CARDIOVASCULAR DRUGS A. POSITIVE INOTROPES: DRUGS THAT IMPROVE CARDIAC CONTRACTILITY 1. Use of positive inotropes revolves around the following factors: a. All of these drugs have the potential to increase myocardial oxygen consumption. b. All increase intracellular calcium levels or increase sensitivity of contractile myofibrils to intracellular calcium. c. None can significantly alter the underlying pathologic conditions that caused the heart to fail. d. Efficacy of most of these drugs is uncertain in many clinical settings and most have narrow therapeutic index. e. These drugs can cause symptomatic improvement and enhance the quality of life of the patient. 2. Specific Agents a. Catecholamines b. Phosphodiesterase inhibitors c. Anticholinergics d. Digitalis glycosides 3. Catecholamines (Beta-adrenergic Blockers) a. Beta-1 receptors are mostly located in the heart and stimulation of these receptors results in positive inotropic and chronotropic response 1) Beta-2 receptors are mostly found in vascular and bronchial smooth muscles and their stimulation can cause relaxation (vasodilatation and bronchodilation)
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CARDIOVASCULAR DRUGS
A. POSITIVE INOTROPES: DRUGS THAT IMPROVE CARDIAC CONTRACTILITY
1. Use of positive inotropes revolves around the following factors:
a. All of these drugs have the potential to increase myocardial oxygen consumption.
b. All increase intracellular calcium levels or increase sensitivity of contractile myofibrils to intracellular calcium.
c. None can significantly alter the underlying pathologic conditions that caused the heart to fail.
d. Efficacy of most of these drugs is uncertain in many clinical settings and most have narrow therapeutic index.
e. These drugs can cause symptomatic improvement and enhance the quality of life of the patient.
2. Specific Agents
a. Catecholaminesb. Phosphodiesterase inhibitorsc. Anticholinergicsd. Digitalis glycosides
3. Catecholamines (Beta-adrenergic Blockers)
a. Beta-1 receptors are mostly located in the heart and stimulation of these receptors results in positive inotropic and chronotropic response
1) Beta-2 receptors are mostly found in vascular and bronchial smooth muscles and their stimulation can cause relaxation (vasodilatation and bronchodilation)
2) Alpha-1 receptors are found primarily in vascular smooth muscle and myocardium and their stimulation results in vasoconstriction and a positive inotropic response
b. Catecholamines increase contractility by the following process.
1) Stimulation of Beta-1 adrenoreceptors stimulates adenylate cyclase.
2) This increases intracellular cyclic AMP concentration which in turn activates CAMP-dependent protein kinase.
3) CAMP-dependent protein kinases catalyze phospphorylation of membrane protein in the sarcolemma and sarcoplastic reticulum.
4) This phosphorylation regulates the movement of Ca++ ions across the sarcolemma and sarcoplasmic reticulum.
5) This increases intracellualar calcium which stimulates contractility of the heart.
c. Commonly used catecholamine
1) Epinephrine
a. Drug of choice for positive inotropic and circulatory support following cardiac arrest.
b. It is a potent alpha-1, beta-1, and beta-2 agonist.c. Increases contractility, heart rate, blood pressure, and
cardiac output.
2) Isoproterenol
a. The prototype beta agonist.b. Used in emergency treatment of complete AV nodal
block that is unresponsive to anticholinergics.c. Not used in the management of cardiac arrest or
myocardial failure because of its arrythmo-genecity and hypotensive effects.
d. Desirable for acute management of heart failure.
3) Dopamine
a. Biosynthetic precursor to norepinephrine.b. Acts on beta-1 and dopaminergic receptors (in renal,
mesenteric, coronary and vascular beds) and also stimulates norepinephrine release.
c. Vasodilatory effects improve renal blood flow.d. Desirable for acute management of heart failure.
4) Dobutamine
a. A synthetic analog of dopamine, but a beta-1 agonist.b. Currently most useful in treating heart failure.c. Positive inotropic effects similar to dopamine but does
not cause vasodilatation of renal, coronary, cerebral and mesenteric vascular beds.
d. Contraindicated in patients with heart disease characterized by ventricular hypertrophy.
e. Side effects similar to dopaminei) Tachyarrhythmiasii) Vomiting
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iii) Nervousnessiv) Seizures (cats)
4. Phosphodiesterase Inhibitors
a. Phosphodiesterase enzymes are responsible for inactivation of Cyclic AMP
1) Inhibition of these enzymes leads to increase intracellular calcium concentration.
2) Drugs that inhibit phosphodiesterasesa) Xanthine derivatives b) Bipyridine derivatives
3) Xanthine derivativesa) May evoke changes in the cardiovascular system (slight increases in blood
pressure, heart rate and stroke volume).b) Tolerance may develop within a few days of chronic intake.c) May also cause CNS stimulation and diuresis.
4) Bipyridine derivatives a. Amrinone
i. Increases cardiac contractility and causes vasodilatation, decreasing preload and after load.
ii. May cause hypotension, arrhythmia, or G.I. distress.
iii. Associated with thrombocytopenia and liver function abnormalities
b. Milrinone
i) Possess 20 to 50 times the potency of amrinone. ii) Approved for use in dogs.
c. Pimobendan
i) A relatively new product in this category ii) Increases sensitivity of myocardial
calcium-regulatory proteins to calcium.
5) Anticholinergic Drugsa. MOA: deny access of acetylcholine to receptors b. Ach causes
i. Negative inotropic effect (decrease force of contraction).
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ii. Negative chronotropic effect (decrease rate of contraction).
iii. Vasodilatation.
6) Cardiac glycosides (Digitalis), Digitoxin and Digoxin.a. Chemical structure
i. Consist of a steroid nucleus bound to an unsaturated lactone ring (combination called aglycone)
ii. The number of sugar molecules attached to the aglycone account for their pharmacokinetic differences.
b. Source: Dried leaf of foxglove plant (Digitalis lanata and Digitalis purpurea)
c. Mechanism of Action1) Positive inotropic effect:
binds to and inhibit sodium pump (Na+-K+-ATPase) at the myocardial cell membrane.
a) Inhibition causes reduction of Na+ transport out of the cell.
b) This causes a transient increase in intracellular sodium concentration.
c) Na+ ions move out of the cell via sodium-calcium exchange mechanism.
d) Results to accumulation of Ca++ in the cell.
2) Negative chronotropic effect (antiarrhythmia): via parasympathetic stimulation (vagus nerve).
a) SA node (increased sensitivity to Ach)i. Increased slope
of phase 4.ii. Toxic levels
slow down heart rate.iii. In diseased
heart, may cause atrial arrhythmias.b) AV node
i) Slow AV nodal conduction.ii) Increase AV nodal refractory period
d. Pharmacokinetic
1) Disposition of drugs varies with the formulation.2) Digitoxin is more lipid-soluble than digoxin.3) Plasma protein binding: digoxin (25%), digitoxin (90%).4) Half-life in dogs: digoxin (1-7 days), digitoxin (8-12 hrs.).
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5) Excretion and metabolism a) Digoxin primarily eliminated via the kidney
unchanged.b) Digitoxin is metabolized by the liver.
6) Digoxin should not be given IM (causes pain necrosis).7) Concurrent use with
a) Quinidine increases toxin effects of digitalis due to displacement from plasma protein binding.
b) Diuretics and amphotericin result to hypokalemia.c) Beta-adrenergic agonist increases likelihood
arrhythmias.e. Toxicity
1) Stimulation of CTZ (early signs of toxicity)a) Vomitingb) Nauseac) Anorexiad) Diarrhea
2) CNS: drowsiness and malaise3) Potentiated by hypokalemia4) Treatment
a) Discontinuation of digitalis therapy b) Discontinuation of K+-depleting diureticsc) Use of antiarrhythmics d) Potassium administration
f. Clinical Uses 1) To restore adequate circulation in animals. 2) To slow down supraventricular arrhythmias.
g. Digitalization 1) Rapid administration of a loading dose followed by maintenance dose
2) Slow giving of a maintenance dose.
B. ANTIARRYTHMICS1. Arrhythmia refers to any deviation from the normal cardiac rate and rhythm. 2. This deviation refers to variation from the normal.
a. cardiac rate or regularity of heart rate.b. Site of origin of initial impulses (ectopic)c. Sequence of activation of atria and ventricles.
3. In general, cardiac arrhythmias can be considered to arise from either of the following or both:a. Abnormal impulse initiation 1. Normal automaticity is enhanced due to increased responsiveness to catecholamine. 2. Abnormal automaticity is enhanced due to decreased oxygen supply to myocardium.
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3. Triggered activity caused by after depolarization that reach threshold potential, probably due to large increase in intracellular calcium.
4. Sick-sinus syndrome wherein vagal activity increases K+ conductance out of the cell causing repolarization.
b. Abnormal impulse condition 1. Re-entry phenomenon: an impulse that enters a slowly conducting region of
the heart goes back to reactivate it again. 2. Condition for re-entry a) There must be blockade in the conduction pathway. b) There must be slow conduction over an alternate route to a point beyond
the block. c) There must be delayed excitation beyond the block.
4. Therapy of arrhythmiasa. Antiarrhythmic drugs have been classified into four groups based on their
predominant effect on AP.b. General Classification:
1) Class I (membrane-stabilizing drugs)2) Class II (beta adrenergic blockers)3) Class III (repolarization prolonging drugs)4) Class IV (calcium-entry blockers ventricular tachycardia with long Q-T
intervals, myasthenia gravis, and severe hepatic failure)c. Procainamide
i. Similar cardiac effects with quinidine but has less ability to induce hypotension and increase AV conduction.
ii. Use with quinidine and other class agents and beta-blockers in treating refractory arrhythmias.
d. Disopyramide i. Second-line drug for refractory arrhythmias ii. Possess strong negative inotropic tendencies.iii. Contraindicated in CHF, pulmonary edema, glaucoma, urinary retention, advanced AV block and SA node dysfunction.
e. Class IB1. Characteristics
a. Shorten APD and effective refractory period. b. Decrease slope of phase 0.c. Depress automaticity.d. Increase threshold for ventricular fibrillation.e. Act selectively on inactivated Na+ channels present in diseased or
ischemic tissues.2. Specific Agents
a. Lidocainei. Used for acute, life threatening ventricular arrhythmias.ii. Causes significant suppression of automaticity, conduction velocity and prolongs refractoriness in diseases cardiac cells.
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iii. Intoxication seizures (controlled by diazepam and short-acting barbiturates).
b. Tocainamide i. May be used to follow-up lidocaine .ii. Causes progressive corneal edema in Doberman pinschers.
c. Mexiletinei. Synergistic with other class I A drugs ii. Needs further clinical evaluation.
d. Phenytoini. Similar to lidocaine but more effective in controlling
supraventricular tachycardiaii. Indicated for controlling digitalis induced arrhythmiasiii. Has minimal hemodynamic effects, wide therapeutic range, and
rare adverse reactionf. Class IC ( flecainide, encainide)
1. Characteristicsa) Causes profound depression of phase 0 and conduction velocity.b) Less effect in refractoriness or APD.c) Seriously depress contractility, cardiac output, and systemic blood
pressure.2. Indicated for supraventricular and ventricular, tachyarrhythmia and those
involving accessory pathways.3. Contraindicated in AV block, bundle branch block and myocardial
depression.
g. Class II Antiarrhythmia1. MOA: Blockade of cardiac Beta-I receptors leading to slow opening of
calcium channels and rate of pacemaker discharge.2. Characteristics
a) Decrease conduction velocity.b) Increase AV nodal refractory period.c) Suppress tachyarrhythmia and ectopic pacemakers which are due to
sympathetic-mediated increased in automaticity.d) Reduction in cardiac output is due to negative inotropic and
chronotropic effects. 3. Indications
a) Supraventricular tachycardia.b) Pre-excitation tachyarrhythmia.c) Atrial flutter and fibrillation.d) Contraindicated in AV block and sick-sinus syndrome.e) Those with Beta-2 blocking activity may cause bronchial smooth
muscle constriction.4. Specific agents
a) Propranololi. The standard beta blocker used in veterinary medicine.ii. Blocks Beta-1 and Beta-2 receptors.
h. Class III Antiarrhythmics1. MOA: Inhibition of K+ channel (inhibition of repolarization) prolonging
APD and refractory period.2. Characteristics
a) Modify velocity of conduction.b) Effective for arrhythmias dependent on re-entry.c) Increase threshold for atrial and ventricular fibrillation.
