This document discusses drugs used for angina pectoris. It defines angina as chest pain caused by insufficient oxygen to the heart muscle. Angina has underlying causes like coronary heart disease and atherosclerosis. The document outlines four types of angina and discusses the mechanisms and pathophysiology of atherosclerosis. It then summarizes various drug classes used to treat angina, including nitrates, beta blockers, calcium channel blockers, nicorandil, aspirin, and clopidogrel. Specific drugs within each class are mentioned along with their mechanisms of action, indications, and side effects.
2. Angina is chest pain or discomfort caused when your heart
muscle doesn't get enough oxygen-rich blood.
Angina is not a disease. It is a symptom of an underlying
heart problem, usually coronary heart disease (CHD).
Angina happens when one or more of the coronary arteries is
narrowed or blocked, also called ischemia.
3.
4. Mechanism include:
ī§Atherosclerosis (plaque-related epicardial coronary
obstruction)
īfocal or diffuse spasm of normal or atheromatous
arteries
īmicrovascular dysfunction
īleft ventricular dysfunction secondary to previous
acute myocardial necrosis/hibernation (ischaemic
cardiomyopathy)
īleft ventricular hypertrophy (hypertension, aortic
stenosis, hypertrophic cardiomyopathy).
7. ī Mechanisms of atherosclerosis
ī The pathophysiology of atherosclerosis, development of
symptomatic angina and subsequent acute coronary
syndrome (ACS) is well characterised.2,3 The microscopic
development of atherosclerotic plaque involves:
ī endothelial dysfunction
ī sub-endothelial accumulation and oxidation of low-density
lipoprotein (LDL)
ī increased expression of adhesion molecules and chemokine
secretion
ī immune cell infiltration and development of foam cells
ī development of fibroatheromatous plaque involving
positive remodelling, neovascularisation, and development
of necrotic core with overlying fibrous cap formation and
calcification.
8. ī Endothelial dysfunction and nitric oxide
ī The endothelium is a single layer of cells lining blood
vessels and performs multiple functions, including:
ī the regulation of coronary blood flow
ī a barrier to toxic substrates
ī regulation of thrombosis and inflammation
ī control of angiogenesis.
9. ī Endothelial dysfunction is characterised by a reduction in the bioavailability of
vasodilators, such as NO, as a result of reduced production and increased
consumption of NO, and an increase in endothelium-derived contracting factors,
such as endothelin and angiotensin II (AII) (figure 1). This is seen as the blood
vessel being unable to dilate. In addition, endothelial dysfunction promotes
platelet and leukocyte activation and the release of cytokines, which increase
vessel permeability. This enables the sub-endothelial infiltration of oxidised
lipoproteins and inflammatory cells.
10. Endothelial dysfunction has been referred to as âthe risk of the risk factorsâ,4 since it has been
shown to occur in the presence of conventional, modifiable risk factors (e.g. cigarette smoking,
high blood pressure, hyperlipidaemia and diabetes). These risk factors are, in turn, associated
with a state of increased oxidative stress and the overproduction of reactive oxygen species. This
all contributes to the complex interplay of endothelial dysfunction since reactive oxygen species
can themselves lead to abnormal NO metabolism (figure 2).
11. Fatty streaks: A fatty streak marks the earliest macroscopic
atherosclerotic lesion. Beginning in early life, these fatty streaks
comprise a focal build-up of various substrates e.g. lipid-rich
macrophages (foam cells), extracellular matrix, smooth muscle cells,
intracellular and extracellular lipid deposits, and T lymphocytes, to
form a minor thickening of the intimal surface.
19. Unstable angina:
âĸAlso called âCrescendo anginaâ
âĸAcute coronary syndrome in which angina worsens
âĸOccurs at rest
âĸSevere and of acute onset
âĸCrescendo pain- pain increases every time
20. Unstable angina:
âĸIncreased frequency , severity or duration of pain
in a apatient of stable angina.
âĸPain occurs with less exertion or at rest.
âĸMyocardial contraction may occur in 10-20%
patients
21.
22. Microvascular angina:
âĸAlso called Syndrome X
âĸCause unknown
âĸProbably due to poor functioning of the small blood
vessels of the heart, arms and legs
âĸNo arterial blockage
âĸDifficult to diagnose because it does not have arterial
blockage
âĸGood prognosis
23. Prinzmetalâs angina or variant angina
âĸPrinzmetalâs angina is a variant form of angina with
normal coronary vessels or minimal atherosclerosis
âĸIt is probably caused by spasm of coronary artery
24.
25.
26.
27.
28.
29.
30. ī Immediate pre exertional prophylaxis of angina:
Sublingual Nitroglycerine 0.5mg or Isosorbide
dinitrate 5mg should be taken within 5 minutes.
