This document discusses various drugs used to treat angina pectoris, which is chest pain due to myocardial ischemia. It describes several classes of antianginal drugs that work by either increasing oxygen supply to the heart or decreasing oxygen demand. These include organic nitrates like glyceryl trinitrate, beta-blockers, calcium channel blockers, and ACE inhibitors. The document provides details on the mechanisms and sites of action of these drug classes as well as their adverse effects. Alternative treatment methods for ischemic heart disease like rotational atherectomy are also mentioned.

1. ANTIANGINAL DRUGSANTIANGINAL DRUGS

2. Angina pectorisAngina pectoris is a symptom of
reversible myocardial ischaemia and is
most frequently experienced as chest painchest pain
on exertionon exertion, which is relieved by rest.
Pain is the consequence of an imbalance
between oxygen supply and oxygen demand
in the ischaemic area of myocardium.

4. This imbalance results from an inability
of the coronary blood flow to meet the
metabolic demands of the heart, due to a
fixed atheromatous narrowing of coronary
artery.
Usually
reversible
coronary
artery
spasm
participates too.

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StressStress
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9. X-rayX-ray
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10. They can be given to relieve rapidly the
ischaemia during an acute attack, or as
prophylaxis to reduce the risk of
subsequent episodes.
Antianginal drugs increase oxygen supply
by improving coronary blood flow or reduce
oxygen demand by decreasing cardiac work.

11. Major sites of actions of antianginal drugsMajor sites of actions of antianginal drugs

12. Glyceryl-
3-nitrate
Isosorbide
dinitrate
. Organic nitrates –
indirect donors of NO

13. Organic nitrates are vasodilators which
relax vascular smooth muscle.
They connect with thiol groups (−SH)
and release nitric oxide (NO).
NO combines with thiol groups in
vascular endothelium to form nitrosothiol
(R−SNO). Nitrosothiol activates guanylate
cyclase which raises the concentration of
cyclic GMP. This reduces the availability
of intracellular calcium and produces
vasodilation in three main vascular beds.

14. Ca2+
Organic
nitrate
(R-ONO2)
Endothelium Smooth muscle
Celullar action of nitrates
SR – sarcoplasmatic reticulum
GTP – guanosine triphosphate
GMP – guanosine monophosphate

15. Organic nitrates dilate:
•Venous capacitance vessels and lower
left ventricular filling pressure (“preload”)
•Arterial resistance vessels and reduce
ventricular emptying (“afterload”).
This is less important than venodilation
during long treatment but it lowers blood
pressure, decreases cardiac work and
contributes to reduced oxygen demand.

16. •Coronary arteries.
Nitrates have little effect on the total
coronary flow but they improve the
blood flow through collateral vessels.
Nitrates also relieve coronary artery
spasm. The net effect is increased
blood flow supply to ischaemic areas
of the myocardium.

18. Glyceryl trinitrate is the most widely used
organic nitrate. It is well absorbed orally
but undergoes extensive first-pass metabo-
lism in the liver to inactive metabolites.
Usually glyceryl trinitrate is given by one
of three routes to avoid first-pass effect
and hence increases its bioavailability:
(1) Sublingually (as a tablets). Its effect
begins after 1−2 min and lasts 18–20 min.
Tablets lose their potency with prolonged
storage.

19. Sublingually (as a spray). A metered
dose aerosol spray is equally effective
and more stable.
(2) Transdermal: glyceryl trinitrate
is absorbed well through the skin and
can be delivered from an adhesive
patch, via a rate-limited membrane or
matrix. The anti-anginal effect is stable
for at least 24 hrs.
(5) Intravenous infusion.

20. Glyceryl trinitrate
•Nitrolingual®
spray: 0.4 mg/dose
•Nitroglycerin®
: ling. 0.5 mg
•Nitroderm®
TTS
•Perlinganit®
− i.v. inf.
(+ Heparin)

21. Isosorbide dinitrate
(prodrug)
•Isoket®
: spray and tabl. (sub linguam)
•Isodinit®
: tablets 20 mg
•Kardiket®
: tabl. 20 mg
Isosorbide-5-mononitrate
•t1/2 4–5 h (Olicard®
40 retard: 12 h)

22. Adverse reactions of nitrates:
•Venodilation may lead to postural hypo-
tension, dizziness, syncope, tachycardia.
•Arterial dilation causes throbbing
headache and flushing, but tolerance is
common during treatment with long-acting
nitrates (retard tablets).
•Tolerance to the therapeutic effects. This
may be due to depletion of vascular thiol
groups. It can be avoided by a “nitrate-low”
period of 10−12 h each day.

23. II. Beta-adrenoceptor
antagonists (β-blockers)
(β1) (β1 & β2 )
Propranolol
Oxprenolol
Pindolol
Carvedilol
(antioxidant)
(β & α )
Atenolol
Acebutolol
Bisoprolol
Celiprolol
Metoprolol

24. VDCC ROCC
Receptor
AP
Ca2+
CaCa2+2+
Sarcoplasmatic
reticulum
Cell
wall
(–)
Beta-blockersBeta-blockers
AP – action potential, NA – noradrenaline
VDCC – voltage dependent calcium channels
ROCC – receptor operating calcium channels
(–)

25. All β-blockers act as competitive antagonists
of catecholamines at beta-adrenoceptors:
•decrease heart rate;
•reduce the force of cardiac contraction;
•lower blood pressure;
•reduce oxygen demand.
Lipophilic β-blockers (e.g. propranolol) are
well absorbed from the gut, but undergo
extensive first-pass metabolism in the liver,
with considerable variability among
individuals.