3. Specific agentsa) Amiodarone i. Control supraventricular and ventricular tachyarrhythmia. ii. Can be used with class IA or IC drugs. iii. Increase serum levels of digoxinb) Bretylium (not used in veterinary medicine).
i. Class IV Antiarrhythmics1. MOA: Block calcium channels, inhibiting calcium entry across the membrane
during phase 1 and 2 of AP.2. Characteristics
a) Slow down sinus rate and AV conduction.b) Interrupt arrhythmia resulting from abnormal automatically and
triggered mechanism.3. Indicated for control of most supraventricular arrhythmia.4. Contraindicated in arrhythmia due to AV blockade (wide QRS) sinus
bradycardia, myocardial failure.5. Specific agents
a) Verapamil (used in dogs to slow sinus rate, increased AV conduction time, or decrease ventricular response).
b) Diltiazemc) Nifedipine
C. VASODILATOR DRUGS
1. The use of vasodilator drugs in the therapy of heart failure is relatively common in veterinary medicine.
2. Vasodilators are classified based on their primary site of action.a) Drugs that dilate systemic veins are called venodilators.b) Drugs that dilate systemic arterioles are arteriolar dilators.c) Drugs that dilate both systemic arterioles and veins are called mixed or
a) Heart failure is characterized by inability of the heart to deliver normal amounts of blood at a rate required for tissue metabolism.
b) It is represented clinically as 1) Backward failure: congestion or edema (congestive heart failure).2) Forward failure: poor tissue perfusion (low – cardiac – output failure).
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c) The amount of blood pumped out of the heart per minute is influenced by the ff:
1) Preload (ventricular end – diastolic volume and pressure), reflects how much the heart is stretched before contraction.
2) After load refers to the pressure of force that the ventricular muscle must overcome to pump blood into the aorta.
3) Heart rate and rhythm4) Size of the ventricles.
d) These factors can be adjusted to compensate for the failing cardiovascular system.
e) Cardiac compensatory mechanisms1) Heart dilates or stretches to increase force of contraction and size of
stroke volume.2) This stretches myofibrils causing hypertrophy and increases metabolic requirements of the heart.3) With accompanying increase in blood volume, the failing heart is
strained4) Eventually, the stroke volume and cardiac output decrease leading to
death.4. Arteriolar dilators decrease resistance to systemic arterial or forward blood
flow (reduce after load).a. Dilation of systemic arterioles lowers arterial blood pressure.b. This decrease intraventricular pressure and tension during systole.c. This also decreases after load leading to shortening of myocardial fibers and
greater expulsion of blood.d. Hydralazine.
5. Venodilators decrease venous return to the heart, intracardiac blood volume and diastolic intracardiac pressure (reduce preload)a. Through pooling of the blood in the peripheral veins, they decrease
intraventricular pressure during diastole, and reduce edema formation.b. Examples: nitroglycerin, isosarbide dinitrate
6. Mixed or balanced vasodilators decreased preload and after load in patients with CHF.
a. Examples: sodium nitroprusside, prazosin, angiotensin converting enzyme (ACE) inhibitors
7. Adverse side effects a. Hypotension, anorexia, dizziness, vomiting, diarrhea.b. ACE inhibitors: azotemia, inability to maintain GFR.c. Nitroprussides: headache, flushing
8. Specific vasodilators a. ACE inhibitors effects are based on decreased concentration of circulating
Angiotensin II1) Angiotensin actions
a) Potent vasoconstrictor b) Stimulates release of aldosterone from adrenal glandc) Stimulates vasopressin (ADH) release from posterior pituitary gland
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d) Preserves glomerular filtration rate (GFR) when renal blood flow is decreased.
2) Inhibition of angiotensin-converting enzyme reduces aldosterone and ADH release, promotes NA+ and water loss thereby reducing edema and causing systemic vasodilation.
3) Examples: captopril, lisinopril
b. Hydralazine 1) Used in the treatment of CHF unresponsive to conventional therapy
with cardiac glycosides and diuretics.2) Direct-acting peripheral arteriolar vasodilator.3) Action: not know presumed to cause local increases in prostacylin
concentration4) Rapidly absorbed PO. IM: widely distributed mostly metabolized by GI
mucous and liver (t1/2-8 hrs.)c) Prazosin
1) Mechanism of actiona) Blocks postsynaptic alpha-1 adrenergic receptors (dilate both
arteries and veins)b) Inhibits phosphodiesterase in vascular smooth muscle (decreased
contractions)2) Effects: lowering of blood pressure; decreased preload and after load.3) Partial absorption after oral administration; wide distribution;
extensively metabolized in the liver d) Nitrates and nitroprusside
1) MOA: stimulate quanylate cyclase to produce cGMP (cyclic guanosine monophosphate)
a) cGMP accelerates Ca++ loss from vascular smooth muscle cells.b) Causes vasodilation
2) Nitroglycerin a) Dilate coronary arteries and improve collateral flow to ischemic
regions of the heart.b) Produces vasodilation (venous > arterial ) c) Decrease preloadd) Reduces myocardial oxygen consumption
3) Nitroprussidea) Produces peripheral vasodilation by direct action on venous and
arteriolar smooth muscleb) Rapidly lowers blood pressurec) Decrease cardiac preload and after load
4) Isosarbide dinitratea) Produces vasodilation (venous > arterial) b) Decreases preload c) Reduces myocardial oxygen consumption d) Dilate coronary arteries and improve collateral flow of ischemic
regions
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e) Relieves anginal attacks and increases cardiac output
D. ANTIANEMIC DRUGS (HEMATINIC DRUGS)1. The oxygen-carrying capacity of blood depends on the adequate number of
erythrocytes and hemoglobin concentration.2. Anemia occurs when there is excessive loss or decreased replacement of
erythrocytes and also when the circulating erythrocytes have inadequate hemoglobin (Hgb).
3) Causes:a. Chronic blood loss b. Abnormal shape or size of erythrocytes c. Nutritional deficiencies d. Chronic disease or malignancies
4) Anemia can be treated bya. Providing the necessary components of RBC production b. Stimulating bone marrow formation of RBC (erythrocytes)
5) Iron a. Necessary for hemoglobin formationb. Distribution
1) It is an integral part of hemoglobin2) Stored in the body as hemosiderin and ferritin3) In the blood, it is bound to transferrin4) About 70% od body iron is functional (hemoglobin, myoglobin, or
enzymes)5) The amount stored in tissues can replace about half the circulating Hgb
c. Absorption, metabolism and excretion1) Absorption, metabolism and excretion2) Absorption is influenced by gastric acidity, reducing agents like
ascorbic and food intake.3) Majority of the iron released via Hgb break down in the liver is reused 4) Demands increased by
a) Rapid growth b) Blood loss (hemorrhage or menstruation)c) Pregnancy
d. Signs of deficiency 1) Paleness of skin and mucous membrane 2) Fatigue/weakness3) Loss of appetite
e. Treatment 1) Ferrous salts (sulfate gluconate, fumarate) – PO2) Iron dextran IM injectable – a complex of ferric hydroxide with dextran
f. Side effects and toxicity (dose-related)1) Oral preparations may cause GIT irritation (eg. abdominal cramping
and diarrhea)2) Parenteral preparations can cause
a) Iron overload
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b) Anaphylactic shockc) Cardiovascular collapse
6. Vitamin B12 (Cyanocobalamin)a A cobalt-containing compound necessary for DNA synthesis.b. It can be derived from microbial synthesis and ingestion of animal
products in the food chain.c. Vitamin B12 is converted to biologically active forms
1) Methylcobalamin: a cofactor in the conversion of hemocysteine to methionine.
2) Adenosylcobalamin: participates in the conversion of methylmalonyl coenzyme A to succinyl coenzyme A.
d. Absorption depends on a thermolabile glycoprotein, known as the intrinsic cofactor which binds to and protects B12 from digestion.
1) Factors that cause loss of intrinsic-factor-secreting gastric cells limit B12 absorption.
3) Concurrent administration of drugs (eg. Vitamin C may limit absorption)
e. B12 is stored in the liver, slowly released as needed: released into the bile but undergoes hepatic recycling.
f. Therapeutic use1)Megaloblastic or pernicious anemia (delayed nuclear maturation due to inadequate DNA synthesis; thymidine)2) Demyelinating neuropathies (inability to synthesize myelin)
g. Deficiency is rare and is usually due to 1) Gastrectomy gastric mucosal lavage2) Malabsorption3) Parasitic infestation (eg. fish tapeworm)
7. Folic acid a. This is pteroyglutamic acid (combination of pteridine, PABA, and glutamic
acid) needed for the synthesis of DNA thymine.b. Essential in tissues where rapid DNA synthesis occurs and the turnover is also
rapid (eg. hematopoeitic tissues, developing embryo).c. The form 5-methyltetrahyhdrofolic acid serves as a methyl donor in the
conversion of hemocysteine to methionine by Vitamin B12.d. It is well absorbed in the proximal intestine and conserved by enterohepatic
recycling.8. Anabolic steroids
a. Mechanism of Action1) Increases erythropoietin production (ERP)2) Promote differentiation of stem cells into ERP-stimulating-factor-
b. Effectiveness in treating anemia depends on1) The cause of anemia
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2) Number of functional RBC3) Adequate ERP levels4) Responsiveness of bone marrow
c. Cells generally classified into two categories1) Alkylated
a) Oxymetholoneb) Stanozolol
2) Nonalkylateda) Nandrolone decanoate
E. AGENTS AFFECTING BLOOD COAGULATION
1) Hemostasis – refers to the prevention of blood loss or spontaneous arrest of bleeding from damaged blood cells.
2) This involves vascular spasms, platelets, plug formation, and coagulation or blood clotting.
3) Blood loss at the site of breakage is permanently prevented when fibrous tissue grows into the clot and seals the hole in the blood vessel.
4) The clotting mechanism is responsible of the formation of fibrin which involves a cascade of reactions which are either intrinsic or extrinsic in origin.
a. Intrinsic system is initiated by the activation of factor x 11 (Hageman factor) which occurs in vivo when the blood is exposed to collagen fibers of the damaged endothelium of blood vessels.
b.Extrinsic system is triggered by factor 111 tissue thromboplastin/released from damaged tissues.c. Both lead to the formation of prothrombin activator that converts prothrombin to thrombin which in turn converts fibrinogen to fibrin.
5) Hemostatics are agents that arrest the flow of blood.a. Local or topical hemostatics
1) Physiological a) Thromboplastin USPb) Thrombin USPc) Human fibrinogen USP
3) Astringent metalsa) Ferric chloride b) Alumc) Tannic acid
4) Adrenergics (used as sprays)a) Epinephrineb) Norepinephrine
b. Systemic hemostatics1) Whole blood or blood components
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2) Vitamin K3) Protamine sulfate
6. Vitamin K a. MOA: activates carboxylase which mediate synthesis of gamma-
carboxyglutamic acid used in the synthesis of factor II, VII, IX, X in the liver.b. Clinical Use
1) Antidote to coumarin group of anticoagulants (eg. warfarin)2) Used in birds under sulfonamide therapy to counteract Vitamin K
deficiency.3) Excessive hemorrhage due to liver failure.
c. Not effective against heparin-induced hemorrhaged. Preparations
1) Menadione (Vitamin K3)a) Slowly absorbedb) Useful for chronic therapy
2) Phytomenadione (Vitamin K1) – from plantsa) Very toxic, can cause dyspnea, backpains, deathb) Slowly administered IV to avoid hypotension (not faster than 5-
10 mg/min7) Protamine sulfate
a. Low MW protein in sperm of certain fish b. Forms stables salt with heparin (acidic)c. Antagonize only heparin-induced hemorrhagesd. Excess can cause coagulation due to interference with the reaction of thrombin
and fibrinogen8. Anticoagulants are agents that prevent blood coagulation.9. Anticoagulants for blood samples
a. For laboratory examination1) Sodium oxalate (20%)2) Sodium citrate (25%)3) Disodium EDTA4) Heparin sodium
b. For blood transfusion 1) Sodium citrate solution 2) Acid citrate dextrose solution
c. MOA: chelate calcium ions10. Systemic anticoagulants
a. Heparin sodium (parenteral anticoagulant)1) MOA: combines with antithrombin III (an alpha globulin) and increases
its effectivity in removing thrombina) Requires the presence of antithrombin III to mediate its
anticoagulant effectb) Antithrombin III combines with thrombin and blocks its effect
on fibrinogenc) It then inactivates the bound thrombin (on fibrin threads) during
the next 12-20 minutes
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d) The heparin-antithrombin III-thrombin complex is completely undissociable
2) Also inhibits active forms of factors IX, X, XI.3) Can inhibit both the generation of thrombin and the formed thrombin4) Rapidly metabolized in the liver by heparinase 5) Endogenous heparin is present in most cells along with histamine and
serotoninb. Vitamin K antagonists/coumarin derivative (oral anticoagulants)
1) Toxicological effect is of primary importance in veterinary medicine.2) Clinical Use
a) Prophylaxis of venous thrombosis and laminitis in horses.b) Oral rodenticidec) Pulmonary thromboembolism in dogs
3) Agents include warfarin and bishydroxycoumarin.4) Absorbed in the gut and stored in the liver.5) Inhibit hepatic utilization of Vitamin K.
c. Aspirin 1) An antithrombotic (agent which prevents or reduce formation of platelet
thrombi in arterial system)2) MOA: inhibit cyclooxygenase enzyme responsible for prostaglandin
synthesis from arachidonic acid that has been released into cell and platelets.
a) Inhibit formation of prostaglandins and thromboxane (potent platelet aggregator and vasoconstrictor)
b) Reduce ADP (adenosine diphosphate) release by platelets impairing their aggregation and formation of platelet plugs.
d. Fibrinolytics (thrombolytics)1) MOA: increase activity of plasmin/fibrinolysin in dissolving clots2) Agents commonly used:
a) Streptokinase and streptodornaseb) These are synthesized by streptococci
3) Used for chronic wounds that are unresponsive to other drugs.4. Available as powder for oral and systemic administration.