ī For long term prophylaxis:
Long acting nitrates, calcium channel blockers,
beta blockers or combination of these drugs.
ī Antiplatelet therapy:
Aspirin small dose 75mg â 150mg once daily orally
or Dipyridimole 75mg orally.
31. ī CORONARY ARTERY REVASCULARIZATION
ī For patients not responding to medical
therapy
īPercutaneous Transluminar Coronary
Angioplasty (PTCA).
īCoronary Artery bypass grafting (CABG)
36. NITRATES
MODE OF ACTION :
ACTS DIRECTLY ON VASCULAR SMOOTH MUSCLE TO
PRODUCE ARTERIAL AND VENOUS DILATATION
EFFECT DURING ANGINA
1.REDUCES MYOCARDIAL OXYGEN DEMAND (LOWERS
PRE-LOAD AND AFTER LOAD)
2. INCREASES MYOCARDIAL OXYGEN SUPPLY
(CORONARY VASODILATATION)
40. DURATION OF ACTION OF SOME NITRTATE PREPARATIONS
PEAK ACTION
DURATION OF
ACTION
Sublingual GTN(Tablet 300-
500Âĩg or metered dose
aerosol 400Âĩg/spray)
4-8 minutes 10-30 minutes
Buccal GTN (1-5 mg tablet 6
hourly)
4-10 minutes 30-300 minutes
Transdermal. GTN (5-10
daily)
1-3 hours Up to 24 hours
Oral isosorbidedinitrate.(10-
20 mg 8 hourly)
45-120 hours 2-6 hours
Oral isosorbide mononitrate
( 20-60 mg once or twice a
day)
45-120 hours 6-10 hours
41. SUBLINGUAL GTN- Administered
a.as a tablet â 300-500 Âĩg to disolve under the tongue
b.As metered-dose aerosol (400 Âĩg per spray)
RELIEVES AN ATTACK OF ANGINA IN 2-3 MINUTES
UNWANTED EFFECTS
ī§HEADACHE
ī§SYMPTOMATIC HYPOTENSION âDIZZINESS, POSTURAL GIDDINESS,
BLURRING OF VISION
ī§RARELY SYNCOPE â FAINTING
ASK PATIENT TO SPIT TABLET IF ABOVE EFFECTS OCCUR
ī§NOT HABIT FORMING
ī§TEACH PATIENTS TO USE PROPHYLACTICALLY e.g. Before exerting
ī§VIRTUALLY INEFFECTIVE IF SWALLOWED DUE TO EXTENSIVE FIRST PASS
METABOLISM IN THE LIVER
CONTINUOUS USE CAUSES PHARMACOLOGICAL TOLERANCE
THERFORE ATTEMPT TO INCLUDE A âNITRATE-FREEâ PERIOD OF 6-8 HOURS
A DAY
42.
43. ī Beta Blockers are effective in Stable and Unstable
Angina.
ī In contrast they are not useful in variant angina may
worsen the condition. This deleterious effect is likely
due to the increase in the coronary resistance caused by
the unopposed effects of catecholamines acting at alpha
adrenoreceptors.
44. âĸī Heart rate
âĸī Contractility
âĸī Preload
âĸī Afterload
âĸī¯ Coronary flow
âĸī¯ Regional
myocardial blood
flow
ī
O2
D
e
m
a
n
d
ī¯
O2
S
u
p
p
l
y
īĸ-Blockers/Ca2+ channel
blockers
Nitrates/Ca2+ channel
blockers
Nitrates/Ca2+ channel
blockers/antithrombotics/
statins
HEART
47. CALCIUM CHANNEL BLOCKERS
MODE OF ACTION
1.DECREASES MYOCARDIAL OXYGEN DEMAND BY REDUCING BLOOD
PRESSURE AND MYOCARDIAL CONTRACTILITY
Mechanism of Action
1.Calcium channel blockers block voltage-gated L-type calcium channels, the calcium
channels most important in cardiac and smooth muscle.
By decreasing calcium influx during action potentials in a frequency and voltage
dependent manner, these agents reduce intercellular calcium concentration and muscle
contractility.
USED IN ALL TYPES OF ANGINA
Verpamil 80-160mg/8hr
Diltiazem 60-120mg/8hr
Nifedipine 10-40mg/8hr
Amlodipine 5mg/day
48.
