Lecture 6: Aortic Dissection Drugs Flashcards
What drug class is used to treat Aortic Dissection and what are 4 drugs of this family? (L/E/N/N)
Intravenous Beta Blockers!!
- block effects of epinephrine
- Labetalol, Esmolol, Nitroprusside, Nitrocardipine
Labetalol
What is its MOA, what pregnancy category is it in, and how is it cleared by pregnant and elderly populations?
MOA: given as racemic mixture (alpha and beta blocking activity) that decreases peripheral vascular resistance
- does not significantly alter HR or Cardiac Output
- 55-60% of dose appears in urine in first 24 hrs
- in Pregnancy Group C: animal studies show adverse fetus effects, but not studies in humans and benefits may outweight any risk (found in breast milk)
Pregnant: clearance inc. due to hormones
- falls below therapeutic value
Elderly: reduced elimination; orthostatic symptoms
Labetalol
What are counseling points for patients taking this drug?
- take exactly as prescribed and should not be discontinued without doctors advice
- consult physician at any signs of cardiac failure or hepatic dysfunction; transient scalp tingling may occur
- monitor other illnesses (renal failure) over regular intervals while on this drug
Esmolol
What is its MOA, what is its main indication, and how does it affect pregnant patients?
MOA: competitively blocks response to B1 adrenergic stimulation with little effect on B2 receptors (unless high dose)
I: used to treat fast HR and high BP during surgery, after surgery, and during other medical procedures
P: short-acting beta-blocker that can be used as alternative agent for hypertensive emergencies in pregnancy (can cause fetal bradycardia)
Esmolol
How does it affect breastfeeding patients?
- not known if present in breast milk, but due to potential serious effects in infants, manufacturer recommends decision to either discontinue breastfeeding OR the drug
- short half-life and fact its not used for CHRONIC treatment should limit potential exposure in breastfeeding infant
Esmolol Adverse Effects
Treatment of Anaphylaxis and Extravasation
- patients taking beta-blockers may become more sensitive to repeated challenges
- anaphylaxis treatment (epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects
- extravasation: can lead to skin necrosis and sloughing, so avoid small vein infusions or use of butterfly catheter
Esmolol Adverse Effects
Hyperkalemia and Hypotension
Hyperkalemia:
- can elevate serum potassium
- seen in pts. with risk factors (renal impairment)
Hypotension:
- can occur during surgery
- reduce dose or discontinue if BP drops
- can reverse within 30 minutes
How is Esmolol metabolized?
- considered a “soft-drug” = rapid metabolism to inactive form (half life = 9 minutes)
- metabolized by esterase enzymes in the cytosol of RBCs, NOT by plasma cholinesterase or RBC membrane acetylcholinesterase
Nitroprusside
What is its MOA, what drugs does it share a similar effect to, and what does it cause systemically?
MOA: sodium nitroprusside breaks down in circulation and binds to oxyhemoglobin, releasing NITRIC OXIDE and CYANIDE (toxic) = vascular smooth muscle relaxation
- similar to mechanism PDE5 inhibitors such as Viagra and Cialis
- lowers blood pressure IMMEDIATELY in adults and kids (acute congestive heart failure and surgery bleed)
Nitroprusside
What is its major precaution and how can it be dealt with?
- too much sodium nitroprusside administration can cause RAPID cyanide generation faster than unaided pt. can eliminate it
- administer sodium thiosulfate = inc. toxic cyanide processing (can be toxic at too high a dose)
- dec. clearance if renal failure
- protect from light, do not use if discolored
- co-infusion of sodium thiosulfate have been administered at rates of 5-10 times that of sodium nitroprusside
Nitroprusside
What are its two Black Box Warnings?
What is a rare condition it can cause?
not suitable for direct injection –> dilute prior to infusion
- Hypotension
- Cyanide Toxicity
- can cause hemoglobin sequestration as methemoglobin (rare in pts. receiving more than 10 mg/kg of drug)
Nicardipine
What is its MOA, what is its major contraindication, and how does it affect pts. with Angina?
MOA: inhibits transmembrane influx of calcium into cardiac muscle and smooth muscle WITHOUT changing serum calcium concentrations
- more selective for vascular smooth muscle
CI: pts. with ADVANCED AORTIC STENOSIS
Angina: inc. frequency/duration/severity but seen in less than 1%
Nicardipine
What are precautions with use in patient who have Heart Failure or Impaired Hepatic Function or Impaired Renal Function?
How should it be used with geriatric patients?
HF: titrate slowly; can possibly cause negative inotropic effects
IHF: consider lower dosages since it is metabolized in liver; closely monitor in pts
IRF: titrate gradually in pts.; lower systemic clearance
Geriatric: use low initial dose
Nicardipine
What does it interact with Cimetidine, Cyclosporine, and Tacrolimus when coadministered?
What is the major metabolizing enzyme and transporter of Nicardipine?
Cimetidine: inc. plasma conc. of oral nicardipine
Cyclosporine: inc. plasma cyclosporine lvls
- nicardipine inhibits CYP3A4 removal
Tacrolimus: inc. plasma tacrolimus lvls
- nicardipine inhibits CYP3A4 removal
Metabolizing Enzyme = CYP3A4
Transporter = P-GP (MDR1) substrate
Nicardipine
How does it affect pregnant patients?
- considered Pregnancy Category C
- minimally excreted into breastmilk, consider possibility of infant exposure when using nicardipine in nursing mothers