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DRUGS AFFECTING RENAL FUNCTION
DIURETIC AGENTS
1. Diuresis refers to increased excretion of urine.
2. Diuretic is a substance that increases the rate of urine output or the volume of urine.
a. Act by suppressing the total amount of fluid absorbed from the renal tubules
b. Reduce the amount of fluid in the body
c. May promote loss of sodium into the urine (natriuresis)
3. The functional unit of the kidney is the nephron.
a. Glomerulus
b. Bowman's capsule
c. Proximal convoluted tubules
d. Loop of Henle
e. Distal convoluted tubule
f. Collecting ducts
4. Diuretic mechanisms and site of action
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a. Glomerular filtration (glomerulus)
1) Blood from afferent arterioles enter the glomerular capillaries and
filtered in the Bowman's capsule
2) Glomerular filtrate goes to the tubule of the nephron
b. Tubular reabsorption
1) Proximal tubular reabsorption of Na+ depends on sodium pump and
carbonic anhydrase isotonic absorption
2) Loop of Henle: only water is reabsorbed
3) Thick ascending limb of loop: impermeable to water, active co
transport of Na+, K+ and Cl-, passive Ca+++ and Mg+ absorption
(hyper osmotic)
4) Distal convoluted tubule: Na+ and Cl- reabsorption with little or no
water, Ca++ reabsorption dependent on parathyroid hormone
(PTH)
5) Collecting duct: permeability to water influenced by ADH
(vasopressin), aldosterone promotes uptake of Na+ into the
interstitium, K+ secreted back to lumen, Cl- follow Na+ or K+
c. Tubular secretion primarily occurs in the proximal convoluted tubules
5. Diuretic agents
a. Classification
1) Minor diuretics (osmotic diuretics) are agents that increase glomerular
filtration rate (GFR)
a) Mannitol
b) Xanthine derivatives
c) Cardiac glycosides
2) Major diuretics
a) Carbonic anhydrase inhibitors (weak)
b) Potassium-sparing diuretics (weak)
c) Thiazides (moderately potent)
d) Loop diuretics (potent diuretics)
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b. Minor diuretics
1) Mannitol (most useful osmotic diuretic)
a) Filtered at the glomerulus but not reabsorbed by the tubules
b) Remains in renal tubules and osmotically attracts large volume
of water which is flushed through the kidney
c) Clinical use
i. Edematous states (eg. Cerebral edema)
ii. Clinical evaluation of acute oliguria
iii. Hasten excretion of certain poisons
d) May cause cardiovascular overload if not excreted
2) Xanthine derivatives
a) Increase GFR
b) Inhibit Na+ reabsorption
c) Causes mild diuresis and potency varies with species of animal
d) Side effects include slight CNS and cardiac stimulation,
bronchodilation
c. Major diuretics
1) Carbonic anhydrase inhibitors
a) Carbonic anhydrase generates H+ that exchange with sodium
on the luminal side of tubule
b) MOA: inhibition of carbonic anhydrase in the proximal
tubule
i. Depresses bicarbonate ion absorption from the tubular
urine (HC03 - remains in the lumen)
ii. Inhibit Cl- reabsorption (remains in lumen)
iii. Causes decreased production of H+ for the H+/Na+
exchange so Na+ remains in the tubular urine (Na Cl or
MaHC03)
iv. These ions in tubular urine attract water
c) Clinical effects
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i. Large loss of Na+ and water
ii. Formation of alkaline urine
iii. Systemic acidosis
iv. Decreased rate of production of aqueous humor in the
eye (lowers in intraocular pressure)
v. CNS depression and antiepileptic action
d) Clinical use
i. Glaucoma
ii. Adjunct to a more powerful diuretic in treatment of
certain edematous states
iii. Udder edema
iv. Non-heart failure conditions where negative Na+
balance or sodium loss is unimportant
v. Alkalinization of urine
e) Inhibition of sodium bicarbonate absorption at proximal tubule
causes K+ wasting because bicarbonate acts as a non
reabsorption at anion and it can draw K+ into the tubular lumen.
f) Specific agents: acetazolamide, dichlorphenamide,
methazolamide, ethoxolamide
2) Potassium-sparing diuretics
a) Spironolactone
i. Competitive inhibitor or aldosterone in the collecting
duct
ii. Block Na+/K+ exchange, converting K+ and
promote Na+ excretion
iii. Useful when combined with more potent diuretics
iv. Onset of action is 2-3 days; tolerance rapidly develops
b) Triamterene
i. Acts on collecting duct
. ii. Inhibits Na+ reabsorption and limits K+ and H+
secretion in distal tubules
Dr. Elmer Q. Abillar Page 19 4/17/2023
iii. Action not associated with aldosterone
iv. More effective when combined with thiazides
c) Amiloride
i. Directly impairs the entry of Na+ and promote
conservation of K+
ii. Action not associated with aldosterone
iii. Rarely used alone, often used with thiazides or loop
diuretics
d) Significance of potassium ~ sparing effect: hypokalemia
increases contractility and automaticity of the heart
3) Thiazides
a) Highly protein bound and mainly excreted in the proximal renal
tubules
b) MOA: inhibits Na+ and Cl~ reabsorption at distal convoluted
tubules (little effect at proximal
c) Action may be related to ATPase activity
d) Tend to increase Ca++ absorption (slight) but promote loss of
K+ and Mg+
e) Uses: hypertension and CHF
f) Effects
i. Pronounced diuresis
ii. Hypokalemia
iii. Metabolic alkalosis
iv. Inhibition of insulin (hyperglycemia Glycosuria)
v. Hypercalcemia
g) Agents: chlorthiazide and hydrochlorthiazide
4) Loop diuretics
a) Most potent of the listed diuretics with sustained effects
b) Actively excreted in the proximal tubule
c) MOA: inhibit sodium-potassium-chloride co transporter
Dr. Elmer Q. Abillar Page 20 4/17/2023
i. Inhibit reabsorption of these ions in the thick ascending
loop of Henle (lead to Na+, K+, Cl- loss into tubular urine
ii. Increase excretion of K+, Mg++ and Ca++ ions
d) Diuretic effect within 30 min. after oral administration/
10-15 min. after IM or IV
e) Specific agents
i . Fu rose nude
ii. Bumetanide
iii. Ethacrynic acid
iv. Muzolimine
f) Clinical use
i.. Edematous conditions
ii. Hypercalcemia
iii. Anion or cation overdose
iv. Acute renal failure
g) Toxicity
i. Hypokalemic metabolic acidosis
ii. Magnesium loss
iii. Ototoxicity (dose-related, not always reversible)
FLUID THERAPY
OBJECTIVES
1. To restore the volume and composition of body fluids to normal.
2. To correct dehydration, hypokalemia, and metabolic acidosis.
3. For specific correction of abnormalities in acid-base balance.
4. To replace essential electrolytes and nutrients.
5. To serve as a vehicle for the infusions of certain intravenous infusions.
PHYSIOLOGY OF THE FLUID COMPARTMENTS OF THE BODY
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1. Water composes 55 to 80 percent (60% on the average) of the weight of an
adult animal.
2. Neonates have higher content (as much as 80 total body water (TBW) to
90%)
3. Obese animal has less body water than a thin animal (fat associates with
little water).
4. Body water is distributed into two major compartment
a. The intracellular fluid (ICF) compartment - composed of approximately
2/3 of TBW
b. The extracellular fluid (ECF) compartments:- composed of
approximately 1/3 of TBW
5. The ICF is the fluid contained in cells and constitute about 40 percent, of
body weight.
6. The ECF is about 20 to 25 percent of body weight and is divided into
plasma (5 to 8%) and interstitial fluid (15%)
a- Plasma is contained in blood vessels and is separated from the
interstitial fluid by the vascular endothelium.
b. Interstitial fluid occupies the interstitial space outside the blood vessels
and bathes the cell membranes.
c. Interstitial fluid includes:
1) lymph
2) volume
3) intestinal fluid volume
4) transcellular fluid
a) found in the GIT
b) aqueous humor
c) CSF
d) synovial fluid
e) pleural and peritoneal fluids
f) bile
Dr. Elmer Q. Abillar Page 22 4/17/2023
7. Changes in the osmolality of ECF can change the size of the ICF:
a. When ECF osmolality is high, water moves from ICF to ECF and the
cells shrink in size
b. When ECF osmolality is low, water is absorbed by cells and cells swell
or enlarge
8. Sodium (Na+) and chloride (Cl-) are the major electrolytes in the ECF and
contribute much to the osmolality of this compartment.
9. Potassium (K+) and phosphates ar.e the principal electrolytes in the ICF.
10. Thirst and renal control of sodium ions (major cation in ECF) and water
excretion play a minor role in maintaining external fluid balance.
C. REQUIREMENT TO DETERMINE - DEGREE FLUID IMBALANCE PRIOR TO
TREATMENT
1. History - obtain information on food and water intake, GI losses (through
vomiting or diarrhea), urine output, recent exercise, exposure to heat,
trauma, hemorrhage,, excessive panting, fever, and use of diuretics
2. Physical, examination - determine hydration -status of patient
3. Laboratory tests - these are vital in establishing the nature and extent of
fluid imbalances and in monitoring treatment (eg. elevations in PCV/ TPP,
urine specific gravity)
D. CAUSES OF DEHYDRATION
1. Decreased water intake due to
a. Lack of food intake
b. Depression of appetite and thirst centers in systemically ill animals
c. Accidental or deliberate deprivation of adequate water and food
2. Increased losa
a . Urinary (polyur i a)
b, Gastrcintestinal (vomiting, diarrhea)
c. Respiratory (panting, fever)
d. Skin (burns/ large wounds)
Dr. Elmer Q. Abillar Page 23 4/17/2023
e. Excessive salivation
f. Peritoneal dialysis
E. TYPES OF DEHYDRATION (based on Na+ ion concentration)
1. Isotonic dehydration
a. Most common type of dehydration
b. Serum Na+ concentration is normal at the time of dehydration (145
to 157 mEq/L)
c. Isotonic loss (loss of water and electrolytes in proportion to
those found in normal serum
2. Hypertonic dehydration
a. The next most common type
b. There is an elevation of serum Na+ concentration (158)
c. Hypotonic loss (predominantly water loss or water lost in excess of
solute found in normal serum)
3. Hypotonic dehydration
a. The least common type
b. Characterized by low serum Na+ concentration (143 mEq/L or less)
at the time of dehydration
c. Theoretical mechanism: Hypertonic loss of solute in excess of
concentration in normal serum)
d. Most probable mechanism: Loss of isotonic fluid with subsequent
intake of hypotonic fluids that diluted Na+ concentration to below
normal
F. DETECTION OF DEHYDRATION
1. History - information obtained leads the clinician to suspect dehydration
2. Physical examination - provides guidelines for detecting dehydration Normal
skin pliability or turgor depends on hydration of tissues in the area tested:
a. Normal skin returns immediately to its initial position.
b. Dehydrated skin shows varying rates of slow return to its original
position.
Dr. Elmer Q. Abillar Page 24 4/17/2023
Degree of Signs
Dehydration
< 5% not detectable; history may suggest dehydration (eg.
vomiting/ diarrhea)
5% subtle loss of skin elasticity, dry oral mucuous membranes
6 - 8% definite delay in return of skin to normal position, eyes may
be sunken in orbits, slightly prolonged CRT (capilla refill
3) Interfere with cytochrome C oxidase and peroxidase (resulting in increased
intracellular peroxide and cell death)
c. Effects:
1) Loss of membrane integrity
2) Increased permeability
3) Cell degeneration
4) Cell death
d. Spectrum of activity
1) Wide: filamentous fungi; dermatophytes, yeasts, and dimorphic fungi
2) Delayed onset of action (5-10 days)
3) Often prescribed with amphotericin B in treating systemic infections
e. Pharmacokinetics
1) Well absorbed orally and widely
distributed in tissues 2) Does not readily cross the CSF
3) Biotransformed in the liver; excreted in bile and urine
f. Adverse reactions
1) Dogs: inappetence, pruritus, alopecia, reversible lightening of hair
2) Cats: anorexia, depression, diarrhea,
fever, cholangiohepatitis
g. Contraindicated in pregnant animals
(embryotoxic teratogenic)
Dr. Elmer Q. Abillar Page 141 4/17/2023
ANTHELMINTIC AGENTS
A. ANTINEMATODALS
1. Arsenicals
a. MOA: Trivalent arsenic salt binds to the sulphydryl (-SH) group of
glycolytic enzymes
1) Alters tertiary structure of proteins and active sites of enzymes in
host and parasite
2) Inhibits glycolysis leading to death of the parasite
b. Thiacetarsemide
1) Also known as arsenimide sodium, an organic arsenical
2) Available as 1% buffered injectable solution (CaparsolateR )
3) Use is limited to the renoval of adult Dirofilaria immitis
(adulticide)
4) Thorough health evaluation of patient is necessary prior to
treatment
5) Highly hepatotoxic and may cause swelling and sloughing
of the skin when injected extravascularly.
