19 - Pharmacology Anti-Anginal Flashcards
Isosorbide Mononitrate
IMDUR
DOSING
Mononitrate = active metabolite of DINITRATE
excellent BV after ORAL admin & longer t1/2 than dinitrate
SUSTAINED RELEASE
IMDUR
ONCE DAILY
VV
formulation already provides nitrate-free interval
Calcium Channel Blockers
DHP = Nifedipine / amlodipine / nicardipine
Verapamil / Diltiazem
MoA for ANGINA
Calcium –> myocyte triggers calcium release
calcium binds TROPONIN
Troponin - Calcium complex allows:
Actin & Myosin to interact & Contract
CCBs BLOCK initial Calcium Influx** –> **↓CONTRACTILITY
2nd effect:
Calcium –> VASCULAR SMOOTH MUSCLE
Calcium - Calmodulin complex permits the same
net effect = VASODILATION
3 Types of Angina:
Unstable Angina
Unstable Angina = Acute Coronary Syndrome
Usually occurs while:
RESTING
Atherosclerotic plaque RUPTURES
plug forms = clotting
VV
Blocks FLOW to heart muscle
EMERGENCY
treatment
3 Types of Angina:
Stable Angina
Classic / Effort / Predictable
Stable plaque –> ↓Maximal Capacity of Coronary Artery
- *Can be relieved by**:
- *Rest** or Nitroglycerin
3 Types of Angina:
Prinzmetal’s Angina
Prinzmetal’s Angina = Vasospastic Angina
Unstable form of Angina
Transient ↓blood flow
caused by
Coronary Artery SPASM
can occur:
with or WITHOUT ACSCD
Ranolazine** = **Ranexa
Angina MoA
Used in those with chronic stable angina who
have NOT had adequate response with other antianginal drugs
INHIBITS:
late entry of SODIUM –> cardiac myocytes
↓Intracellular Na –> ↑Calcium Expulsion via Na/Ca Transporter
↓accumulation of Na/Ca in myocardial cells
VV
Helps myocardium use energy MORE EFFICIENTLY
UNIQUE:
- does NOT effect:*
- *HR / BP / Vascular Resistance**
DHP CCB’s
Angina Action & ADR
↑Selectivity for Vascular Smooth Muscle >> myocardium
↑Vasodilation >> verapamil/diltiazem
Vasodilation -> ↓BP -> ↓cardiac work -> antiANGINAL effect
↓Coronary Resistance** –> ↑**Coronary Blood Flow
Strong reflex beta-adrenergic effect:
offsets negative inotropic drug effect like reflex tachycardia
ADR:
Peripheral Vasodilation** –> **Peripheral Edema** & **Flushing Headaches
more common in SHORT ACTING nifedipine
Beta Blocker’s
ADRs
↓HR ↓Contractility ↓AV Node conduction
Bronchoconstriction
due to b2 blockade = non-selective agents & high doses of selective ones
Peripheral Artery disease** or **Raynaud’s Disease
from non-selective drugs
CNS effects
Nigtmares / insomnia / hallucinations
Fatigue
↓cardiac output or CNS effect
Erectile Dysfunction
due to low BP
Ranolazine = Ranexa
ADR / Contraindications
Prolongation of QT** / **↑BP
Can be used in COMBO with:
Beta Blockers / Nitrates / AMLODIPINE
Contraindications:
Patients with preexisting QT prolongation or drugs that do so
DILTIAZEM** & **VERAPAMIL
potent / moderate INHIBITORS of CYP3A4
hepatic disease
Nitrate
Effect
- ↓*Myocardial O2 Demand=main effect
- workload of heart reduces*
Dilates systemic VEINS
↓Preload = left ventricular end diastolic pressure
↓ventricular wall stress
↓CO
Secondary Effect = not thought to be main therapeutic effect
Coronary Vasodilator
↓arterial spasm of variant angina
