Drugs Affecting the Cardiovascular System by kellena97

VIEWS: 301 PAGES: 54

									   Drugs Affecting the
  Cardiovascular System
Ion Channels Blockers
Antihypertension Drugs
The Treatment of Congestive Heart Failure
Antiarrhythmic Drugs
Antianginal Drugs
Antihyperlipidemic Drugs and
       Anti-artherosclerosis Drugs
     Antihypertensive Drugs
    Hypertension is defined as a sustained diastolic blood pressure
greater than 90 mmHg (mercury) accompanied by an elevated
systolic blood pressure(>140 mmHg). Hypertension results from
increased peripheral vascular smooth muscle tone, which leads to
increased arteriolar resistance and reduced capacitance of the
venous system. Elevated blood pressure is an extremely common
disorder, affecting approximately 10-15% of the population. Although
many of these individuals have no symptoms, chronic hypertension-
either systolic or diastolic can lead to congestive heart failure,
myocardial infarction, renal damage, and cerebrovascular accidents.
The incidence of morbidity and mortality significantly decreases
when hypertension is diagnosed early and is properly treated.

• Essential/primary hypertension: more than 90% of patients
   have essential hypertension, a disorder of unknown origin affecting
   the blood pressure-regulating mechanism.
• A family history of hypertension in creases the likelihood that an
  individual will develop hypertensive disease.
• Essential hypertension occurs more often among middle-aged
  males than among middle-aged females.
• Environmental factors such as a stressful lifestyle, high dietary
  intake of sodium, obesity, and smoking all further predispose an
  individual to the occurrence of hypertension.

Secondary hypertension: occurs in 5-10% of
  patients. The cause is usually one of the
• Renal disease which activates the Renin-
  Angiotensin-Aldosterone System (RAAS)
• Endocrine disease, steroid-secreting turmour
  of the adrenal cortex, adrenaline-secreting
  tumour of the adrenal medulla.

• Arterial blood pressure is regulated within a narrow range
  to provide adequate perfusion of the tissues without
  causing damage to the vascular system, particularly the
  arterial intima. Arterial blood pressure is directly
  proportional to the product of the blood volume, cardiac
  output and the peripheral vascular resistance. In both
  normal and hypertensive individuals, blood volume cardiac
  output and peripheral resistance are controlled mainly by
  two overlapping control mechanisms: the baroreflexes
  mediated by the sympathetic nervous system, and the
  renin-angiotensin-aldosterone system (RAAS). Most
  antihypertensive drugs lower blood pressure by reducing
  cardiac output and /or decreasing peripheral resistance.
Classification of Antihypertension:

  I. Sympatholytic drugs
  II. Vasodilators
  III. Inhibitors of RAS
  IV. Diuretics
Classification I :
drugs (drugs that
alter sympathetic
nervous system
Classification I :Sympatholytic drugs (drugs
  that alter sympathetic nervous system function)

1.central antihypertensive drugs
   Clonidine可乐定, Methyldopa甲基多巴

2.ganglion-blocking agents( ganglionic blocking drugs)

3.adrenergic neuron blocking
   agents( antipostganglionic sympathetic neurons)
  reserpine利血平, guanethidine 胍乙啶
4.adrenoceptor antagonists (adrenergic receptor
     blocking agents)
①β-adrenoceptor-blocking agents
②α-adrenoceptor-blocking agents
③αand β-blockers
   labetalol 拉贝洛尔
Classification II : Vasodilators

1. direct vasodilators
•      hydralazine 肼苯哒嗪
•      sodium nitroprusside 硝普钠
2. calcium channel blockers( calcium antagonists)
•       nifedipine 硝苯地平
•       nitrendipine 尼群地平
3. potassium channel openers
•       minoxide 米诺地尔(长压定)
•       diazoxide 二氮嗪
•       pinacidil 吡那地尔
Classification III : Inhibitors of RAS

1.angiotensin converting enzyme inhibitors. ACEI
• captopril 卡托普利
• enalapril 依那普利
2.angiotensin receptor-blocking agents
• losartan 氯沙坦
• valsartan 缬沙坦
3. renin inhibitors:
    Enalkiren(依那吉仑) ,
Classification VI : Diuretics
 hydrochlorothiazide 氢氯噻嗪
 indapamide 吲达帕胺
   Classification I. Sympatholytic drugs

Subtype 1. Central antihypertensive drugs
Normal regulation of blood pressure in CNS:

