

AV negative chronotropic

Verapamil exerts a ________ inotropic effect on cardiac muscle and produces a moderate degree of ________ of the coronary arteries and systemic arteries

negative vasodilation

An estimated ___ % of an injected dose of verapamil is eliminated by the _______, whereas up to ___% may be present in the _____

70% kidneys 15% bile

The need for a large oral dose of verapamil is related to the extensive ______ ______ effect that occurs with the oral administration

hepatic first-pass

Verapamil side effects ____ block is more likely in patients with _______ defects in the conduction of cardiac impulses

AV preexisting

Verapamil side effects Direct _______ ________ and decreased ________ ______ are likely to be exaggerated in patients with poor ________ ________ function

myocardial depression cardiac output left ventricular

Verapamil side effects ____________ _________ may contribute to hypotension

Peripheral vasodilation

Verapamil side effects There may be potentiation of anesthetic-produced _______ ______, and the effects of _______ ________ _______ may be exaggerated

myocardial depression neuromuscular blocking drugs

Digitalis preparations such as digoxin are effective cardiac antiarrhythmics for stablization of _____ electrical activity and the treatment and prevention of ______ tachyarrhythmias

atrial atrial

Because of digoxin's _________ effects, these drugs can also slow conduction of cardiac impulses through the ______ node and slow the ventricular response rate in patients with ______ _____

vagolytic AV atrial fibrillation

Digitalis can enhance conduction of cardiac impulses through ______ _____ _____ and can dangerously increase the ventricular response rate in patients with _______ syndrome

accessory bypass tracts WPW

The usual oral dose of digoxin is ____ to ____ mg in divided doses over ___ to ___ hours

0.5 to 1.0 mg divided in doses over 12 to 24 hours

Digitalis toxicity is a risk and may manifest as virtually any _______ _______ Most commonly ______ ______ with ______

cardiac arrhythmia atrial tachycardia with block

Adenosine is an endogenous _______ that slows the conduction of cardiac impulses through the ____ node

nucleoside AV

Adenosine is an alternative to ______ ______ _____ for treatment of acute paroxysmal _________ _________

calcium channel blockers supraventricular tachycardia

Adenosine can be used in patients with _______ syndrome

WPW

Adenosine is not effective in the treatment of _______ ______, ________ ______, or ________ ________

atrial fibrillation atrial flutter ventricular tachycardia

Usual dose of adenosine is ___mg IV followed, if necessary, by a repeat injection of ___ to ___mg IV about __ minutes later

6mg 6-12mg 3 minutes

Adenosine receptors represent a local target for treatment of ______

pain

Adenosine MOA Adenosine stimulates cardiac adenosine receptors to increase ____ ion currents, ______ action potential duration, and _______ cardiac cell membranes

potassium shorten action potential duration hyperpolarize

Adenosine's short-lived cardiac effects (elimination half time ___ sec) are due to carrier-mediated cellular uptake and metabolism to _______ by ______ _______

10 seconds inosine by adenosine demaminase

Adenosine may produce transient _____ ______ ____________ has been observed after IV administration

heart block bronchospasm

The pharmacologic effects of adenosine are antagonized by methylxanthines (________, ________) and potentiated by _________

theophylline, caffeine dipyridamole

Which drug is associated with systemic lupus?

procainamide