Drugs acting on cardiovascular system(CVS)

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Chapter 6.
Drugs acting on cardiovascular system(CVS)
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Part 1. Drugs Acting Ion Channels in
CVS(????????????)
Part 2. Antiarrhythmic Drugs(??????)
Part 3. Drugs for Treatment of Chro-nic Cardiac
Dysfunction
Part 4. Antianginal Drugs(?????)
Part 5. Antiatheroscleotic drugs(????????)
Part 6. Antihypertensive Drugs(?????)
Part 6. Antihypertensive Drugs(?????)
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Part 6. Antihypertensive Drugs (?????)
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Contents
?. Overview ?. Antihypertensive drugs most in
use ?. Other antihypertensive drugs ?. Rational
application of anti-hypertensive drugs
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?. Overview
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?. Overview
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?. Overview
Hypertension can be divided into Essential
hypertension 9095 Secondary
hypertension 510 Normal blood pressure(BP),
2004 Diastolic BP 80 mmHg Systolic
BP 120 mmHg Criterion of hypertension
Diastolic BP 90 mmHg Systolic BP 140
mmHg
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?. Overview
2004????????? ?1999??????,
????????????????lt120/80mmHg(1999????130/85mmHg).
???????????????????????. ???????,
???gt115/75mmHg?, ??????, ?????????.
???20/10mmHg, ???????????????1?.
????????????????????????.
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?. Overview
???????120/80mmHg????, ??????????????????,
???????????????????????????.
???????????????????7???(JNC7)??,
??gt18?????????????lt140/90mmHg, ??????????lt130/80mm
Hg, ?????????????lt125/75 mmHg.
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?. Overview
Major factors influencing blood pressure
Arterial blood pressure
Cardiac output
Peripheral resistance
arteriolar tone
?
?
Blood volume
Heart rate
Filling pressure
Contractility
Venous tone
Baroreceptors and sympathetic nervous system
Renin-angiotention-aldosterol system (RAAS)
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Peripheral resistance and vascular tone and
elasticity
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Arterial wall hypertrophy and sclerosis
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Classification of Antihypertensive Drugs
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Classification of Drugs
1. Drugs most in use
(1)Diuretics (2)Adrenoceptor blockers (3)Calcium
channel blockers (4)Regin-angiotensin system
inhibitors
2. Other drugs
(1)Centrally-acting drugs (2)Ganglion
blockers (3)Noradrenergic nerve ending
blockers (4)Vasodilators
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?. Antihypertensive drugs most in use
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?. Drugs most in use(1)
Diuretics 1. Pharmacological effects
(1)Reducing plasma volume ? cardiac output ?
(2)Owing to excretion of Na ?, ? Na-Ca2
exchange ? in vascular smooth muscle cells,
Ca2i ?, ? peripheral resistance ?.
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Mechanism of diuretics ?blood vol-ume
? ?Na-Ca2 exchange?, ?Ca2i in va-scular
smo-oth muscle cells
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Diuretics
2. Clinical uses (1)Hypertension single
or combined with other drugs mild to
moderate hypertension particularly useful in
the treatment of elderly patients, pure systolic
hyperten-sion, hypertension with heart
failure. (2)Other uses diuresis, anti-CHF,
etc.
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Diuretics
3. Adverse effects plasma levels of renin
? hypokalemia hyperuricemia
hyperglycemia hyperlipidemia
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Diuretics
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?. Drugs most in use(2)
Adrenoreceptor blockers ? Receptor blockers
propranolol 1. Pharmacological effects (1)Decreas
ing cardiac output (2)Inhibiting the release of
renin from kidney(to inhibit formation of
angio-tension and secretion of aldosterone)
(3)Decreasing sympathetic outflow from
CNS (4)Decreasing releasing of noradrenalin (NA)
from peripheral nerve endings (5)Increasing
production of PGs.
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Main actions of ß receptor antagonists on blood
pressure
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? Receptor blockers
3. Clinical uses (1)Hypertension All
kinds of hypertension, more effective in young
patients than eld-erly. Useful in treating
coexisting con-ditions, such as
supraventricular tachycardia, previous
myocardial infarction, angina pectoris, glauco-ma
and migraine headache.
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? Receptor blockers
(2)Other uses angina pectoris
arrhythmias. 3. Adverse effects cardiac
depression drug withdrawal inducing
attack of asthma, etc.
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? Receptor blockers
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?. Drugs most in use(2)
?1 Receptor blockers
Prazosin(???)
Terazosin(????)
Doxazosin(????)
Trimazosin(????)
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?1 Receptor blockers
Prazosin(???)
1. Pharmacological effects (1)Blocking
?1-receptor of blood smooth muscles and relaxing
small artery and vein (2)Decreasing peripheral
resistance.
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?1 Receptor blockers
Prazosin
2. Clinical uses Hypertension mild
to moderate(single) severe
hypertension(combined with diuretics and ?
blockers). minimal changes in renal blood
flow, glomerular filtration, and renin
release. 3. Adverse effects first dose
phenomenon(postural hypo-tension) water and
sodium retention.
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?1 Receptor blockers
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?. Drugs most in use(2)
? and ?1 Receptor blockers
Labetalol(????)
Carvedilol(????)
Amosulalol(????)
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? and ?1 Receptor blockers
Characteristics of ? and ?1 Receptor
blockers (1)? blood pressure moderately (2)Minim
al changes in cardiac output and heart
rate (3)Used for all kinds of hypertension,
including hypertensive emergency (4)Less adverse
effects.
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?. Drugs most in use(3)
Calcium channel blockers
Nifedipine(????)
