SYSTEMIC VETERINARY PHARMACOLOGY

GROUP OF DRUGSACTING ON DIFFERENT BODY SYSTEMS

MAJOR DRUGS ACTING ON SYSTEMS

DIGESTIVE HAEMATOPIETIC SYSTEM CARDIOVASCULAR SYSTEM GENITOURINARY RESPIRATORY CNS MUSCULOSKELETAL

DIGESTIVE SYSTEM
Emetics Antiemetics Appetite stimulants Antiulcer drugs Prokinetics /Gastrokinetics Antidiarrhoeals Cathartics /Laxatives Rumenotorics Antifoaming agents Ruminoreticular antacids and acidifying agents Ruminoreticular Motility modifiers

EMETICS Apomorphine Xylazine Syrup of ipecac Hydrogen peroxide (3%) Salt (1-3 tsp) in warm water or Large crystal of NaCl / Sod. carb. (washing soda)

ANTIEMETICS
Phenothiazine tranquilizers acepromazine, triflupromazine, chlorpromazine, and prochlorperazine. Anticholinergic:methscopolamine., glycopyrrolate, propantheline,isopropamide,scopalamine(hyoscine) dicyclomine

Antihistaminics: diphenhydramine, dimenhydrinate, promethazine, buclizine, cyclizine, and meclizine.

Dopamine antagonists: metoclopramide, clebopride, bromopride ,alizapride, domperidone Serotonin (5-HT) antagonists: Ondansetron and dolasetron

ANTIEMETICScontd
Cannabinoids- Cannabis (Marijuana), Dronabinol, Nabilone Butyrophenone tranquilizers- Butorphanol, Droperidol, Haloperidol Steroids - Dexamethasone , Betamethasone, methyl prednisolone Benzodiazepines -Midazolam Lorazepam , Alprazolam Neurokinin type 1 (NK-1) receptor antagonistsAprepitant , Maropitant citrate Others: Trimethobenzamide ,Ginger ,Propofol, Peppermint

Metoclopramide Antiemetic effects via 3 mechanisms. Anti dopaminergic (D2) transmission in the CNS 5HT4 agonistic on GIT 5HT3 antagonistic in CTZ Effects In the upper GI tract, it increases Ach release stimulates and coordinates esophageal, gastric, pyloric, and duodenal motor activity Increases lower esophageal sphincter (LES) tone and stimulates gastric contractions Relax the pylorus and duodenum. Inadequate cholinergic activity is incriminated in many GI motility disorders; hence - most effective in diseases where normal motility is diminished or impaired.

5-HT3 receptor antagonists

Specific inhibitors of 5-HT 3 (Serotonin) receptors in the CTZ

Cytotoxic drugs and radiation -release of serotonin.

Most effective antiemetics in radiation and chemotherapy induced , not effective for emesis caused by motion sickness n

APPETITE STIMULANTS
B vitamin preparations Glucocorticoids -prednisone Anabolic steroids Stanozolol Benzodiazepines -in cats -Diazepam Cyproheptadine- serotonin antagonist Megestrol acetate -Progestin

ANTIULCER DRUGS
Acetylcholine M1 Receptor Antagonists: Pirenzepine, telenzipine Antacids Histamine (H2)-receptor Antagonists Proton-pump inhibitors Cytoprotective drugs Prostaglandin E1 Analogues

Antacids
Systemic antacid
NaHCO3, Na citrate, Na acetate

Water soluble, rapid CO2 liberation Rebound hyperacidity, lead to perforation, ulcer, belching Metabolic alkalosis Non systemic water insoluble Al: OH3, PO4, Mg silicate- 30g,
Mg : OH, O, CO3, Mag aldrate, Mag trisilicate, (Milk of magnesia- MgOH) Ca : CO3, PO4

Antacidscontd

Alginates form a raft that floats on the surface of the stomach contents provide a physical barrier to gastro-oesophageal reflux. Simethicone(activated dimethicone) An anti-foaming agent to relieve wind/ flatulence Lowers surface tension,allows small bubbles froth to coalese into large bubbles that are more easily passed up from stomach or down from colon. Effective in releiving frothy bloat in ruminants palliative treatment of hiccups .

