Download Decrease O 2 demand by venodilatation - e

Vilasinee Hirunpanich
B.Pharm (Hon), M.Sc in Pharm
(Pharmacology)
Angina pectoris
 Imbalance of O2 demand and supply
 myocardial O2 consumption > O2 supply
symptoms
เจ็บแน่นหน้าอกเหมือนมีสิ่งมากด
ทับบริ เวณลิ้นปี่
อาจมีอาการปวดร้าวและแผ่
กระจายไปที่คอ ไหล่และแขนซ้าย
Pathophysiology
1. decrease coronary blood flow
coronary spasm
Atherosclerosis
Traumatic injury
Embolic event
2. Increase O2 demand
increase physical activity which result in the
increase of sympathetic activity
3. Reduce blood O2
 anemia
ปัจจัยที่มีผลต่อการทางานของหัวใจ
Oxygen demand
Oxygen supply
 heart rate
 myocardial blood flow
 contractility
 afterload
 preload
Type of angina pectoris
 Stable angina
 Unstable angina
 Variant angina (Prinzmetal’s angina)
Stable angina
Coronary artery spasm
Treatment goals
 Alleviate symptoms
 Control & modify risk factors
– Smoking, HT, DM, obesity, dyslipidemia, stress
 O2 supply and  O2 demand
 Pharmacologic therapy
– Nitrate, beta-blockers, CCB
 Intervention therapy
– PTCA
– CABG
กลุ่มยาหลักที่ใช้ในการรักษา
Organic nitrate
calcium channel blockers
beta-blocker
1. Organic Nitrate
Mechanism of action
 Internalized metablolite to…. NO
 Increase cGMP……smooth muscle
relaxation and vasodilatation
 Stimulate PGI & PGE2
 Antianginal effects
– Decrease O2 demand by venodilatation
– Increase O2 supply by coronary vasodilation
Mechanism of nitrate
Sulfhydryl group
nitrate
NO2
NO (active)
Stimulate guanylate cyclase
Stimulate cGMP
Decrease Ca level
vasodilation
Pharmacological effects
1. Smooth muscle relaxation
 Vein sensitive than arteries
 Venodilatation…..decrease ventricular
preload, pulmonary pressure (O2 demand)
SE>>>orthostatic hypotension, syncope
 Vasodilatation…..decrease peripheral
resistance (O2 demand)
SE>>> flushing, throbbing headache
Pharmacological effects (cont)
2. Smooth muscle relaxation at other
organ
Not widely use in clinic except
Sidenafil (Vigra)
3. Antiplatelet activity
decrease platelet aggregation
not widely use
Nicorandil stimulate K+ channel + NO
Pharmacological effects (cont)
4. Other effects
Methemoglobin
large dose cause cyanosis, tissue
hypoxia, death
Pharmacokinetic
Extensive first pass metabolism
Low availability
Onset 2-8 min
Duration 15-30 min
Several preparation available …..
Sublingual, sustained release,
transdermal, buccal
 Acute adverse effects
– Headache (prevent by paracetamol)
– orthostatic hypotension
– reflex tachycardia
– flushing
–Chronic use result in
tolerance
–Long acting preparation
usually cause tolerance
Possible causes of tolerance
 Systemic compensation
 Stimulate aldosterone release
 free radical that degradation NO
 Vascular sulfhydryl depletion
(decrease NO release)
Method to prevent tolerance
 Maintain at least 8-12 h nitrate-free interval
Pts education: for use NG SL
 Sit or lay down
 Place tablet under the tongue
(do not swallow)
 If symptom are not relief within 5 min, place
another tablet under the tongue.
 Pt may use a maximum of 3 tab over15 min
 If pain is not relieve within 20-30 min ..go to
hospital
Clinical use
 stable, unstable, variant angina
– Short acting nitrate…
prn
– NG SL, ISDN SL
 Angina prophylaxis
– Monotherapy limited by tolerance & reflex
tachycardia
– Best use combination with -blocker, CCB,
diuretic
Calcium channel blocker
(CCB)
 Increase myocardial O2 supply
– Coronary vasodilatation.. All agents
 Decrease myocardial O2 demand
– Decrease afterload and preload.. All agent
– Decrease contractility and HR.. Non-DHP
group.
CCB-Clinical Use
 Prophylaxis
 Monotherapy
– Verapamil & diltiazem may be used
– Short acting DHP CCB is generally avoided
due to reflex tachycardia.
 Combination therapy
– Often use with nitrate, beta-blocker
 DHP
– Reflex tachycardia
– Headache
– Edema
 Verapamil/diltiazem
– Bradycardia
– Heart block
– Constipation (esp. verapamil)
ADR
 Stable, unstable, variant angina
Short acting CCB increase risk of MI
Mechanism of action
Antagonize effect of catecholamine on the
heart by blocking the beta-receptor
Antianginal effect
Decrease contractility and HR
Not use in variant angina
Ex. Propranolol, metoprolol, atenolol
Hypotension
Bradycardia
Heart block
Withdrawal syndrome.. Taper dose
Bronchospasm
Other…fatigue, CNS depression, mask of
hypoglycemia, dyslipidemia
Clinical use
 Decrease O2 demand in the resting and
exercise state
 Stable, unstable angina
Combination therapy
 Nitrate & beta-blocker
 Nifedipine & beta-blocker
 CCB & nitrate
 Beta-blocker & nitrate & CCB