Prof. Dr Khaled Abo EL-Sooud

The cardiovascular systemHEART, BLOOD VESSELS, AND BLOOD

Responsible for transporting oxygen, nutrients, hormones INSIDE

and cellular waste products OUTSIDE the body,

The heart, easily pumps LITERS of blood throughout the body every minute.

▪ Cardiac tonics or Cardiac glycosides or

INOTROPIC drugs

▪ Cardiac stimulants

▪ Anti-arrhythmic drugs

❖VASOCONSTRICTORS or hypertensive drugs

❖VASODILATORS or hypotensive drugs

▪Anti-anemic drugs or HAEMATINICS▪Coagulants

▪Anticoagulants.

Cardiac tonics or Cardiac glycosides or Inotropic drugs: Definition: These are drugs which improve the functional

activity of diseased heart by increasing the force of contractility (inotropic) without requiring increased energy consumption or increased rate of contractility.

Source: Include a variety of glycosides extracted from plants which include: DIGITALIS, STROPHANTHUS & SQUILL.

Plants Glycosides CumulativeProtein

bindingRoute

Datura purpurea

Digitoxin

Gitoxin

Gitalin

++

++

+

++

++

+

oral

oral

oral

Datura lanata

Lantocid A,

B, C+ + oral

Strophanthus gratus

Ouabain _ _ i.v.

Strophanthus kombé

Strophanthin

K+ + i.v.

Squill (Scilla) Scillarin + + oral

Comparison between different glycosides:

The molecule of the glycoside contains: Sugar moiety attached to the carbon atom 3 and

responsible for pharmacokinetic properties.

Non sugar part called aglycone or genin which is attached to carbon 17 and consist of steroid alcohol and unsaturated lactone ring which is responsible for cardio-tonic activity of the glycosides.

Digitalis has 2 main effects on diseased heart not in normal animals.

1- Positive inotropic effects: Digitalis increases the force of myocardial contractility as a result of

increased Inhibition of Na+--K+ ATPase which energizes Na+

pump→impaired Na+ outflow→ increased Ca++ intracellularly.

Increased Ca++ inflows through Ca++ channels.

Increased Ca++ releases from its stores in sarcoplasmic reticular.

Digitalis decreases the rate of myocardial contractility through:

Depression of SAN and AVN, so it slows the rate of conduction.

Stimulation of VAGAL CENTER either centrally or

reflexly through the chemoreceptors in the carotid sinus of the heart. The delayed conduction improves coronary perfusion during the extended period of diastole. This effect when followed by powerful systole, improves general circulation, so digitalis acts as cardiotonic.

Treatment of congestive heart failure (CHF) due to myocardial weakness or valvular diseases as valvular incompetence.

Tachycardia or arrhythmias in aged dogs and horses.

Oedema and ascitis of cardiac origin.

1- Reduce the overload on the heart: limit activity, reduce weight, and reduce high blood pressure. Reduce movement of the animal even by cage restriction.

2- Restrict sodium intake. Canned and dried food should be avoided

3- Drug therapya-In mild cases one of the xanthine derivatives (etamiphylline)

is used for their direct inotropic effect.

b-When the heart is severely decompensated, diuretics asFUROSEMIDE are used but potassium syrup should be given.

c- When the heart is more severely decompenated, digitalis is used for its direct inotropic and indirect chronotropic effects.

d- -adrenoceptor blockers: have been used together with cardiac glycosides.

Administration of atropinesulphate to stop excess vagal stimulation caused by digitalis.

Treatment of cardiac arrhythmia by anti-arrhythmic as qunidinesulphate, verapamil and or disopyramine.

increase heart rate and contractile power in Acute Heart

Failure (arrest or shock).

Their effect is RAPID IN ONSET but TRANSITORY

IN DURATION.

They may be classified into 4 main groups

Adrenaline: It acts on -and -adrenoceptors and increases the rateand force of contraction.

It also elevates blood pressure andcardiac output and induces peripheralvasoconstriction and dilatation of bloodvessels of skeletal muscles. Its effect israpid in onset and short in duration. Itis mainly used in cardiac arrest but notdue to chloroform anesthesia.

Isoprenaline: It is a non specific -agonist. It decreases blood pressure but increases cardiac output, heart rate and force.

Dopamine: It is a D1- receptor agonist which increasing force but not rate of cardiac contraction.

Dobutamine: It is a selective 1-

adrenoceptor agonist and acts as dopamine.

BLOCKING THE M cholinergic receptors of

the heart.

They are used mainly in case of bradycardia associated with Insecticide poisoning in dogs

DIRECT INOTROPIC EFFECT on the cardiac muscle and increase the cardiac output.

They induce coronary dilatation and increase blood supply to cardiac muscles.

Side effects are vagal stimulation which antagonizes the vasomotor effect resulting in minimal effect on heart rate.