26. Hydrophilic beta-blockers (e.g. atenolol) are
less completely absorbed from the gut and
are eliminated unchanged by the kidney.
The dose range to maintain effective plasma
concentrations is narrower than that for drugs
which undergo metabolism and the clinical
response in angina pectoris is more
predictable.
Adverse reactions of beta-blockers
•Blockade of beta1-receptors may cause
bradycardia, AV block, heart failure.

27. •Blockade of beta2-receptors may
cause bronchospasm, intermittent
claudication (reducing peripheral
blood flow) and hypoglycemia.
•CNS effects: sleep disturbance, dreams and
hallucinations (more common with
lipophilic drugs which cross the BBB).
•Most β-blockers raise the plasma concentration of
triglycerides and lower the concentration of HDL.
•Induratio penis pastica (fibrosis …)
•Sudden withdrawal syndrome: Beta-blockers
should be stopped gradually.

28. III. Calcium antagonists
Calcium is essential for excitation and
contraction in muscle cells. Free calcium
must either enter the cell or be released
from intracellular stores (e.g. SR).
Calcium antagonists have widely different
chemical structures.

29. Calcium antagonists block predominantly L-type
calcium channels, localized in myocardium
and myocytes
of blood
vessels.
L-type channels
are connected
to the plateau
of the AP.
Plateau phase of AP

30. VDCC ROCC
Receptor
AP
Ca2+
Ca2+
Sarcoplasmatic
reticulum
Cell
wall
NA
(–)
CalciumCalcium
antagonistsantagonists
AP – action potential, NA – noradrenaline
VDCC – voltage-dependent calcium channels
ROCC – receptor operating calcium channels

31. Calcium antagonists
cause a reduction
in coronary and
peripheral resistance,
lower the blood pressure
and oxygen demand.
Dihydropyridine derivatives
(e.g. amlodipine, felodipine, nifedipine,
nisoldipine) have no negative
chronotropic effect and do not impair
myocardial contractility.

32. (Tipathy, 2003)

33. Calciumantagonists Amlodipine
normal frequently dihydropyridine
t1/2 31–47 h, 55–91% p.o. bioavailability
5–10 mg/24 h p.o. (once daily)
Nifedipine (tachycardic dihydropyridine)
– effective in vasospastic angina
Diltiazem (in SR dosage forms)
Verapamil (Isoptin SR®
– tabl. 120 mg)
(22% p.o. bioаvailability, first pass effect –
extensive liver metabolism)

34. ADRs of calcium antagonists
•Arterial dilation: headache, flush, dizziness,
ankle swelling (resistant to treatment with
diuretics but not with ACE inhibitors).
•Bradycardia and AV block (verapamil).
•Verapamil + beta-blockers: potentiate
cardiodepression.
•Tachycardia (nifedipine, nisoldipine).
•Constipation
(verapamil 8%, nifedipine 3%)
•Haemorrhagic gingivitis
(inhibition of collagen synthesis)

35. 4. Metabolic cardioprotective agents
Trimetazidine (Preductal MR®
) has prolonged
concentration plateau lasting up to 11 h.
It increases ATP synthesis and decreases acidosis
in ischemic tissues.
Trimetazidine supplies energy for the Na+
/K+
transmembrane pump, but can cause parkinsonismparkinsonism.

36. Angiotensinogen
Angiotensin I
Angiotensin II
AT1-
receptor
AT2-
receptor
ACE Enalapril
(−)
Kinins
PGs:vasodilation
(kininase II)
(−)
ACE
5. ACE inhibitors:
Enalapril, Lisinopril
Ramipril, Trandolapril …

37. 6. If-blockers
delays pulse rate with

38. IV. OTHER DRUGS
USED IN CORONARY
HEART DISEASE (CHD)
Platelet antiaggregants
Antifibrinolytics (Alteplase - t-PA)
Antidyslipidemic drugs
Anxiolytics, etc.

39. V. ALTERNATIVE METHODS
FOR TREATMENT OF
ISCHAEMIC
HEART
DISEASE

42. Rotational atherectomy (Rotablation) –
Chronic narrowing's or blockages may become calcified or have a lot
of atheroma in them making them very difficult to treat with just a
balloon. Rotablation is a procedure where, once again, a very fine
wire is guided through the narrowing and then a catheter with a small
device called a burr, similar to drill, mounted at its tip is guided to the
beginning of the narrowing. The burr is connected to an external
device which when activated by the cardiologist causes the burr to
spin at very high speeds inside the narrowing, thereby creating a
channel wide enough for a balloon or stent to then be used.

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47. RegenerativeRegenerative
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51. •BMI > 30:
>>> saturated fatty acids
>>> salt and >>> sugar
>>> alcohol
<<< fruits and vegetables
•Smoking
•Lipid status
•Stress
2/3
of the
risk
Risk factors for CVDRisk factors for CVD
•Chomocysteine > 15 mmol/l

•Diabetes mellitus
•Metabolic syndromeMetabolic syndrome
•Sedentary life style
•Tachycardia

52. Никотинът е иНикотинът е и
ензимен индуктор.ензимен индуктор.

55. ““The heart never stops. When it stops, it stopsThe heart never stops. When it stops, it stops
forever”. Leonardo da Vinciforever”. Leonardo da Vinci
ModernmedicineoftenModernmedicineoften
disprovesthissaying.disprovesthissaying.