GLAD ATORS

GLAD ATORSMEMBERS :

SEEMAHARSHA SAWANTADHYESH SAWANTHARISH MEHTARAHUL CHAKRAPANINITIN RASKARPARESH REKHIJAY UPADHAYMOHAMMAD SHAHID

The heart is a very specialized

muscle that pumps blood through the body, transporting oxygen, carbon dioxide, nutrients and waste.

THE HUMAN HEART

NO

6 – thickness of heart

9 – width of heart

12 – length

Located behind rib cage

It lies in the MEDIASTINUM

Major mass is to the left side

EPICARDIUM

MYOCARDIUM

ENDOCARDIUMepicardium

myocardium

endocardium

epicardium

Atrium is a chamber that pumps

blood into the heart.

Ventricle is a chamber that Pumps blood out of the heart.

The atria and the ventricles regulate blood flow by pumping blood in and out of the heart.

ADHYESH V. SAWANTHARISH MEHTA

As each chamber of heart contracts, it pushes a volume of blood into a ventricle or out of the heart into artery.

Valves open and close in response to pressure change as the heart contracts and relaxes.

1. Atrioventricular (AV) valve

Bicuspid valve Tricuspid valve

2. Semilunar valve (SL) valve

Pulmonary valve Aortic valve

(Bicuspid valve )(Tricuspid valve )

Stenosis : valves are not open fully.

Incompetance : valves are not close completely.

Coronary circulation to supply adequate

circulation to cardiac muscle and surrounding

tissue.

1. Atherosclerosis

2. Angina pectoris

3. Heart attack

(myocardial infarction)

Coronary heart disease

• It is caused by a build up of plaque in the inner lining of an artery.

It is discomfort or pain in the chest that happens when not enough oxygen-rich blood reaches the muscle cells of the heart.

• It is the death of heart muscle from the sudden blockage of a coronary artery by a blood clot.

• Vasodilators ( dilates artery and veins):

Nitrodialators - Na nitroprussides,Nitrates

ACE inhibitors - Captopril, Enalapril

• Cardiac depressant: Beeta blocker - Propanolol, Atenolol

• Antithrombotics: Anticoagulant - Heparine

• Thrombolytic agent- Streptokinase, Urokinase

• Analgesic - Morphine, Pentazocine.

MEDICATIONS

ANGIOPLASTY

BYPASS SURGERY

“Blood is a connective tissue composed of a liquid matrix called plasma that dissolves & suspends various cells & cell fragments.”

‘O’ group- Universal donor ‘A’ group ‘B’ group ‘AB’ group- Universal Acceptor

“Identification of blood group- WHY?” Accident Heredity Disease

Transportation

Regulation

Protection

Whole blood has 2 component :-

Blood Plasma (55%).

Formed element (45%).

ANEMIA:-

Important type of Anemia :- Iron deficiency anemia. Pernicious anemia. Hemorrhagic anemia. Hemolytic anemia. Thalassemia. Aplastic anemia.

LEUKEMIA :-

Type of leukemia :– Acute leukemia. Chronic leukemia.

• A closed system of vessels that moves blood around the A closed system of vessels that moves blood around the bodybody

• Arterial vessels: aorta, arteries, arterioles (vascular Arterial vessels: aorta, arteries, arterioles (vascular resistance)resistance)

• Carry blood away from the heart to the:Carry blood away from the heart to the:

• Capillary bedsCapillary beds

• Venous vessels: venules, veins, venae cavae Venous vessels: venules, veins, venae cavae

• Carry blood toward the heartCarry blood toward the heart

DIFFUSIONe.g. CO2, wastes, O2, amino acids,

glucose, hormones, etc (Lipid Soluble)

TRANSCYTOSISe.g. insulin, antibodies, etc (Lipid

Insoluble)

