Vasodilators, Antihypertensives and Negative Inotropes Flashcards
What are the primary actions of Calcium channel blockers?
Negative inotropic effect
Negative dromotropic effect (AV conduction block)
Vasodilation of systemic, splanchnic, coronary and pulmonary beds
What are the 3 classes of calcium channel blockers?
Phenylalkylamines
Benzothiazines
Dihydropyridines
What drug is a phenylalkylamine and what is its use?
Verapamil Used for conversion of supraventricular (atrial) tachycardia Coronary artery spasm Aortic stenosis and IHSS Vasospastic angina Essential HTN
What drug is a benzothiazine and what is its use?
Diltiazem
Used for rate control of tachycardia, tachyarrhythmias
Renal protection
What drugs are dihydropyridines?
Nifedipine Nicardipine Nimodipine Nitrendipine Isradipine
What are the indications of dihydropyridines?
Hypertension
Afterload reduction
Cerebral vasospasm, ischemia
Renal protection
Is the Dihydropyridine class pure arterial or veno-vasodilators?
Pure arterial vasodilators but with minimal reflex tachycardia
What is Cardene?
Potent vasodilator of systemic, coronary and cerebral circulations without important negative inotropic or dromotropic effects
An arteriole specific vasodilator
Is coronary steal present with the use of Cardene?
No coronary steal syndrome, favorable myocardial oxygen supply/demand
What are the pharmacokinetics of Cardene?
Onset: 20-30 seconds
Duration: 15-20 minutes
Why is Cardene useful for IV control of HTN in the PACU or ICU?
Slower onset and offset that SNP Easier to use with less swings in BP No rebound HTN with W/D Reflex tachycardia <10 bpm Prolonged DOA may be a benefit postop
What are the advantages to Cardene?
Dose dependent arterial vasodilation No arterial cath No coronary steal Cerebral and coronary vasodilation Minimal effects on contractility/conduction Mild natriuretic effect
What are the disadvantages to Cardene?
Slow onset/offset May accumulate Variable DOA Hypotension Venous irritation May cause tachycardia
What is Clevidipine?
Newest IV CCB
A dihydropyridine
Vasodilation reduces PVR, arteriole specific
What are the pharmacokinetics of Clevidipine?
Onset: <5mins
Peak: 10 mins
Duration: 10-20 minutes
Half-life: 1 min
What are the advantages to Clevidipine?
Rapid onset/offset Reduced need for other antihypertensives Reliable control No dose adjustments for renal/hepatic disease Ready to use vial No significant myocardial depression No effect on preload Low potential for drug interactions
What are the disadvantages to Clevidipine?
Lipid emulsion Continuous monitoring required Contraindicated with egg and soy bean allergy Pancreatitis HLD
What is the max amount of Clevidipine are you allowed to give
No more than 1L or 21 mg/hr recommended
Are Dihydropidines arterial or venous vasodilators?
Virtually pure arterial vasodilator
Which drug has the most Negative inotropy and AV block?
Verapamil
What are the adverse effects of CCBs?
CNS: dizziness, HA, fatigue, insomnia, nervousness
CV: flushing, edema, palpitations, bradycardia
Respiratory: nasal congestion, dyspnea, cough
GI: NVD
Other: Arthralgias, joint stiffness, ittching
How does Verapamil and Diltiazem enhance myocardial oxygen balance?
Decreasing myocardial oxygen consumption by afterload reduction and/or negative inotropic effect
Increasing O2 delivery through coronary vasodilation
What is Dihydropyridines’ effect on myocardial oxygen balance?
May worsen MvO2 by causing diastolic hypotension and reflex tachycardia (except Nicardipine)
What are CCBs effect on renal function?
Increase RBF and GFR and induce a naturesis
Protective in renal transplantation against a variety of nephrotoxic drugs and radiocontrast media
How can the benefits of CCBs on renal function be reversed?
Hypotension, reflex catecholamine release or angiotensin activation leading to decreases in RBF and GFR
T/F: It is safe to continue CCBs up to the time of surgery without risk of significant drug interactions
True
What may CCBs do to neuromuscular blocking agents?
May potentiate the effects of neuromuscular blocking agents
Does Clevidipine speed up or slow down gastric emptying?
Reduced gastric emptying
Which CCB increases sedative effects of midazolam?
Diltiazem
Droperidol, Haloperidol, and Phenothiazines can cause vasodilation how?
