CARDIOVASCULAR

DRUGS

CARDIAC CONGESTIVE HEART FAILURE

HYPERTENSION
ANGINA PECTORIS
MYOCARDIAL INFRACTION
The Heart
 CARDIAC CONGESTIVE HEART
FAILURE

 Heart is unable to provide adequate blood supply to meet

the body’s O2 demand.
 Heart Pumping ability is decreased.
 Resulting in reduced cardiac output.
 Leads to tachycardia, dyspnoea, pulmonary & peripheral
oedema, heart & & liver enlargement.
 Compensatory mechanism- + Adr.system, RAS, ANP-
help in maintain the C.O.
 Types of CHF
 Low output failure-IHD, HTN, Valvular & Congenital heart disease
(CHD). Respond to Rx.

 High output failure- Anaemia, thyrotoxicosis, beriberi, CHD

causing AV shunts. Poorly respond to Rx.

 Systolic/ejection failure- inability to pump & empty adequately.

IHD & myocarditis- contraction & ejection are reduced. Ventricular
dilation- high tension in the wall is required to eject the blood.

 Diastolic/filling failure- occurs when ventricles are not filled

adequately due to stiffening & inadequate relaxation during
diastole.
 classification
1. Diuretics- Loop, Thiazide & K+ sparing diuretics.
2. Cardiac glycosides- Digoxin, Digitoxin.
3. Vasodilators-
 Arteriolar dilators- Hydralazine, Minoxidil, Nicorandil.
 Venodilators - Nitrates
 Arteriolar & Venodilators- ACE inhibitors, ARB’s,
Na.prusside & prazosin
4. β-Blockers- Metoprolol, Bisprolol, Carvedilol.
5. Symp.mimetics (β agonist) - Dopamine, Dobutamine.
6. PDE inhibitors- Amrinone, Milrinone.
7.Newer agents-Istaroxime & Levosimendan
Diuretics
 Loop Diuretics- inhibits Na-K-2Cl
 A/C-Severe CHF, Pulmonary oedema & refractory
failure
 Thiazides- inhibits Na-Cl symport
 Mild – Moderate Cardiac failure.
 K+ sparing diuretics.
 Diuretics- Promotes Na & H2O excretion
- Reduce ECF volume-relives edema
- Decrease preload & work load.
- Improve ventricular efficiency.
Digoxin
Chemistry:-

NON
SUGA ---------0--------
SUGA
R
R
Source:-
Digitalis lanata---Digoxin, Digitoxin
Digitalis purpurea-- Digoxin, Digitoxin
Strophanthus grantus—Ouabain(strophanthin-G)
Pharmacokinetic properties of digoxin
and digitoxin
Digitoxin Digoxin
Oral absorption v.Good Good

Plasma protein 95% 25%

binding
t1/2 5-7days 40hrs
Therapeutic plasma 15-30ng/ml 0.5-1.4ng/ml
concentration

Daily maintenance 0.05-0.2mg 0.125-0.5mg

dose
 Pharmacological actions:-
Cadiac actions:-
ECG:-
 Inversion of T wave
 ↑ PR interval
 Shortening of Q-T interval
Extra cardiac action:-
Blood vessels-vasoconstriction, ↑ PVR in normal
individuals
↓ in peripheral resistance in CHF patients
CNS-nausea, vomiting, hallucination, visual disturbance
Kidney – diuresis, ↓renin, ↓AT11, ↓ aldosterone release
Therapeutic uses:-
 CHF
 Arrhythmias (PST)
 Atrial flutter & atrial fibrillation
 Dilated heart
Adverse effects:-
 Pulsus bigeminus
 Anorexia, nausea, vomiting, diarrhoea
 Gyanecomastia
Precautions and contraindications:-
Hypokalemia
Renal/hepatic diseases
MI
Hypothyroidism
Ventricular tachycardia
Drug interactions:-
Drug that enhance digoxin toxicity:-
 Diuretic-
 Calcium-
 Quinidine, verapamil, methyldopa– ↑ digoxin
levels
Drugs that reduces digoxin levels:-
 Antacids, neomycin, metaclopramide-↓ abs
 Rifampicin, phenobarbitone-
Treatment of digoxin toxicity
 Stop digitalis
 Give K+ supplements
 Ventricular arrhythmias are treated with IV
phenytoin/lignocaine
 Bradycardia is treated with atropine
 Digibind
Vasodilators

 Venodilators- Reduce preload.

 Arteriolar dilators- Reduces after load.

 Mixed dilators- Reduce preload & after load.