Oxygen

Carbon Dioxide

O2 uptake and CO2 loss from blood

Chloride Shift

Optimal : 120 / 80 mm Hg

Normal : 130 / 85 mm Hg

High-normal : 130–139 / 85–89 mm Hg

HYPERTENSION

Stage 1 140–159 / 90–99

Stage 2 160–179 /100–109

Stage 3 180 or higher / 110 or higher

SOURCE : Joint national commission 7

1 ) Alpha (α)-adrenergic blocking drugs—

Terazosin and prazosin

2 ) Beta (β) adrenergic blocker –

-Selective – Atenolol, Propranolol. -Non Selective – Metoprolol

-α + β receptor Blocker- labetalol

3) Vasodilators –

-Arteriodilators(Ca Channel Blockers ) – Nefidipine, Amilodipine, Verapamil,

Diltiazem.-Mixed : Hydralazine -Arteriolar + Venous – Na Nitroprusside

SOURCE : GENERAL PHARMACOLOGY BY : KD TRIPATHI

4 ) Diuretics –

- Thiazide – Hydrochlorothiazide - Loop Diuretics – Furosemide

- K+ Sparing Diuretics – Spironolaclone - Carbonic Anhydrase Inhibitors – Acetazolamode

5 ) ACE Inhibitors –

Ramipril, Enlapril

SOURCE : GENERAL PHARMACOLOGY BY : KD TRIPATHI

MECHANISM OF ACTION

DRUG INTERACTION -Beta Blockers -Ca channel blocker -Diuretics

MECHANISM OF ACTION

- Selective – Atenolol, Propranolol. -Non Selective – Metoprolol

-α + β receptor Blocker- labetalol

DRUG INTERACTION

1) ATENOLOL

Antacid- reduced atenolol absorptionAntiarrythmics- increased cardiac adverse effects

2 ) METOPROLOL

-Increased effects with diuretics NSAIDs

MECHANISM OF ACTION

Arteriodilators(Ca Channel Blockers ) – Nefidipine, Amilodipine, Verapamil, Diltiazem.

-Mixed : Hydralazine -Arteriolar + Venous – Na Nitroprusside

DRUG INTERACTION 1 ) Amlodipine – avoid beta blockers 2 ) Nifedipine – Increased level of phenytoin and

digoxin

MECHANISM OF ACTION

- Thiazide – Hydrochlorothiazide - Loop Diuretics – Furosemide - K+ Sparing Diuretics – Spironolaclone - Carbonic Anhydrase Inhibitors – Acetazolamode

DRUG INTERACTION

Furosemide, Hydrochlorothiazide Thrombocytopenia- with cotrimoxazole Increased lithium level Hypokalemia – digitalis toxicity

MECHANISM OF ACTION

DRUG INTERACTION 1) Ramipril – increased level of potassium , so

decrease effects with NSAIDS

Smoking

Age (women older than 65 years and men older than 55 years of age)

Obesity

Diabetes

Lack of physical activity

Chronic alcohol consumption

Family history of cardiovascular disease

Sex (men and postmenopausal women

SOURCE : General Principles Pharmacology by Lippincott’s

METABOLISM OF PROPANOLOL

By :- Seema SinghRoll no :- 38

Arrhythmia – is an abnormality of rate, origin or conduction or spread of cardiac impulses.

Rhythm – automaticity & rhythmicity Action potential –it has 4 phases, phase 0 : influx of Na+ & depolarization phase 1 : Na+ & K+ conduction decreases phase 2 : influx of Ca+ & plateau achieved phase 3 : influx of K+ & repolarization phase 4 : slow depolarization of membrane Action potential duration Refractory period

Wave/ segment

Potential

Time Significance

P 0.2mV 0.08 sec. Atrial depolarization

QRS 1.8mV 0.06 sec. ventricular depolarization

T 0.4mV 1.12 sec. Ventricular repolarization

P-R interval

- 0.12 – 0.2 sec.

Indicates the conduction of impulse from SA node to AV node.

