anatomy of heart circulation of heart electrial conduction system of heart
TRANSCRIPT
ANTI - HYPERTENSIVE
Anatomy of Heart
Circulation of Heart
Electrial Conduction System Of Heart
HYPERTENSION
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated.
Normal blood pressure is 120/80 mm of Hg.
High blood pressure is anything above 140/90 mm of Hg.
Hypertension is classified into : Primary hypertension (Essential hypertension)
-90-95% cases –high blood pressure
with no medical cause.
Secondary hypertension -5%cases –caused by
conditions that affect kidneys,arteries,heart or endocrine systems.
Antihypertensive Drugs
• All antihypertensive drugs act on the familiar formula…
• BP = SVR x CO (HR v SV)• They act by1. Reducing SVR .. or by...2. Reducing cardiac output …by…3. Reducing heart rate …or by…4. Reducing stroke volume
Classes of Antihypertensive Agents Diuretics
ACE Inhibitors
Angiotensin-II Receptor Blockers
Renin Inhibitors
Calcium Channel Blockers
Beta Adrenergic Blockers
Alpha Adrenergic Blockers
Centrally acting Sympatholytics
Vasodialators
Potassium Channel Openers
Endothelin Antagonist
Diuretics
• A reduction in blood volume reduces blood returning to the heart and so preload is reduced
• A reduction in preload reduces stroke volume
• CO = HR x SV
• Stroke volume and cardiac output decrease
• BP = CO x SVR
• Blood pressure decreases
1. Diuretics1. Thiazides
Hydrochlorothiazide (HydroDIURIL, Esidrix);Chlorthalidone (Hygroton)
2. Loop diureticsFurosemide (Lasix); Bumetadine (Burmex);Ethacrynic acid (Edecrin)
3. K+ SparingAmiloride (Midamor); Spironolactone (Aldactone);Triamterene (Dyrenium)
4. Osmotic Mannitol (Osmitrol); Urea (Ureaphil)
5. OtherCombination - HCTH + Triamterene (Dyazide)Acetazolamide (Diamox)
Diuretics
Diuretics reduce the rate at which water is reabsorbed. This results in more water being lost from the body and
ultimately a fall in blood volume
Loop diuretics
Thiazide diuretics
Potassium sparing
diuretics
2. Mechanism of Action
Urinary Na+ excretionUrinary water excretion
Extracellular Fluid and/or Plasma Volume
3. Effect on Cardiovascular System
Acute decrease in CO
Chronic decrease in TPR, normal COMechanism(s) unknown
1. Site of Action
Renal Nephron
4. Adverse Reactions
Dizziness, Electrolyte imbalance/Depletion,Hypokalemia, Hyperlipidemia,Hyperglycemia (Thiazides)Gout ( Hyperuricaemia)
5. Contraindications
Hypersensitivity, Compromised kidney functionCardiac glycosides (K+ effects)Hypovolemia,Hyponatremia
Angiotensin Converting Enzyme (ACE) inhibitors
• Examples – captopril, ramipril, perindopril etc.
• Used to treat hypertension and also heart failure
• ACE inhibitors interfere with the renin, angiotensin, aldosterone system that regulates long term BP. This system responds to a drop in blood pressure and works in conjunction with the baroreceptor reflex.
Renin, angiotensin, aldosterone system
Angiotensinogen
Angiotensin I
Angiotensin II
BP Renin
Angiotensin Converting Enzyme
Renin, angiotensin, aldosterone system
Vasoconstriction
Thirst Aldosterone
Blood Pressure
Sodium retention
Angiotensin IIADH-vasopressin
2. ACE Inhibitors & Angiotensin-II Receptor Blockers
2. Ang II Receptor Antagonists
Losartan (Cozaar); Candesartan (Atacand); Valsartan (Diovan)
1. Angiotensin Converting Enzyme Inhibitors
Enalapril (Vasotec); Quinapril (Accupril); Fosinopril (Monopril); Moexipril (Univasc); Lisinopril (Zestril) Benazepril (Lotensin); Captopril (Capoten)
Ang I
Ang II
ACE
ACE
Ang II
Renin
Angiotensinogen
Ang IAT1
AT2
LungVSMBrainKidneyAdr Gland
3. Effect on Cardiovascular System
Volume Aldosterone Vasopressin
CO
Angiotensin II
Vasoconstriction
TPR
SymNS
HR/SV Angiotensin II Norepinephrine
CO
SymNS
4. Adverse Effects
Hyperkalemia Angiogenic edema (ACE inhib); Cough (ACE inhib); Rash; Itching;
5. Contraindications
Pregnancy; Hypersensitivity; Bilateral renal stenosis
3. Calcium Channel Blocker
Effect on Cardiovascular system
Vascular relaxationDecreased TPR
Adverse Effects
Nifedipine – Increase SymNS activity; Headache; Dizziness; Ankle edema(joint btn leeg &feet
4. β Adrenergic Blocker
Drugs: Propranolol (Inderal); Metoprolol (Lopressor)
Atenolol (Tenormin); Nadolol (Corgard);
Pindolol (Visken)
Mechanism of ActionCompetitive antagonist at β- adrenergic receptors
3. Effects on Cardiovascular System
a. Cardiac-- HR, SV CO
b. Renal-- Renin Angiotensin II TPR
5. ContraindicationsAsthma;
Diabetes; Bradycardia;
Hypersensitivity
4. Adverse EffectsImpotence;
Bradycardia; Fatigue; Exercise intolerance;
5. A) Peripheral α-1 Adrenergic Blocker
Drugs:
Prazosin(Minipres); Terazosin (Hytrin)
Site of Action- Peripheral arterioles, smooth muscle
2. Mechanism of Action
Competitive antagonist at α-1 receptors on vascular smooth muscle.