6) Activity of treated dogs must be restricted to reduce
danger of massive pulmonary emboli resulting from drying
adult heartworms
c. Melarsomine
1) A relatively new trivalent arsenical marketed as immiticideR
2) Efficacy of adult Dirofilaria immitis from 92-98%
3) Less arsenic content than thiacetarsaraide and apparently less toxic
patient
4) Well tolerated in dogs
2. Benzimidazoles
a. Characteristics
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1) Broadspectrum anthelmentics
2) MOA:
a) Bind to tubulin molecules and inhibit the formation of microtubules and
distrupt cell division
b) Inhibit fumarate reductase and block mitochondrial function depriving the
parasite of energy resulting death
3) Poorly soluble and are genrally given per orem
4) More effective in horses and ruminants due to their slow transit through the cecum
and rumen
5) Three members are teratogenic: albendazole, membendazole , and oxfendazole
b. Albendazole
1) The newest benzimidazole with potent broadspectrum anthelmentic
2) Used in the treatment of intestinal helmith infections, hydatid disease, and
cysticercosis of man ( Zentel )
3) Used in cattle and sheep (Valbazen ) to treat a wide variety of nematode parasites,
including inhibited larval forms, cestades and lung and liver trematodes
4) Wide margin of safety in cattle but must not be used in female dairy wattle of
breeding age and given to pregnant cows during the first 45 days of gestation and in
sheep during the first 10-17 days of pregnancy
5) Withdrawal period in cattle is about 27 days; in sheep, 10 days
c. Fenbendazole
1) Not embryotoxic and teratogenic
2) Formulated as Sageguard and Panacur suspension, premix pellets, deworming
block, and free-choice mineral supplement for oral administration
3) With activity against lung and GI nematodes and cestodes of cattle, sheep, swine,
horses, dogs, and cats
c. Mebendazole
1) Formulated as powder, paste, or suspension (Telmintic) for control of intestinal
helminth parasites of dogs and horses
2) Has wide margin of safety fo domestic animals but was found to be teratogenic and
embryotoxic in rats and mice
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e. Oxfendazole
1) Metabolized in ruminants to oxfendazole sulfone and fenbendazole
2) Approvced for use in cattle (Synanthic) Syntex
Rumen Injector) and in horses (Benzelmin paste, suspension, or powder)
f. Oxibendazole
1) Active vs. benzimidazole-resistant small strongyles in horses (Anthelcide ECy
paste or suspension)
2) Not effective vs. stomach bots in horses
3) Available in combination with diethylcarbamazine for dogs
ANTIPROTOZOAN AGENTS
A. Introduction
1. Considerationsa. Many protozoan parasites require arthropod intermediate hosts.b. They have closer biochemical make-up to the mammalian cells than are
pathogenic bacteria and fungi.
B.Anticoccidials
1. Amprolium – 1st generation schizontsa. Used as anticoccidial, especially against 1st generation schizonts b. MOA: Antagonism the physiological role of thiamine as a coenzyme.c. Effective in the early stages of infectiond. Fed in poultry rations or drinking water, to prevent or treat cocidiosis e. Given as drench, mixed in drinking water, ot top dressed on the feed for
treatment and prevention in cattl, goat, and sheep.2. Arprinocid
a. A purine analogueb. MOA: interfere with nucleic acid synthesis, especially the interconversion
of purines, thereby blocking nucleic acid synthesis.
1) MOA: Unknown2) Anticoccidial which has inhibitory effect on second generation
schizonts.3) Suitable for broilers and given for the first 12 weeks of the chicken
life. 4) Not suitable for layers or breeding stock because of its effect on egg
color and hatchability5) Interrupts egg-laying period; reduces hatchability; mottled egg yolk
b. Nitrophenide – E. tenella and E. necatrix (2nd generation schizonts)1) Active vs. Eimeria tenella,, E. necatrix, E. acervulina, and E. maxima2) Given at 0.025% in feed 3) Inhibits 2nd generation schizonts and reduces hatchability
c. Trithiadol - E. tenella, necatrix, acervulina nad maxima1) Active vs E. tenella, E. necatrix, E. acervulina, and E. maxima2) Given at 0.06% to 0.09% in feed3) Reduces hatchability; do not use in breeders
4. Clopidol – coccidiosis (broilers)a. MOA: unknownb. Used for prevention of coccidiosis in broilers and replacement birdsc. Should not be given to birds producing eggs for human consumption.
5. Decoquinate a. A 4-hydroxyquinolone b. MOA: affects energy metabolism by interfering with cellular respirationc. Approved coccidiostatic drug for the control and prevention of Emeria
infections in chicken, cattle, and goats.d. Indicated fro prevention of coccidiosis in cattle and goats e. Should not be fed to breeding animals or lactating dairy cows or goats.f. Bentonite should not be used indecoquinate feedsg. Co-members: Bequinolate, Methyl Benzoquate
6. 2, 4 – Diaminopyrimidinesa. MOA: Inhibit dihydrofolate reductaseb. Combinations with sulfonamides are synergesticc. Both block synthesis of tetrahydrofolic acidd. Diaveridine, Ormethoprim, Pyremethamine
7. Halofuginone a. Used for prophylaxis of coccidiosis.b. Not used in poultry > 8 weeks old c. Administered in feed.d. MOA: Unknown
Dr. Elmer Q. Abillar Page 145 4/17/2023
8. Ionophore antibiotics a. Characteristics.
1) MOA: Forms ionophores with sodium and potassium in the host and in the parasite. It renders the parasite membrane permeable to K+ and Na+ ions. Mitochondrial function is inhibited.
2) Acts on first sexual cycle by preventing development of 1st generation schizonts.
3) Continued use retards development of 1st generation schizonts.4) Suitable for addition to feeds for broilers but not for laying birds.5) Toxic to horses and other equines.6) Not to be used 7 days before and after tiamulin administration (can be severe
growth growth depression)b. Lasalocid
1) Closely related to monensin 2) The least toxic of the ionophores 3) Approved for use in cattle, sheep, and poultry fro control of coccidia and
improve feed efficiency.4) Should not be fed to claves processed for veal
c. Monensin1) Antibiotic product of Streptomyces cinnamonensis2) Used in poultry and cattle (as feed additive) for its coccidiostatic and growth
promoting activities.3) Not approved for use in sheep but may be tolerable at low doses.
d. Others: Salinomycin, Narasin, Maduramicin
9. Nitrobezamides a. Inhibit development of second generation schizonts but do not inhibit
development of immunity.b. MOA: Unknown c. Dinitolmide (Zoalene), Nitromide.
10. Robenidine (Robenzilidine) 1st and 2nd generation schizontsa. For prophylaxis and treatment of coccidiosis in chickens b. Both coccidiostatic and cocciocidalc. MOA: Inhibits the respiratory chain phosphorylation and ATPase activity in rat
liver mitochondria and may have similar action in coccidian.d. Affects the late first generation and second stage schizonts.
11. Sulfonamides and Substituted PABAa. MOA: Interfere with cofactor synthesis. As an analogue of the growth factor
PABA, these block the synthesis of tetrahydrofolate synthetase b. Sulfadimethoxine
1) Useful in small animals2) Therapy is continued until the animal is asymptomatic for at least 48 hours
c. Sulfamethazine
Dr. Elmer Q. Abillar Page 146 4/17/2023
1) Its sodium salt may be administered in water or feed, or IV to cattle, sheep, and goats for control of coccidiosis
2) During outbreaks, it may be given in feed.3) Animals should be provided with plenty of drinking water.4) Withdrawal recommendations should be followed for food animals.
d. Sulfaquinoxaline 1) Approved for use in poultry, cattle, and sheep2) Administered in water for 3 – 5 days.3) Do not give to lactating dairy cattle.
e. Others: Sulfanilamide, Sulfamethoxine, Ethopabate (substituted PABA)
C. MISCELLANEOUS ANTIPROTOZOALS
1. Metronidazole – Trichomonas, Giardia, Entamoebaa. A 5 – nitroimidazoleb. MOA: Inhibits DNA synthesis by disturbing the helical structure causing
DNA strand breakage and inhibition of DNA repair enzyme (DNAassel)c. Used in man (Flagyl) for treatment of Trichomonas vaginalis, Giardia
lamblia, and Entamoeba hystoliticad. Indicated for the treatment of giardiasis and trichomoniasis in dogs.e. Causes pulmonary tumors in mice and increases incidence of neoplasms.
2. Dimetridazole – (blackheads) histomonas, swine dysentery and trichomoniasis in pigeons.
a. Also a 5-nitromidazoleb. Used to prevent and treat infections of Histomonas meleaqridis (blackhead) in
poultry and game birdsc. Also used for treatment and prophylaxis of swine dysentery and trichomonas in
pigeonsd. Should not be used in egg-laying birds.
3. Furaltadone – Histomoniasis (Chicken & Turkey)a. A nitrofuran (broadspectrum amtibiotic)b. Used to prevent histomoniasis in chickens and turkeysc. Administered in drinking water (10-40 g/100 L) for 7 days
4. Quinacrine – Giardia, Taenia, Diphyllobothriuma. MOA: Incorporated into DNA resulting to inhibition of RNA and DNA
synthesisb. Originally used as antimalarial drug but has been replaced by other
antimalarialsc. Indicated in dogs for the control of Giardia, Taenia, and Diphyllobothrium
infections
ANTINEOPLASTIC AGENTS
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A. CANCER THERAPHY
1. Treatment of Cancer involvesa. Surgical excisionb. Radiationc. Chemotheraphy
2. The apeutic goals are aimed to allow the patient toa. Live prolonged disease-free intervalb. Have an improved quality of lifec. Have an increased survival time
3. Surgical excision and/or radiation is usually used for localized, solid tumors (local and regional neoplasia)
4. Chemotheraphy involves the use of one or more combinations of antineoplastic agents to treat nonlocalized malignancies, advanced metastatic tumors, and for residual malignancies after surgery or radiation.