Vasomotor centers   • Inhibiting neurons:α2
                    receptor resulting in blood
Center nervous      pressure lowering
system controls     bradycardia vasodilatation
peripheral          • Exciting neurons: β
sympathetic         receptors resulting in blood
activity in brain   pressure enhancing
stem                tachycardia
• Clonidine可乐定 and Methyldopa甲基多巴
  may stimulate inhibiting neurons of central
  adrenoceptors-α2 receptor, resulting in
  vasodilation, blood pressure lowers.
 Drug 1. Clonidine(可乐定)
又称氯压定, 2- imidazoline derivation
• Lipid-soluble, rapid absorption by oral
• F, 75%       t1/2 8~12 hours
• 30%~ 50% metabolisms in liver
• Others are eliminated unchanged in urine
Mechanism of action:
1.stimulating postsynaptic α2 adrenoceptors in
  brain stem peripheral sympathetic activity↓ 
  blood pressure↓ producing sedation
2.stimulating Ⅰ1-imidazoline咪唑啉 receptor in
  rostral ventrolateral medulla oblongata (RVLM延
  髓腹外侧核吻侧端)peripheral sympathetic
  activity lowering
3.stimulating opium receptor
  relieving abstinence syndrome戒断症状
1. Relaxation of arterial vessels reduction in
  peripheral vascular resistance blood pressure↓
2. Contracting force of cardiac muscule↓
  reduction of cardiac output heart rate↓
3. Decreased renal vascular resistance and
  maintenance of renal blood flow
4. Inhibiting movement and secretion of
  gastrointestinal tract  hypertensive patients with
  ulcer is the better
Adverse reaction:
1.dry mouth/ xerostomia (dry nasal mucosa, dry
  eyes), nausea, dizziness头晕, sedation嗜睡,
  parotid gland swelling and pain腮腺肿痛,sleep
  disturbances with vivid dreams or nightmares噩
2.water and sodium (Na+) retention
3.withdrawal syndrome停药反应
  headache apprehension(恐惧忧虑), tremors(震
  颤),abdominal pain, sweating, tachycardia
 treatment: ①α-adrenergic blocker (phentolamine)
            ②continuative administration clonidine
Drug 2. Methyldopa
1.center antihypertension drug
2.treatment: mild to moderately severe
    hypertension with renal failure
3.reducing peripheral vascular resistance,
    with a variable reduction in heart rate
    and cardiac output
4.no decreasing renal blood flow and
    glomerular filtration rate
Clinical uses:
1.moderate hypertensive disease
2.iv drop, therapy of hypertensive crisis高血
3.controlling abstinence syndrome of opium
Subtype 2. ganglion-blocking
agents( ganglionic blocking drugs)

    Drug: Mecamylamine美加明
 Subtype 3. Adrenergic neuronblocking agents

 Drug 1. Reserpine利血平
Pharmacological action:
1. lower blood pressure, with long-term therapy with
     cardiac output↓
     peripheral vascular resistance↓
     heart rate↓
     rennin secretion falls↓
     salt and water are retained
2. sedative and neuroleptic (精神安定)effect
  reserpine depletes catecholamine(儿茶酚胺) and 5-
   hydroxytryptamine (5-HT)
Mechanism of action:
• Reserpine can remain bound to amine
  pump of vesicular membranes in central
  and peripheral adrenergic neurons for
  prolonged periods of time.
• The storage vesicles are destroyed as a
  result of their interaction with reserpine
  and nerve endings lose their ability to
  concentrate and store norepinephrine and
• Catecholamines leak into the cytoplasm,
  where they are destroyed by intraneruronal
  monoamine oxidase (MAO), depressing
  the ability to uptake norepinephrine

• Reserpine -induced depletion of biogenic
  amines correlates with evidence of
  sympathetic dysfunction and
  antihypertensive effects.
• Recovery of sympathetic function requires
  synthesis of new storage vesicles, which
  takes days to weeks after discontinuation
  of the drug, so effect of reserpine is slow
  and persistent.

Clinical uses:
• Mild hypertension
• Cooperative administration
Adverse effects:
 Sedation and inability to concentrate or
 perform complex tasks are the most
 common adverse effects.

 More serious is the occasional psychotic
Drug 2. Guanethidine 胍乙啶

Mechanism and sites of action:
• Guanethidine inhibits the release of
  norepinephrine from sympathetic nerve
• Guanethidine nerve concentration in
  transmitter vesicles replaces
  norepinephrine causes gradual
  depletion of norepinephrine stores in the
  nerve ending
Subtype 4. adrenoceptor antagonists (adrenergic
           receptor blocking agents)

   ①β-adrenoceptor-blocking agents
   ②α-adrenoceptor-blocking agents
   ③αand β-blockers
     labetalol 拉贝洛尔
   Drug1.β-adrenoceptor-blocking agents
1.Mechanism and sites of action
①blocking β-receptor in heart, decreasing cardiac output
②depressing secretion of rennin, inhibiting the rennin-
     angiotensin-aldosterone system, decreasing level of
     angiotersin in plasm
③β-blockers may also block β-receptor of presynaptic
     membrane in peripheral prejunctional to reduce
     sympathetic vasoconstrictor nerve activity
   decreasing secretion of norepinephrine
④in never center, affecting sympathetic regulation
⑤changing sensitivity of baroreceptor
⑥increasing synthesis of prostaglandin
•    普萘洛尔 propranolol β1 β2
•    美托洛尔 metoprolol β1 intrinsic
    sympathetic mimetic activity
•    阿替洛尔 atenolol       β1 intrinsic
    sympathetic mimetic activity
Clinical uses:
• Moderate hypertension or severe
  hypertension of therapeutic ineffective with
  other antihypertensive drugs.
Adverse reaction:
• Postural hypotension, dizziness, nausea,
  vomiting, diarrhea
• Severe diseases accompanied heart,
  brain, kidney, arteriosclerosis, dysfunction
  of circulation
   Drug 2. α1-adrenoceptor-blocking agents
1. Mechanism:
  1). blocking selectively postsynaptic α1
     receptors in arterioles and venules
  2). dilating both resistance and
     capacitance vessels
2. Drugs:
  1). prazosin 哌唑嗪
  2). terazosin 特拉唑嗪
  3). urapidil 乌拉地尔
Drug 3.α and β adrenoceptor -blocking agents