Ectopic Focus – abnormal pacemaker activity

Circus movement Atrial Tachycardia Atrial Flutter Fibrillation

Atrial flutter

Specifically correct or prevent development of arrhythmia.

Their mechanism of action:1. Slowing diastolic depolarization & decrease in

automicity of ectopic foci.2. Elevation of threshold potential for myocardial cells.3. Increase the refraction period.4. Decrease in conduction velocity.5. Slowing of K+ efflux.6. Affecting adrenergic mechanism.

Group 1: drugs which block voltage- sensetive Na+ channels, may be further divided into three :

1A : slow down depolarizatin rate in phase 0 & moderately prolong repolarization - Quinidine

1B : shorten repolarization ( phase 3) – Lidocaine 1C : strongly slow down depolarization (phase 0)

– Amiodarone Group 2 : drug acting through inhibition of

sympathetic nerves, suppress phase 4 depolarization – Propranolol.

Group 3 : drugs that prolong action potential & repolarization in phase 3 – K+ channels blockers

Group 4 : Ca+ antagonists – shorten action potential duration & decline plateau - Verapamil

CO = SV * HR (ML/MIN) = (ML/ beat) (beat/mint)

= 70*75 = 5250 ml /min= 5.25 l / min

Preload- effect of stretching - Flank-starling law of heart

Contractility

Afterload

A) Autonomic regulation of HR

B) Chemical Regulation – Hormones - Cations –

Calcium ,sodium

C) Other factors- Age, Gender , Physical Fitness,

High Body Temperature

Risk factors for a stroke

Atherosclerosis (hardening of the arteries) Uncontrolled diabetes High blood pressure High cholesterol level Smoking Myocardial ischemic attack Heart disease Carotid artery disease.

Drug Treatment

Mechanisam of action- ACE inhibitor Pharmacokinetics-

Interaction - Indomethacin - K Supplements / K sparing diuretics

Mechanisam of action - Decrease the CH synthesis by inhibition of rate limiting HMG- CoA reductase

Pharmacokinetics-

Interaction – Lower the absorption of Warfarin, barbiturate ,digoxin.

So, which is drug that can be helpful in severe CVS disorders

Inhibitor or Inducer? Agonist or Antagonist? None of these…….

It is a precursor to NO NO is found in the body to maintain

some physiological functions

Nitric Oxide Anabolism:Nitrites/Nitrates Converted to NO by:1. NOS2. Nitrite reductase activity in mammalian

tissues has been linked to the mitochondrial electron transport system , protonation, deoxyhemoglobin, and xanthine oxidase

3. Intestinal Flora

Nitric oxide, synthesized from the oxidation of L-arginine by nitric oxide synthase (NOS), is a major contributor to the normal homeostasis of the cardiovascular system.

NO NO2 NO3

The oxidation of NO by molecular oxygen is second order with respect to NO:

2NO +  O2 -> 2NO2 (1) 2NO + 2NO2 -> 2N2O3 (2) 2N2O3 + 2H2O -> 4NO2

- + 4H+ (3)

NO and nitrite are rapidly oxidized to nitrate in whole blood. (Why?) NO2- derived from NO autoxidation is rapidly converted to NO3- via its

oxidation by certain oxyhemoproteins (P-Fe2+O2) such as oxyhemoglobin or oxymyoglobin :

2P-Fe2+O2 + 3NO2- + 2H+-> 2P-Fe3+ + 3NO3

- + H2O (4)or

4P-Fe2+O2 + 4NO2- + 4H+ -> 4P-Fe3+ + 4NO3

- + O2 + 2H2O (5) What About Direct NO metabolism P-Fe2+O2 +  NO -> P-Fe3+ + NO3

-  

Therefore •NO-derived oxidants impose a nitroxidative stress in the cardiovascular system

Nitrated protein Methodology Major observationsPlasma proteinsFibrinogen IP of fibrinogen; 3-NO2-Tyr determination by HPLC-ESI-

