Drugs for Aortic Dissection Flashcards
How do Beta Blockers work for treating Aortic Dissection?
- Block Epinephrine’s effects
- Cause heart to beat slower and with less force, lowering BP
- Opens arteries/veins to improve flow
What are four common Beta Blockers used for aortic dissection?
Labetalol
Esmolol
Nitroprusside
Nicardipine
What is the MOA for Labetalol?
alpha and beta blocker
What are the indications for Labetalol?
treatment for arterial hypertension
used alone or in combo with other antihypertensives
What are contraindications for Labetalol?
HYPERSENSITIVITY
cardiac failure
2-3’ AV block
severe bradycardia
cardiogenic shock
severe hyptension
obstructive airway disease (Asthma)
What are the adverse effects of Labetalol?
Dizziness, tingling, fatigue, HA
What are the warnings and precautions for Labetalol?
hepatic injury
cardiac failure
worsening ischemic heart disease
bronchospasm
pheochromocytoma
DM, hypoglycemia
major surgery
What are some drug interactions of Labetalol?
Tricyclic antidepressants
Beta-Receptor agonists
Cimetidine
Halothane Anesthesia
NTG
Calcium antagonists (verapamil)
Digitalis
What are the pregnancy/lactation warnings for Labetaloll?
Cat. C in pregnancy
Small amount excreted in milk
What are the pediatric and geriatric indications for Labetalol?
Peds: Nothing established
Geratrics: caution, lower dose, concern for orthostatic hypotension
What percentage of Labetalol dose appears in urine as a conjugate or unchanged drug within the first 24 hours of dosing?
55-65%
How does pregnancy hormones effect Labetalol metabolism?
increase in progesterone causes an increase in labetalol glucoronidation, thereby allowing labetalol concentration to fall below the therapeutic value
What is the MOA of Esmolol?
Class II Antiarrhythmic
Blocks B1 adrenergic with no effect on B2 (except at high doses)
What are the indications for Esmolol?
Control rapid heartbeats or abnormal rhythms
used to treat fast heart rate and HTN during/after surgery or during other procedures
What are the contraindications for Esmolol?
Asthma
cardiac failure
shock
bradycardia
hypersensitivity
What are the pregnancy/lactation concerns for Esmolol?
Fetal bradycardia
may be used in hypertensive emergencies
unknown if present in milk
What are adverse reactions to Esmolol?
Anaphylactic reactions
*giving epinephrine to pt’s on beta-blockers may promote undesirable effects or be uneffective (Big Yikes)*
Extravasation with skin necrosis
Esmolol carris a concerning risk for what associated with serum K?
Hyperkalemia leading to renal impairment
*monitor serum K during therapy
Esmolol can cause what effect in BP?
Hypotension
reduce dose or D/C to reverse BP drop usually within 30 min.
What is the metabolism of Emsolol like?
“soft drug” that is metabolized rapidly to an inactive form by the hydrolysis if ester linkages
What is the MOA for Nitropursside?
Na Nitroprusside breaks down in circulation to release NO
(Mechanism similar to Cialis-elevates cGMP)
What are the indications for Nitroprusside?
Lower BP immediately via injection
Reduce bleeding during surgery
treat acute HF/CHF
What are some contraindications for Nitroprusside?
Do not use for:
Compensatory HTN (AV stent/Coarctation of aorta)
Pt’s with inadequate cerebral circulation
Pt’s nearing death
What are common Adverse Reactions to Nitroprusside?
Bradyarrhthymia/Tachyrrhytmia
Hypotension
Palpitations
Ileus
Hemorrhage
CN poisoning
What is a concerning toxicity of Nitroprusside?
How to avoid this?
When more than 500mcg/kg is given faster than 2mcg/kg/min CN is generated faster than it can be eliminated
Giving with Na Thiosulfate can increase the rate of CN processing and reduce the hazard of CN toxicity
Pt’s receiving more than 10mg/kg of Nitroprusside will develop what?
Those with impaired renal function will predictably develop what?
Methemoglobinemia (rare)
Thiocyanate toxicity after prolonged rapid transfusions
What is the Black Box warning for Nitroprusside?
Excessive Hypotension
Cyanide Toxicity
What is Nitroprusside metabolized to? (thus contributing to it’s toxic effects)
One molecule of Nitroprusside is metabolized to Cyanomethemoglobin and four CN- ions
Thiosulfate reacts with CN to form thiocyanate which is eliminated in the urine
What is the MOA of Nicardipine?
Ca entry blocker
inhibits the transmembrane influx of Ca into cardiac muscle and smooth muscle without changing serum Ca concentration
*more selective to vascular than to cardiac muscle
What are the indications for Nicardipine?
short term injectable for HTN
oral medication for long term HTN control
What are the contraindications for Nicardipine?
advanced aortic stenosis
What are the adverse effects of Nicardipine
HA
Hypotension
tachycardia
N/V
What are the warnings of Nicardipine based on pharmacodynamic effects?
monitor for hypotension/tachycardia and avoid use in patients who have had cerebral ischemia or hemorrhage
What are the precautions of nicardipine in patient’s with angina?
can see increase in frequency, duration or severity of angina
What are the warnings of nicardipine in patients with heart failure?
titrate slowly when using IV nicardipine esp. in combo with beta-blockers in patients with heart failure due to negative inotropic effects
What are the warnings of nicardipine in patients with impaired renal function?
there is lower systemic clearance and higher AUC in those with moderate renal impairment when given IV or oral nicardipine
*titrate gradually in these patients*
Are there fertility, carcinogenesis or mutagenesis concerns in humans with Nicardipine?
unlikely
What are some reproductive/developmental toxicity concerns for nicardipine?
embryotoxic in white rabbits at higher doses but not at 16mg/kg/day-8x the max human dose
What is the pregnancy category for nicardipine?
Cat. C
What are the effects on pregnancy in animal studies of Nicardipine
IV on rats/rabbits during organogenesis only showed toxic effects at high doses
organogenesis issues only happened at really high doses
What are the Lactation concerns for nicardipine?
minimally excreted in milk
no adverse effects seen in infants
No pediatric effects studied
What are the concerns of Nicardipine in geratric populations?
Use a low dose initially
What are the greatest precautions for Nicardipine?
excessive pharmacodynamic effects
-closely monitor BP and heart rate
What are the four drug-drug interactions with Nicardipine?
B-Blockers
Cimetidine
Cyclosporine
Tacrolimus
What happens when Nicardipine and B-Blockers are mixed?
usually okay, but titrate slowly with Iv Nicardipine and B-blockers in heart failure patients
What happens when Nicardipine and Cimetidine are mixed?
increases nicardipine concentrations in plasma
What happens when cyclosporine and nicardipine are mixed?
elevates cyclosporine concentration through nicardipine inhibition of CYP3A4
What happens when nicardipine and tacrolimus are mixed?
elevated tacrlimus levels thorugh nicardipine inhibition at the CYP3A4
How is Nicardipine metabolized?
Mainly via CYP3A4
transported via P-Gp