↑Coronary perfusion / ↑ Oxygen delivery
Isosorbide Mononitrate
ISMO / MONOKET
DOSING
Mononitrate = active metabolite of DINITRATE
excellent BV after ORAL admin & longer t1/2 than dinitrate
IMMEDIATE RELEASE TABLET
Ismo / Monoket
2 Times Daily - 7 Hours apart
VV
provides nitrate-free interval
Therapeutic Uses of:
SL Nitroglycerin
&
Translingual Nitroglycerin Spray
- *TERMINATE**
- *Acute Anginal Attacks**
- *PROPHYLAXIS**
- *Acute Anginas**
Sublingual Nitroglycerin
COUNSELING
Place under tongue & leave there to dissolve
CONTACT EMERGENCY MEDICAL SERVICES
if there is
no pain relief or pain WORSENS after 5 minutes
Continue to take
- *ADDITIONAL SL NITROGLYCERIN** while waiting for ambulence
- *_<_3 doses** @ 5 minute intervals
Nitrates
MoA
Nitroglycerin –> Vascular Smooth Muscle
converted into
Nitric Oxide** –> activates **Guanylyl Cyclase
↑cGMP –> dephosphorylates MYOSIN-LC-P
VV
instead of contraction –> RELAXATION of myosin
Higher Doses of Nitrates
Effect
Higher doses –> further venous pooling
↓Arteriolar Resistance
↓Peripheral Resistance –> ↓BLOOD PRESSURE
VVV
REFLEX TACHYCARDIA POSSIBLE
Angina
What is seen on an ECG?
DEPRESSED** - **ST-Segment
Verapamil
non-DHP CCB
Angina Action / ADR
↓Myocardial Oxygen
negative inotrope & chronotrope
↓BP
do NOT use with BETA BLOCKERS
more PRONOUNCED negative inotrope/chronotrope effect
Nitrate
Pharmacokinetics
low oral Bioavailability
due to nitrate reduction in liver
Nitroglycerin Oral = 6-8 Hours of action
Isosorbide DiNitrate = 4-6 Hours of action
- *SUBLINGUAL_ & _Isosorbide Dinitrate** = PREFERRED
- AVOIDS FIRST PASS METABOLISM*
Fast acting = 2-5 minutes
Wears off in 30 minutes
Therapeutic Uses of:
Long Acting Nitrates:
Topical / Transdermal Patches
&
Isosorbide MonoNitrates:
Isomo / Monoket / Imdur
SUSTAINED PROTECTION
against Angina Attacks
Angina Definition
Chest Pain** or **Discomfort
due to:
Coronary Artery Disease
Consequence of:
Myocardial Oxygen DEMAND >>> Supply
Caused by:
Accumulation of ACIDIC METABOLITES
that result from myocardial ischemia
stimulating myocardial pain nerve endings
Tolerance to Organic Nitrates
- after repeaded dosing –> loss of:*
- *Hemodynamic** & Anti-anginal effects
sustained use –> DESENSITATION
↓NO Formation
Avoid by:
INTERMITTENT DOSING
Nitrates
Drug Interactions?
SILDANAFIL
can take nitrates 24 hours after taking viagra or levitra
48 hours for cialis
Due to:
Life Threatening HypoTention
Sildenafil –> ↑cGMP by inhibiting its BREAKDOWN** by **PDE-5
BUIDLUP of ↑cGMP
VVV
Severe HypoTension & Few MIs
Nitrate
ADRs
HEADACHE
caused by cerebral vasodilation = meningeal arterial dilation
- *Cutaneous FLUSHING**
- *arterial dilation of FACE**
Postural HypoTension** / **Tachycardia** / **Dizziness
compensatory effects resulting from baroreceptor reflex
- *Beta-Blockers**
- olol’s
Action in Angina
B1 Effect:
↓MYOCARDIAL OXYGEN DEMAND by decreasing:
↓HR ↓Contractility
↓Blood Pressure
(↓left ventricular wall stress)
possible ↑Coronary Blood Flow
heart spends more time in diastole –> ↓HR
- *All Beta Blockers = Equally Effective**
- can be used with Nitrates** –> *_PREVENT reflex Tachycardia_