By acting at the alpha1 or DA1 receptors
How do you treat reflex tachycardia and increased contractility?
With a BB or Trimethaphan
What are the actions of beta blockers?
Decrease CO (HR and contractility) Decrease renin release
T/F: Beta blockers vasodilate
False
What are the advantages of beta blockers over vasodilators?
No reflex tachycardia or widening of pulse pressure
Improved MvO2 (decrease HR and contractility)
Intrinsic antiarrhythmic activity
No effect of hypoxic pulmonary vasoconstriction
What are the Beta1 selective drugs?
Metoprolol Atenolol Acebutolol Bisprolol Esmolol
What is the mechanism of action of the Beta1 selective drugs?
Decrease velocity of AV conduction, HR, contractility, renin release and lipolysis
What are the non-selective beta drugs?
Propanalol Nadolol Timolol Pindolol Cartelolol
How do the non-selective beta drugs work?
On beta1
On beta-2 causing bronchoconstriction, peripheral vasoconstriction and decrease glycogenolysis
What are the combine alpha1 and non-selective beta drugs?
Carvedilol and labetalol
What is the elimination half-life of beta blockers?
Long-acting (glucuronide hepatic biotransformation)
Intermediate-acting (rapidly hydroxylated by the liver, first pass effect)
Short-acting (red cell esterases)
What are the long-acting beta blockers?
Nadolol
Atenolol
What are the intermediate-acting beta blockers?
Propanolol
Metoprolol
What are the ultra short-acting beta blockers?
Flestolol
Esmolol
Which drugs have low lipophylicity?
Acebutolol Atenolol Bisoprolol Cateolol Nadolol
Which drugs had moderate lipophylicity?
Metoprolol
Pindolol
Coreg
Labetalol
Which drugs have high lipophylicity?
Penbutolol
Propanolol
What are the adverse effects of beta blockers?
Non-selective blockade of beta 2 receptors–>vasoconstriction and worsening PVD, bronchospasm
Myocardial depression (decreased contractility could precipitate CHF)
Life-threatening bradycardia or asystole
Hyperkalemia in renal failure
Use BB with caution with which 2 drugs?
Verapamil (decrease HR and contractility)
Digoxin (decrease HR and conduction)
What is the treatment if overdose of BBs occur?
Treat with atropine
May need isoproterenol, dobutamine and/or glucagon infusion
Ultimately may need pacing
What are the preop indications of beta blockers?
Control intra and postop HTN and tachycardia
Rate control and/or conversion of SVT, afib and aflutter
Myocardial protection in ischemic heart disease, AS, or IHSS
Sympathetic response to ECT
Peripheral manifestations of hyperthyroidism
Which BB is effective in limiting HTN during induction and emergence?
Esmolol
What are the contraindications to BBs?
Severe bradycardia
>1st degree heart block
Cardiogenic shock
Raynaud’s disease
What type of patients do you use caution with when giving BBs?
Asthma/COPD
Diabetes
Heart failure
What is propranolol?
Proptotype non-selective BB
Lipid soluble and can penetrate CNS
Undergoes first pass effect (up to 70% metabolized by the liver)
T/F: Esmolol is more likely than verapamil to convert afib to SR
True
What are the pharmacokinetics of Esmolol?
Rapid onset and offset Metabolized by red cell esterases Short t1/2: 9-10 minutes Peak effects: 5-10 mins Duration: 20-30 mins
What is Metoprolol?
Beta 1 selective agent
Treatment of angina and acute MI
Antihypertensive
How does Labetalol work?
Combines weak alpha blockade with weak non-selective beta blockade
Negative inotrope and chronotrope with vasodilatation provides effective antihypertension action
What are the indications for Labetalol?
Hyperdynamic HTN (blunts CV response to tracheal intubation)
Treatment of aortic dissection
Tachyphylaxis with SNP
Intracranial HTN (does not increase ICP)
Toxemia of pregnancy (Not in first trimester, uterine blood flow is preserved)
What are the adverse effects of Labetalol?
Unwanted negative inotropy
Prolonged DOA with high doses
Bronchospasm in high doses (not beta1 selective)
Acute hyperkamlemia in renal failure (large doses)
Use caution when treating postop HTN in hypothermic patients: when patients rewarm, persistent beta blockade may blunt increases in CO and exacerbate rewarming hypotension (vasodilatation)
How does Coreg work?
Combines alpha blockade with nonselective beta blockade
Decreases myocardial O2 demand and cardiac work
What are the uses of Carvedilol?
