Vasodilators/Antiarrhytmic/Diuretics Flashcards
Calcium Channel Blocker (CCB) Mechanism of Action
Inhibit Ca2+ influx through L-type Ca2+ channels in vascular smooth muscle
- Arterial specific
Nicardipine Drug class & Dosing
Dihydropyridine CCB
- Bolus: 100-400mcg
- Infusion: 5-15mg/hr
Nicardipine Onset/Half-life/Metabolism
- Onset: 2-10 min
- Half-life: 2-4 hrs
- Liver
Clevidipine Drug class & Dosing
Dihydropyridine CCB
Infusion: 1-16mg/hr
Clevidipine Onset/Half-life/Metabolism
- Onset: 2-4 min
- Half-life: 1 min
- Plasma esterases
Hydralazine Onset/Half-life/Metabolism
- Onset: 5-20min
- Half-life: 2-8hrs
- Hepatic
Hydralazine Drug class & dosing
Arteriolar Dilator
5-20mg IV Bolus
Fenoldopam Drug Class & Dosing
Dopamine type 1 agonist
- Infusion: 0.05-1.6mcg/kg/min
Fenoldopam Onset/Half-life/Metabolism
- Onset: 5-10 min
- Half-life: 5 min
- Hepatic
S/E of Fenoldopam
- Increase in HR (baroreceptor) & catecholamines
- Increase IOP pressure don’t give with glaucoma
Sodium Nitroprusside Drug class & Dosing
NO donor
Infusion: 0.25-4mcg/kg/min
Sodium Nitroprusside Onset/Half-life/Metabolism
Onset: 1-2min
Half-life <10min
Erythrocytes & hepatic
S/E of Nitroprusside
- Baroreceptor reflex tachycardia
- Coronary steal -> Inc. MI damage area
- Cyanide Toxicity
- Methemoglobinemia
Clinical use of SNP?
- Use significantly declined
- Controlled HoTN
- HTN emergency
- Ao. & Cardiac Surgery
- HF
Nitroglycerin Drug class & Dosing
NO donor
- Bolus: 20-400 mcg
- Infusion: 10-400 mcg/min
Nitroglycerin Onset/Half-life/Metabolism
Onset: 1-2min
Half-life: 1-3 min
Hepatic/Erythrocytes/vascular walls
Hepatic dysfunction pts receiving Nitroglycerin are @ high risk for what?
High dose -> methemoglobinemia
Clinical use of Nitroglycerin
- Most common use: Angina Pectoris (IV/sublingual)
- MI
- Controlled HoTN (tolerance is problem)
- Not for Ao. Stenosis or HCM
Should chronically administered antiarrhytmics be taken up until induction? Why or Why not?
Should be continued up to induction
- Pose little threat to anesthesia
Catheter ablation techniques are the preferred treatments for what arrhythmias?
- Supraventricular arrhythmias
- Afib/flutter
When might pharmacologic management of arrhythmias be appropriate?
- Suppression of Afib/flutter not responsive to catheter ablation
- Pts with AICDs who be getting zapped alot
What are the two physiological mechanisms by which ectopic cardiac arrhythmias occur?
- Reentry
- Enhanced automaticity
What factors that facilitate arrhytmias may be encountered perioperatively?
(7)
- Hypoxemia
- Electrolyte imbalance
- Acid/Base abnormalities
- Myocardial ischemia
- Altered SNS activity
- Bradycardia
- Certain drugs
How do antiarrhythmic drugs exert their pharmacological effects?
Blocking passage of ions across ion channels in the heart
Which ions may be blocked by antiarrhythmics?
- Na+
- K+
- Ca2+
What factors determine the clinical effects of antiarrhythmics?
Their effects on:
- Action potentials
- Effective refractory period
Grouping of antiarrhythmics are based on what two abilities?
- Control of arrhythmias by blocking specific ion channels
- Altering currents during the action potential
What historical use is lidocaine no longer recommended for?
Prophylaxis for pts presenting with an early MI
without ventricular ectopy
What is a common complication after heart surgery that is associated with prolonged hospitalization & CV morbidity?
A fib
Prophylactic treatment of Afib with what drugs is effective in reducing what?
Drugs:
* Amiodarone
* β blockers
* Sotalol
* Magnesium
Effective in reducing:
* Afib occurrence
* Length of hospital stay
* Cost of tx
* risk of stroke
When is the benefit of antiarrhythmics clear?
Results in termination of a sustained tachycardia
What class is Quinidine? Arrhythmias it treats?
Class IA
* Acute/Chronic SVT
* SVTs associated with WPW (quite effective)
Would you treat a patient in SVT with quinidine? Why or why not?