Histamine (H2)-receptor Antagonists

Famotidine >Nizatidine >Ranitidine >Cimetidine
Food delays the absorption of cimetidine, minimal effect on ranitidine enhances absorption of famotidine Cimetidine- hepatic microsomal enzyme inhibitor, reduces the metabolism of other drugs

Proton-pump inhibitors (H+,K+ATPase Inhibitors)

Omeprazole, Pantoprazole, (caps, injectables) Lansoprazole, Rabeprazole, Esomeprazole( caps) 24 hours single oral dose More effective than H2 blockers Microsomal enzyme inhibitor

Omeprazole mucosal cell hyperplasia, hypertrophy and development of carcinoids.

Cytoprotective agents
Prostaglandin E1 Analogues Promote gastric mucosal defense mechanisms, inhibiting parietal cell acid secretion , stimulating mucosal blood flow ,bicarbonate secretion, mucus secretion and epithelial cell renewal Misoprostol methyl PGE1 ester poorer in releiving ulcer pain shorter DOA Slow healing rate employed for GI bleeding and ulceration from NSAID therapy less efficacious than H2blockers for treatment of ulcers not associated with NSAIDs Side effects - diarrhea and flatulence CI: pregnancy

Ulcer protectives/ Ulcerhealing drugs Sucralfate Cytoprotective drug cross-polymerized to form a viscous gel that binds to the necrotic tissue proteins in an ulcer to act as a diffusion barrier Additional beneficial effects - stimulation of PG production, adsorption of bile salts, and inactivation of gastric pepsins Minimal oral absorption . Combination therapy (sucralfate + histamine H2 antagonist, or sucralfate + H+, K+ - ATPase inhibitor) is frequently employed Effective and safest drug in treating gastric erosion/ulcer and patients receiving NSAID therapy

PROKINETICScontd Cisapride Without antidopaminergic effects (antiemetic action) No extrapyramidal effects ( do not cross BBB) More potent and broader prokinetic activity, 5HT 4 agonistic Increases the motility of the colon, as well as that of the esophagus, stomach, and small intestine improves coordination of the ileocecal-colonic junction Withdrawn from market in abroad potent cardiovascular side effects- heart rhythm disorders in humans. Indications Gastric stasis,, gastroesophageal reflux, postoperative ileus (horse) and intestinal pseudo-obstruction (dogs and cats) In idiopathic megaesophagus (dogs) that continue to regurgitate frequently despite a carefully managed, elevated feeding program Rational agent in the treatment of idiopathic constipation (cats)

PROKINETICScontd

Domperidone Regulates the motility of gastric and small intestinal smooth muscle very little physiologic effect in the colon superior to metoclopramide in stimulating antral contractions Macrolide antibiotics Erythromycin & Clarithromycin - at much lower than antimicrobial dose

PROKINETICScontd
Histamine H2-receptor antagonists Ranitidine and nizatidine. Stimulate GI motility by increasing the amount of AChE available to bind smooth muscle muscarinic receptors Stimulate colonic Sm.M contraction in cats by cholinergic mechanism AChE inhibitors Neostigmine indicated in paralytic ileus, ruminoreticular atony, paresis. Increase secretion into the GI tract, contraindicated in SI disease Increase frequency, rather than strength, of ruminoreticular contractions Stimulatory effect not always reliable, and some inhibition of motility can be seen as in n horses, it may decrease small-intestinal propulsive contractions and delay gastric emptying

DRUGS USED IN THE TREATMENT OF DIARRHOEA

Mucosal Protectants and Adsorbents a. Kaolin-pectin -reduce bioavailability b. Activated charcoal -common nonspecific treatment c. Bismuth subsalicylate- Salicylate toxicosis in cats Anticholinergic drugs Hyoscine, Aminopentamide, isopropamide, propantheline and dicyclomine side effects- Urine retention,tachycardia, and CNS excitement, intestinal atony Opiates antisecretory & antimotility effects, not to be used in infection Diphenoxylate and Loperamide Overdose: abnormal pupillary response to light,circling, constant vocalization, head pressing, mydriasis Paralytic ileus, toxic megacolon, pancreatitis, and CNS effects in cats.(collies)

