Regional and

local
vasodilators
Overview
- angina pectoris is reversible myocardial ischemia due to a coronary artery disorder

Myocardial Blood Flow

Myocardial O2 Demands

Transient Myocardial
ischemia

Severe Chest pain Angina Pectoris

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Chest pain caused by transient
myocardial ischemia due to an
imbalance between myocardial
oxygen supply and demand.

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 TYPE DESCRIPTION

• SILENT MYOCARDIAL ISCHEMIA

• STABLE ANGINA - narrowed coronary
artery lumen
• UNSTABLE ANGINA - occluded coronary
artery lumen
• MIXED ANGINA - both narrowed and
occluded lumen at distinct locations
• PRINZMETAL ANGINA - vasospasms of
the coronary arteries
• if angina pectoris remains untreated it
can progress to irreversible myocardial
ischemia (acute myocardial infarction,
AMI)
Classification of drugs used in angina pectoris
• I. Remedies decreasing the oxygen consumption and
increasing the oxygen delivery to the myocardium
• Organic nitrates
– nitroglycerin isosorbide dinitrate
– sustac (mite, forte) isosorbide mononitrate
– trinitrolong
– nitrong
• Ca channel-blocking drugs
– nifedipine diltiazem
– verapamil mibefradil
• K channel activators
– minoxidil pinacidil
– nicorandil diazoxid
• Various drugs
– amiodarone
 II. Remedies that decrease the oxygen
consumption:
a.)-adrenoblockers b) remedies causing bradycardia
– propranolol - alinidine
– talinolol - falipamil
– metoprolol
– atenolol
III. Remedies increasing the oxygen delivery to the
myocardium
A. myotropic coronarodilators
phosphodiesterase inhibitors
– aminophylline
– xantinol nicotinates
– carbocromen
with adenosinic mechanism
– dipyridamol
– lidoflazine
NO donators
– molsidomine
B. Reflex coronarodilators
– validol
 Organic nitrates
• MECHANISM OF ACTION
 Cellular Mechanism of Vasodilatation
Nitrates Formation of
Nitric oxide (NO)

Synthesis of Activation of
cyclic GMP Guanylate cyclase

Relaxation of Vascular
smooth muscles

N.B. (-SH) groups are required

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for formation of NO.
 Effect of Nitrates :
On Stable Angina :
Arteriolar
1- Venodilatation dilatation
Preload Afterload

Myocardial
Oxygen demand

2- Redistribution of coronary flow towards

subendocardium
3- Dilatation of coronary collateral vessels.
On Variant Angina :

Relax smooth muscles of the

epicardial coronaries  relieve
coronary artery spasm

On Unstable Angina :

Dilatation of epicardial coronary

arteries + reducing O2 demands

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 Adverse Reactions :
1- Postural Hypotension & 2- Tachycardia
Syncope

3- Drug Rash

4- Facial Flushing

6- Prolonged high dose

Methaemoglobinaemia

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 The main limitation of chronic nitrate therapy is
TOLERANCE

How does it occur?

It develops as SH groups in vessel wall become oxidized by
constant exposure to nitrates, this prevents the production of
NO.

“NITRATE FREE INTERVAL” of 8-10 hrs reduces or prevents

development of nitrate tolerance.

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In contrast they are not useful for
vasospastic angina (Variant) {Prinzmetal} &
may worsen the condition.
 Mechanism of antianginal action:
The effectiveness of  -adrenoceptor blockers in the
treatment of exertional angina is attributable to a fall
in myocardial O2 requirement at rest & during
exertion due to :
1- N -ve chronotropic effect (particularly during
exercise).

2- N -ve inotropic effect.

3- A reduction in arterial blood pressure (particularly

systolic pressure) during exercise.
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 Adverse Reactions :

Bronchospasm
CHF A-V block

Cold
extremities Worsening Hypotension
symptoms of PVD
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 Adverse Reactions :

Fatigue & Mask signs of Nightmares , Hallucinations ,

weakness Hypoglycemia Depression.