5. ANTINEOPLASTIC AGENTS are drugs used for the treatment of malignant diseases
6. Requirements prior to therapya. Cytologic or histologic diagnosis of the tumor typeb. Knowledge of drugs the tumor is sensitive toc. Measurable parameters by which to gauge the response
7. Neoplastic disease of veterinary importance that are responsive to chemotherapy includea. Canine lyphosarcomab. Felome lymphosarcomac. Mastocytomad. Transmissable veneral tumore. Multiple myeloma
B. GENERAL PRINCIPLES
1. Normal and neoplastic cells follow the same cell division cycle2. Tumor cells, even if they are immune from the attack by host defenses, still differ
from the normal cells by virtue of their rapid rate of division and growth3. Tumor cells may also reach the terminal stage of differentiation and may be
temporarily quiescent or no longer divide4. Actions of cytotoxic neoplastic agents are directed at the different stages of the
cellular life cycle5. Some chemotherapeutic drugs exert their greatest toxicity on rapidly dividing
cells while some are effective during certain phases of the cell cycle
Dr. Elmer Q. Abillar Page 148 4/17/2023
6. Use of drug combinations in the therapeutic protocols increases the chance of killing resistant tumor cells and decreases the chance of temporarily dormant or become fully differentiated
C. CELL AND TUMOR KINETICS
1. Normal and neoplastic cells follow the same cell division cycle
2. Cell division cyclesa. M (mitosis) phase
(1) Period of mitosis where rapid cell division takes place(2) Lasts for about 30-90 minutes
b. GO (gap 0) phase(1) The true resting phase(2) Cells are temporarily dormant or become fully differentiated(3) Cells may leave the dividing phase and enter the resting phase which can
last for years(4) As tumors increase in mass, more cells enter this phase
c. G1 (gap 1) phase(1) The period of increased biosynthetic activity (RNA and protein synthesis)
before replication takes place(2) Variable duration (10-72) hours
d. S (synthesis) phase(1) A period during which DNA synthesis (replication of DNA and
chromosomes) takes place in preparation for the next mitosis(2) Lasts for about 6-8 hour
e. G2 (gap 2)phase(1) Postreplication period(2) More RNA and protein synthesis takes place before the next M phase(3) Approximately 2 hours in duration
3. The number of tumor cells in the G0 phase increases as the mass of tumor cells increases
4. Malignant tumors are therefore more susceptible to antineoplastic agents when the masses are still small because majority of the cells are still dividing
D. MECHANISMS OF RESISTANCE TO ANTINEOPLASTIC AGENTS
1. Pharmacokinetica. The target cell is not able to maintain an effective drug concentration for a
period of time sufficient for it to be destroyed by the agentb. This may be due to alteration in the pharmacokinetic of the drug
Dr. Elmer Q. Abillar Page 149 4/17/2023
c. Majority of tumor cells are in the G0 phase because of the marginal blood supply and poor nutrient supply
2. Cytokinetica. Based on the growth rate and fraction of tumor cellsb. Resistant tumors usually have lower growth rates and lower growth fraction
than curable tumors
3. Biochemicala. Defective transport of antineoplastic drug into tumor cellb. Impaired drug activation within the cellc. Increased intracellular nucleotide poolsd. Altered patterns of DNA repaire. Gene amplification and increased RNA coding for certain necessary enzymes
that can biotransform and inacrivate the drugf. Altered receptor structure or decreased concentration of receptorsg. Changes in the rate of cellular proliferation due to unknown factors
E. CONSIDERATIONS 1. Most chemotherapeutic drugs are dosed based on body surface area in square
meters rather than the body mass2. This correlates better than bodyweight does to the different sized patients3. This is more physiologically accurate and is done to minimize the toxic effects of
these agents (k) x (bodyweight in grams) 2/3
Body surface area (m²) = -------------------------------------------------------------------
104
where k = 10.1 (dogs); 10.0 (cats)
4. Effects of anticancer drugs on neoplastic cells follow the first order kinetics ( a constant proportion is killed)
5. Antineoplastic agents given at higher dose rates for short intermittent periods usually destroy more tumor cells than prolonged low dosage rates
6. Possible clinical responses to cancer chemotherapya. Palliation (remission of secondary clinical signs)b. Regressionc. Partial remission (decrease in size or amount of neoplastic tissue)d. Complete remission (disappearance of clinically detectable tumors)e. Cellular cure (complete elimination of all neoplastic cells)
7. Sources of failurea. Excessive chemotherapy-related side effecta
Dr. Elmer Q. Abillar Page 150 4/17/2023
b. Progressive tumor growth due to(1) Intrinsic resistance
(a) Tumors are found in sites which are protected(b) Tumor cell dormancy/insensitivity to specific drug actions(c) Insufficient drug delivery
(2) Acquired resistance(a) Development of alternate metabolic pathways(b) Change in transport mechanisms(c) Initiate cellular repair(d) Inhibit drug activation(e)
F. TOXICITY PATTERNS / COMPLICATIONS
1. Hematologic toxicitya. Bone marrow suppression is the most common toxicity associated with
chemotherapeutic agentsb. Characterized by
(1) Leukocytopenia (increased incidence of infection)(2) Thrombocytopenia (uncontrolled bleeding, anemia)
c. Normal life span of cells(1) Canine neutrophils = ²-8 hours(2) Canine platelets = ²-6 days(3) Canine RBC = 120 days
2. Gastrointestinal toxicitya. Less common than myelosuppressionb. Major types of G1 complications
(1) Nausea/vomiting(2) Gastroenterocolitis
3. Hypersensitivitya. Clinical signs similar to those of other hypersensitivity reactionsb. Signs begin shortly after administration and include head shaking (due to ear
pruritus), generalized urticaria and erythema, restlessness, occasional vomiting, and (rarely) collapse by hypotension
c. May necessitate administration of H1 antihistamines 30 minutes prior to drug administration
4. Cardiotoxicitya. Often associated with use of doxorubicin in dogsb. Exhibited as arrhythmiasc. Relatively rare in cats
c. Alopeciad. Tissue necrosis (when injected extravascularly)
6. Urinary Toxicitya. Nephrotoxicityb. Sterile hemorrhagic cystitis: pollakiuria, hematuria, dysuriac. Discontinue drug and administer furosemide (diuretic) and sulfadiazine-
7. Neurotoxicitya. Uncommon in dogsb. Frequent and fatal in catsc. Often seen with use of 5-flourouracil
G. CLASSIFICATION OF ANTINEOPLASTIC AGENTS
1. Different types of anticancer drugs act by different mechanismsa. Cell cycle-phase nonspecific drugs: act on several phases of the cycleb. Cell cycle-phase specific drugs: selectively kill tumor cells during a given
phase of the cell cyclec. Cell cycle-nonspecific drugs: kill resting and dividing cells and are extremely
myelosuppressive that they rarely used in Vet. Med.
2. Anticancer drugs are commonly classified in the following categoriesa. Alkylating agents d. Plant alkaloidsb. Antimetabolites e. Hormonesc. Antitumor antibiotics f. Miscellaneous
3. ALKYLATING AGENTSa. Examples
(1) CYCLOPHOSPHAMIDE – most frequent used(2) CHLORAMBUCIL(3) BUSULFAN(4) MELPHALAN(5) TRIETHYLENETHIOPHOSPHORAMIDE(6) MECHLORETHAMINE HCI(7) CISPLATIN: platinum-containing compound fatal to cats
b. Action: Crosslink DNA, preventing its replicationc. Cell cycle-nonspecific
4. ANTIMETABOLITES: Structural analogues of normal metabolites of nucleic acidsa. Purine analogues
(1) 6-MERCAPTOPURINE (AZATHIOPRINE) and 6-THIOGUANINE(2) Actions: Feedback enzyme inhibitor of DNA synthesis(3) S-phase specific
Dr. Elmer Q. Abillar Page 152 4/17/2023
b. Pyramidine analogues(1) 5-FLUOROURACIL inhibits enzyme thymidylate synthetase (results in
thymidine deficiency leading to inhibition of DNA synthesis)(2) CYTOSINE ARABINOSIDE (CYTARABINE): appears to inhibit DNA
polymearse activityc. METHOTREXATE: Conpetitive enzyme inhibitor of folic acid reductase
5. VINCA (PLANT) ALKALOIDS (“Spindle Poisons”)a. VINCRISTINE – most frequent used
- binds the mitotic spindle, arresting mitotic division in metaphase
b. VINBLASTINE – affects cell energy production and disrupt mitotic spindlec. Both are M phase specific
b. Action: Crosslink DNA and cause free-radical damages; inhibit RNA and protein synthesis; bind to membranes and alter ion transport
c. Cell cycle nonspecific
7. HORMONAL AGENTS (often used for hemolymphatic malignancies or endocrine-related tumors)a. PREDNISOLONE’ and PREDNISOLONE – most common hormones used
to treat tumors and are primarily used to treat lymphomas and mast cell tumors(1) Action: Penetrates to nucleus and affects RNA production(2) G1–phase specific
b. DACARBAZINE(1) Action: Exhibits alkylating and antimetabolite activity (exact MOA
unknown)(2) Cell cycle nonspecific
c. HYDROXYUREA(1) Action: Inhibits DNA synthesis without interfering with mRNA and
protein synthesis(2) S-phase specific
ANTIVIRAL AGENTS
1. ANTIVIRAL CHEMOTHERAPYa. Still in an early stage of development but has excellent long-term prospects
Dr. Elmer Q. Abillar Page 153 4/17/2023
b. Most of antiviral drugs used in humans and experimental drugs in human medicine are still further investigated for their potential veterinary use
2. Mechanisms of action of various antiviral agentsa. Inhibition of penetration of cellsb. Inhibition of intracellular viral protein synthesisc. Inhibition of virus assembly or released. Inhibition of assembly of viral particles
3. Inhibition of penetration to cellsa. GAMMA GLOBULINS
(1) Passive immunization in IgG (IM, IV, SC) can prevent entry of viruses into cells
(2) Protection may last for several weeks but not complete(3) May be used to control distemper, rabies, Aujesky’s disease, TGE in swine(4) Offspring that have taken colostrums from vaccinated dams are usually
protected from enteric viral infectionsb. AMANTADINE
(1) A synthetic tricyclic amine with a symmetric structure(2) Activity limited to influenza A viruses in humans and animals(3) Most effective as prophylactic; moderately effective early in the course of
disease(4) Experiments as prophylactic in infected chickens and turkeys proved
successful
4. Inhibition of intracellular viral protein synthesisa. Inhibition of early protein synthesis: Bisbenzimidazoles
(1) Formation of RNA po;ymerase is inhibited(2) Ready development of resistance
b. Inhibition of nucleic acid synthesis(1) IDOXURIDINE – vs. herpesvirus
a. Converted into an iodoanalogue of thymidilateb. Inhibit virus-specified DNA polymerase c. Defective viral proteins will e producedd. Topical use onlye. Used for treatment of feline herpesvirus keratoconjuntivitis
and herpetic keratitis in other species(2) VIDARABINE
a. An analogue of adenine deoxyribosideb. Acts by inhibiting viral DNA polymerasec. Effective vs. viruses with DNA polymerase activityd. Low olubility and rapid systemic deamination makes it unsuitable for
systemic use in animals(3) RIBAVIRIN
a. Resembles guanosine and interferes with formation of guanosine phosphate in DNA and RNA synthesis
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b. Has broad antiviral activity vs. many DNA and RNA virusesc. Clinical use does not induce viral resistanced. Low toxicity upon systemic administratione. Prolonged treatment in cats may produce profound
thrombocytopenia(4) ACYCLOVIR
a. An acyclic nucleoside analogue of 2’-deocyguanosineb. One of the first new antivirals licensed for use in humansc. Highly effective vs. herpesvirus by inhibiting herpes-specified
DNA polymerased. Potential in veterinary medicine needs further studies
(5) GANCICLOVIRa. Active vs. all herpesvirusesb. More active than acyclovir vs. cytomegalovirusc. Outstanding activity vs. equine herpesvirus-1
(6) TRIFLURIDINEa. A halogenated thymidine analogueb. Drug of choice for herpetic keratitis because of superior
ability to penetrate the cornea(7) AZIDOTHYMIDINE
a. A dideocynucleoside thymidine analogueb. Inhibits viral reverse transcriptase in retroviral replicationc. HIV reverse transcriptase 100x more susceptible than mammalian DNA
polymerased. Prolongs survival in advanced cases of HIV-AIDS by 12-30 months and
delays progression of asymptomatic infectione. Tested in FeLV and FIV infections
(8) PHOSPHONOFORMATE (FOSCARNET)a. A pynophosphate analogueb. Inhibits DNA polymerase of herpesviruses and RNA
polymerase of influenza virusesc. Being investigated for treatment of herpesvirus infections and
AIDS in humansc. Inhibition of late protein synthesis: METHISAZONE
(1) Inhibits transcription of proteins required for development of mature virus
(2) Effective prophylactically vs. human poxviruses (vaccinia, small pox)
(3) Possible use as prophylactic in infectious canine hepatitis and bovine respiratory disease
5. Inhibition of virus assunbly or release: 2-DEOXY-D-GLUCOSEa. Inhibits a wide range of enveloped DNA and RNA viruses (esp.