 These drugs dilated blood vessels & more blood is

accommodate in the blood.V- reduces amount of blood
reaching heart- reduces the heart workload.
β-blockers
 Useful in mild-moderate failure.
 Long term therapy improves symptoms of failure.
 Blocking the β- receptors- improves the left ventricular
structure & function.

Sympathomimetic amines-
 Dopamine- dilates renal, mesenteric & cardiac blood
vessels by acting on D1 receptors.
Also + β 1-receptors-Increases HR, Contractility & C.O
Uses- A/C heart failure with renal impairment.
 Dobutamine- acts on α and β receptors.
 Selective + ve inotropic and increases C.O.

 I.V- short term management of A/C heart failure

due M.I or cardiac surgery.

PDE inhibitors- CAMP levels

 Administered as I.V
 +ve inotropic & vasodilator actions.
 Used as short term management of sever heart
failure.
 HYPERTENSION

 Increase in B.P 140/90mm of Hg.

 Prolonged HTN damages B.V of heart, brain &

kidneys- results in Stroke, IHD, & Renal failure.

 B.P is controlled by ANS & RAS.

 Antihypertensive drugs act by influencing these

systems- PVR, C.O or lower plasma volume-----

B.P.
Introduction

> 140 mmHg Hypertension > 90 mmHg

****************************************************

Systolic Blood Diastolic Blood

Pressure (SBP) Pressure (DBP)
 Types of
Hypertension

Essential Secondary

A disorder of unknown
origin affecting the Secondary to other
Blood Pressure disease processes
regulating mechanisms

****************************************************

Environmental
Factors

Stress Na+ Intake Obesity Smoking

Classification-
1. ACE inhibitors- Captopril, Enalapril, Lisnopirl.

2. ARBS- Losartan, Candesartan, Valsatan, Irbesartan.

3. Ca2+ blockers- Nifedipine, Amlodipine,Nicardipine

Nimodipine & Verapamil, Diltiazem.

4. Diuretics- Loop, Thiazides & K+ sparing diuretics.

5. Sympatholytic drugs-

a) Centrally acting agents- Clonidine, Methyldopa.

b) Ganglionic blockers- Trimethapan.

c) Neuronal blockers- Resperpine.

d) α- blockers- Phenoxybenzamine, Prazosin, Terazoxide

e) β-blockers- Propranolol, Atenolol, Metoprolol.

6. vasodilators- Arteriolar & Mixed dilators.

RAS - Physiology

Increased
Blood Vol.

Rise in BP

Vasoconstriction

Na+ & water

retention

Kidney

(Adrenal cortex)
ACE inhibitors-
M.O.A- X generation of Angiotensin-II- vasoconstrictor.
• aldosterone production & Na+ & H2O absorption.
• Reduces Symp. Activity.
• Dilates both arteries & veins-reduces after & preload.
Uses-HTN, CCF, M.I , D.Nephropathy.
ARBS-
• Competitively inhibit the binding of Angiotensin-II to AT1

receptor.
• ARBs produces effects similar to ACE inhibitors.

• Efficacy & Tolerability are also similar.

ACE inhibitors
C.C.B- cardiac depressants
• Blocks L-type Ca2+ channels, prevents the entry of Ca2+
into cell.

• No E.C.C in heart & vascular Sm.Muscles.

• Dilates arterioles-reduces T.P.V.R- B.P

• DHPs( nifedipine, amlodipine) are preferred because more

selective action on blood vessels.

• Long acting DHPs-1st line drugs Anti-HTN agents.

• Uses-Elder pt’s, Angina, Asthma, PVD, Migraine,

Diabetes & Renal dysfunction.
Diuretics-
• Thiazides(X Na+-Cl symport) & Loop-(X Na+-K+-2Cl
co-transport).
• Diuretics acts by promoting Na & H2O Excretion.
• Reduces Na+ conc. in vascular smooth muscle
• Reduces P.V.R & C.O- B.P.
• Thiazides are 1st line drugs in mild-moderate HTN.
Sympatholytic agents-
Clonidine & Methyldopa-
+ α2receptors in Vasomotor center- Symp. Outflow
from VMC---- H.R & PVR--- B.P
 α- blockers-
• Phenoxybenzamine(X α-1,2 receptors in blood vessels).
• Prazosin(X α-1 receptors in blood vessels ).
• α- Blockers- produces vasodilation- reduces B.P.
• Used along with diuretics/β- blockers/other agents.
β- blockers-
• Reduces symp. outflow--- B.P
• Blocks receptors in heart- H.R, F.O.C, C.O & B.P.
• Uses-young hypertensive pt’s with high Renin levels.
• Pt’s associated with angina, M.I & migraine.
Vasodilators-
Activate K+channels -hyperpolarisation-vasodilation- B.P
Treatment of hypertension
Rx of HTN-

Mild-low dose of a single drug- Thiazides / β-blockers.

-If pt doesn't respond-ACE inhibitors/CCB’s- tried.
Moderate- Diuretic + Sympatholytic agents.
Severe-associated with cardiac or renal failure.
-Vasodilator + Diuretic + β-blockers.
 HTN emergencies- like HTN encephalopathy, A/C cardiac failure.
 I.V route is preferred.

 Na. Nitroprusside (I.V route) - D.O.C.

 B.P should be continuously monitored- as Nitroprusside
causes hypo perfusion of vital organs.
 I.V esmolol /diazoxide / sublingual Nifedipine -
alternatives.
HTN in Pregnancy-

 Methyldopa orally for maintenance and Hydralazine

(parental) for reduction of B.P emergency.

 They should be used after 1st trimester.

 Cardio selective β- blockers can also be used.

Nursing implications-
 Most of them vasodilators causes postural hypotension-risk
of fall on standing & needed to be guarded.
 Palpitation is due to reflex tachycardia induced by a
vasodilator.
 Points to be noted while using Nitroprusside-
 It acts within minutes-BP should be monitored.
 Drug should be dissolved in 2ml of 5% dextrose & diluted
in I.V fluids.
 Light sensitive- infusion bottle & set should be rapped.
 If colour changes- bottle should be discarded.
 Blood levels of cyanide & thiocyante should be checked.
 Used only for emergencies & not more than 2-3days.
ANGINA & MYOCARDIAL INFRACTION
 Angina pectoris is the symptom of IHD Characterised by
sudden & severe chest pain.

 Pain may radiate to left shoulder & along the inner surface
of the left arm.

 Its due to imbalance b/w O2 supply and O2 demand of the

myocardium.

 Pain is induced by exercise, emotion & other conditions

which increase O2 demand of the heart.

 Coronary arteries are unable to supply blood to heart

because of atherosclerosis- narrowing & spasm of C.arteries.
 •Anginal drugs act by reducing O2 demand of the heart/
by increasing blood supply to it.

 Types-
 Angina occurs in three overlapping
patterns:
 Stable angina
 Unstable angina
 Prinzmetal (variant) angina
classification

I. For A/C anginal attack-Nitroglycerine, Isosorbide

dinitrate.
II. For chronic prophylaxis-
a) Nitrates- Nitroglycerine, Isosorbide dinitrate/ mononitrate.
b) β-Blockers- Propranolol, atenolol, Metoprolol
c) CCB’s- Nifedipine, Amlodipine,Nicardipine Nimodipine
& verapamil, Diltiazem.
d) K+ channel opener-Nicorandil, pinacidil
e) Others- low dose aspirin, trimetazidine, oxyfedrine.
Major sites of actions of antianginal drugs
Nitrates- common drugs used in angina.
M.O.A

 Nitrates CGMP levels--- Ca2+ levels--- relaxes vascular

Sm.Muscles---leads to veno/ arterial/ coronary dilation.

 Venodilatation- preload & workload- O2demand.

 Arterial dilatation- afterload & workload - O2 demand.

 Coronaries dilation- increases blood supply to ischaemic

area.
 Preparations-Sublingual, Oral, Transdermal, Intravenous
& Ointment.

 Sublingual- A/C attack, Oral- to prevent anginal attack.

 A/E-headache, dizziness, flushing, hypotension,

tachycardia.

 Nitrates are C.I in pt’s a taking Sildenafil.

 Tolerance
 Common and serious problem
 Magnitude is dose dependent
 Develops and disappears rapidly
Uses-
 To prevent & treatment of all types of angina.
 Isosorbide dinitrate- for A/C angina.
 Isosorbide mononitrate- for chronic angina.
 Nitrates- M.I, CCF, Biliary colic & cyanide poisoning.
β-Blockers-
Blocks β1– H.R, F.O.C, cardiac work & output-
O2consumption.
 These have slow onset of action & are useful in angina
prophylaxis.
 the exercise tolerance & the frequency of attacks.
 Disadvantages of them can countered by combining with
nitrates.
CCB’S-
 Prevents the entry of ca2+in cardiac & Sm.Muscles.
 Relaxes the coronary & peripheral blood vessels.
 Depress the myocardial contractions
 In angina- cardiac work load & myocardial O2 supply-
due to coronary dilation.
 Other uses- SVT, HTN, hypertrophic cardiacmyopathy,
migraine, Raynaud's syndrome.
 Nifedipine- uterine relaxant-premature labour.

 Nimodipine- prevent & termination of cerebral vasospasm

& neurological defects in pt’s with subarachnoid

haemorrhage. SVT- supraventricular arrhythmias
Aspirin-

 low dose aspirin is adm in all angina pt’s.

 It prevents the formation of clots & there by prevents

myocardial infraction in such pt’s.

Myocardial infraction
 When atheromatous plaque in the coronary artery
ruptures, a clot is formed.

 This blocks the blood supply to a portion of the heart

resulting in MI.

 Process of MI develops over 6-8hrs & cell death in

infracted area.
Rx of MI -
1. Analgesia- Morphine 10mg/pethidine 50mg –I.V.

Reduces pain & anxiety, prevents increase in H.R.

2. Diazepam- reduces anxiety & produces sedation.

3. Thrombolytics -
• Reduces damage & mortality.
• streptokinase/ urokinase & alteplase - break up the clot &
restore blood supply to the infracted area.
Streoptokinase-1.5million units infusion given in 1hr.
4.Low dose aspirin- 300mg orally.

5. Oxygen

6. Antiemetics- Promethazine / domperidone.

7.β-blockers-I.V atenolol 5-10mg in 5min- short term

mortality & lowers the incidence of arrhythmias.

8.ACE inhibitors- should be given within 24hrs.

8.Statins- started within 24hrs or prior to

discharge.(atorvastatin).

9. Acidosis- corrected by I.V NaHCo3.

10. Antiarrhythmics - arrhythmias are common in pt’s in
A/C MI.
- suitable antiarrhythmics should be used depending on the
arrhythmias.
Long term Rx of MI-

 Patient stabilization.

 Low dose aspirin

 Adrenergic blocker- atenolol.

 ACE inhibitor- Enalapril.

These drugs have to give on long term Rx.

Risk factor management-

 Smoking should be stopped.

 Hyperlipidemia if any should be controlled.

 B.Wt should be reduced.

 Regular moderate exercises should be advised.

 Adequate control of diabetes & HTN if any.

 Antiarrhythmics drugs.
 Arrhythmias- an arrhythmia is an abnormality of H.R,

cardiac rhythm, site of origin of cardiac impulse or

abnormality in impulse conduction.
Drugs used in arrhythmias are-
1.Na channel blockers- quinidine, procainamide, lignocaine,
phenytoin.
2.β -adrenergic blockers- propranolol ,Esmolol.
3.K channel openers- Amiodarone, sotalol
4. CCB’s- Verapamil, dilitazam.
Hypolipidemic Drugs
 Hyperlipoproteinaemias – is a condition in which the conc. of
CH or TG carrying lipoproteins exceed the normal limits.
 in lipoproteins can develop atherosclerosis & risk factor for
MI.
 Lipoproteins- complex of lipid & ptn’s, circulate in blood.

 5 types of lipoproteins- IDL, LDL, HDL, VLDL &

chylomicrons.
 LDL is 10 carrier of CH & VLDL is of TG’s.

 Transport - Endogenous & Exogenous pathways.

 TC LDL-CH HDL-CH TG’s
Desirable < 200 < 100 > 40 men <150
> 50 women
Border line 200-239 130-159 - 15-199
High > 240 >160 > 60 > 200

National cholesterol Education Programme 2001- Plasma Lipid levels- mg/dl

CH are more atherogenic while TG’s have more thrombogenic effects.
 1% reduction in LDL levels approximately reduces mortality &
morbidity by 1% over 5yrs.
Classification:
1. HMG CoA reductase inhibitors- Lovastatin, Simvastatin,
Pravastatin, Atorvastatin, Rosuvastatin & Fluvastatin
2. Fibric acid- Gemfibrozil, Clofibrate, Colesevalam, Fenofibrate,
Bezafibrate, Ciprofibrate.
3. Bile acid binding resins- Cholestyramine, Colestipol,
Colesevalam.
4. Antioxidants- Probucol
5. Dietary cholesterol absorption inhibitor- Ezetimibe.
6. Inhibitor of TG synthesis & lipolysis- Nicotinic acid.
7. Others-Neomycin, Gugulipid & Omega-3 fatty acids.
 Anti-Dyslipidemic Drugs- 1st line drugs include Statins, bile
acid binding resins & intestinal cholesterol absorption inhibitors
whereas 2nd line drugs include fibrates & niacin.
 •Smoking
2/3

•Lipid status Risk factors for CVD

of the
risk

•Chomocysteine > 15 mmol/l

•Diabetes mellitus
•Metabolic syndrome
•Sedentary life style
•Tachycardia
•BMI > 30:
>>> saturated fatty acids
>>> salt and >>> sugar
>>> alcohol
<<< fruits and vegetables
•Stress