1 PHARMACOLOGY 2

Drugs for Angina Pectoris

Made by: KAVJ

DRUGS FOR ANGINA PECTORIS - Complete damage (Infarction)

o Absence of oxygenation leading to
Angina Pectoris
myocardial necrosis or cell death
- Chest pain o 100% absent oxygen
- Resultant pathologic condition: CAD → Decreased Oxygen → Ischemia → Infarction
o Ischemia
o Infarction
▪ Coronary artery disease
ANGINA PECTORIS

CORONARY ARTERY DISEASE

Coronary Artery
- A type of blood vessel that supply oxygenated blood to
the cardiac cells
- Heart pumps and relax because cardiac cells.
- The driving force of cardiac cells for it to pump & relax,
which is oxygen
- Gasoline Station: Coronary Artery
- CHD: obstruction (pagbabara)
CORONARY ARTERY DISEASE
- Also known as Ischemic Heart Angina Pectoris
Disease; Coronary Heart
Disease - Less oxygen accepted by cardiac cell
- Is a condition where insufficient - Is a characteristic chest pain or discomfort due to
blood flow can occur in one or myocardial ischemia or infarction
more coronary arteries - May be regarded as an expression of a coronary blood
o Only a segment of the supply-demand mismatch
heart is affected - UNDERLYING DISEASE: CAD
(barado)
Types of Angina Pectoris
- Can produce characteristic pain in the chest but pain
may not necessarily occur - Chronic Stable Angina
- Can be temporary, lasting for a few minutes, or Pectoris (CSAP)
permanent leading to death of tissue - Prinzmetal Angina

Causes of Coronary Artery Disease

- Not enough blood
(oxygenation)
o Atherosclerosis CHRONIC STABLE ANGINA PECTORIS
▪ Plaque - aka Effort angina,
formation classic angina
made out of - Chest pain lasting for 2-
fats 5 minutes
o Thrombosis - Provoked by physical
▪ Blood clot exertion, emotional
▪ Stationary clot: thrombus stress, exposure to
o Embolism cold, or smoking
▪ Blood clot - No increase in severity,
▪ Travelling clot: embolus duration and frequency
o Vasospasm for the last 1-2 months
- If you rest, it is relieved, no pain will be felt.

Coronary Artery Disease PRINZMETAL ANGINA

MAY RESULT TO: - Also called Variant

Angina; Vasospastic
- Partial damage (Ischemia) Angina; Angina Inversa
o Decreased - Due to transient spasm of
oxygenation of localized portions of the
myocardium but blood vessels, usually
myocardial cells are associated with underlying
still viable atheromas
2 PHARMACOLOGY 2
Drugs for Angina Pectoris
Made by: KAVJ

o Can cause significant myocardial ischemia Classifications of Antianginal Drugs

and pain
o Pain occurs principally at rest, usually I. Vasodilators
unprovoked by physical exertion - Targets the coronary arteries
o Nitrovasodilators
▪ Nitrate/nitrites are converted into
Nitric Oxide
PATHOPHYSIOLOGY OF ANGINA
▪ Nitric oxide activates GC which
- Imbalance between the oxygen requirement of the forms cGMP
heart and the oxygen supplied to it via coronary ▪ cGMP removes phosphate from
vessels MLC-PO4, which leads to relaxation
o Hindi balance ang oxygen supply and oxygen o Calcium Channel Blockers
demand ▪ Blocks L-type calcium channel,
o Supply: Supplier / Coronary artery which leads to relaxation
o Demand: Acceptor / Heart o Dipyridamole - Non-nitrate coronary
vasodilator
- In CSAP ▪ Phosphodiesterase metabolizes
o Because of the effort, you feel the pain = cGMP making it GMP (inactive)
heart pumps faster = more workload = ▪ Phosphodiesterase inhibitor
demands more oxygen ▪ Inhibits the PDE, increase cGMP,
o Coronary arteries cannot give what the relaxation of blood vessel
heart needs → heart feels the pain
(imbalance)
o Myocardial oxygen requirement is not
proportional to coronary blood flow
o Ischemia usually leads to pain, but is some
individuals, not accompanied by pain (“silent”
or “ambulatory” ischemia)
o TOO DEMANDING