1. Pharmacological effects Relaxing vascular
smooth muscles. 2. Clinical uses Mild to
severe hypertension.
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Calcium channel blockers
3. Adverse effects Peripheral edema
Reflex sympathetic activation Renin
activity ?. Other calcium channel blockers
Amlodipine(????), etc.
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Calcium channel blockers
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?. Drugs most in use(4)
Renin-angiotensin system inhibitors ACEI
captopril (????), enalapril
(????) AT1 receptor antagonists
losartan (???) Renin inhibitors
enalkiren (????)
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Renin inhibitors
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?. Drugs most in use(4)
angiotensin converting enzyme inhibitors(ACEI)
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ACEI
1. Pharmacological effects (1)Inhibiting the
production of Ang? (2)Inhibiting the
degradation of bradykinin, to vasodilatation
(3)Decreasing the activity of sympa-thetic
system (4)Inhibiting ventricular remodeling
(5)decreasing aldosterone.
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ACEI
2. Clinical uses Hypertension not
reflexly increasing the activity of sympathetic
system effective in the patients with CHF,
diabetes and ischemic heart disease also.
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ACEI
3. Adverse effects hypotension(first dose
phenomenon) renal injury dry cough
hyperkalemia angioneuroedema rashes and
altered tastes Contraindications renal
artery stenosis, pregnant and lactational women.
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?. Drugs most in use(4)
AT1 antagonists
Losartan(???)
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AT1 antagonists
Compared with ACEI (1)Block actions of
angiotensin ? di-rectly (2)Not influence
bradykinin metabo-lism (3)Protect renal
funtion (4)Used for mild to moderate
hyper-tension (5)Less adverse effects.
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?. Drugs most in use(4)
Renin inhibitors Enakiren(????) Remikiren(????)
peptide or nonpeptide renin inhibitors.
They inhibit whole RAAS Other drugs
renin antibody.
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ACEI AT1antagonists
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?. Other anti-hypertensive drugs
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?. Other Drugs(1)
Centrally-acting drugs
Clonidine(???)
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Centrally-acting drugs
Clonidine
1. Pharmacological effects Diminishing
central adrenergic outflow Activating ?2 and
I1 receptor in medulla. 2. Clinical uses
Hypertension mild to moderate hyper-tension that
has not responded adequa-tely to treatment with
diuretics alone. minimal changes in renal
blood flow and glomerular filtration inhibit
gastro-intestinal secretion and mobility.
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Centrally-acting drugs
Clonidine
3. Adverse effects (1)Central and atropine-like
side effects (2)long-term uses water and
sodium retention rebound phenomenon.
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?. Other Drugs(2)
Ganglionic blockers
Trimetaphan(???)
Mecamylamine(????) Short-acting
Tolerance For controlling hypotension.
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?. Other Drugs(3)
Noradrenergic nerve ending blockers
Reserpine(???, ???) Guanethidine(???) (1)D
ecresing NA storage in noradre-nergic nerve
endings (2)Slow and lasting effects (3)Central
depression.
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?. Other Drugs(4)
Vasodilators (Peripheral vasodilators)
Hydralazine (???)
Dihydralazine (????)
Sodium Nitroprusside (???)
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?. Other Drugs(4)
Vasodilators
Hydralazine(???) (1)Dilating arteries and
arterioles (2)Decreasing peripheral
resistance (3)Reflexly elevating heart rate,
cardiac output and renin release. Combined
with ? blockers and diuretics.
Adverse effects due to vasodilation
and lupus-like syndrome.
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?. Other Drugs(4)
Vasodilators
Nitroprusside sodium(???) Dilating small
arteries and veins. Clinical Uses
(1)emergency hypertension (2)hypertension
with CHF and obstinate CHF (3)controlled blood
pressure in surgical operation.
Adverse effects due to hypotension in
excess and sulfocyanate(????) poisoning.
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?. Other Drugs(4)
Potassium channel openers Including
minoxidil(????), nicorandil(????), diazoxide
(???), etc. (1)Dilating arteries (Ca2 influx
?) (2)Reflexly elevating heart rate, cardiac
output and renin release.
Used for treatment of obstinate(???) and
severe hypertension Adverse effects
include sodium retention, palpitation, etc.
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?. Rational application of antihypertensive drugs
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?. Rational application of antihypertensive drugs
1. Prescription according to the degree of
hypertension
(1)Mild single drug diuretics, ?
blockers, ACEI, calcium channel blockers, ?1
blockers, or AT1 blockers. (2)Moderate
combined with two above drugs. (3)Severe
adding centrally acting drugs or vaso-dilators to
the two combined drugs.
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?. Rational application of antihypertensive drugs
2. Prescription according to compli-cations

indicated
contraindicated
CHF and/or COPD, Asthma Diuretics, ACEI, Prazosin ? Blockers
Renal failure ACEI, Methyldopa
Tachycardia ? Blockers
GI ulcer Clonidine Reserpine
Diabetes and gout(??) ACEI, prazosin Thiazides
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?. Rational application of antihypertensive drugs
(1)Hypertensive emergency
vasodilators(nitroprusside sodium, diazoxide),
labetalol, loop diuretics. (2)Elderly patients
avoiding drugs that could induce postural
hypotension(eg. ?1blockers) and influence the
cognizant ability. (clonidine, methyldopa).
(3)Cardiac ischemia avoiding (peripheral)
vasodilators.
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?. Rational application of antihypertensive drugs
3. Combination of drugs 4. Avoid blood pressure
to decrease too rapidly and excessively 5.
Individual therapy.
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• The class is over !