Plasma Triglycerides & HDL

Cholesterol Discontinuation after
long ttt exacerbates
Angina
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 Contraindications :

Bronchial
CHF A-V block asthma

Peripheral Hypotension
Vascular 19
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Verapamil Diltiazem
Dihydropyridine group
Nifedipine
Amlodipine

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 Block

Voltage -dependent calcium

channels (L-type) in cardiac and
smooth muscles.

C
A
L
C
I
U
M
Mechanism of anti-anginal action :
1 - Coronary artery dilatation and relief
of coronary spasm (variant angina)

2 -Decrease myocardial O2 demand due to:

•Arteriolar Vascular
dilatation Afterload
resistance

•(Verapamil & Diltiazem)

•Decrease HR.
•Decrease contractility
•Decrease AV conductivity
 Adverse reactions :

Ankle
Dizziness edema
Headache Hypotension

Constipation
A-V block & HF only
with Verapamil &
Diltiazem
 Contraindications of
Verapamil & Diltiazem:

1 - HF

3 - Bradycardia.
 Myotropic coronarodilators
• phosphodiesterase inhibitors inhibit
phosphodyesterase →↑ cAMP quantity → inhibit
Ca channels and → vasodilatation.
• Effects: coronarodilatation
• Increase glucose utilization ,
• Increase intracellular K quantity
• Decrease the myocardial needs in oxygen
• Side effects: tachycardia, cardiac pains, vertigo,
headache
• with adenosinic mechanism
• Dipyridamol - ↓adenosindesaminase → ↑
the adenosine quantity. Adenosine has
vasodilator effect.
• Side effects: headache, dyspepsia,
hypotension and Crash syndrome.( It
dilates only healthy vessels but have no
action on ischemic area).
 Drugs used in Miocardial infarction:
• 1. Opioid drugs (fentanyl, morphine, trimeperidine)
• 2. anxiolitcs : tranqulisators (diazepam), neuroleptics.
• Neurolepanalgesia (fentanyl, droperidol or talamonal)
• 3. Prevention of arrhythmias: antiarrhythmics (lidocaine)
• 4. For improvement of circulation in the hypertonic state :
(hexamethonium, furasemide, triperium iodide)
• in the hypotonic state : dopamine, norepinephrine,
phenylehrine)
• 5. Prevention of thromboses: anticoagulators (heparin)
• antiagragants (fibrinolysine, aspirin)
• 6. for acido-basec equilibrium: Na bicarbonate, Dextran40,
70
• 7. in cardiac failure : cardiotonics (dopamine, glycosides)
• 8. to decrease necrotic area : nitroglycerine
• 9. to ameliorate the myocardial metabolism
- cardioprotectors: omopatrylate, trimethasidine
- antioxidants: coenzyme Q10
 Cerebral and peripheral vasodilators
Classification
• A. Myotropic vasodilators:
– Alkaloids from Vinca minor: vincamine, vinpocetine, vincapan
– Xantines derivates: aminophylline, pentoxiphylline, xantinol
nicotinate, coraldon
– Ca channel blockers.: nimodipine, cinnarizine
– antispastic drugs: papaverine, parasol, nicoverine, drotaverine
• B. Neurotropic vasodilators
• 1.alkaloids from Ergot: ergotamine,
dihydroergotamine, dihydroergotoxine
• 2. -adrenoblockers: nicergoline, tolasoline
• 3. -adrenomimetics: buphenine, isoxuprine
• 4. antiserotoninics: cinnarizine, metysergide,
lisurid
• C) Remedies that influence the metabolism
• Nootrops, cerebrolisine, tanacan
 1.Alkaloids from Vinca-minor:
• Mechanism of action- block Na channels.
• Effects: - spasmolitic action; cerebral
vassodilation, antiagregant effect
Indications: chronic cerebral failure, stroke,
vestibular deregulations.
• Side effects: hypotension, tachycardia,
allergy