49. ī VERAPAMIL AND DILITIAZEM-SUITABLE FOR PATIENTS
WHO ARE NOT RECEIVING BETA BLOCKERS AS THEY
DECREASE THE HEART RATE ( DANGEROUS ADDITIVE
EFFECT
ī Adverse Drug reactions:
Facial puffiness
Pedal edema
Flushing
Headache
Contraindications: Heart failure, Bradycardia
50. POTASSIUM CHANNEL ACTIVATORS
MODE OF ACTION: DILATES ARTERIES AND VEINS
DOES NOT EXHIBIT TOLERANCE SEEN WITH NITRATES
NICORANDIL- 10-30 mg 12 hourly
Caution in:
hypovolaemic patients
Patients with pulmonary oedema
Side effects:
a.Headache
b.Flushing
c.Dizziness
d.Weakness
e.May cause a dose dependent increase in heart rate
f.Myalgia
g.Angioedema
51. ī Potassium channel openers:
ī Types of potassium channels: Voltage gated, calcium
activated, ATP acyivated
ī Nicorandil is a newer agent activates ATP sensitive
potassium channel and hyperpolarises vascular
smooth muscles.
ī Decreases pre and after load and produce coronary
dilation
52. Ranolazine
ī§Reserve agent for chronic, resistant angina
ī§Inhibits cardiac late Na Current influx ,
there by reducing calcium flow into the cells
thus help the heart to relax improve the
blood flow
ī§Decreases cardiac contractility
ī§No change in Heart rate and BP
ī§Prolongs QT interval so it is containdicated
with drugs that prolong QT interval.
ī§Dose: 500mg, 1000mg
53.
54. IVABRADINE
ī§Direct Bradycardic agent or pure HR lowreing agent
ī§Blocks hyperpolarazation activated if current through Na
channel present in SA node which get activated during early part
of slow diastolic depolarization durring ischemic episodes.
ī§Heart rate decreased and Oxygen demand decreased
ī§No fall in BP
ī§Dose: 5mg
56. ASPIRIN
ANTIPLATELE T EFFECT BY INHIBITION OF THROMBOXANE A 2
NSAID, INHIBITS COX-1 AND COX -2 WHICH LEADS TO
DECREASED PROSTAGLANDIN SYNTHESIS
USES
THROMBO-EMBOLIC CVA, ISCHAEMIC HEART DISEASE-
PROPHYLAXIS (75MG/DAY) AND ACUTE TREAMENT (375 MG)
CONTRAINDICATIONS
1.THOSE UNDER AGE OF 16Y-CAN INCREASE INCIDENCE OF
REYEâS SYNDROME, LIVER/BRAIN DAMAGE
2.GASTRO-INTESTINAL ULCERS
3.BLEEDING DISORDERS
4.GOUT
5.HYPERSENSITIVITY TO ANY NSAID
6.GFR <10ML/MIN
57.
58. ASPIRIN
CAUTION
1.ASTHMA
2.UNCONTROLLED HYPERTENSION
3.ANY ALLERGIC DISEASE
4.G6PD DEFICIENCY
5.DEHYDRATION
OTOTOXIC IN OVERDOSE
MAY INCREASE EFFECTS OF SULPHONYL UREAS AND OF METHOTREXATE
FOR ANALGESIA- 300-900 MG 4-6 HPOURLY âMAXIMUM DOSE4G/DAY
STOP 7 DAYS BEFORE SURGERY IF SIGNIFICANT BLEEDING IS EXPECTED
IF CARDIAC SURGERY OR PATIENT HAS ACUTE CORONARY SYNDROME-
CONSIDER CONTINUING
59. CLOPIDOGREL
ANTIPLATELET AGENT- The active metabolite of clopidogrel
selectively inhibits the binding of adenosine diphosphate (ADP) to
its platelet P2Y12 receptor and the subsequent ADP- mediated
activation of the glycoprotein GPIIb/IIIa complex, thereby
inhibiting platelet aggregation. This action is irreversible
USE
PROPHYLAXIS OF ANTI-THROMBOTIC EVENTS IN NONâST
ELEVATIONMYOCARDIAL INFARCTION AND IN ST ELEVATION
MYOCARDIAL INFARCTION-IN COMBINATION WITH ASPIRIN
MYOCARDIAL INFARCTION (WITHIN A âFEWâ TO35 DAYS)
ISCHAEMICCEREBROVASCULAR ACCIDENT- WITHIN 7 DAYS TO 6
MONTHS
PERIPHERAL ARTERIAL DISEASE
CONTRAINDICATION
ACTIVE BLEEDING
NOT RECOMMENDED WITH WARFARIN
60. CLOPIDOGREL
SIDE EFFECTS
ī§ HAEMORRHAGE (ESPECIALLY GASTRO-INTESTINAL OR
INTRA-CRANIAL
ī§ GASTRO-INTESTINAL UPSET
ī§ PEPTIC ULCER
ī§ PANCREATITIS
ī§ HEADACHE
ī§ FATIGUE
ī§ DIZZINESS
ī§ PARAESTHESIA
ī§ RASH/PRURITUS
MONITOR FULL BLOOD AND FOR SIGNS OF OCCULT BLEEDING
61. STREPTOKINASE
THROMBOLYTIC AGENT
INCREASES PLASMINOGEN CONVERSION TO PLASMIN WHICH
INCREASES FIBRIN BREAKDOWN
USES
1.ACUTE MYOCARDIAL INFARCTION -1.5 MILLION UNITS
INTRAVENOUS INFUSION OVER 60 MIN
2.THROMBOEMBOLISM OF ARTERIES
3.PULMONARY EMBOLISM
4.CENTRAL RETINAL ARTERY THROMBOSIS
5.DEEP VEIN THROMBOSIS
OTHER DOSES-250,000 UNITS INTRAVENOUS INFUSION OVER
30 MIN, THEN 100,000 UNITS EVERYHOUR FOR UPTO12-72
HOURS
62. ALTEPLASE
(RECOMBINANT) TISSUE-TYPE PLASMINOGEN ACTIVATOR.
