DRUGS ACTING ON CVS · CARDIAC CELL Resting membrane potential for cardiac cell is -90 mV. Action...

DRUGS ACTING ON CVS

Presented by

Dr. Sannithi Nagarjuna

Coordinator for RIPER-GPAT Cell,

Hyderabad Academy &

Online GPAT Academy

7899107907

9885784793

nagarjunaspharma@gmail.com

❑ The cardiovascular system refers to the heart, blood vessels and the

blood.

❑ Blood contains oxygen and other nutrients which your body needs to

survive.

❑ The body takes these essential nutrients from the blood. At the same

time, the body dumps waste products like carbon dioxide, back into the

blood, so they can be removed.

❑ The main function of the cardiovascular system is therefore to maintain

blood flow to all parts of the body, to allow it to survive.

The major functions of the cardiovascular system are

❖ To transport nutrients, gases and waste products around

the body.

❖ To protect the body from infection and blood loss.

❖ To help the body maintain a constant body temperature

('thermoregulation')

❖ To maintain fluid balance within the body.

HEART

❖ The heart is a muscular organ which

pumps blood through the blood vessels of

the circulatory system. The pumped blood

carries oxygen and nutrients to the body.

❖ The heart is a muscular organ about the size of a fist.

❖ It is a very strong muscle. It is on the left side of the

body in humans.

BLOOD VESSELS

❖ The blood vessels are the components of the circulatory system

that transport blood throughout the human body.

❖ These vessels transport blood cells, nutrients, and oxygen to the

tissues of the body.

❖ They also take waste and carbon dioxide away from the tissues.

Blood vessels are needed to sustain life, because all of the

body's tissues rely on their functionality.

There are two types of blood vessels

1. Coronary Blood Vessels

Which supply blood to Heart

2. Peripheral Blood Vessels

Which supply blood to various parts of the body

DISORDERS RELATED TO CVS

1. CONGESTIVE HEART FAILURE/

CONGESTIVE CARDIAC FAILURE (CHF/CCF)-

❖Where the heart is unable to pump sufficient blood to

various parts of the body.

❖ As a result of this condition blood supply decreases to

various parts of the body.

Source: Google

2. ATHEROSCLEROSIS

❖ It is characterized by deposition of lipids and lipid

related materials like cholesterol, triglycerides and

lipoproteins in blood vessels specially coronary blood

vessels.

❖ As a result of this condition blood supply decreases to

heart.

Source: Google

3. ANGINA PECTORIS

It is characterized by the development of pain in the chest due to

decreased blood/oxygen supply to muscle of the heart (Myocardium)

—Myocardial ischemia/ Myocardial hypoxia.

One of the main reason for angina pectoris is Atherosclerosis.

Source: Google

4. MYOCARDIAL INFARACTION

It is a death of the myocardium due to decreased/loss of

blood/oxygen supply to muscle of the heart (Myocardium) for long

period of time.

One of the main reason for myocardial infaraction is angina

pectoris.

It is otherwise called as heart attack.

Source: Google

5. HYPERTENSION

Increase in blood pressure

6. HYPOTENSION

Decrease in blood pressure

Source: Google

7. ARRHYTHMIAS

Irregular or abnormal heart beat

Abnormal heart rhythm

Heart beat may be increases or decreases

ELECTROPHYSIOLOGY OF

CARDIAC CELL

IMPULSE/ACTION POTENTIAL GENERATION IN

CARDIAC CELL

❖ Resting membrane potential for cardiac cell is -90 mV.

❖ Action potential/ impulse generation begins with the

opening of sodium channels.

❖ Due to opening of sodium channels influx of sodium

ions will take place as a result potential will be

increases (Phase 0).

❖ Sodium ions enter into the cell at a very faster rate of

107 ions/sec.

❖ After some time sodium channels will be closed and

potassium channels will be opened because of which

potential will be decreases (Phase 1).

❖ After some time opening of calcium channels will take place

when potassium channels are in open state as a result influx

of calcium and efflux of potassium ions take place, so there

is no change in the potential and called as Plateu Phase

(Phase 2).

❖ After some time, Calcium channels will be closed and only

opening of potassium channels hence there is continuous

efflux of potassium ions and potential will be decreases

(Phase 3).

❖ At this stage sodium is present inside and potassium is

present outside and finally there is an activation of the

enzyme Na+ K+ ATPase which will keep potassium inside

and sodium out side, cell reaches resting state (Phase 4).

Source: Google

PHASES OF ACTION POTENTIAL

Phase 0 –Due to opening of sodium channels

Phase 1 –Due to opening of potassium channels

Phase 2 –Due to opening of calcium channels

Phase 3 –Due to opening of potassium channels

Phase 4 –Due to activation of Na+ K+ ATPase

IMPULSE PROPAGATION/CONDUCTION

IN CARDIAC CELL

AUTOMATICITY

❖ Capacity to generate action potential on its own without

any external stimulus called as automaticity.