No, it is rarely used because of its side effects
MoA of Quinidine
- Decreases slope of phase 4 depolarization
- via suppression enhanced automaticity
Where is Quinidine metabolized? Eliminated?
- Hydroxylated in Liver
- Inactive metabolites in urine
Side effects of Quinidine
- Heart Block
- HoTN
- Proarrhythmia effects
Class of Procainamide? Arrhythmias it treats?
Class IA:
* V. tachyarrhythmias > A. tachyarrhythmias, compared to quinidine
* pSVT
* PVCs
How is procainamide metabolized? What can this effect?
- Via acetylation by N-acetyltransferase enzyme
- Genetically determined -> Rapid acetylation = Half-life 2.5 hrs
- Slow acetylators = 5 hrs
S/E of Procainamide?
- HoTN r/t myocardial depression > vasodilation
- Chronic use -> lupus erythematosus like syndrome
Like qunidine, Procainamide use has what?
Decreased due to:
* Side effects
* Availability of newer agents
Antiarrhythmic strengths & weaknesses of Lidocaine?
- Suppression of V. arrhythmias
- minimal (if any) effect on SVTs
Class of Lidocaine & advantages over IA?
Class IB:
* Rapid onset/offset
* Reduced S/E profile
* Greater therapeutic index
Clinical effect of Lidocaine?
- Decreases rate of spontaneous depolarization in ventricular cells -> decreases PVCs
- Not so much in atrial cardiac cells
Clinical use of Phenytoin as an antiarrhythmic
- Suppress V. arrhythmias r/t digitalis toxicity
- pVT
- TDP
Dosing of Phenytoin
- 100mg (1.5mg/kg) q 5 min until arrhythmia controlled
- or 10-15mg/kg (1000mg MAX)
Which drug has more of an effect on QTc? Phenytoin or Lidocaine?
Phenytoin
- shortens QTc more than any other antiarrhythmic
What are some concerns about co-administration of Phenytoin and Volatile anesthetics?
Phenytoin depresses SA node
* Volatile Anesthetics depress SA node too
S/E of Phenytoin?
- Toxicity causes CNS disturbances
- Inhibits insulin secretion
- Bone marrow suppression -> Leukopenia, granulocytopenia, & thrombocytopenia
Symptoms of Phenytoin CNS toxicity?
- Ataxia
- Nystagmus
- Vertigo
- Slurred Speech
- Confusion
What is Flecanide and what does it treat?
Class IC antiarrhythmic
- Treats PVCs & VT > quinidine & procainamide
- Treats A. tachyarrhythmias
S/E of Flecanide
- Proarrhythmic w/ LV dysfunction
- Prolonged QRS & depress SA node function (NO Heart blocks)
- Dose-dependent blurred vision
- Increases threshold potential of PPMs
Most Common non-cardiac adverse effect of Flecainide?
Dose dependent blurred vision
Flecainide’s effects on PPMs?
Increases the capture threshold
Class of Propafenone and effects?
Class IC
- Supresses V. & A. tachy arrhythmias
S/E of Propafenone?
- Depress myocardium
- AV Block
- BBB
- SA node slowing
What dysrhythmias are β-blockers effective at treating
Cardiac arrhythmias r/t enhanced activity of the SNS
Which β-blockers are approved for prevention of sudden cardiac death following MI?
- Acebutolol
- Propanolol
- Metoprolol
Propanolol may be effective in controlling what arrhythmias?
TDP for pts w/ prolonged QTc
Class of Amiodarone and treated arrhythmias?
Class III (K channel inhibitor)
* V. Tachyarrhythmias
* Refractory SVTs
* V-tach/Vfib resistant to defibrillation
* WPW tachyarrhythmias
Preoperative oral administration of Amiodarone decreases the incidence of what?
Atrial fibrillation post cardiac surgery
Mechanism of action of Amiodarone?
Non-competitive β & αÂblockade
* Prolongs refractory period in all cardiac tissues
* Dilates coronary arteries -> antianginal
Half-life of Amiodarone?
29 days
Side effects of Amiodarone
8
- Pulmonary alveolitis
- QTc Prolong
- HR slowing resistant to atropine
- Corneal Microdeposits
- Optic neuropathy
- Neurologic toxicity
- Inc. plasma transaminase
- Fatty liver infiltration
What drugs are Class IV antiarrhythmics, what do they do?
CCBs or inhibit slow Ca2+ channels
* Verapamil
* Diltiazem
What arrhythmias is Verapamil effective in treating?
- pSVT
- reentrant tachycardia
- Afib/Flutter by controlling V. rate
Dose of Amiodarone for defibrillation resistant Vfib/Vtach?
300 mg IV
Dose/dosing of verapamil for pSVT?