Theophylline is powerful and replaced by aminophylline because of its higher water solubility. Xanthines are used in case of Pulmonary Emphysema In Horse And Congestion In Dogs.

Camphor S.C.acetic acid and alcohol orallyammonia inhalationirritates the sensory nerve endings causes reflex stimulation of the vasomotor centre, so improve circulation.

ARRHYTHMIA Is an irregular heartbeat - the heart may beat Slow heartbeat: bradycardia. Fast heartbeat: tachycardia. Irregular heartbeat: flutter or fibrillation. Early heartbeat: premature contraction.Arrhythmias occur when the electrical signals to the heart that

coordinate heartbeats are not working properly.

Arrhythmia is caused by either

ABNORMAL PACE MAKER ACTIVITY or ABNORMAL CONDUCTION AND PROPAGATION OF IMPULSES

The antiarrhythmic drugs may be classified into FOUR groups according to their mode of action.

I- MEMBRANE STABILIZERS (NA+ CHANNEL BLOCKERS)

QUINIDINE SULFATE:

PROCAINAMIDE

LIDOCAINE (LIGNOCAINE):

DISOPYRAMIDE

II- Ca2+ CHANNEL BLOCKERS

VERAPAMIL

III- - ADRENOCEPTOR BLOCKERSPROPRANOLOL:

IV- REFRACTORY PERIOD EXTENDERS

BRETYLIUM

Quinidine sulfate: It blocks the activated sodium channel. It depresses the pace maker activity, conduction and excitability. It prolongs the refractory period and the duration of action potential.

include alpha blocking,

antimalarial,

antipyretic and

oxytocic effects.

Side effects: some CNS and GIT disturbances as well as skin rash.

Therapeutic uses:

in case of atrial fibrillation, flutter and ventricular tachycardia in aged horses and dogs.

It is used mainly in atrial arrhythmia. It can be used by all routes at a dose of 25 mg/ kg orally. The dosage should be discontinued if gastrointestinal side effects occur.

It has similar effects to quinidine but it has a local anesthetic effect and it blocks both activated and non activated sodium channels.

It has some actions similar to quinidine and others similar to lignocaine. It is less likely to cause loss of appetite and disturbance of the gastrointestinal function. It is more effective in ventricular arrhythmia

Verapamil:

It is a papaverine derivative, controls arrhythmia of atrial origin in dogs. It is a calcium channel blocker, slows conduction through A-V node. It has a hypotensive effect. Other Ca2+channel blockers include nifedipine, phenylamine that are used in man.

The -blocker propranolol has been used to control sinus tachycardia, atrial flutter and atrial fibrillation. It is of value when the heart is sensitized by adrenaline, halogenated anaesthetics, digitalis or myocardial infarction. Large doses may cause severe cardiac depression and hypotension and care should be taken where pulmonary disease occurs.

Bretylium: it is an adrenergic neuron-blocking agent. Its antiarrhythmic activity is due to its ability to prolong the duration of action potential and refractory periods. The drug is not widely used in veterinary medicine.

Hypertensive drugs:

elevate a low blood pressure. They include

a- Vasomotor center stimulants e.g. analeptics

b- Sympathomimetics: They are now used in case of acute vasodilatation and to control local hemorrhages e.g. adrenaline, noradrenaline, ephedrine and amphetamine.

c- Direct stimulation of smooth muscles of blood capillaries, as ergot alkaloids, vasopressin which is used in circulatory collapse.

cause dilatation of blood vessels and lower the elevated blood pressure. They are useful for treatment of

Hypertension,

Peripheral Vascular Diseases,

Coronary Insufficiency And

Angina Pectoris

1- Centrally acting vasodilators:

Reserpine: which debilities noradrenaline and 5-HT stores.

Chlorpromazine: is an -blocker, centrally and peripherally acting hypotensive.

Clonidine: is -adrenoceptor agonists (presynaptic

2- Ganglionic blockers such as penta- and hexamethonium.

3- Antiadrenergic agents such as -methyldopa

4-Adrenergic blocking agents such as phentolamine, phenoxybenzamine, prazosin (- blocker), propranolol, hydergine(β- blocker).

5- Direct smooth muscle relaxants such as nitrites and nitrates Sodium nitroprusside Hydralazine: Papaverine

6- Diuretics especially saluretic diuretics such as e.g. furosemide,

1- Antianaemic drugs (haematinics):

These drugs are used for treatment of anemia. The correct diagnosis of the cause of anemia is essential for the success of treatment.

Causes: Deficiency of iron or inability to utilize it. This is because of the absence of other factors as copper, cobalt. Deficiency of protein in diet is also claimed.

Ferrous sulfate is an adequate source of iron for oral treatment. It has an astringent effect. It causes irritation and gastric pain, vomiting, diarrhea followed by constipation. It is used with copper sulfate (5:1) as pills for dogs.