❖ SA Node is having the property of automaticity.

❖ Hence SA Node is otherwise called as Pace Maker of the

cardiac cell.

SA NODE

ATRIA

AV NODE

BUNDLE OF HIS

PURKINJE FIBRES

VENTRICLES

Source: Google

ECG/EKG/ELECTROCARDIOGRAM

Source: Google

ARRHYTHMIAS

Mean abnormal heart beat or irregular heart beat.

Heart beat may be increases or decreases.

Normal heart beat is 72 beats/minute

Normal heart beat range is 60-100 beats/minute

Which are of 2 types

1. Tachyarrhythmias

Above 100 beats/minute

2. Bradyarrhythmias

Below 60 beats/minute

Most of the patients are suffering from

tachyarrhythmias

TACHYARRHYTHMIAS

Reasons include

1. Increased impulse generation in SA node due

to increased activity of Sympathetic Nervous

System

2. Fast impulse conduction i.e. time required for

impulse conduction decreases

3. Ecotopic foci i.e. Apart from SA node other

parts also exhibit the property of automaticity

BRADYARRHYTHMIAS

Reasons include

1. Decreased impulse generation in SA node due to

increased activity of Parasympathetic Nervous System

2. Slow impulse conduction i.e. time required for impulse

conduction increases

3. Heart Block i.e. Blockade in any part of the cardiac cell

results in failure of impulse conduction to the

ventricles that result in decreased heart beat

ANTIARRHYTHMICS

Which are used for the treatment of arrhythmias

preferably for the treatment of tachyarrhythmias.

They are classified into:

CLASS I DRUGS -- Sodium Channel Blockers

CLASS II DRUGS -- β Blockers

CLASS III DRUGS – Potassium Channel Blockers

CLASS IV DRUGS – Calcium Channel Blockers

CLASS I DRUGS

They are further classified into 3 types

Ia --- Quinidine, Procainamide, Disopyramide

Ib --- Lignocaine, Tocainide, Phenytoin

Ic --- Flecainide, Propafenone, Moricizine

Ia --- Intermediate association/dissociation

Ib --- Fast association/dissociation

Ic --- Slow association/dissociation

Onset of action is in the order of

Ib > Ia > Ic

Duration of action is in the order of

Ic > Ia > Ib

Quinidine – It is an alkaloid obtained from

Cinchona bark. In higher doses it causes

cinchonism characterized by tinnitus.

Procainamide – It is an amide derivative of

local anesthetic drug Procaine.

Disopyramide – Which produces

anticholinergic side effects

Lignocaine- Which undergoes high first pass

metabolism.

Not suitable for oral and given by IV route. Also used

as local anesthetic agent.

Tocainide - Oral route

Phenytoin – Also used as Antiepileptic agent

Therapeutic uses of sodium channel

blockers

1. Antiepileptics

2. Antiarrhythmics

3. Local anesthetics

CLASS II DRUGS

They are classified into 2 types

1. Nonselective β blockers

Ex: Propranolol, Pindolol, Timolol, Sotalol

2. Selective β1 blockers

Ex: Atenolol, Acebutalol, Bisoprolol, Nebivolol

CLASS III DRUGS

Ex: Bretylium, Amiodarone, Sotalol

Sotalol which acts as both class II and class III

drug.

Amiodarone is an iodine containing drug which

causes bluish-grey colour to the urine.

CLASS IV DRUGS

Ex: Verapamil, Diltiazem

Dihydropyridines like Amlodipine, Nifedipine,

Nimodipine, Nitrendipine block calcium channels

in blood vessels but not in heart.

Hence they are not used for the treatment of

arrhythmias.

DRUGS USED FOR BRADYARRHYTHMIAS

1. Anticholinergics

Ex: Atropine

2. Sympathomimetics (Selective β1 receptor

agonists)

Ex: Dobutamine

DRUGS FOR CONGESTIVE HEART

FAILURE/CONGESTIVE CARDIAC FAILURE

(CARDIOTONICS)

❖ Congestive heart failure is a condition where the heart

is unable to pump sufficient blood to various parts of

the body.

❖ As a result of this condition blood supply decreases to

various parts of the body.

Source: Google

The right and left sides of the heart work together.

The pattern described below is repeated over and over

(heart rhythm), causing blood to flow continuously to the

heart, lungs, and body to supply oxygen and nutrients to

the body cells and to deliver waste products to organs that

remove them from your body.

Right side of the heart

❖ Blood enters the heart through two large veins, the inferior and

superior vena cava, emptying oxygen-poor blood from the body

into the right atrium of the heart.

❖ As the atrium contracts, blood flows from your right atrium into

your right ventricle through the open tricuspid valve.

❖ When the ventricle is full, the tricuspid valve shuts. This prevents

blood from flowing backward into the atria while the ventricle

contracts.

❖ As the ventricle contracts, blood leaves the heart through the

pulmonic valve, into the pulmonary artery and to the lungs where

it is oxygenated. Note that oxygen-poor or CO2 containing blood

goes through the pulmonary artery to the lungs where CO2 is

exchanged for O2.

Left side of the heart

(operating at the same time as the right side of the heart)

❖ The pulmonary vein empties oxygen-rich blood from the lungs into the

left atrium of the heart.

❖ As the atrium contracts, blood flows from your left atrium into your left

ventricle through the open mitral valve.

❖ When the ventricle is full, the mitral valve shuts. This prevents blood

from flowing backward into the atrium while the ventricle contracts.

❖ As the ventricle contracts, oxygen-enriched blood leaves the heart

through the aortic valve, into the aorta and to the arteries and

eventually into veins to complete the blood circulation in your body.

Source: Google

SYMPTOMS IN CHF

❖ Fatigue (Tiredness)- Decrease in blood supply to all

parts of the body

❖ Dyspnea (Breathlessness)- accumulation of blood in

lungs

❖ Heart congestion- accumulation of blood in heart

TREATMENT OF CHF

Heart Contractions/Heart Beat

1. No. of Contractions

2. Force of Contraction

To treat CHF we have to increase the force of contraction

Force of contraction depends upon the availability of

calcium and cAMP.

So mechanisms of drugs used for CHF include

I. Drugs which increase the levels of Calcium

II. Drugs which increase the levels of cAMP

DRUGS WHICH INCREASE THE

LEVELS OF CALCIUM

CARDIAC GLYCOSIDES

Ex: Digitalis

Stropanthus

Squill

Thevetia

Digitalis ---

Digitalis purpurea (Digitoxin)

Digitalis lanata (Digoxin)

Stropanthus ----

Stropanthus kombe (K-Stropanthin)

Stropanthus gratus (G-Stropanthin/Ouabain)

MECHANISM OF ACTION OF

CARDIAC GLYCOSIDES

Which act by inhibiting Na+ K+ ATPase thereby they increase

the intracellular levels of sodium which increase the

intracellular levels of calcium by which they increase the force

of contraction.

Source: Google

Source: Google

PHARMACOLOGICAL ACTIONS

OF CARDIAC GLYCOSIDES

1. INOTROPIC ACTION ( FORCE OF CONTRACTION)

They increase the force of contraction by increasing calcium hence

Positive Inotropic action

2. CHRONOTROPIC ACTION (NO OF CONTRACTIONS)

They decrease the number of heart betas by vagus nerve stimulation

and by increasing refractory period hence Negative Chronotopic action

PHARMACOKINETICS OF

CARDIAC GLYCOSIDES

1. Which are highly plasma protein bound drugs hence they have

2. Which are having very narrow therapeutic index hence they are

1. Which are highly plasma protein bound drugs

hence they have very longer duration of action

2. Which are having very narrow therapeutic

index hence they are highly toxic

SIDE EFFECTS OF CARDIAC

GLYCOSIDES

1. Hypokalemia

2. Cumulative toxicity

3. Visual disturbances

4. Nausea and vomiting

DRUG INTERACTIONS OF

CARDIAC GLYCOSIDES

1. Cardiac glycosides + Diuretics -→ Severe Hypokalemia

2. Cardiac glycosides + Quinidine -→ Toxicity

THERAPEUTIC USES OF CARDIAC

GLYCOSIDES

1. For the treatment of CHF

(due to Positive Inotropic action)

2. For the treatment of tachyarrhythmias like tachycardia,

flutter and fibrillation

(due to Negative Chronotopic action)

TOXICITY TREATMENT

1. DIGIBIND- a specific antidote

2. Potassium supplements

DRUGS WHICH INCREASE THE

LEVELS OF CAMP

ADENYL CYCLASE PATHWAY

ATP -------------→ cAMP -----------→ Inactive

❖ cAMP acts as a second messenger

❖ Enzyme Phosphodiesterase involved in the inactivation of

cAMP

1. Sympathomimetics (Selective β1 receptor agonists)

Ex: Dobutamine

2. Phosphodiesterase inhibitors

Phosphodiesterase III present in heart and

Phosphodiesterase IV present in bronchi.

Selective Phosphodiesterase III inhibitors

Ex: Amrinone, Milrinone

Presented by

Dr. Sannithi Nagarjuna

Coordinator for RIPER-GPAT Cell,

Hyderabad Academy &

Online GPAT Academy

7899107907

9885784793

nagarjunaspharma@gmail.com