75-150 mcg/kg over 1-3 min
- Follow by 5mcg/kg/min infusion
Administration of what drug and dose to reduce Verapamil induced HoTN? When do you give it?
1gm IV of Calcium gluconate
* 5 min before
Verapamil/Diltiazem Mechanism of Action?
Inhibit flux of Ca2+ across slow channels in vascular/cardiac smooth muscle
* Decreased rate of spontaneous (phase 4) depolarization
Verapamil/Diltiazem S/Es?
- AV HB in pts w/ pre-existing conduction defects
- Myocardial depression -> Dec. CO
- Vasodilation -> HoTN
- Effects of NMB exaggerated
What arrhythmias are Digitalis preparations effective treating?
Atrial tachyarrhythmias via Atrial stabilization
What patients might you want to avoid Digitalis in? Why?
Wolf-parkinson-white syndrome
* enhances conduction through acessory bypass tracts
* Increases ventricular response rate
Dosing of Digitalis?
0.5 - 1 mg over 30 min-1 hr
Most common sign for Digitalis toxicity?
May manifest as any arrhythmia but most commonly atrial tachycardia w/ block
Adenosine clinical action & arrhythmias treated?
Slows conduction of cardiac impulses through AV node
* Alternative of CCBs for pSVT
* WPW syndrome
What arrhythmias is Adenosine poor at treating?
- Afib
- Aflutter
- ventricular tachycardia
Dosing of Adenosine
6mg IV
May repeat 3 min later with 6-12mg IV
Adenosine mechanism of action?
Stimulates cardiac adenosine1 receptors to increase K+ currents
* Shortens action potential duration
* hyperpolarize cardiac cell membrane
S/E of Adenosine?
- Transient AV HB
- Bronchospasm after IV administration
How do most diuretics exert their effects?
Block Na+ reabsorption in differeent locations of the nephron
* Increases Na+ delivery to distal tubules
Loop diuretics are first-line therapy in what population
Pts w/ fluid retention with HF
Maximum dose of Furosemide in pts w/ normal renal function?
40mg IV will produce max naturiuresis
How do loop diuretics manage hypertension?
By their effects on fluid volume & Salt excretion
Is Furosemide or Mannitol more effective in managing ICP?
Combination of Furosemide & Mannitol most effective in decreasing ICP compared to each drug alone
How does Furosemide lower ICP?
- Systemic diuresis
- Decrease CSF production
Furosemide dosing? With Mannitol?
0.5-1.0 mg/kg IV
* 0.1-0.3 mg/kg w/ Mannitol
S/E of Furosemide?
- Hypokalemia
- Tolerance
- HoTN
- Exacerbation of Renal ischemic injury
Loop diuretics increase renal concentrations of what drugs? What effect is this?
Aminoglycosides (gentamycin, tobramycin, neomycin) & Cephalosporin
* nephrotoxic effects
What drugs are potentiated by Loop diuretics?
ND NMBs
What is a transient or permanent, but rare, side effect of Loop Diuretics?
Ototoxicity that is dose-dependent
Thiazide diuretics are most often recommended and administered for what disorder?
Long-term treatment of essential HTN
What effects are synergistic in the treatment of essential HTN?
Combination of:
* Diuresis
* Natiruresis
* Vasodilation
Where does the sustained control of HTN in Thiazide diuretics come from?
Peripheral vasodilation that requires several weeks of therapy to develop
Describe osmotic diuretics
Inert substances that do not undergo metabolism & are freely filtered @ the glomerulus
What drugs are osmotic diuretics?
- Mannitol
- Urea
- Isosorbide
- Glycerin
Mechanism of Action of Osmotic Diuretics?
- Increased plasma & renal tubular fluid osmolality
- Results in osmotic diuresis
Which osmotic diuretic is the only one in use?
Mannitol
Describe Mannitol’s structure?
6 carbon sugar alcohol that does NOT undergo metabolism
Primary uses of Mannitol?
- Acute elevation of ICP
- Tx of Glaucoma
What is required for cerebral effects of mannitol?
Intact blood-brain barrier
What are you worried about if the blood-brain barrier isn’t intact with Mannitol administration?
It may enter the brain while drawing fluid with it
* worsening of the cerebral edema
What additional benefit does Mannitol exert on the body? what can this benefit do?
Scavenges free-radicals
* Protects the kidneys
What has Mannitol NOT been shown to prevent?
Perioperative renal failure in cardiac & major vascular surgery
Which diuretic may be preferred in patients with increased ICP & LV dysfunction?
Furosemide
Long term effects of Mannitol?
- Hypovolemia
- Hypokalemic/hypochloremic alkalosis
- Plasma hyperosmolarity 2/2 Na+ & H2O excretion