RECOMBINANT FIBRINOLYTIC
USE
ACUTE MYOCARDIAL INFARCTION (TOTAL DOSE 100MG-
REGIMEN DEPENDS ON TIME SINCE ONSET OF PAIN
0-6HOURS: 15 MG INTRAVENOUS BOLUS,FOLLOWED BY 50 MG
INTRAVENOUS INFUSION OVER 30 MINUTES AND 35 MG INTRAVENOUS
INFUSION OVER 60 MINUTES
6-12 HOURS-10 MG INTRAVENOUS BOLUS FOLLOWED BY 50 MG
INTRAVENOUS INFUSION OVER 60 MIN, AND FOUR FURTHER 10 MG
INTRAVENOUS INFUSIONS, EACH OVER 30 MIN)
DECREASE DOSE IF PATIENT WEIGHS LESS THAN 65 KG
RETEPLASE
RECOMBINANT PLASMINOGEN ACTIVATOR; THROMBOLYTIC
USED ONLY FOR MYOCARDIAL INFARCTION
DOSE-10 UNITS AS SLOW INTRAVENOUS INJECTION OVER 2 MINUTES,
REPEAT AFTER 30 MIN
63. Newer Drugs
A) Ranolazine appears to act mainly by reducing a late,
prolonged sodium current in myocardial cells.
1.The decrease in intracellular sodium causes an increase in
calcium expulsion via the Na/Ca transporter and a reduction in
cardiac force and work.
2.Ranolazine is moderately effective in angina prophylaxis.
B) Dipyridamole
1.It is a powerful coronary dilator;
increases total coronary flow by preventing
uptake and degradation of adenosine.
2.It dilates resistance vessels and abolishes autoregulation.
3.Inhibit platelet aggregation.
4.Not useful as an anti-anginal drug but used for prophylaxis of
Coronary and cerebral thrombosis in post-MI and post stoke
patients.
Editor's Notes
The principal mechanism by which the endothelium modulates coronary perfusion is by regulating coronary vascular tone through the production of nitric oxide (NO). NO is synthesised from the amino acid L-arginine by means of the enzyme endothelial NO synthase (e-NOS). Endothelial cells express e-NOS, producing a low level of NO, which is under the control of regulatory factors. NO has paracrine effects by readily permeating cell membranes where it activates the synthesis of cyclic guanylate cyclase (cGMP). Through this intracellular signalling pathway, it has a number of effects including vasodilation, angiogenesis, and reducing platelet adhesion and vascular smooth muscle proliferation.
Relieving pain is one of the main goals of treating coronary microvascular disease (MVD). Treatments also are used to control risk factors and other symptoms. Treatments may include medicines, such as:
ACE inhibitors and beta blockers to lower blood pressure and decrease the heartâs workload
Aspirin to help prevent blood clots or control inflammation
Nitroglycerin to relax blood vessels, improve blood flow to the heart muscle, and treat chest pain
Statin medicines to control or lower your blood cholesterol.
Causes of Variant (Prinzmetal) Angina: The pain from variant angina is caused by a spasm in the coronary arteries (which supply blood to the heart muscle).The coronary arteries can spasm as a result of:Exposure to cold weather
Stress
Medicines that tighten or narrow blood vessels
Smoking
Cocaine use
Symptoms of Variant (Prinzmetal) Angina:Â The pain or discomfort:Usually occurs while resting and during the night or early morning hours
Are usually severe
Can be relieved by taking medication
Treatment of Variant Angina | Prinzmetal's AnginaMedicines can help control the spasms. Drugs such as calcium antagonists and nitrates are the mainstays of treatment.