Ischemic HD Tx Flashcards
Most important use of organic nitrates in IHD?
termination of stable and variant angina episodes
Which vessels are more responsive to organic nitrates?
veins > arteries (decreased pre-load)
large vessels > small vessels
How does NO relax smooth muscle?
- pro drugs are converted to NO by aldehyde dehydrogenase in the mito
- NO activates guanylate cyclase = inc cGMP
- inhibition of calcium channels
How does the liver metabolize organic nitrates?
hepatic enzyme nitrate reductase pulls nitrate groups off
How do the pharmacokinetics of NG and isosorbide dinitrate differ?
- NG = 2-5 minutes (great substrate for nitrate reductase); TERMINATION of angina; pro-phylaxis requires extended release
- ID = 1 hour; better oral viability – prophylaxis
What is the most common method of using NG for termination of angina?
sublingual tablet (also spray, IV)
What two forms of NG are formed for prophylaxis of angina?
- transdermal match (long duration)
- chest ointments (medium duration)
WHat is the big problem with organic nitrates? How is this avoided?
- tolerance
- vascular smooth muscle loses ability to convert organic nitrates to NO (aldehyde dehydrogenase in mito)
- nitrate free periods every day to avoid tolerance
Three adverse effects of organic nitrates?
- due to excessive vasodilation
- headaches (inc cerebral flow, avoid in migraneurs)
- hypotension (careful in the elderly; sit them down)
- tachycardia (reflex response to dec BP)
When is an acute anginal episode Tx with organic nitrates considered an emergency?
doesn’t terminate within 15 minutes
What is an absolute contraindication of nitrate use?
within 24 hours of sildenafil use (inhibits PDE 5 = inc cGMP)
What calcium channels are usually inhibited by CCB’s?
L-type = cardiovascular contraction type
How do half lives differ among dihydropyridine prototype drugs?
- amiodipine = 40 hours
- nifedipine = 2-4 hours
Which CCB class is more often associated with reflex tachycardia?
- dihydropyridines
- non’s additionally directly inhibit SAN which compensates for reflex tachycardia in response to vasodilation
DOC indication for CCB’s in myocardial ischemia?
variant angina (direct vasodilators, no drug-free periods)
Why are fast-acting dihydropyridines avoided?
- significant reflex tachycardia because you experience a high, fast peak of drug causing a rapid drop in BP
- may exacerbate ischemia by increasing oxygen demand
What two drug classes can cause gingival overgrowth?
- phenytoin
- dihydropyridines
What is the new, anti-ischemic drug of last resort that is never used on its own?
Ranolazine = blocker of ‘late’ cardiac V-gated Na+ current seen in ischemia – prevents excessive entry of Na+ into cardiac myocytes during ischemia
Indication of ranolazine?
- prophylaxis of stable angina resistant to other therapies
- symptomatic relief of ischemia resistant to other drugs in ACS
What are the potential effects of this ‘late’ Na+ current?
- excess Na+ may cause abnormally high diastolic ventricular wall tension and stiffness by excess Na+ efflux and Ca influx which keeps myofilaments contracted
- inc tension/stiffness inc O2 consumption, compresses intramural small vessels
What 4 agents decrease oxygen demand?
Dec HR, contractility, preload, after load
What are the 3 ACS?
Unstable angina, NSTEMI, STEMI
What differentiates stable and variant angina?
- stable is initiated by exercise and terminated by rest
- variant is neither initiated by exercise not terminated by rest = due to sudden construction of CA
What is the most useful anti-ischemic drugs for ACS?
Metoprolol (BB)
Which ischemic disease is not helped by BB?
Variant angina - BB don’t relax vasospasms
What is the usual DOC for stable angina prophylaxis?
BB
BB dose should be adjusted to achieve a HR range of:
55-60
Why are CCB’s the DOC for prophylaxis of variant angina?
Direct vasodilator and drug free periods aren’t necessary like with the nitrates
What kind of vasodilators are CCB’s?
Arteriolar - cause more edema than balanced vasodilators because there is increased capillary pressure
Which drug is as effective as BB’s but has minimal effects on hemodynamics?
Ranolazine
When and how is ranolazine used?
- when traditional therapies are ineffective
- in combination with dihydro’s, BB’s, or nitrates
What are two drug interactions of ranolazine?
- CYP3A inhibitors increase plasma levels (diltiazem, verapamil)
- Ranolazine inc plasma levels of P glycoprotein substrates (digoxin)
Two common AE’s? One uncommon AE? Potential arrhythmic AE?
- dizziness and constipation
- syncope
- blocks cardiac K+ channels and prolongs QT (but studies show it has a novel arrhythmic effect)
Two vasodilator classes for IHD Tx?
CCB’s and nitrates