- In Variant Angina
o The problem is the vasospasm = low
oxygen supply
o Even no effort/demand, there is pain
o Oxygen delivery decreases as a result of
reversible coronary vasospasm
o LOW SUPPLY OF OXYGEN

II. Non-vasodilator
Therapeutic Objectives of Antianginal Agents o β-adrenergic Receptor Antagonists

- To restore the balance between myocardial O2 supply

and demand
o Decrease O2 demand and increase the
perfusion of ischemic subendocardial tissue:
CSAP
▪ β-blockers
▪ Nitrovasodilators
▪ Ca2+- channel blockers
o Counteract vasospasm and increase O2
supply : Variant Angina
▪ Nitrovasodilators
▪ Ca2+- channel blockers

Beta 1 in the heart:

DRUG ACTION IN ANGINA
- Stimulation
- Decrease myocardial oxygen requirement by
- Increase contraction
decreasing the determinants of oxygen demand
- Gs linked → increase cAMP
o heart rate
o cAMP – responsible for activation of Protein
o ventricular volume
kinase A (PK-A)
o blood pressure
o PK-A facilitates opening of L-type calcium
o contractility
channel
- Increase myocardial oxygen delivery by reversing
coronary artery spasm
3 PHARMACOLOGY 2
Drugs for Angina Pectoris
Made by: KAVJ
o L-type calcium channel will let trigger
calcium enter
o Contraction
Beta blockers:
- Competitively block binding of NE to its receptors
o NE cannot bind to B1 receptor
o No cAMP
o L-type calcium channel closes, no entering of
trigger calcium
o Depression of heart
Nitrovasodilators
- Organic Nitrite and Nitrates (R-NO2)
MOA:
- Organic nitrates are converted into Nitric oxide by
Nitric oxide synthase, where NO cause increase
levels of cGMP → vasodilation (relaxation)
- Nitroprussides increase NO → increase cGMP →
vasodilation
- To activate NO synthase, it needs a cofactor
o Groups containing -SH
o Thiol-requiring
Pharmacologic Effects of Nitrates
- At regular/ low doses (ISDN 5 mg SL, NTG 0.6 mg SL)
o Used for CSAP
o Effect is PERIPHERAL VENODILATION
o Venodilation: dilation of veins = more
reservoir (capacitance) = less preload =
less workload = less oxygen
o HEART IS NOT SO DEMANDING
▪ Increased peripheral pooling of
blood
▪ Decreases preload/venous return
▪ Decreased myocardial wall tension
▪ Decreased O2 requirements and
reduce tissue pressure
- At high doses (High Dose IV Infusion)
o Used for Prinzmetal
o Additional arteriolar and coronary artery
vasodilation
o CA vasodilation = more oxygen supply
▪ Reduced mean arterial pressure
▪ Reduce afterload
▪ Diminish O2 requirements
▪ Increased O2 supply
Other Effects of Nitrates
- Nitrates are generally vasodilators
- Relaxation: Increase in cGMP
▪ Very brief ang effect (mabilis lang)
▪ Short lived ang effect
▪ Don’t provide clinical benefit
o Bronchi
o GIT
o Biliary Tract
o GUT
o Corpus Cavernosum (penile tissue)
▪ Vasodilation
▪ More blood goes into the penis →
erection
- Platelets – decreased aggregation
o Potentially cause bleeding
o Not significant clinically
- Other effect: Methemoglobinemia
o Observed in using Amyl nitrite
D/I with PDE5 INHIBITORS
o Phosphodiesterase 5 inhibitors
o In the penile tissue, it degrades and
metabolize cGMP into inactive GMP
o cGMP causes erection (dilation)
- SILDENAFIL, TADALAFIL, VARDENAFIL
o Erectogenic drugs
o Block of PDE5 → Increase cGMP → penile
erection
- Used in the treatment of Erectile dysfunction
NOTE:
o PDE5 inhibitors also acts in the blood
vessels like arteries and veins.
(VASODILATION). Hypotension
o Mas safer ang mga nagc-cause ng
erection na local administration. (turok sa
penis)
o It is commonly taken by elderly, they are
more prone to cardiac problems, cardiac
arrest.
o Both nitrates and PDE5 inhibitors cause
increase in cGMP levels in the blood
vessels.
- Sildenafil (Viagra) potentiates the action of nitrates
o Severe hypotension and a few myocardial
infarctions have been reported in men taking