 •   Blocking α1 and β receptors
 •   Blocking action of β R> blocking action of α1
 •   labetalol 拉贝洛尔
  Classification II. Vasodilators
Summary of the Action and Mechanism
1. Dilating directly arterioles but no veins, lowering blood
       pressure, relaxing smooth muscle of arterioles.
2. Eliciting compensatory responses, mediated by
       baroreceptors压力感受器 and the sympathetic
       nervous system, as well as rennin, angiotension and
       aldosterone opposing the antihypertensive effect of
       vasodilator such as:tachycardia心动过速; cardiac
       output↑; plasma rennin activity↑; retention of salt
       and fluid.
3. Vasodilators are used common by combination with
       other antihypertensive drugs that oppose the
       compensatory cardiovascular response.
Subtype1. direct vasodilators
Action: relaxing smooth muscle in arterioles
   ①via release of nitric oxide (NO) in vascular
   ②interfere with Ca2+ entering into cell
2.sodium nitroprusside 硝普钠
   ①.treating hypertensive emergencies and severe
      cardiac failure, crisis
  ②.dilating both arterial and venous vessels decreasing
      cardiac preload and afteroad
Subtype 2. Calcium channel blockers

  – Antianginal effects抗心绞痛
  – Antiarrhythmic effects抗心律失常
  – Dilating peripheral arterioles扩张外周血管
    Reducing blood pressure

Mechanism of action: inhibiting calcium influx
  into arterial smooth muscle cells
2. Dihydropyridine family:
•    amlodipine,
•    felodipine,
•    isradipine,
•    nicardipine,
•    nifedipine,
•    misolipine,
①more selective as vasodilators
②treating selectively angina or coronary spasm
③prolong effect, slow, persist, smoother, reflex sympathetic
   activation with slight
Subtype 3. potassium channel openers

   •   minoxide 米诺地尔(长压定)
   •   diazoxide 二氮嗪
   •   pinacidil 吡那地尔
Classification III. Inhibitors of RAS

                   NO     PGI2
       ACEI and AT blocker


    Subtype I. Angiotensin converting
         enzyme inhibitors ACEI

Drugs: Captopril, 卡托普利
Mechanism of action:
1.inhibiting ACE
  angiotensinⅠ------angiotensin Ⅱ
                 ACE ← (-) inhibitors
2.inhibiting RAS( rennin- angiotensin system) in local tissue
3.inhibiting the kalliurein-kini system(激肽释放酶-激肽系统)
4.Accelerating release of prostacyclin(PGI2)
         decreased peripheral
          vascular resistance
       decreased blood pressure
5.accelerating release of nitric oxide (NO)
6.improving myocardial hypertrophy of left ventricle,
     inhibiting hyperplasia of vascular smooth muscles.
     decreasing formation of AngⅡ, inhibiting remodeling of
     myocadia and vascular smooth muscles.
7.cleansing free radical(自由基), protecting tissue ischemia
     and reperfusion injury
8.affecting metabolism
   decreasing cholesterol and triglyceride
    increasing HDL (high density lipoprotein)
  Subtype II. Antagonist of Angiotensin II
Receptor (Angiotensin II Receptor Blockers

    Losatan 氯沙坦; Valsartan 缬沙坦

 Subtype III. renin inhibitors:
    Enalkiren (依那吉仑) ,
    Remikiren (瑞米吉仑)
Classification VI : Diuretics
• hydrochlorothiazide 氢氯噻嗪,
• indapamide   吲达帕胺
      Mild hypertension can often be controlled with a
 single drug. More severe hypertension may require
 treatment with several drugs that are selected to
 minimize adverse effects of the combined regimen.
 Treatment is initiated with any of four drugs depending
 on the individual patient: a diuretic, a b-blocker, an ACE
 inhibitor, or a calcium channel blocker. If blood pressure
 is inadequately controlled, a second drug is added. A b-
 blocker is usually added if the initial drug was a diuretic,
 or a diuretic is added if the first drug was a b-blocker. A
 vasodilator can be added as a third step for those
 patients who still fail to respond.
  Drugs Affecting the
 Cardiovascular System

Antihypertension Drugs
The Treatment of Congestive Heart Failure
Antiarrhythmic Drugs
Antianginal Drugs
Ion Channels Blockers
Antihyperlipidemic Drugs

To top