orthomyxo-,paramyco-, and herpesviruses)b. A glucose analogue
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c. Interferes with the synthesis of oligosaccharides that are part of viral specific surface glycoproteins
d. Results to decrease infectivity of viruses because of their inability to penetrate cells or to become uncoated
e. Topically applied on to genital herpes in womenf. Potential application as prophylaxis in CD, equine influenza, and parainfluenza
infections
6. Interferonsa. Families of glycoproteins with antiviral immuno-modulatory and antiproliferative
effectsb. Produced most animal speciesc. Indirect antiviral activity: alter host metabolism t impair synthesis and assembly
of viral componentsd. Immuno-modulating activity:
(1) Increased antibody production(2) Increased natural killer activity(3) Enhanced antigen expression on cell enhances recognition of
virally infected cellse. Types: alpha (leukocyte) and beta (fibroblast) are released in viral infections
while gamma (T-lymphocytes) are released in response to antigen or mitogen stinulation
f. Clinical application still under studyg. Studies have also been conducted to stimulate endogenous interferon production
but has not yet yielded satisfactory results
7. Inhibition of assembly of viral particles: REFAMPINa. Inhibits DNA-dependent RNA polymerase in bacteria and mammalian cellsb. Prevents assembly of enveloped mature particles in mammalian cells in
poxvirusesc. Effect is reversible upin removal of drug
(1) Claimed toa. Increase B and T lynnphocyte activityb. Increase matural killer cell activity
(2) No evidence of its value in veterinary medicinec. Bacterial adjuvants
(1) Both Bacillus Calmette-Guerin (BCG) and Corynebacterium parvum are nonspecific adjuvants that increase activation of macrophages through an effect on T lymphocytes
(2) Others require additional study
PESTICIDES
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A. PRINCIPLES OF THERAPY
1. Definitiona. Compounds that destroy insect parasitesb. Term usually applied to substances which are active against skin parasites or
those which spend part of their life cycle in the body of animals
2. Characteristics of an ideal pesticidea. Effective against all stages of the parasite’s life cycleb. Fast-acting and prolongedc. Low or no toxicity to hostd. Provide minimum residue in hoste. Does not accumulate in the environmentf. Minimal ecologic interferenceg. Inexpensive or economicalh. Convenient to administer or usei. Well tolerated by the animalj. Cosmetically appealing to the pet owner
3. Route of entrya. Stomach poisons - need to be ingested or eaten by the parasites and become
distributed within their bodiesb. Contract poisons – enter the body of the parasites via the skin as these crawl on
the surface to which pesticide has been appliedc. Fumigants – released into the atmospheres as gas or as fine suspension and enter
the respiratory system of the parasitesd. Systemic pesticides – absorbed through the animal’s skin, stomach, or
subcutaneous injection and become distributed throughout its body
4. Systems of parasiticidal applicationa. Prediluted spraysb. Emulsifiable concentratesc. Dips and washesd. Shampoose. Dustsf. Foggersg. Systemics
5. A successful treatment program requires knowledge of thea. Life cycle of the parasiteb. Habitat of the parasitec. Asymptomatic carrier stated. Contagiouness of the parasite to humans or other animalse. Recognized activity of the parasite
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B. FORMULATIONS AND ACTIVE INGREDIENT
1. Botanicalsa. Characteristics
(1) Derived from plant materials (flowers, leaves, stems, roots)(2) Have excellent toxic effects on a variety of crop and animal insect pests(3) Have very short persistence in the environment(4) Relatively have low toxicity to mammals
b. ROTENONE(1) MOA: Inhibit mitochondrial respiratory enzymes(2) Insoluble in water but soluble in m any organic solvents(3) First used by natives of South America to paralyze fish, causing them to
surface(4) Used in 1800s to control leaf-eating caterpillars(5) It is the insecticidal component of derris root, cube root, and several other
leguminous shrubs(6) May be applied to cats and dogs as an ointment, dip, or in liquid form, for the
control of a variety of arthropod parasites(7) Not for kittens less than four weeks old and suckling puppies(8) May induce vomiting once ingested by dogs and cats(9) Toxic to swine, fish, and snakes; carcinogenic in rats
c. PYRETHRINS(1) MOA: Disrupt Na+ and K+ transport in nerve membranes thereby disrupting
neurotransmission along the axon and at the synapse(2) Include six closely related insecticidal substances (pyrethrin I and II, cinerin I
and II, jasmolin I and II)(3) Obtained from the flower head of pyrethrum plant Chrysanthemum
cinerariaefolium(4) Rapidly biodegradable and are rapidly degradable in the presence of moisture,
air, and light(5) Usually combined with synergists to increase their insecticidal activity ten to
twenty times(6) Toxic to fish and arthropods(7) Should not be applied to kittens less than 4 weeks old or to suckling puppies
d. Pyrethroids(1) Characteristics
a. Synthethic pyrethrum-like substancesb. MOA: Initially stimulate then depress nerve cell function and eventually
cause rapid muscular paralysisc. More potent than plant pyrethrins, biodegradable, and are sufficiently
stable when exposed to air and lightd. Low mammalian toxicity but are toxic to fish
(2) First generation pyrethroids
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a. Represented by ALLETHRIN, a synthetic duplicate of cinerin Ib. Have similar properties with natural pyrethrinsc. Formulated in an aerosol spray with synergists to control flies, mosquitoes,
ticks, and fleas in animal quarters and also formulated into fles shampoo for removing fleas in dogs and cats
(3) Second generation pyrethroidsa. Potency 10-50x the natural pyrethrinsb. Not much more stable in sunlight than natural pyrethrinsc. Examples: RESMETHRIN, TETRAMETHRIN
(4) Third generation pyrethroidsa. Has increased potency and photostabilityb. Available in a variety of formulations for use on or around animals, and to
livestock buildings or animal quartersc .Examples: CYFLUTHRIN, CYPERMETHRIN,
LAMBDACYHALOTHRIN, ZETAMETHRIN
2. CARBAMATESa. Characteristics
(1) MOA: Blind to and inactivate AChE leading to accumulation of Ach at neural synapses
(2) Carbamate forms a carbamate-AChE complex thereby inactivating the enzyme but it is later cleaved away
(3) Similar to organophosphates in activity but are more reversible and have lower mammalian toxicity
(4) Antidote of choice is atropine(5) Not to be used with other AChE inhibiting chemicals
b. CARBARYL(1) Also known as SEVIN(2) Introduced in 1956 and was first commercially successful carbamate(3) Used alone or in combination with other products(4) Formulated as sprays or dusts for use on animals and animal quarters(5) Not recommended on puppies and kittens under 4 weeks of age
c. METHOMYL(1) Introduced in 1966 and more potent than carbaryl(2) Very toxic to mammals, fish, and honeybees(3) Has broadspectrum of activity vs. insects infesting vegetables and field crops(4) Used as fly bait together with a synthetic fly-attractant pheromone, (2)-9-
tricosene
d. PROPOXUR(1) Introduced in 1959(2) Has quick knockdown effect and residual effect of 4-6 weeks(3)Toxic to birds and honeybees but can be safely used and around domestic
animals (BAYGON®, SENDRAN®)
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(4) Commonly used in flea collars for dogs and catse. Others: MOBAN, ALDICARB, ZECTRAN
3. CHLORINATED HYDROCARBONSa. Characteristics
(1) Have high lipid solubility and are very persistent(2) As a contact poisons(3) Stimulate the CNS causing incoordination and neuromuscular
hyperexcitability(4) MOA: Believed to attach into the sodium gate causing inward flow of Na+
and prevent repolarization
b. DDT (DICHLORO DIPHENYLTRICHLOROETHANE)(1) First drug introduced in this group(2) Its spectacular success in 1939 resulted in widespread use and overuse(3) Primarily used vs. mosquitoes that carry malaria, body lice that carry typhus,
and fleas that are vectors for plague(4) Persisted in body fat, accumulated in the food chain thereby affecting wildlife
species, and has caused thinning of eggshell among raptors
c. LINDANE(1) A gamma isomer of hexachlorohexane (HCH)(2) Stimulates mammalian CNS resulting in hypertension, bradycardia, polypnea,
restlessness, body tremors, salivation, grinding of teeth, and convulsions
(3) High rate of biodegradability and high volatility(4 Available as aerosol spray for each ticks and screw worms on farm animals(5) Not approved for whole animal treatment, do not apply to humans, household
pets, lactating animals, and young animals < 3 months old
d. METHOXYCHLOR(1) A methoxy analogue of DDT(2) Has prolonged residual insecticidal activity(3) Little tendency to accumulate in animal fat(4) Available in combination with pyrethrin and synergists or with carbaryl(5) Can be sprayed or rubbed on animal or applied to premises or given as powder
or dust in dogs and cats(6) Not to pregnant animals, nursing pups and kittens, or young animals < 4
weeks old
4. ENDECTOCIDESa. Developed from macrocyclic lactones produced by various Streptomycesb. Invermectin and milbemycin are currently used in veterinary dermatologyc. MOA: Potentiate the release and effects of GABA which is peripheral
neurotransmitter in susceptible arachnids and insects
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d. Main action is paralysisi of the parasite but can also suppress egg production and molting in ticks
e. IVERMECTIN(1) Has good activity against nematodes, microfilariae, and mites(2) Not found to be effective against Demodex but has been advocated as
beneficial when used concurrently with topical amitrazf. MILBEMYCIN
(1) Similar to ivermectin in activity(2) Effective against amitraz-resistant generalized demodecosis
5. FORMAMIDINESa. Characteristics
(1) Acaricidal comppunds effective vs. cattle ticks and mange mites of swine and dogs
(2) MOA:a. Inhibit monoamine oxidaseb. Inhibit voltage sensitive sodium gates in the nerve membrane
(3) Found very effective vs. pests that have developed resistance to Ops and carbamates
b AMITRAZ(1) The only formamidine approved for use in animals(2) Well tolerated by dogs but many produce transient sedation, depression of
rectal temperature, and elevation of blood pressure
(3) Available as MITABAN® (19.9%) liquid and as diluted to a 0.025% solution in treating generalized demodicosis in dogs (3-6 treatments spaced 14 days apart)
(4) Available as TACKTIK EC® (12.5%) emulsifiable concentrate for use vs. ticks, mange mites, and lice on beef cattle, dairy cattle, and swine
(5) No slaughter withdrawal in beef cattle and no milk withdrawal in dairy cattle are required but swine must not be treated within three days of slaughter
(6) Must not be used in horses since fatal colon impaction may occur
(7) Mitaban concentrate is flammable, rubber gloves must be worn when preparing dilutions and applying these to dogs
(1) Break the life cycle by killing immature insects where they grow and develop(2) IGRs are juvenile hormone mimics that bind to juvenile hormone receptors in
the immature insect and prevent survival to the next stage of development
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(3) Cannot have biologic response on the host because mammals have no analogons systems that can be affected
(4) Effective in insect control programs when used properly(5) Use of these products also minimizes the use of toxic adulticides
b. CRYOMAZINC(1) An IGR whose use is limited to the filth flies (eg. Houseflies)(2) No effect on most of other beneficial insects(3) MOA: Block the formation of new cuticle in fly larvae so that the insect
cannot survive the molt from the first to the second instar stage(4) Formulated as a feed premix (LARVADEX 1% PREMIX®) and a liquid
concentrate (LARVADEX 2 SL®)(5) As feed premix, it passes through the bird and is deposited in the manure
where it controls developing filth flies(6) Surface sprays are for the control of fly larvae in breeding places like feed
spills, dead bird piles, and manure storage areas
c. DIFLUBENZURON(1) Is a contact and systemic insecticide and not a true IGR(2) MOA: Interferes with chitin deposition and prevents shedding of old skin
leading to death of the l;arvae or pupae as well as hatching of eggs(3) Available as a bolus (VIGILANTE®) to beef and dairy cattle for the control
of horn flies, stable flies, and houseflies(4) About 80% is eliminated unchanged in the feces and interfere growth of larvae
in manure
d. FENOXYCARB(1) A broadspectrum IGR classified chemically as carbamate but has no activity
against AChE(2) MOA: Blinds to the juvenile hormone receptor and is not readily broken down
by juvenile hormone esterases in the insect larvae(3) It is very stable in the environment(4) Larvicidal and ovicidal against fleas(5) For use against fleas (BASUS®, ECTOGARD®, IM[PASS®), cockroaches
(TORUS®), AND FIRE ANTS (LOGIC®)(6) Available as fenoxycarb alone for use as flea preventive, and in combination
with adulticides for the treatment of existing flea infestations
e. LUFENURON (FLUFENACUR)(1) A benzoyl urea which inhibits insect development(2) MOA: Disrupts chitin synthesis and deposition on the immature flea(3) Chitin is a major component of flea exoskeleton(4) Given orally to dogs for 30 days and is deposited in fats which serves as
storage for release into blood stream(5) Ingested by adult flea when they feed and is passed transovarially to the flea
egg
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(6) Flea eggs exposed to lufenuron fail to hatch, those that hatch die during their first molt.
