Aortic Dissection Drugs Flashcards
What is the most important drug used to treat acute aortic dissection?
IV B blockers
What are the 3 MOAs of Beta blockers?
1) Block effects of epinephrine
2) Less contractility
3) Vasodilation
What are the 4 drugs used to treat aortic dissection?
1) Labetalol, 2) Esmolol 3) Nitroprusside 4) Nitrocardipine
LENN
MOA of labelatol? (3)
1) Typically given as a racemic mixture
2) Achieves both alpha and beta blocking activity
3) Decreases PVR without affecting CO or HR
When do we want to be careful with labetalol administrations?
Heart, liver, lung, pheochromocytoma, DM
What are the contraindications of labetalol/esmolol? (7)
Overt cardiac failure, severe bradycardia, cardiogenic shock, severe hypotension, history of obstructive airway disease like asthma, hypersensitivity to drug
greater than first degree block = specific to labetalol
Dizziness, tingling of scalp, lightheadedness, excessive tiredness, headache, upset stomach, stuffy nose are adverse effects of?
Labetalol
Explain the relationship between Labetalol and pregnancy
1- Animal reproduction studies show it’s bad but we still give if it’s needed
2- Small amounts excreted in milk
3- Don’t know in pediatrics
4- Clearance goes up in pregnancy because increased glucuronidation - falls below therapeutic value
What do we warn geriatrics about labetalol?
Orthostatic symptoms - reduced elimination, so lower doses
The metabolism of labetalol?
Conjugate to glucuronide metabolites, excrete in the urine OR excrete via bile into feces (approximately 55-60% appear in the urine as conjugates), crosses placental barrier
It is 50% protein bound, neither hemodialysis or peritoneal dialysis removes labetalol from the circulation
What are your counseling points for labetalol?
1) Take as prescribed 2) Don’t interrupt or discontinue 3) Consult doctor if you have cardiac failure or hepatic dysfunction 4) Transient scalp tingling may happen 5) Appropriate tests should be done to monitor these conditions over regular intervals of treatment with Labetalol
What is the MOA of esmolol?
Affects the response to nerve impulses in the heart, heart beats slower = lower BP so increased blood to the heart
Class II antiarrythmic so: 1- blocks B1 adrenergic stimulation (ABEAM), 2- no intrinsic sympathomimetic activity, 3- no membrane stabilizing activity
Patient has fast heartbeat and high BP during surgery, after surgery, or during other medical procedures. What do you give?
Esmolol to control rapid heartbeats or abnormal heart rhythms
Contraindications to esmolol?
Don’t give this drug with beta blocker ->
- Hx of hypersensitivity
- Asthma/airway disease
- Heart block greater than first degree except in patients with ventricular pacemaker
- Decompensated heart failure
- CCB while in use
- Pulm. HTN
How does pregnancy work with esmolol?
- Can cause fetal bradycardia that can continue even after drug stops
- Monitor fetal growth and newborn 2 days after delivery for bradycardia, low glucose, respiratory depression
- Alternative agent for hypertensive emergencies in pregnancy
- Decision to discontinue drug depends on importance of treatment
EVIL ESMOLOL
Is esmolol good for chronic treatment of
HTN?
No, short acting
What are the drug interactions of esmolol?
THERE ARE MANY
What are considerations of esmolol in geriatrics?
Bradycardia so lower dose
EVIL ESMOLOL bradycardia
Which drug do we want to be careful with anaphylactic patients and allergens?
Esmolol - more sensitive to repeated challenges - treatment of anaphylaxis in patients taking beta blockers are ineffective and promote undesirable effects
What are the adverse effects of esmolol? (3)
1 - Extravasation (skin necrosis and sloughing so be careful with butterfly catheters or small veins insertion), 2
2 -Hyperkalemia = associated with renal patients
3- Hypotension can occur during surgery so need to monitor BP careful, if not good then drop doses to reverse within 30 min
What about esmolol is ERYTHROCYTIC - talk about half life and metabolism
Soft drug - rapidly metabolized to inactive form
Elimination half life is 9 minutes
Rapidly metabolized by hydrolysis of ester linkages, mainly by esterases, not metabolized by plasma cholinesterases, or RBC acetylcholinesterases
What is the MOA of nitroprusside?