3. Effects on Cardiovascular System
Vasodilation, Reduces peripheral resistance
4. Adverse effects
Nausea; Drowsiness; Postural hypotenstion;(first dose phenmenone)
B) Central Sympatholytics (α-2 Agonists)
Drugs: Clonidine ( Direct α-2 Agonist ) Methyldopa ( False Neurotransmitter )
Site of ActionCNS medullary Cardiovascular centers
Mechanism of Action CNS α-2 Adrenergic Stimulation Peripheral Sympatho inhibition
Decreased norepinephrine release
Effects on Cardiovascular System
Decreased NE Vasodilation Decreased TPR
Adverse EffectsDry mouth;
Sedation; Impotence;
6 ) Vasodialators
Drugs: Hydralazine (Apresoline); Minoxidil (Loniten); Nitroprusside (Nipride); Diazoxide (Hyperstat I.V.);
Fenoldopam (Corlopam)
Site of Action- Vascular smooth muscle
Mechanism of action
MinoxidilDiazoxide
Hydralazine(directly acting arteriolar vasodilator)
Fenoldopam(Dopamine D1 Agonist)
NO
Nitroprusside
Ca++
Ca++Na+ K+
DA
Effect on cardiovascular systemVasodilation,
Decrease TPR
Adverse Effects Reflex tachycardia Increase SymNS activity (hydralazine, minoxidil,diazoxide)
Lupus (hydralazine)
Hypertrichosis (minoxidil)
Cyanide toxicity (nitroprusside)
7) Endothelin Antagonist
Bosentan, a non-selective ET-1 receptor antagonist (blocks for ETA and ETB receptors) is currently used in the treatment of pulmonary hypertension
SummarySites and Mechanisms of Action
1. Can alter CO/TPR at number of sites and/or mechanisms.
2. Antihypertensives mechanistically specific, and alter blood pressure through physiologically diverse effects on CO/TPR.3. All organ systems and/or effector mechanisms are p’col targets.
3. -2 agonists4. β-blockers
Receptor antag. 2. α-antag. 5. A-II Antag. 7. Vasodilators 6. Ca2+ Antag.
1. Diuretics4. b-blockers
Other- 5. ACE inhibitors Lung, VSM, Kidney, CNS
CRITICAL POINTS!
Antiarrhythmic Drugs
Normal heartbeat and atrial arrhythmia
AV septum
Normal rhythm Atrial arrhythmia
ECG (EKG) showing wave segments
Contraction of atria
Contraction of ventricles
Repolarization of ventricles
Phase 0>Rapid depolarization>Opening fast Na+ channels→ Na+ rushes in
→depolarization
Phase 1>Limited depolarization>Inactivation of fast Na+ channels→ Na+ ion conc equalizes>↑ K+ efflux & Cl- influx
Phase 2>Plateau Stage>Cell less permeable to Na+>Ca++ influx through slow Ca++
channels>K+ begins to leave cell
Phase 3>Rapid repolarization>Na+ gates closed>K+ efflux>Inactivation of slow Ca++
channels
Phase 4>Resting Membrane Potential>High K+ efflux>Ca++ influx
PHASES OF ACTION POTENTIAL
ARRHYTHMIA Absence of rhythm
DYSRRHYTHMIA Abnormal rhythmARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction Block results from severely depressed conduction
Re-entry or circus movement / daughter impulse
• Supraventricular:- Atrial Tachycardia
- Paroxysmal Tachycardia
Multifocal Atrial Tachycardia
- Atrial Fibrillation
- Atrial Flutter
• Ventricular:- Wolff-Parkinson-White
(preexcitation syndrome)
- Ventricular Tachycardia- Ventricular Fibrillation- Premature Ventricular
Contraction
ARRHYTHMIAS:
• IA - lengthen AP duration- Intermediate interaction with Na+ channels- Quinidine, Procainamide, Disopyramide
• IB - shorten AP duration- rapid interaction with Na+ channels- Lidocaine, Mexiletene, Tocainide,
Phenytoin• IC - no effect or minimal AP duration
- slow interaction with Na+ channels- Flecainide, Propafenone, Moricizine
CLASS I : Sod i um Channe l B l ock i ng Dr ugs
• Increase AV nodal conduction• Increase PR interval• Prolong AV refractoriness• Reduce adrenergic activity• Propranolol, Esmolol, Metoprolol,
Sotalol
CLASS II: BETA-BLOCKING AGENTS
• Prolong effective refractory period by prolonging Action Potential
Drugs :– Amiodarone – Ibutilide – Bretylium – Dofetilide– Sotalol BIDAS
CLASS I I I : POTASSIUM CHANNEL BLOCKERS
Blocks cardiac calcium currents
→ slow conduction
→ increase refractory period
*esp. in Ca++ dependent tissues (i.e. AV node)
Verapamil, Diltiazem, Bepridil
CLASS IV: CALCI UM CH ANNEL BLO CK ERS
• ADENOSINE → Inhibits AV conduction & Increases AV refractory period
• MAGNESIUM → Na+/K+ ATPase, Na+, K+, Ca++ channels
• POTASSIUM → Normalize K+ gradients
Miscellaneous:
Implantation of Pacemaker