CATHARTICS AND LAXATIVEScontd Stimulant Cathartics Emodin Castor oil , Raw linseed oil olive oil glycerine, Phenolphthalein ,bisacodyl Osmotic (Saline) Cathartics Mg salts- MgSO4(Epsom salt, not for horse), MgO. MgOH, Mgcitrate,MgCO3, NaCl, Na2SO4(Glaubers salt), NaPO4, KNa tartrate Sugar alcohols -mannitol and sorbitol, Lactulose Bulk Laxatives -methylcellulose, psyllium, prunes, wheat bran, and canned pumpkin. Lubricant Laxatives -Mineral oil( Liquid paraffin) Fecal Softeners (Surfactants)- Docusate sodium docusate calcium docusate potassium

CATHARTICS AND LAXATIVEScontd

Neuromuscular purgatives Cholinergic agents with muscarinic actionParasympathomimetics- arecholine, carbachol, bethanecol, physostigmine, neostigmine Prokinetic agents 5HT4 agonists & opoid receptor antagonists

Ruminotorics
Fresh ruminal fluid is considered to be the best available ruminotoric Magnesium hydroxide Dioctyl sodium sulfosuccinate ( 90-120 mL in 1-2 L of water)

With ruminal massage helpful in promoting the dissolution , passage of impacted fibrous ruminal contents. markedly depress rumen protozoa; thus, ruminal fluid transfaunation needed

ANTIFOAMING AGENTS
Poloxalene Polymerized methyl silicone Docusate sodium in emulsified soybean oil Vegetable oils alone, such as peanut oil, sunflower oil, or soybean oil Ionophores (such as monensin) in the ration

RUMINORETICULAR ANTACIDS Magnesium hydroxide (cattle: 100-300 g; sheep: 10-30 g) Magnesium carbonate (cattle: 10-80 g; sheep: 1-8 g). Mixed in10 L of warm water to ensure adequate dispersion through the ruminoreticular contents. Activated charcoal (2 g/kg) to protect the ruminoreticular mucosa from further injury by inactivating toxins

RUMINORETICULAR ACIDIFYING AGENTS

Ruminal stasis or simple indigestion Acute ammonia poisoning. Administration of weak acids in cold water returns the pH of ruminoreticular content toward physiologic levels promotes the uptake of volatile fatty acids.

Acetic acid (4-5%) or vinegar (cattle: 4-8 L; sheep: 250-500 mL)

Drugs acting on respiratory system

Expectorants/mucokinetics 1)Secretory expectorants A)Reflex acting: ipecacunha,balsam of tolu B)Direct acting: guiacol, guiaphenesin C)Mixed acting/saline: potassium iodide,NH3Cl

2) Mucolytic: bromhexine, acetyl cysteine, ambroxol, dembrexine

3) Diluent: steam,propylene glycol and glycerine 4) Miscellaneous: CO2, antimony tartarate
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Antitussives
Peripherally acting: A) Demulscents: honey, glycerine B)Mucosal anaesthetics: benzoate C)Bronchodilators: ephedrine, theophylline D) Expectorants: bromhexine, steam Centrally acting: A) Opioids: codeine, hydrocodeine, morphine B) Non opioids: dextromethorphan, pholcodeine and noscapine
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Bronchial asthma
1)Bronchodilators: a) Beta 2 agonists: salbutomol, terbutaline b)Methyl xanthines: Theophylline, aminophylline c)Anticholinergics: glycopyronium, atropine, ipratropium, 2) Leukotriene antagonists: Montelukast, zafirlukast 3) Corticosteroids: hydrocortisone, prednisolone,

beclomethasone
4) Mast cell stabilizers: sodium cromogylate, Ketotifen
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Analeptics
Doxapram Nikethamide( coramine) Bemegride Methyl xanthines Pentylene tetrazol Picrotoxin Opioid antagonists
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DRUGS ACTING ON HAEMATOPOIETIC SYSTEM

DRUGS
HAEMATINICS/ ANTIANAEMIC DRUGS ANBOLIC STEAROIDS HAEMOSTATICS/ COAGULANTS ANTICOAGULANTS ANTITHROMBOTICS

HAEMATINICS/ ANTIANAEMIC DRUGS:

Minerals: Iron, Cobalt and Copper Vitamins:VitaminB12,Folicacid,Pyridoxine, Ascorbic acid Anabolic steroids: Nandrolone decanoate, stanozolol etc

IRON
Oral preparations Ferrous ( - sulphate, fumarate, succinate, gluconate) Ferric (-ammonium citrate, hydroxide and glycerophosphate). Ferrous sulphate and ferrous fumarate salts are preferred as rapidly,better absorbed. adverse effects nausea, epigastric discomfort, abdominal cramps, constipation, and diarrhea. These effects are usually dose-related and can often be overcome by lowering the daily dose of iron or by taking the tablets immediately after or with meals

IRON
Parenteral preparations Iron-carbohydrate complexes( Iron dextran and iron sorbitol) Iron dextran, both IM and IV routes . Iron sorbitol is used clinically only by IM route, Iron-sucrose complex and iron sodium gluconate complex are newer, alternative preparations, given deep intramuscular injection or by intravenous infusion.

Adverse effects of parenteral iron therapy

local pain,tissue staining (brown discoloration of the tissues overlying the injection site) fever, arthralgias flushing, urticaria, bronchospasm anaphylaxis and death.

ANABOLIC STEROIDS

synthetically produced variants of the naturally occurring male hormone testosterone promote the growth of skeletal muscle, and the androgenic effects promote the development of male sexual characteristics Nandrolone decanoate and Stanozolol.

HAEMOSTATICS

Topical hemostatics
Feracrylum : is another topical haemostatic solution applied as spray/ gel for capillary bleeding, surface bleeding. Adrenaline and Noradrenaline induce localized haemostasis by virtue of their vasocconstrictive effects. They are applied intranasally(1%) to decrease capillary bleeding, epistaxis. Styptics (Astringents) that arrest bleeding by precipitation of proteins of blood and soft tissues; should not be used in high concentration as they irrite and can damage the surrounding tissue. Examples include: ferric sulphate,ferric chloride, silver nitrate, tannic acid, alum, zinc chloride, zinc oxide

HAEMOSTATICS:

Topical haemostatics Thromboplastin, Thrombin,

Fibrin foam and Fibrinogen

in capillary bleeding , dental sockets, epistaxis, surgery of nose , throat and glandular tissues.
Gelatine sponge ( Absorbable) moistened with saline or thrombin is left in bleeding area, which is completely absorbed within 4 weeks.

Calcium alginate dressing may also be left at bleeding site in the same manner

Systemic Haemostatics Adrenochrome monosemicarbazone (carbazochrome salicylate): is an oxidation product of adrenaline used for systemic control of capillary bleeding associated with increased capillary permeability. both orally and parenterally , often given in combination with vitamin K for variety of bleeding disorders like: epistaxis, haematuria, secondary haemorrhage from wounds etc.

Rutin: is a a plant glycoside that improves capillary fragility used orally in combination with vitamin C and vitamin K. Protamine sulphate clinically (slow IV) as an antagonist for heparin overdosage associated bleeding only.

Ethamsylate reduces capillary bleeding by correcting abnormal platelet adhesion leading to the repair of capillary wall. capillary haemorrhage haematemesis epistaxis post partum haemorrhage etc. 250-500mg. IM, PO CI: pregnancy

Bothrops venom coagulant compound derived from the venom of SouthAmerican pit vipers. Excellent haemostatic-coagulant It should not be used as a coagulant in viper bites as it simply prolongs the coagulation abnormality. 10.0 ml in 500 ml of DNS/NSS, I.V. daily for two days. (94.40% accuracy)

N-Butanol
with Citric acid ( vit c)-REVICI- 5ml Amp Ext , int haemorraghes- surg procedures capillary haemorrhage haematemesis epistaxis post partum haemorrhage etc.