3-5 times more potent that Labetalol in decreasing BP
Treat angina, CHF and dysrhythmias
Why do you not abruptly stop BBs?
Rebound HTN and tachycardia
What might BBs mask?
Hypoglycemia and hyperthyroidism
What do you do if your patient becomes hypertensive intraop?
Check depth of anesthesia and administer sufficient analgesia
R/O hypercarbia, distended bladder, hyperthermia, hypoxia, thyroid storm, malignant hyperthermia
What is the first line therapy of intraop HTN?
BBs then... Vasodilators (hydralazine, NTG, SNP) CCBs Diuretics (for patients with evidence of pulm edema or with increased ICP and HTN) Alpha2 agonists ACE inhibitors
Which antihypertensive is favored in pregnancy?
Alpha-methyldopa
T/F: ACEI can be used in the 2nd and 3rd trimesters
False, cause fetal morbidity and mortality
Labetalol can be used in 2nd and 3rd trimesters. BBs are associated with growth retardation in 1st trimester
What is a hypertensive emergency?
Acute elevation of SBP >180 or DBP >120
What is the goal if you have a hypertensive emergency?
Reduce MAP by no more than 25% within minutes to hours. Reach 160/100 within 2-6 hours
What happens if you have excessive correction of HTN?
Renal, cerebral, coronary ischemia
What is a hypertensive urgency?
Accelerated, malignant, or perioperative increase in BP without target organ damage
What type of therapy is preferred for a hypertensive urgency?
PO therapy and immediate BP lowering is not required
These are drugs used to control the primary determinants of myocardial oxygen consumption in ischemic heart disease
Negative inotropes and chronotropes
What is the mechanism of action for negative inotropes/chronotropes?
Beta1 antagonists (propranolol, esmolol, metoprolol) Calcium channel antagonists Direct effects (inhaled anesthetics)
What are the hemodynamic effects of negative inotropes/chronotropes?
Decrease contractility and HR
Decrease CO and BP and may increase RA and LA pressures
T/F: Calcium channel blockers are vasodilators and will decrease arterial resistance
True
What are the indications for negative inotropes/chronotropes?
Decrease myocardial O2 consumption
Treatment of arrhythmias (sinus tach, SVT)
Myocardial preservation
What are the contraindications to using negative inotropes/chronotropes?
Low CO
Bronchospastic pulmonary disease
Prolonged conduction block (2nd degree heart block may progress to 3rd degree block with beta blockers or verapamil)
Myocardial ischemia represents what?
A mismatch of oxygen delivery and oxygen demand on a regional or global basis
What is resting fractional O2 extraction from myocardial capillary blood?
65-75%
How is O2 delivery determined?
Arterial O2 content x CBF
How is CBF determined?
CPP/coronary vascular resistance
What is the essence of myocardial perfusion?
CPP
How is CPP determined?
Driving pressure - intramyocardial pressure
Myocardial blood flow can increase 5 fold by what?
By local metabolic vasodilation
Patients with CAD, vascular resistance is more fixed and depends on what?
Atheromatous stenosis
Active coronary vasomotor tone
Collateral blood flow
Duration of ___ regulates the time available for coronary perfusion to the LV endocardium
Diastole
MvO2 is primarily regulated by what?
Wall stress (preload and afterload)
Contractility
Heart rate
___ work requires more energy than ___ work
Pressure
Volume
Increased HR, contractility or pressure work by 50% increases MvO2 how much?
50%
Increasing volume work by 50% increases MvO2 how much?
<5%
The force or load acting to stretch ventricular fibers at end-diastole
Preload
The force that myocardial fibers sense that opposes fiver shortening once contracting is initiated
Afterload
What is used as an index of afterload instead of ventricular wall stress?
SVR
T/F: in a normal ventricle, inotropes increase contractility and reduce ESV, EDV, and ultimately wall stress and MvO2
False, in a dilated ventricle
T/F: in a normal ventricle, heart size and wall stress are not substantially reduced by an inotrope so MvO2 parallels the increased contractility
True
Does an increased or decreased HR reduce EDV and consequently SV so that CO remains constant
Increased HR
T/F: Increasing HR decreases MvO2 and the extent of myocardial ischemic injury
False, increasing HR increases MvO2
What are the therapeutic goals for myocardial ischemia?
Maintain normal value of CPP with the smallest heart size possible
Any therapy that decreases CPP below normal values or increases CPP to supranormal values will increase the amount of injury
