Anatomy of Heart Circulation of Heart Electrial Conduction System Of Heart

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