f. METHOPRENE(1) MOA: Arrests larval development by acting as s juvenile hormone mimic (2) Sensitive to UV degradation(3) Formulated in combination with natural pyrethrins (OVITROL®, OVITROL
FLEA EGG COLLAR®) for use on dogs and cats and with synthetic pyrethroids and chlorpyrifos (SIPHOTROL®) for indoor control of fleas
(4) Ovicidal and larvicidal vs. fleas
7. ORGANOPHOSPHATESa. Characteristics
(1) Yellow to deep brown oily liquids, or yellow to white crystalline powders which may have garlic odors
(2) These are synaptic poisons that work by inactivating AChE enzymes in two steps(a) OP first binds reversibly to the active site of AChE(b) The phosphate later becomes irreversible bound to the AChE(c) Once bound, the inzyme cannot be regenerated and so the tissue must
synthesize new enzymes(3) OP toxicity is a medical emergency and requires
a) Treatment with activated charcoal and bathing to decrease absorption
b) Pralidoxime (2-PAM) to reverse binding to the enzyme (first reaction)
c) Atropine to decrease clinical signs of Ach excess(4) Groups
(a) Simple in structure(b) Rapidly broken down in the animal and in the environment(c) First group available commercially
(2) DICHLORVOS(a) Has quick knockdown insecticidal action as contact, systematic, and
fumigant agent, but little residual effect(b) Also available in slow-release pharmaceutical forms for use against
nematodes of dogs, cats, swine, and horses(c) Used as spray or backrubbers in beef cattle; collars in dogs and cats;
resin strips, baits, foggers, spray for the surrounding, resting, and breeding areas
(d) Apply to animals q. 7-14 days; do not slaughter food animals within 1 day of treatment
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(3) TRICHLORFON(a) Hydrolyzed in vivo dichlorvos(b) Has high insecticidal activity and low mammalian toxicity(c) Treated animals must not be slaughtered for 21 days(d) Do not use milk treated animals for human consumption for 7 days
c. Phenyl derivatives(1) Characteristics
(a) Have a benzene ring in their structure(b) Longer lasting than aliphatic derivatives
(2) CYTHIOTE(a) Effective systematically vs. adult fleas when given PO in dogs(b) Safe for oral administration(c) May be useful vs. Demodex, Otodectes, lice, and ticks
(3) PENTHION(a) A potent and highly persistent insecticide(b) Applied as pour-on over back of cattle: ear tags (1-5 months)(c) Given PO to control Hypoderma(d) Withdrawal period is about 35 days(e) Should not be given in cows within 28 days of calving, lactating cows,
calves < 3 mos. Old, or in animal under stress(4) TETRACHLORVINPHOS
(a) A phenyl derivatives OP with low mammalian toxicity(b) Available as wettable powder, dust, and in emulsifiable concentrate
d. Heterocyclic derivatives(1) Characteristics
(a) The last group to be developed(b) All have ring structure where at least one of the atoms in the ring is
oxygen, nitrogen, or sulfur(c) Heterocyclic ring may have 3, 5, or 6 atoms(d) The longest lasting of all Ops
(2) CHLORPYRIFOS(a) Moderately persistent in the environment(b) Useful for control of mosquito and fly larvae, fire ants, and termites(c) Available as premise sprays and dips; flea and tick collars for dogs only;
ear tags(d) Should not be administered to pregnant bitches and pups < 10 weeks old(e) Should not be used in veal calves, dairy cattle of any age, cows within 21
days before or 14 days after calving, or cattle for slaughter within 14 days of slaughter
(3) COUMAPHOS(a) Relative low toxicity for mammals; mice are very sensitive(b) Hydrolyzes slowly under alkaline conditions(c) Rapidly degraded in liver of cattle
Dr. Elmer Q. Abillar Page 164 4/17/2023
(d) Available as emulsifiable concentrate, wettable powder, dust for use on animals and premises
(4) DIAZINON(a) Relatively safe with good record of safety(b) Available as flea collar (dogs), ear tags (beef and non-lactating dairy
cattle)(5) PHOSMET
(a) Used as spray for control of horn flies and ticks in cattle(b) Available in aromatic petroleum solvents for control of fleas, ticks,
sarcoptic mange mites in dogs and cats(c) Calves < 3 months old, dairy cattle, and beef cattle within 21 days of
slaughter, and dogs <8 weeks old should not be treated
8. REPELIENTSa. These are compounds that prevent or discourage pests from approaching a treated
area, or include them to leave soon after approachingb. DEET
(1) N,N-Diethyl-3-methylbenzamide or N,N-Diethyl-m-toluamide(2) Used as repellent for mosquitoes, gnats, fleas, ticks, and shiggers(3) Frequent applications are necessary for continuing protection
c. DI-N-PROPYL ISOCINCHOMERONATE(1) A relatively safe insect repellent(2) Marketed as MGK REPELLENT 326®(3) Formulated with other insect repellents, insecticides, or synergists for use on
(1) Enhance activity of insecticides, particularly pyrethrins(2) MOA: Inhibit mixed-function oxidases in the insects which metabolize foreign
compoumds (Inhibits microsomal detoxification of insecticides)(3) Makes the insect unable to metabolize the insecticides)
b. N-OCTYL BICYCLOHEPTANE DICARBOXAMIDE(1) Also known by the designation MGK 264(2) Can be used in beef and dairy cattle, sheep, goats, horses, swine, dogs, and
cats, and to agricultural buildings and animal quarters(3) Formulated with piperonyl butoxide and insecticides as aerosols, pressurized
sprays, free-flowing dustsc. PIPERONYL BUTOXIDE
(1) A pale yellowish liquid soluble in alcohols, benzene, freons, and other organic solvents
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(2) Synergizes chlorinated hydrocarbons, carbamates, Ops, pyrethrins, and rotenone
10. MISCELLANEOUS INSECTICIDESa. BENZYL BENZOATE
(1) MOA: unknown(2) Effective vs. most ectoparasites but used in dogs vs. sarcoptic, otodectic, or
demodectic mites(3) Marketed as 36% solution (MANGE TREATMENT®) for spot treatment or
as mange bath
b. BORAX (ORTHOBORIC ACID)(1) A cellular toxin applied as fine powder in indoor environment for the control
of fleas(2) Flea larvae that ingest the material are killed(3) Has no effect on flea eggs, pupae, or adults
c. SULFUR(1) Used as external antimange dressing for veterinary use and for routine baths
in dogs(2) May be applied as ointments, oily suspensions, powders with talc, or
dispersable bath powder combined with soaps and wetting agents
d. BUTAMISOLE HYDROCHLORIDE(1) An analogue of levamisole(2) Primarily effective (STYQUIN®) against canine whipworms and adult
hookworms(3) Use with caution in very young or old and debilitated dogs and those with
history of renal or hepatic disease(4) Contraindicated in debilitated or heartworm-positive dogs (fatal adverse
reactions may occur)4. MACROLIDES
a. Characteristics(1) Macrocyclic lactone antibiotics produced by streptomycete microorganisms(2) Regarded as the most effective and least toxic paraciticides developed(3) MOA: Inhibit transmission of signals between interneurons and excitatory
motor neurons by potentiating the inhibitory GABA neurotransmitter(4) Death results from paralysis(5) GABA neurons are largely confined to the CNS in vertebrate hosts and these
agents cannot cross the blood-brain barrier in the most adults(6) Does not affect trematodes and cestodes, because GABA is not a
neurotransmitter in these species(7) Not approved fpr use in cats
b. IVERMECTIN(1) The first commercially available macrolide
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(2) Isolated from the fermentation broth of Streptomyces avermitilis(3) Effective vs. many nematodes and arthropods as well as immature heart
worms(4) Teratogenic to pregnant rats, mice, and rabbit, but not in cattle, sheep, and
dogs(5) Toxic for aquatic animals(6) Formulated as EQVALAN® paste or liquid PO for horses; IVOMEC® as
liquid for SC injection in cattle and swine and drench in sheep; HEARTGUARD 30V tablets for dogs
(7) Some genetic lines of Collie dogs may develop adverse reactions at higher doses
c. MILBEMYCIN OXIME(1) The second macrocyclic lactone approved for use in animals(2) A fermentation product of Streptomyces hygroscopicus aureolacrimosis(3) Formulated in tablets (INTERCEPTOR®) for heartworm preventation in
dogs(4) Relatively nontoxic to Collies and safe to give in pregnant and nursing
animals(5) Kill heartworm microfilariae and inhibit the release of new microfilariae
d. MOXIDECTIN(1) The third macrolide to enter the parasite market(2) A chemically altered product of Streptomyces aurelacrimosus
noncyanogenus(3) Has the same range of activity and safety margin as ivermectin(4) Shows good activity against ivermectin-resistant strains of nematodes
5. ORGANOPHOSPHATES (OP)a. MOA: Kill nematodes by phosphorylation and inactivation of their
acetylcholinerases(1) Normal AChE eliminates Ach when it is released at the post-synaptic junction(2) When AChE is inactivated, Ach accumulates at the junction(3) Results in continued depolarization leading to paralysis of the parasite(4) Toxicity is related to their ability to inactivate AChE of the host
b. DICHLORVOS(1) Effective vs. many internal and external parasites(2) Rapidly degraded in mammals(3) Specially formulated (resinated) dichlorvos is used as an anthelmentic for
dogs and cats (TASK, TASK TABS®), for horses (CUTTER DICHLORVOS®), and for swine (ATGARD®)
c. TRICHLORFON(1) Very effective against large strongyles and bots of horses(2) U\Only used internally in horses to control bots (COMBOT LIQUID®,
PURINA BOT CONTROL®)
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(3) Should not be used to foals under 4 months old, mares in the last month of pregnancy, severely debilitated horses, horses exposed to other cholinesterase-inhibiting chemicals, and those suffering from disease conditions.
6. SIMPLE HETEROCYCLIC COMPOUNDSa. PIPERAZINE
(1) Used as anthelmentics in swine, poultry, horses, dogs and cats(2) Salts: adipate, hydrochloride, sulfate, monohydrate, citrate, and
dihydrochloride(3) MOA: Cause paralysis of worms by blocking the action of Ach at the
neuromuscular junctions (nondepolarizing or curare-like NM blockade)(4) Available as tablets, solution, and soluble powder under several proprietary
names(5) Worms are eliminated by peristaltic action
b. DIETHYLCARBAMAZINE(1) A bitter-tasting heterocyclic compound closely related to piperazine(2) MOA: Hyperpolarization of postsynaptic membrane causing relaxation and
subsequent expulsion of the parasite(3) Marketed in many pharmaceutical forms under several proprietary names(4) Almost exclusively used in dogs to prevent infection with Dirofilaria immitis(5) Given daily during mosquito season until 2 months after(6) Not for dogs with circulating microfilariae: sudden massive destruction of
microfilariae may produce fatal anaphylactic reaction(7) Still used against immature lung worms in cattle and sheep
c. PHENOTHIAZINE(1) One of the older anthelmentics: precursor of broadspectrum anthelmentics(2) MOA: Believed to be related to microtubular binding(3) Has a broader spectrum of action than piperazine(4) Readily absorbed from the alimentary tract and excreted along with its
oxidation products, thionol and leucothionol, in urine, bile, and milk(5) Urine is red in color or turns red when exposed to air(6) Can be toxic to horses at therapeutic dose (wealness, dullness. Anorexia, colic,
constipation, fever, tachycardia)(7) Presently used for preventation rather than for treatment purposes
7. TETRAHYDROPYRIMIDINESa. Characteristics
(1) These are depolarizing neuromuscular blocking agents(2) MOA: Persistent nicotinic activation resulting to
(a) Spastic paralysis of worms(b) Inhibition of neuromuscular transmission
(3) 100 times more potent than acetylcholine(4) Rapidly metabolized to inactive metabolites in ruminants
b. PYRANTEL
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(1) The most widely used in this group(2) Salts
(a) Tartrate salt is a while powder, soluble in water, absorbed from the gut, and is used as powder and pellets in horses and swine
(b) Pamoate salt is a yellow powder, insoluble inwater, poorly absorbed from the intestines, and is used as ready-to-use suspension and tablets for dogs and horses
(3) Pyrantel salts are stable in solid form but photodegrade when dissolved or suspended in water
(4) Pyrantel tartrae or pamoate is safe for use in the horses and ponies of all ages(5) Pyrantel pamoate is recommended for use in dogs and cats(6) Pyrantel tartrate should not be mixed in feed rations containing bentonite(7) Can be used concurrently with insecticides, carbon disulfide, tranquilizers,
muscle relaxants, and CNS depressants(8) Not compatible with piperazine
c. MORANTEL TARTRATE(1) A 3-methyl analogue of pyrantel(2) Used for the control of G1 nematodes in cattle (RUMATEL®)(3) Topdressed or mixed in feed(4) It may be administered simultaneously with vaccines, injectable drugs, and
external parasiticides(5) Cattle should not be slaughtered within 14 days after treatment
d. OXANTEL(1) An analogue of pyrantel(2) Effective against Trichuris
8. MISCELLANEOUS ANTHELMENTICSa. N-BUTYL CHLORIDE
(1) Used in the control of ascarids and hookworms in dogs and cats(2) Has little or no effect against migrating larvae(3) Fast dog or cat 18-24 hours prior to oral administration(4) Should not be followed with a laxative/cathartic 30 minutes to 1 hour after
medication to maximize its anthelmentic effect(5) Feeding can be resumed within 4-8 hours after treatment(6) Nontoxic but do not give to debilitated or very young animals
b. THENIUM CLOSYLATE(1) A narrow-spectrum anthelmentic, effective against immature and adult
hookworms(2) Available as talets alone (CANOPRA®) or in combination with piperazine
phosphate (THENATOL®)(3) Bitter taste causes salivation(4) Causes vomiting which does not lessen effectivity of the drug
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(5) Has caused sudden deaths in Airdales and Collie dogs (do not use in thses breeds)
(6) Not for suckling pups or recently weaned pups < 2-3 kg(7) Do not feed milk or fatty foods to dogs during treatment
c. TOLUENE(1) Also known as methylbenzene, a hydrocarbon derived from coal tar(2) Commonly available with dichlorophene(3) Effective against ascarids and hookworms in dogs and cats(4) MOA: Believed to be due to irritant or to depressant effects on neural cells of
nematodes(5) Fast animal 12 hours before and 4 hours after medication
d. DISOPHENOL(1) Effective against adult hookworms of dogs and cats(2) MOA: Uncouples oxidative phosphorylation(3) Use with caution in sick and debilitated animals(4) Avoid hot environment and restrict exercise for 2 days after treatment(5) Toxicity: hyperthermia, tachypnea, dyspnea, convulsions
ANTICESTODALS1. Benzimidazoles
a. MEBENDAZOLE(a) Effective in removing Taenia of dogs and cats and Echinococcus
granulosus of dogs(b) Not effective against Dipylidium canium(c) Also removes Monieza in ruminants
b. FENBENDAZOLEc. Those with activity against Monieza when given at regular doses
(1) ALBENDAZOLE(2) CAMBENDAZOLE(3) OXFENDAXOLE
2. BUNAMIDINE HYDROCHLORIDEa. A naphthamidine originally developed in 1960s to replace arecoline I
eliminating Echinococcus granulosusb. MOA: Damages cestode tegument leading to digestion by hostc. Marketed as SCOLABAN® and given orally to dogs for the removal of
Dipylidium, Taenia, and Echinococcus granulosusd. Worms disintegrate within the host’s intestinal tracte. Give on an empty stomach and feed animal 3 hours after medicationf. Do not give to unweaned puppies, puppies < 6 months old, male dogs for
use within 28 days in breeding or animals with cardiac or hydatid diseaseg. Frequent adverse effects vomiting, diarrhea, and heart failureh. Concurrent use with butamisole may cause an acute fatal reaction
3. DICHLOROPHENE
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a. A chlorinated analogue of diphenylmethaneb. Has bacteriostatic, fungicidal, and cestodal properties c. MOA: Uncouples oxidative phosphorylation in para
site mitochondriad. Poorly absorbed from the gute. Used alone or in combination with other anthelmenticsf. Fast animal prior to treatmentg. Tapeworms are killed, digested, and eliminated in unrecognizable formh. May cause occasional vomiting or diarrhea
4. ISOQUINOLONESa. Characteristics
(1) The safest and most effective so far(2) MOA: Cause paralysis and tegumental destruction(3) Molecular basis of action is unknown but is believed to be associated
with increased Ca++ release from muscle cell storesb. PRAZIQUANTEL
(1) The first isoquinolone cestocide marketed (DRONCIT®)(2) Affects adult and juvenile forms of tapeworm species, certain lung and
pancreatic flukes(3) Not embryotoxic, teratogenic, mutagenic, or carcinogenic
c. EPSIPRANTEL(1) The second isoquinolone approved(2) High doses are well tolerated in cats and dogs(3) Compatible with other drugs(4) Slightly absorbed from the gut(5) All are eliminated in feces unchanged(6) Not for use in young animals < 7 weeks old
5. NICLOSAMIDEa. A halogenated salicylanide derivativeb. MOA: Inhibit anaerobic phosphorylation ADP on the mitochondria of
parasite (an energy-producing process dependent upon CO2 fixation)c. Marketed as YOMESAN®d. Effective against Monieza, Taenia and Dipylidium but not against .