Activates guanylate cyclase enzyme -> vascular smooth muscle so increase cGMP and activates PKG and phosphatase, phosphatases inactivate myosin light chains involved in muscle contraction
BLOOD VESSEL DILATE
VASCULAR SMOOTH MUSCLE RELAXES
Sodium nitroprusside binds to oxyhemoglobin to release:
NO, CN, Methaemoglobin
Indications for Nitroprusside?
Lowering BP immediately in kids and reduce bleeding during surgery, treats CHF
CIs for Nitroprusside?
- Compensatory hypertension (AV stent, coarc aorta)
- Conditions with high cyanide/thiocyanate ratio: Leber’s optic atrophy, Tobacco Amblyopia leading to vision impairment
- Acute CHF
- Hepatic impairment
- Hypothyroidism
- Pregnant women maybe
Lots of side effects with this one, including low HR, low BP, high HR, twitchy, renal issues, dizziness, headache, rash. What are the serious ones?
Nitroprusside
1- Cyanide poisoning can develop within an hour >10mcg
2- Thiocyanate toxicity
What is the antidote to too much nitroprusside?
Sodium thiosulfate: increases rate of toxic CN poisoning and reduces hazard of it, can be toxic at too high of dose (can infuse at 5-10x sodium nitroprusside)
What are the 3 things to monitor in nitroprusside patients?
1- CN toxicity
2- Thiocyanate levels
3- Monitor pulse ox (thiocyanate clearance decreased with renal failure, protect from light and don’t use if discolored)
What are the considerations of methemoglobinemia and thiocyanate toxicity in nitroprusside patients?
Sequester hemoglobin as methemoglobin:
- other patients especially those with bad kidneys develop this after lots of infusions
Black Box Warning for Nitroprusside: (3)
- No direct injection, need to dilute 2. Hypotension leading to irreversible death and injury so monitor properly 3. Cyanide toxicity because cyanide ion accumulates
What is the metabolism of nitroprusside?
One molecule of nitroprusside is metabolized in combination with Hg to make 1 molecule of cyan-methemoglobin and 4 CN- ions. Thiosulfate reacts with cyanide to make thiocyanate which is eliminated in urine
Nicardipine MOA?
- Calcium ion antagonist
- Inhibits calcium influx into cardiac muscle and smooth muscle without changing serum calcium (selective to smooth muscle)
What do you give to treat short term hypertension?
Nicardipine
What drug should you not give with patients with aortic stenosis?
Nicardipine
What are the 4 adverse effects with nicardipine?
Headache, hypotension, tachy, N/V
What are the precautions of nicardipine?
- Excess pharm effects: so monitor BP and HR
- Produce hypotension or tachycardia so avoid to patients who have acute cerebral infarction or hemorrhage
- Induction or angina exacerbation is seen in less than 1% of coronary artery disease patients but can make angina worse
What are the considerations of nicardipine in heart failure patients?
Titrate slowly when using IV premixed injection in combo with beta blocker because negative inotropic effects
What are the considerations of nicardipine in impaired liver function?
Lower dosages and closely monitor responses in patients with impaired liver function or reduced liver flow
What are the considerations of nicardipine in patients with impaired renal function?
Lower clearance and higher AUC, so titrate gradually
What are the considerations of nicardipine in geriatrics?
Low doses please because decreased organ function
Nicardipine + beta blocker considerations
Safely used, but titrate slowly in HF patients
Nicardipine + cimetidine considerations
Increases N concentrations so monitor, data with other histamine 2 not available
Histamine blockers HELP increase nicardipine
Nicardipine + Cyclosporine considerations
Increased cyclosporine through nicardipine inhibiting CYP3A4
Nicardipine + Tacrolimus considerations
Increased tacrolimus because nicardipine inhibits CYP3a4 so closely monitor
Nicardipine in pregnancy?
Pregnancy Cat C
No labor or delivery
Nursing: minimal in milk, so maybe exposure
How is nicardipine metabolized?
CYP450, MAJOR IS CYP3A4
Transporters: PGP (MDR1) SUBSTRATE