Ferrous carbonate given as pills or tablets with arsenic or ferrous phosphates.

Ferrous gluconate and succinate are the best source of iron because they are less irritant, less astringent and better absorbed.

Iron dextran (iron carbohydrate complex) is the most common source of iron for intramuscular (rapidly absorbed) or i.v. administration. It is very effective when there is malabsorption by oral route.

Copper is essential for normal utilization of iron in hemoglobin formation. Cobalt enhances the synthesis of erythropoietin in the kidney. The latter stimulates stem cell division and red cell maturation.

3- Administration of protein-rich diet for the synthesis of globinrequired for hemoglobin.

It is caused by deficiency of cyanocobolamin (Vit B12) and or folic acid which is essential for the synthesis of nucleoprotein. The cell divisions will stop at the normoplast stage. There are few of enlarged RBCs.

1- Vitamin B12:It is found and synthesized by certain microorganisms. It acts

as an extrinsic factor which is absorbed by the aid of the intrinsic factor from the gastric mucosa. Then it reaches the liver and stimulates the production of the antianaemic factor. It acts also as a growth promoter as it is included in fat, carbohydrate and protein metabolism. It should be noticed that a deficiency in the dietary intake of cobalt is a common cause of vitamin B12 deficiency in cattle, sheep and goats.

2- Folic acid (Vitamin M, Pteroglutamic acid):

It is found in yeast, milk, eggs, and meat. Folic acid is reduced to folinic acid by the help of vitamin C. Uracil is converted to thymine by the aid of folinicacid. Thymine is changed to thymidine by vitamin B12 which is then converted to nucleotides and then to nucleic acid.

A - Coagulants

These are agents which accelerate blood coagulation and clot formation. They are used for local and internal hemorrhage.

Vasoconstrictors (epinephrine), which is used for nasal hemorrhage (epistaxis) and nasal congestion as decongestants.

Astringents (styptics) such as ferric chloride, tannic acid, which precipitate protein of superficial blood vessels.

Physiological coagulants such as thromboblastin, thrombin, and fibrin. They hasten the process of blood coagulation.

Surgical haemostatics such as oxidized cellulose, calcium alginate and absorbable gelatin sponge. They are used to stop bleeding during surgical operations.

Vitamin K which is essential for synthesis of prothrombin (factor II) by the liver and clotting factors VII, IX and X.

Calcium preparations: soluble calcium ions activate conversion of prothrombin into thrombin which converts soluble fibrinogen into insoluble fibrin. It used also in hypocalcaemia and blood transfusion where blood contains all the physiological coagulants.

These are drugs which delay or prevent the blood coagulation and clot formation. They are used for blood sampling, during blood transfusion and for thrombosis.

1- In vitro anticoagulants (Chelating agents):

EDTA, sodium citrate, sodium editate, sodium fluoride and oxalate. They act by chelation of Ca2+ ions to form bound complex but Ca2+ is still soluble, so it prevent clot formation. . They are mainly used for collection blood for analysis and blood transfusion

Heparin:It is a mucopolysaccharide synthesized by liver

cells and stored in the intema of blood vessels and basophiles. Its action is rapid in onset and short in duration. It is given by slow i.v injection. It binds with plasma -globulin called antithrombin-III increasing its activity and thus inactivates thrombin and interferes the conversion of fibrinogen into fibrin. It is effective both in vivo and in vitro. Heparin is used in blood transfusion, and for treatment of thrombosis and blood sampling

Coumarins:It present in spoiled sweet clover. The active principle was

found to be bishydroxycoumarin (dicoumarol) which is still used as anticoagulant. Many other coumarins are synthesized, the best known of them is Warfarin sodiumwhich is of interest because it is used as rodenticide and may cause potential toxicity to farm animals. They are not effective as anticoagulant in vitro.

Their action is due to inhibition of the synthesis of prothrombin and clotting factors VII, IX and X because they have anti-vitamin K effect due to its similarity in chemical structure to vitamin K. Their action is slow in onset and prolonged in duration.

as coumarin but given by all routes and used as rodenticide

Comparison Heparin Dicoumarol

Source Animal liver hepatocytes

Plant (Spoiled sweet clover)

Type of action In vivo and in vitro In vivo only

Administration Slow i.v. Oral

Onset of action Rapid Slow

Duration of action Short (few hours) Long (few days)

Mechanism of action Antithromboplastin,Antiprothrombin

Antithrombin

Anti-vitamin K due to its chemical

similarity

Uses For blood samplingFor blood transfusion

Treatment of thrombosis

For thrombosisRodenticide (warfarin)

Antidote Protamine, Toludine blue

Vitamin K

Comparison between

Heparin and Dicoumarol: