DRUGS FOR ANGINA - ORGANIC NITRATES

They decrease myocardial oxygen requirement or increase myocardial oxygen supply.

The summary of drugs for angina MOA

Organic nitrates

CCB

Beta blocker

Pfox Inhibitors

Bradycardic Drugs

Nicorandil

Usual drugs for angina

Organic nitrates

This drug for angina helps as a vasodilator (increase blood supply)

CCBS

This drug for angina helps for vasodilators and cardiac depressants (Decrease oxygen demand)

Beta blockers

This drug for angina as a cardaic depressants

increase oxygen delivery

In some patients, a redistribution of coronary flow may ____ to ischemic tissue.

increase myocardial oxygen delivery

coronary arterial spasm

In variant angina, the nitrates and the calcium channel blockers may also _____ by reversing____

The major acute toxicities of organic nitrates are direct extensions of therapeutic vasodilation:

• Orthostatic hypotension

• Reflex Tachycardia (indirect ADR ; compensatory response)

• Throbbing headache

Acute adverse effect of organic nitrate

decrease in drug response due to depleted levels of sulfhydryl moieties

• Tachyphylaxis

• Monday headache and dizziness

Adverse effect of organic nitrate as tolerance

Acute adverse effect

Tolerance

Methmoglobinemia

Organic nitrate Adverse effect

Nitroglycerin

universal vasodilator and prototype

Nitroglycerin

This is the mainstay treatment for angina

dynamite

not explosive

Although, it is used in the manufacture of ____, the formulation of nitroglycerin used in medicine are ____

lose potency: volatilization & adsorption: plastic surfaces

tightly closed glass containers

light

Proper storage of NItroglycerin

The conventional sublingual tablet form of nitroglycerin may____ when stored as a result of ____and _____to _____. Therefore, it should be kept in _______. Nitroglycerin is not sensitive to____.

….

MOA of nitroglycerin

Dephosphorylation of myosin light chains

prevents the interaction of actin and myosin, leading to vasodilation.

Traditional oral nitroglycerin has a very low (typically <10-20%) bioavailability- organic nitrate reductase.

The sublingual route, which avoids the first-pass effect, is therefore preferred for achieving therapeutic blood level rapidly

Pharmacokinetics of Nitroglycerin

Sublingual -0.15 or 0.3 mg. The referred route

Classification based on duration on Short (Nitroglycerin)

Oral (extended release capsule 2.5, 6.5, 9, or 13 mg)

Classification based on duration on Intermediate (Nitroglycerin)

Transdermal patch – can deliver up to 0.8 mg of nitroglycerin per hour

Classification based on duration on Long (Nitroglycerin)

2% ointment, Buccal tablets, Translingual spray

Classification based on duration on other preparation (Nitroglycerin)

Amyl nitrate

A highly volatile liquid

fragile glass

ampules: protective cloth covering

crushed: inhaled

Amyl nitrate is stored in ____, ___ packaged in a _____ ; granules are ____and ____

inhalation route

Amyl nitrate ____ provides very rapid absorption and like the sublingual route, avoids the hepatic first-pass effect. FAST ONSET OF Action

Unpleasant odor

Short duration of action

Extensive cutaneous vasodilation (kahit other parts of body naeexpose (nadilate) skin flushing)

It is now OBSOLETE for angina.

Amyl nitrate is less desirable than nitroglycerin due to:

Antidote for cyanide poisoning

Amyl nitrate is now currently used as an __ if sodium nitrite is not available

Amyl nitrate

Same as sodium nitrite, it oxidizes hemoglobin to methemoglobin resulting to decrease cyanide affinity

Methemoglobinemia

Adverse effect of amyl nitrate

Isordil

Isosorbide dinitrate (ISDN) BN?

Isosorbide dinitrate (ISDN)

Has active initial metabolite administered orally (white tab) or sublingually (pink tab) better bioavailability and longer half life compared to nitroglycerin

Isosorbide dinitrate (ISDN)

Long acting ; converted to ISMN

Imdur

Isosorbide mononitrate (ISMN) BN?

Isosorbide mononitrate (ISMN)

Active metabolite of ISDN and has a bioavailability of 100%