MS-MS; Electron microscopy

30% increase on nitrated fibrinogen in CAD; accelerated clot formation; fragile clot

Plasmin IP with anti-3-NO2-Tyr antibody of plasma proteins; WB to

major plasma proteins

Increase in nitration of plasmin and fibrinogen in smokers; in vitro inactivation by nitration of plasminogen

Apo A-I IP with anti 3-NO2-Tyr antibody from plasma and apo-1

isolation from biopsies; proteomic methodology for protein identification; HPLC-ESI MS-MS for the determination of 3-

NO2-Tyr and 3-Cl-Tyr

Apo-1/MPO interaction; nitration and chlorination of Tyr192; two-fold increase of nitrated Apo-1 in CAD; preferential nitration of Apo-1 in plasma when compared to other nitrated plasmatic proteins

 Vessel wallApo B LDL purification by ultracentrifugation of human plasma and

aortic lesion; 3-NO2-Tyr was determined after hydrolysis and

derivatization by GC–MS

90-fold concentration of nitrated LDL in aortic lesion when compared to plasma nitrated LDL

COX IP of COX-1 from smooth muscle cells and from human atheroma plaques; WB and spectrophotometrical determination of nitrated COX-1; COX-1 EPR studies; trypsin digestion, HPLC purification and amino acid sequencing

In vitro inactivation by nitration of COX-1; identification of nitrated COX-1 in smooth muscle cells and in human atheroma plaques; identification of nitrated Tyr385 by •NO and Tyr•

PGIS IP of endothelial nitrated proteins; WB; immunohistochemistry; thermolysin digestion of nitrated PGIS and high resolution MS (FT-ICR) of nitrated peptides

Nitration of PGIS at low ONOO– (1 µM); IC50 for inactivation

100 nM; colocalisation of nitrated proteins and PGIS in the endothelium bovine coronary artery; specific nitration at Tyr430

Mn-SOD In vitro nitration of human Mn-SOD by ONOO–; ESI-MS analysis of digested SOD; amino acid sequencing; IP of Mn-SOD of aged rat aorta; WB; immunoelectron microscopy anti

3-NO2-Ty; development of specific Ab against nitrated SOD

at Tyr34; angiotensin-II induced hypertension in rats

Identification of specific nitration at Tyr34; distribution of nitrated SOD in rat aorta; age-increase in nitrated SOD; distribution of nitrated SOD at Tyr34 in the kidney mainly in cortical collecting ducts

MyocardiumMM-CK IP of CK from heart failure in rats; WB and

immunohistochemistry; human biopsy of atrial fibrillation

Nitration and inactivation of MM-CK in heart; in vitro inactivation of MM-CK by ONOO– but not myosin ATPase; selective reduction of MM-CK activity in human biopsies; increase nitration and carbonyl formation of MM-CK in atrial fibrillation

-actinin IP of -actinin from human cardiomyocytes

and WB against 3-NO2-Tyr

Contractile dysfunction of cardiomyocytes after exposure to ONOO–; detection of nitrated -actinin as the only nitrated protein at the concentration used

SERCA IP of nitrated proteins from SR of age rat skeletal muscle; WB; protease digestion HPLC-ESI-MS; amino acid analysis; IP of

SERCA 2a and Western Blot against 3-

NO2-Tyr

Nitration of Tyr294,295 in the M4–M8 transmembrane

domain of SERCA 2a; correlation between reduction in Ca

ATPase activity and nitration; age-dependent increase in

nitration of SERCA 2a; nitration of Tyr294,295 in SERCA 2a

in rat heart; nitration of SERCA 2a in patients with

idiopathic dilated cardiomyopathy

BIOMARKER for1. Hypertension2. CAD

INCREASES SCOPE OF DRUG RESEARCH

1. SOD2. Peroxynitrate decomposition catalysts