granulosusie. Removed scolex and segments may be partially digested and become
unrecognizablef. Purging with adequate purgative within 3-4 hours is necessary in T.
solium infection to minimize risk of cysticercosis if viable ove are liberated in the gut
6. NITROSCANATEa. A phenylisothiocyanateb. Indicated for control of cestodes and nematodes of dogs
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c. High doses produce vomiting, diarrhea, anorexia, tranquilization, and temporary elevations of liver enzymes
ANTITREMATODALS1. Benzimidazoles
a. ALBENDAZOLE(1) Active against adult Fasciola hepatica(2) Also has antinematodal and anti cestodal activities
b. TRICLABENDAZOLE(1) Drug of choice for acute fascioliasis(2) High efficacy against immature and mature flukes(3) No effect on roundworms and tapeworms
c. NETOBIMIN(1) A probenzimidazole(2) Active against adult flukes(3) Do not administer to cattle in the first 7 weeks of pregnanacy
2. CLORSULONa. A benzene sulfonamideb. Very effective against immature (8 weeks old) and adult Fasciola
hepatica c. MOA: Inhibit glycolytic enzyme phosphoglycerate by competing with 3-
phosphoglycerate and 2,3-diphosphoglycerated. Action stops energy generation in flukes]e. Binds to carbonic anhydrase in RBC which favors blood ingesting flukesf. Available as drench (CUTRATREM®) and as an injectable solutiong. Cattle must not be slaughtered within 8 days of treatment
3. DIAMPHENITIDEa. An aromatic amide indicated for acute infestation of flukesb. Affects the youngest immature stages of liver flukesc. Effectivity diminishes as the fluke matures
4. SALICYLANILIDESa. MOA: Uncouple oxidative phosphorylatiion in adult flukes (effectivity in
(1) 100% effective against immature flukes(2) DIBROMSALANS
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(3) TRIBROMSALANS(4) HILOMID (1:1 mixture of di- and tribromsalans)(5) DIAPHENE (1:3 mixture of di- and tribromsalans)
c. HEXACHLOROPHENEd. BITHIONOL (BITHIONOL SULFOXIDE®, BITHELMIN®)e. NICLOFOLAN (BILEVON®)f. NITROXYNIL
ANTIMICROBIAL THERAPY
I. CHEMOTHERAPEUTIC DRUGSA. Ideal Drug
1. specific and lethal to pathogens2. no adverse reactions to the animal
B. Sources1. natural2. synthetic
C. Antibacterial Drugs are either1. bacteriostatic2. bactericidal
D. Mechanism of Action1. nucleic acid inhibition – sulfas, rifamycim2. protein synthesis inhibition – tetracycline, macrolides, aminoglycosides3. cell wall effect – penicillins, cephalosphorins4. cell membrane effect – colistin, polymixin B
E. Spectrum of Activity1. narrow spectrum2. broad spectrum
F. Successful antimicrobial therapy includes:1. clinical and microbiological diagnosis2. culture and sensitivity testing3. appropriate antimicrobial agent4. correct dose and route of administration5. supportive therapy
I. A. SULFONAMIDES1. Complex synthetic organic chemical compounds with chemotherapeutic
activity2. 2 main groups
a. Systematic sulfasb. Gut-active sulfa
3. Structurally related to PABA4. MOA – substitution and replacement of essential vitamins upon which
bacteria are dependent; inhibits biosynthesis of folic acid and thus RNA formation
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5. Bacteriostatic – body defense mechanism must overcome disease by phagocyles of bacteria
6. Effective blood vessels – 5-15 mg/mL of blood7. Fairly well distributed to all tissues8. Broad spectrum9. Principles of therapy
a. treat early in course of diseaseb. use proper dosage and schedulec. administer plenty of fluids
B. SULFA – TRIMETHOPRIM COMBINATIONS1. Combination attacks bacterial metabolism (protein synthesis) at 2 points2. Broader spectrum3. Bactericida5. Lesser risk of bacterial resistance6. Lower dosage of each mg needed7. Dosage: 5-25 mg/kg bwt orally
II. PENICILLINS1. Produced by liquid Penicillin spp2. An organic acid3. By themselves are unstable – converted into various salt esters by the substitution
of Na, Ca, K, procaine, etc.4. First antibiotic discovered5. Penicillin G not feasible orally degraded by stomach acid6. Penicillin VK – orally stable7. Effective blood vessels8. Bacteria should be rapidly multiplying9. Bactericidal various spectrum (primary G+) – Pen G10. Newer synthetic penicillins are broad spectrum and bacrtericidal11. Dose Pen G – 10,000 to 15,000 IU/kg bwt Parenterally
Pen VK – 8,000 to 40,000 IU/kg bwt orally
III. STREPTOMYCIN1. An aminoglycoside2. An organic base3. Rapidly absorbed from IM or SC injection4. Not well absorbed from GI tract5. Bactericidal6. Narrow-apectrum (g-), bactericidal7. Adverse reaction – chronic
Streptomycin – vestibular apparatus, loss of balance Dihydrostreptomycin – hearing
8. Dose 10 mg/kg bwt Parenterally BID
IV. TETRACYCLINES
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1. Organic bases2. Produced by
S aureofaciens – ChlortetracyclineS amustos – OxytetracyclineSynthetic alteration – tetracycline
3. Chemically related4. Fairly absorbed after oral administration: effective blood vessels in 2 to 4 hours5. Rapidly absorbed form IM injection: effective blood vessels in 2 hours6. Differs rapidly into most tissues and fluids7. Higher billary secretion rate make CTC preferred over OTC for hepatic
infections e.g. leptospirosis8. Dose OTC – 10 to 20 mg/kg bwt Orally
OTC – 10 to 20 mg/kg bwt Orally 5 to 10 mg/kg bwt Parenterally
9. OTC – suitable for parenteral administration
V. TYLOSIN1. From S fradiae2. Feed additive – phosphate salt Water additive – tartrate salt3. Resistance to Tylosin develops rather slowly4. Well distributed to most tissues; passes readily into lungs5. Bacteriostatic6. Spectrum – essential G+ bacteria, spirochetes, large viruses and mycoplasma7. Relatively safe antibiotic, wide margin of safety8. Dose
Broiler - 800 to 100 g/ton of feed OrallyLayer - 20 to 50 g/ton of feed Orally
ANTI-PARASITIC
The parasite problems is one of HEALTH and ECONOMICS
A. INTERNAL PARASITE PATHOPHYSIOLOGY1. Diarrhea – Loss of fluid and electrolytes and protein
Poor nutrient absorption2. Anemia3. Tissue result from larval migration
Pneumonia
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Enteritis – Intestinal ruptureCirrhosis and liver abscesses
4. Animal is more susceptible to viral and bacterial invasion5. Animals are unthrifty, do poorly6. Decreased productivity, as such as:
Weight gains and feed efficiency, carcass value, milk
B. EXTERNAL PARASITE PATHOPHYSIOLOGY1. Skin irritation – loss of hair, sunburn, infection2. Upset of animal’s nervous system3. Loss of blood and fluids – anemia4. Decreased productivity, such as:
Decreased weight gains and feed efficiency;Decreased hide and carcass value;Decreased milk or wool production
5. Insect vectors that may transmit disease
C. GENERAL SUMMARY OF PARASITE CONTROL MEASURES1. Management husbandry and sanitation2. Natural immunity, may possibly be trait to be selected for3. Acquired immunity, possibly a control of the future4. Anti-parasitic drugs
D. WAYS ANTI-PARASITIC DRUGS ARE USED:1. Individual animal
a. Fecal check and clinical exam a teach animal to establish the need for treatment and identify the parasite(s) involved.
b. Treat if needed2. Herds – flocks – stables – kennels
a. Examine and fecal check few, and treat all if needed, orb. Treat as a part of routine processing, orc. Set up an established treatment program
E. ANTI-PARASITIC DRUG JUDGEMENT1. Efficacy
a. Spectrum and efficacy against mature and/or immature forms and/or inactive forms
b. Timirs – when efficacacy is maximum2. Safety: Are there adverse effects of the drugs and what is their relationship to any
other disease present?3. Might there be any drug interactions, what other drugs are being used
concurrently?4. Must figure out if treatment is economically sound
BENEFIT vs. RISK
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a. Drug costsb. Benefit or gain to animalsc. Cost of handling the animals, man hours,d. Compatibility with simultaneously procedures; ande. Stress to animals due to gathering them up, handling and restrain
F. FOR GREATEST EFFICACY OF ANTI-PARASITIC DRUGS:1. Incorporate the choice of drug(s) and the timing of the drug administration with:
Good management procedures and the life cycle of the parasite(s) (mature – larval – inactive) and any intermediate hosts
2. Objective is to treat the animal when the parasite is most susceptible and/or treatment is best able to break the cycle.
G. PRECAUTIONS WITH ANTI-PARASITIC DRUGS1. All are potentially toxic2. Follow label directions: Dose
Route of AdministrationPrecautions
3. Use care: Young animals Old animals Debilitated animals
4. Do not use in pregnant animals unless so labeled.5. Know whether they are absorbed into systemic circulation if given orally or
applied to skin6. Know now they are secreted and/or inactivated if they become systematic7. Know contraindications
H. MECHANISM OF ACTIONCan be grouped into 2 as it affects:1. Energy Processes
a. inhibitors of mitochondrial reactions and or glucose transport – benzimidazoles
b. uncouplers of oxidative phosphorylation – substituted phenolsc. inhibition of enzymes in glycolytic pathway – clorsulon
I. TETRAMISOLE1. Rapidly absorbed and carned to all parts of the body2. Experts most nematodes within 24 hours3. Broad-spectrum, active against larval and adult stages4. Active even at low drug levels5. Dose: pigs – 5 to 15 mg/kg bwt
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chickens – 18 to 36 mg/kg bwt6. Well tolerated safe lack of tetragenic effects7. Immunostimulant effect – restore number of T – lymphocytes to normal when
these are depleted
II. ALBENDAZOLE1. very low toxicity2. slowly metabolized and slowly excreted3. broad-spectrum4. activity against flukes
IV. AVERMECTIN1. Ivermectin – product of most interest2. Active against internal and external parasites3. Cause paralysis and death of nematodes, arachnids and insects4. Acts at pre-synaptic neuron endings to enhance the release of GABA-an
inhibitory transmitter that block the post-synoptic stimulation of the next neuron (in nematodes) or muscle fibers (arthropods). Without this stimulation, the parasites are paralyzed and then die.