both drugs
o It is recommended that at least 6 hours pass
between use of a nitrate and the ingestion of
sildenafil
- Sildenafil also has effects on color vision, causing
difficulty in blue-green discrimination
o Men at risk for impotence are aged 50-60
yrs old and above.
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Drugs for Angina Pectoris
Made by: KAVJ
Classes of Nitrovasodilators
I. Very Short-acting (<5-10 minutes)
o Amyl nitrite – the only nitrite (inhalation)
II. Short-acting (10-30 minutes)
o ISDN SL, NTG SL
▪ Isosorbide Dinitrate Sublingual
▪ Nitroglycerin Sublingual
III. Intermediate-acting (5-8 hours)
o ISDN tab PO, NTG-SR tab PO
▪ Isosorbide Dinitrate tablet taken by
mouth
▪ Nitroglycerin Sustained Released
tablet taken by mouth
IV. Long-acting (10-24 hours)
o ISDN-SR tab PO, ISMN tab PO, NTG
Transdermal Patches
▪ Isosorbide Dinitrate Sustained
Release tablet taken by mouth
• Isordil
▪ Isosorbide Mononitrate tablet taken
by mouth
• Imdur
▪ Nitroglycerin Transdermal patch
Clinical Uses of Nitrovasodilators
- Management of Angina pectoris
o ACS (Acute Coronary Syndrome) – IV
Infusion
o CSAP – PO or transdermal
o Prinzmetal Angina – IV Infusion + Beta
Blocker
▪ High dose nitrate: arteriolar
dilation → decrease arterial
pressure → negative feedback of
baroreceptor → reflex tachycardia
(baroreceptor activation) → more
stress in the heart → more oxygen
needed (demanding)
▪ Combined with beta-blocker, for the
concealing of reflex tachycardia
- Alternative in the Management of Hypertensive
Emergency – IV Infusion
- Add-on in the Management of CHF
o ISDN w/ Hydralazine
o Effective only on African-American px
- Acute Pulmonary Edema (TDDS or SL)
o Transdermal delivery system
o Sublingual
- Initial Management of Cyanide Poisoning
o Amyl Nitrite
Adverse Effects of Nitrovasodilators
- Tolerance
o Develops when nitrate serum levels are
sustained over time
- Vascular Headache
o Throbbing headache due to dilation effect
- Monday Disease
o Historical
o Headache, tolerance
o Based from the workers that manufactures
bombs, nitrates are API in bombs. If high
doses, it is explosive.
o Monday, fresh from off, sensitive ang workers
sa effects.
- Reflex tachycardia
o Felt at high dose nitrate, mask using beta-
blockers
- Postural hypotension
- Nitrite ions oxidize iron atoms of hemoglobin to
methemoglobin – hypoxia (methemoglobinemia)
Beta-Blockers in Angina
Beta-Blockers
- Cardiac depressants and do not act on the blood
vessels.
- Decreases the heart’s oxygen demand
- First line maintenance treatment for CSAP
o Decrease myocardial oxygen requirement by
reducing heart rate, blood pressure and
contractility at rest and during exercise
o Appear to be the most important mechanism
for relief of angina and improved exercise
tolerance
- Prevent reflex tachycardia associated with
nitrovasodilators at high doses
o Can reduce the frequency of anginal attack
- Note: If the patient has on-going angina pectoris,
NEVER give beta blockers as single agents
because of compensatory mechanisms that may
occur.
CCBs in Angina
Calcium Channel Blockers
1. Dihydropyrimidines
o Acts on the arteries
2. Non-Dihydropyrimidines
o Acts in the heart
- Reduce myocardial oxygen requirements
o Verapamil is applied
o decrease in myocardial contractile force
o decrease arterial and intraventricular
pressure
- Relieve and prevent the focal coronary artery spasm
involved in variant angina
o DHPs are used (ending in -dipines)
o most effective prophylactic treatment
CCBs in Angina
- Non-DHP
o Verapamil, Diltiazem
o Alternative to beta blockers as maintenance
treatments for CSAP
- Long-acting DHP CCBs
o Lercanidipine, Lacidipine, Amlodipine
o Alternative treatments
- Short-acting DHP CCBs
o Generally avoided unless for prinzmetal
(given with beta blockers)