Angina pectoris is a sudden chest pain often radiating to the left arm, neck, or back, treated with antianginal drugs like nitrates that reduce cardiac work by dilating blood vessels. Nitrates come in various forms, including short-acting and long-acting options, each with specific dosages and pharmacokinetic profiles. Side effects include headaches and dizziness, with important drug interactions noted, particularly with erectile dysfunction medications that can cause dangerous hypotension.

1. Presented by
Nikhil Peter
Pharm D intern
Annamalai university

2. BACKGROUND
Angina Pectoris is a form of paroxysmal (sudden onset) chest pain that
is felt beneath the sternum, and commonly radiates down the left arm
&/or shoulder. It can also radiate or originate in the neck or upper back
as well.

3. Drugs Used to Treat Angina
Antianginal drugs are those that prevent, abort or terminate attacks of
angina pectoris

4. Nitrates
Short acting:
Glyceryl trinitrate (GTN, Nitroglycerine)
Long acting:
Isosorbide dinitrate (short acting by sublingual route),
Isosorbide mononitrate, Erythrityl tetranitrate, Pentaerythritol
tetranitrate
All organic nitrates share the same action; differ only in time
course. The only major action is direct nonspecific smooth
muscle relaxation

6. Preload reduction
The most prominent action is exerted on vascular smooth
muscle.
Nitrates dilate veins more than arteries → peripheral pooling
of blood → decreased venous return, i.e. preload on heart is
reduced → end diastolic size and pressure are reduced →
decreased cardiac work
Laplace relationship
Wall tension = intraventricular pressure × ventricular radius
Afterload reduction
Nitrates also produce some arteriolar dilatation → slightly
decrease total peripheral resistance (t.p.r.) or afterload on heart;
BP falls somewhat; systolic more than diastolic (reflex
sympathetic activity tends to maintain diastolic BP). This action
contributes to the reduction in cardiac work

7. Mechanism of action

8. NITROGLYCRIN[short acting]
S.No Forms and strength Indication Dosage Pharmacokinetic profile
1 infusion solution
 25mg/250mL
 50mg/250mL
 100mg/250mL
injectable solution
 5mg/mL
Angina
Myocardial
Infarction
5 mcg/min continuous IV infusion
via non-absorptive tubing; increase
by 5 mcg/min every 3 to 5 minutes
as needed up to 20 mcg/min, then
by 10 or 20 mcg/min if needed
Half life:1-4 min
DA:3-5 min
onset:1-3 mn
Metabolism:liver(1,3-
glyceryl dinitrate, 1,2-
glyceryl dinitrate, and
glyceryl mononitrate
(inactive)
Eliniation: Urine
2 capsule, extended release
 2.5mg
 6.5mg
 9mg
Angina prophylaxis ER capsule: Initial 2.5-6.5 mg PO
q6-8hr
Titrate up to effect dose.
Half life:1-4 min
DA: up to 4-8hr
onset:1-4 hr
3 tablet, SL
 0.3mg
 0.4mg
 0.6mg
powder, SL (GoNitro)
 0.4mg
Angina Pectoris
(Acute Relief)
0.3-0.6 mg SL q5min up to 3 times;
use at first sign of angina
Half life:1-4 min
DA: up to 30 min
onset:1- 3 min
Angina Pectoris
(Prophylaxis)
1 tablet SL 5-10 minutes before
activities likely to provoke angina
attacks

9. S.No Forms and strength Indication Dosage Pharmacokinetic profile
4 spray
 0.4mg/spray
Angina 1-2 spray(s) PRN for angina,
may repeat q3-5min, not to
exceed 3 sprays in 15 minutes
Half-Life: 1-4 min
Onset: 2min
Duration: Up to 1 hr
5 patch
 0.1mg/hr
 0.2mg/hr
 0.3mg/hr
 0.4mg/hr
 0.6mg/hr
 0.8mg/hr
Angina Pectoris 1 Patch day; Start with
smallest unit in series & titrate
Nitrate-free period of 10-12
hours duration (overnight)
needed to prevent tolerance
Half-Life: 12-33 min
Onset: 60 min
Duration: 10-12 hr
6 ointment
 2%
Angina Pectoris
(Long-Term
Prophylaxis
0.5-2 inches applied in arm
and 6 hours later to truncal
skin
Half-Life : 1-4 min
Antianginal effects: 30mn
Hemodynamic effects:1hr
Duration Up to 7 hr
(topical)
Peak Plasma Time: 3-4 hr
Congestive Heart
Failure
1.5 inches, increase by 0.5-1
inch up to 4 inches, q4hr
7 ointment, intra-anal
 0.4% (4mg
nitroglycerin/1g of
ointment)
Chronic Rectal
Fissure Pain
applied intra-anally q12h until
pain abates, not to exceed
treatment duration of 3 weeks
Half-life (mean): 2-3
minutes

10. Long acting nitrates
S.No DRUG PREPARATION DOSE AND ROUTE DURATION OF
ACTION
1 Isosorbide dinitrate SORBITRATE 5, 10
mg tab
5–10 mg sublingual 20–40 min
ISORDIL 5 mg
sublingual and 10 mg
oral tab
10–20 mg oral 2–3 h
DITRATE 5, 10 mg
tab; 20, 40 mg SR
Tab
20–40 mg oral 6–10 hr
2 Isosorbide 5 mononitrate MONOTRATE 10,
20, 40 mg tab
25, 50 mg SR tabs
20–40 mg oral 6–10 hr
Erythrityl-tetranitrate CARDILATE 5, 15
mg tab
15–60 mg ora 4–6 hr
3 Pentaerythritol tetranintrate PERITRATE 10 mg
tab
10–40 mg ora 3–5 hr
PERITRATE-SA 80
mg SR tab
80 mg oral 8–12 hr
4 Amyl nitrate 0.3 ml crushable
glass ampule
0.3 ml crushable glass
ampule by inhalation
repeat q3-5 min
3-15 min

11. NITRATE SIDE EFFECTS
Headache (due to meningeal vasodilation),Dizziness
Reflex Tachycardia :(baroreceptor mediated due to a fall in arterial
BP produced by higher doses of NTG)
Orthostatic hypotension (less common), rashes,weakness
CI and SP: Allergic reaction, Anaemia, head trauma.sp required
in pregnancy and lactation, hepatic and renal disease and
hypotension
Tolerance
tolerance can be reversed by omitting dosing at night
“anginal rebound” episodes can occur during nitrate-free
intervals
The mechanism of nitrate tolerance is not well understood. Reduced
ability to generate NO due to depletion of cellular SH radicals has
been demonstrated experimentally. However, thiol replenishing
agents only partially overcome nitrate tolerance. This form of
therapy has not met clinical success

12. NITRATE DRUG INTERACTIONS
Sildenafil & other Type 5 Phosphodiesterase Inhibitors
(Erectile Dysfunction Drugs)
unsafe hypotensive episodes of >25 mm Hg can occur if
nitroglycerin is used within 24 hours after taking sildenafil (Viagra or
within 2 days after taking tadalafil.
This interaction occurs because there is a low level of type 5
phosphodiesterase expressed in systemic arterial smooth muscle.
When patients take nitroglycerin alone, cGMP levels in arterial
smooth muscle are increased, resulting in a normally safe level of
arterial vasodilation. However, when type 5 PDE has been inhibited
by prior administration of a Type 5 PDE inhibitor, the vasodilator
effect of the nitrate can be intensified to the point of potentially
producing an excessive lowering of blood pressure that can
precipitate a myocardial infarction & death