Fibrinolytic inhibitors
Epsilon Aminocaproic Acid: (EACA), Tranexamic acid and Aprotinin primarily used as therapy for bleeding from fibrinolytic therapy as prophylaxis for rebleeding postsurgical gastrointestinal bleeding and postprostatectomy bleeding and bladder hemorrhage secondary to radiation

Vitamin K

is used therapeutically in the prophylaxis and treatment of bleeding disorders due to deficiency of vitamin K dependent clotting factors as in warfarin rodenticide poisoning. Used as haemostatic agent in the oral anticoagulant rodenticide (Coumarin derivatives- warfarin, dicoumarol, acenocoumarol) poisoning,indanedione derivatives rodenticide(phenindione, diphenadione, anisindione)

Available as: the natural plant form-Phytomenadione (vitamin K1) Synthetic vitamin K compounds; Menaquinones (vitamin K2 ) and Menadione (vitamin K3).

Antihemostatic drugs
A) Anticoagulants: 1)Invitro: a) Lab use: oxalates, NaF, EDTA b) Blood transfusion: heparin, Na citrate and acid citrate dextrose 2)Invivo/systemic: a) parenteral: heparin and heparinoids b) Oral anticoagulants: coumarin derivatives ie., warfarin, dicoumarol
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B) Antithrombotics: aspirin, sulphinpyrazone, ticlopidine, timolol C) Thrombolytic drugs: streptokinse, urokinase, anistreplace

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Antithrombotics/Antiplatelet drugs

aspirin, dipyridamole, ticlopidine e useful in the prevention of arterial thrombosis, thus inhibiting the growth/ reoccurrence of thrombus formation as in conditions of feline cardiomyopathy, canine heart worm infection etc.

DRUGS ACTING ON CVS

Antihypertensives Antiarrythmics Ionotropics Cardiotonics and Cardiac glycosides (in CHF) Vasodilators Antihyperlipedmics Pressors

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Antihypertensive Agents( Antianginals)

Adrenergic agents
Alpha1 blockers- doxazosin prazosin, terazosin Beta blockers (cardioselective and nonselective)
metorprolol, propranolol, acebutalol, pindolol,

Centrally acting alpha blockers

clonidine, methyl dopa

Combined alpha-beta blockers - labetalol Peripheral-acting adrenergic agents

ADNB- reserpine, guanethedine

Angiotensin-converting enzyme (ACE) inhibitors

captopril, enalapril, lisinopril

Angiotensin II receptor blockers

losartan, irbesartan,candesartan, telmisartan

Calcium channel blockers

ampldipine,diltiazem, nifedipine, verapamil

Diuretics
thiazide, frusemide

Vasodilators
sodium nitroprusside, diazoxide, glyceryl trinitrate, isosorbide, minoxidil

Cardiac glycosides
Digitalis purpurea or Purple foxglve (leaf) Digitoxin, Gitoxin, Gitalin Digitalis lanata or White foxglove (leaf) Digitoxin, Gitoxin, Digoxin Strophanthus kombe (seed) - Strophanthin K Strophanthus gratus (seed) - Strophanthin G (Ouabain) Thevetia neriifolia (nut) - Thevetin Convallaria majalis - Convallotoxin Bufo vulgaris (Toad skin) - Bufotoxin
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Antiarrythmics
Class I drugs act by blocking the sodium channel.
Subclass IA drugs Eg. quinidne, procainamide, disopyramide Subclass IB drugs Eg. lidocaine, phenytoin Subclass IC Eg. flecainide, encainide

Class II drugs -by blocking beta-adrenergic receptors (increasing PR).

eg. propranolol

Class III drugs -interference with potassium conductance is one possible mechanism),
eg. sotalol, amiodarone

Class IV drugs act by blocking the voltage-sensitive calcium channels.

eg. verapamil, nifedipine
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PRESSORS (VASOCONSTRICTORS)
1 adrenergic agonists
epinephrine, norepinephrine, dopamine, PPA, oxymetazoline, phenyl ephrine,

Drugs that release noradrenaline from the sympathetic nerve terminals or inhibit its reuptake
ephedrine, amphetamine,

Eicosanoids like thromboxane A and several peptides like endothelin, angiotensin and vasopressin
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Drugs acting on Uterus and cervix

Myometrial stimulants Uterine relaxants cervical dilators Hormones

Drugs acting on Urinary system

Diuretics Drugs for urinary retention and incontinence Urinal acidifiers Urinary alkalisers Drugs for urolithiasis

Myometrial Stimulants (ECBOLICS)

stimulate contraction of the oestrogen-sensitised uterine myometrium and mammary myoepithelial cells. Indications: In dystocia due to secondary uterine inertia. However, should not be used when dystocia is due to malpresentation or obstruction. Control of postpartum hemorrhage to hasten uterine involution immediately after parturition in all species, to aid clearance of uterine discharge they have no effect on separation of the placenta in ruminant species To reduce the size of a uterine prolapse after replacement in cattle. agalactia due to failure of milk let down Examples- Oxytocin, PGF2alpha, ergot alkaloids

Prostaglandin F2alpha and derivatives

Alfaprostol, cloprostenol, dinoprost, etiproston, luprostiol and tiaprost are synthetic As ecbolics: in obstetrics are dinoprostone (PGE2), carboprost (15-methyl PGF2) cloprostenol, and gemeprost or misoprostol (PGE1 analogues)

PGF2alpha
causes myometrial contraction cervical relaxation luteolysis. regression of the corpus luteum to treat open pyometra in bitches to terminate pregnancy in bitches in combination with cabergoline.

ERGOT ALKALOIDS

stimulate uterine smooth muscle directly, thereby increasing muscular tone enhancing the rate and force of rhythmical contractions. Ergometrine (ergonovine) maleate and Methylergometrine (methyl ergonovine) maleate

the routine expulsion of the placenta after delivery postpartum and postabortal atony and hemorrhage. Ergonovine also stimulates cervical contractions. These drugs are capable of inducing a sustained tetanic contraction, which can shorten the final stage of labor and aid in the reduction of postpartum blood loss

Ergot alkaloids
excreted in milk should not be administered longer than necessary,since prolonged use can lead to ergot poisoning (ergotism) should not be used in cases of threatened spontaneous abortion .

MYOMETRIAL RELAXANTS( Tocolytics)

inhibit uterine contraction or result in relaxation of uterus to aid obstetrical manoeuvres during dystocia to facilitate handling of the uterus during caesarean operation. to facilitate the recovery of embryos from donors for embryo transfer to facilitate replacement of a prolapsed uterus. to delay parturition so that it may occur when greater observation and care are available In addition, when used in heifers, calving can be delayed sufficiently to allow better relaxation of the birth canal and perineum. incomplete cervical dilation (ringwomb) in sheep, although their effect is questionable

TOCOLYTICS 2-adrenoceptor agonists clenbuterol( Cattle: 300 micrograms as a single dose, IM,IV) terbutaline, isoxsuprine, ritodrine or salbutamol isoxsuprine, terbutaline Magnesium sulfate prevents convulsions in preeclampsia and directly uncouples excitationcontraction in myometrial cells. Mg toxicity can be life threatening.

Tocolyticscontd
Indomethacin given orally or rectally for 24 or 48 hours to delay premature labor. . Long-term use of maternal indomethacin is associated with primary pulmonary hypertension, of intraventricular hemorrhage in the newborn.

Tocolyticscontd

Nifedipine calcium channel blocking agent Hydroxyprogesterone . A concern relating to teratogenic potential has limited its use.

DIURETICS
increase urine flow by increasing renal plasma flow or by altering nephron function indicated to reduce oedema in cases of heart failure, hepatic disease, cerebral oedema, hypoproteinaemia, inflammation, and trauma.

Diuretics Loop diuretics: furosemide, bumetanide, ethacrynic acid- Most potent ones Thiazide diuretics: hydrochlorothiazide, chlorothiazide Potassium-sparing diuretics: spironolactone, triamterene,amiloride Osmotic diuretics: Mannitol, urea, glycerol CAse inhibitors: Acetazolamide Methyl xanthines: theophylline

Drug interactions

Acetazolamide aminoglycoside antidiabetic drugs beta-blockers, captopril cardiacglycosides cephalothin and other cephalosporins corticosteroids lignocaine, quinidine

Osmotic Diuretics

Hypertonic solutions of mannitol, urea, glycerol mannitol causes water retention with in the nephron,which dilutes urinary sodium and opposes its reabsorption especially in the proximal tubule and loop of Henle.

Mannitol
used to promote urine output, as in acute renal failure, or to reduce cerebral oedema. s not suitable for the mobilization of general or local oedema because it may lead to cardiac overload. Excessive administration- severe hypovolaemia and maintenance of extarcellular fulid volume may require administration of an electrolyte solution such as compound of sodium lactate intravenous infusion. Indications.:Cerebral oedema, forced osmotic dieresis. Extravasation causes inflammation and thrombophlebitis.

Potassium sparing diuretics

Act by inhibiting the action of aldosterone on distal tubular cells or blocking sodium reabsorption in the latter regions of the distal tubule and collecting tubules. Weak diuretics when used alone as diuretics and thus should never be used as sole agents In a patient, refractory to other diuretics. administered with other diuretics, potassium loss is decreased Spironolactone: used in combination with other diuretics, primarily furosemide, to produce additional diuresis/ to decrease potassium excretion. used in the management of fluid retention associated with non cardiac disease-hepatic disease and nephrotic syndrome.

Diuretics Interactions

ACE inhibitors, potassium supplements increased risk of hyperkalaemia with potassium sparing diuretics Acetazolamide increased risk of hypokalaemia with loop and thiazide diuretics Aspirin antagonism of diuretic effect of spironolactone Beta-adrenoceptor blocking drugs increased risk of ventricular arrhythmias in the presence of hypokalaemia

URINARY ACIDIFIERS

Ascorbic acid (Horses: 2 g/kg daily,PO; Dogs: 100500 mg 3 times daily,PO; Cats: 100 mg 3 times daily) Ammonium chloride (Dogs: 100 mg/kg 12 times daily,PO; Cats: 400 mg/4.5 kg body-weight twice daily with food. Adjust dose until desired urinary pH change achieved) ; Ammonium sulfate (Horses: 175 mg/kg daily,PO); ethylenediamine, arginine HC1, Calcium chloride , methionine and sodium acid phosphate

URINARY ALKALINISERS Sodium bicarbonate, sodium citrate, and potassium citrate some antibacterial effects, as well as decreasing irritation or inflammation in the urinary tract. Potassium citrate: Dose: . Dogs, cats: 75 mg/kg , PO, twice daily or 2mmol/kg twice daily Sodium bicarbonate: Dose. Dogs, cats: 1050 mg/kg 23 times daily,PO

DRUGS FOR UROLITHIASIS

Urate uroliths are more soluble in alkaline urine. Dietary control to reduce protein intake and urine alkalinisers Allopurinol (Dogs: urate calculi, 10 mg/kg,PO, 3 times daily for 4 weeks then 10 mg/kg once daily) reduces the formation of uric acid from purines by inhibiting xanthine oxidase. Penicillamine (Dose. Dogs: cystine calculi, 15 mg/kg,PO, twice daily preferably on an empty stomach. Thiazide diuretics may be used to reduce the recurrence of calciumcontaining uroliths (for example, calcium oxalate calculi) in dogs. Dietary management and potassium citrate have also been used in the control of calcium oxalate urolithiasis.

DRUGS ACTING ON CNS

Nervous system
Central nervous system(CNS): Brain and spinal cord Peripheral nervous system 1. Sensory (affarent) system: somatic sensory nerves, autonomic/visceral sensory nerves 2. Motor(efferent ): somatic motor nerves, autonomic motor nerves

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CNS Depressants
Injectable anesthetics and sedatives
Barbiturates, benzodiazepines, alpha 2 agonists(xylazine, romifidine), chloral hydrate, propofol, dissoaciative anaesthetic (ketamine) steroidal(altheisn), chloralose, urethane, propanidid, metomidine

Inhalational anesthetics
Volatile Chlorofor, ether, halotahne, methoxy flurane, enflurane, isoflurane, sevoflurane, desflurane

Gaseous:
Nitrous oxide, cyclopropane, xenon
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Barbiturates
Thiopentone Ultra short acting Phenobarbitone- Long acting anticonvulsant Pentobarbitone

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Benzodiazepines ( BZDs)
Anxiolytics work by enhancing the action of GABA (gammaaminobutyric acid), an inhibitory neurotransmitter. oxazepam, clorazepate, lorazepam, temazepam, clonazepam, diazepam and alprazolam The last two being most commonly indicated for treatment of anxiety related behaviour problems like urine spraying and short treatment for sound phobias (eg: fireworks, thunderstorms) because of their episodic nature and the rapid onset of action in dogs and cats. At therapeutic levels there is calming effect but little or no effect on motor or mental functions. Cats may stagger for the first 3 - 4 days but this resolve spontaneously. Oxazepam has non active metabolites and is biotransformed by conjugation not oxidation, it is preferred in patients with liver disease.

Tricyclic antidepressants (TCAs)

Closely related to phenothiazines and block amine (serotonin,norepinephrine, dopamine) re-uptake Antianxiety effects . Take about two wks to produce any beneficial effects . Indicated for anxiety related behavioural disorders in dogs and cats such as separation anxiety, obsessivecompulsive behaviors, stereotypies, aggression, and inappropriate elimination, urine spraying in cats, feline hyperaesthesia, compulsive disorders and behavioural problems secondary to idiopathic cystitis. Clomipramine and amitryptilline are the TCAs licensed for use in veterinary medicine

Selective Serotonin ReUptake Inhibitors (SSRIs)

Selectively block the reuptake of serotonin Indicated for the treatment of behavioural conditions which involve a component of impulsivity Fluoxetine, sertraline and fluvoxamine For treating psychogenic alopecia, allergy-related pruritus, anxiety related condition, s dominance-related aggression, fearful behaviors, obsessive-compulsive behaviors, and urine marking Fluoxetine is approved drug in dogs, useful in the treatment of some but not all forms of aggression. It is used for inter-dog aggression in conjunction with behavioral training and neutering of the less dominant dog. Fluoxetine is also used for the treatment of obsessive-compulsive disorders in dogs.

Monoamine oxidase inhibitors(MAOIs)

Selegiline
For treatment of behavioural disorders with an emotional origin, which includes fears and phobias.
Used to increase the confidence of a dog that has become afraid of going outside after dark due to a number of fearful experiences Approved drug for Canine cognitive dysfunction syndrome

Antiepileptics
Mood-stabilizing drugs, primarily indicated in those cases where epileptic activity is in the etiology of the condition Agents: phenobarbitone, carbamazepine, and valproic acid are unrelated chemical compounds that are used in human medicine to treat bipolar disorder, impulsivity, emotional reactivity, and aggression. Carbamazepine in cats decrease fear-related aggression against people, but it may paradoxically increase aggression against same species. Lithium (75 mg total dose, bid) has been used to treat dominancerelated aggression and psychotic behavior (random air-snapping, pawing) in a Cocker Spaniel; has narrow therapeutic index exhibiting side effects like polyuria, polydipsia, memory problems, weight gain, and diarrhea.

Muscle relaxants

Directly acting
Dantrolene sodium- in malignant hyperthermia (halothane)

Centrally acting
Baclofen, mephenesin

Peripherally acting
Depolarizing( Noncompetitive)
succinyl choline(suxamethonium), hexamethonium, decamethonium

Nondepolarizing (Competitive)
Curare, Atracurium, pancuronium, vancuranium, gallamine(FLAXEDIL)
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Autonomic nervous system(ANS)

Visceral, vegetative, involuntary N.S Regulates vital body functions viz., BP, body temperature. Heart beat, urination etc Differences between somatic and autonomic nervous system ANS: sympathetic and parasympathetic Differences, preganglionic, postganglionic nerve fiber, location of ganglia Type of neurotransmitter involved
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 Neurotransmission, neurohumaoral transmission Neurotransmitter Neuromodulator Neuromediator Criteria for neurotransmitter Steps involved in neurotransmission
91

Adrenergic receprors
Two families alpha () and Beta () Adrenergic agonists: adrenaline, noradrenaline and isoprenaline 1 and 2 1, 2 and 3 All are G-protein coupled receptors(GPCR) - excitatory response, except in GIT - inhibitory response, except on heart
92

Adrenergic receptors
receptors: 1 receptors: mainly heart, JG cell sof kidney 2 receptors ;blood vessels of skeletal muscles, liver and smooth muscles of intestine, bronchi and uterus 3 receptors: adipose tisue, cause lypolysis.

93

Cholinergic transmission
Acetyl choline(ACh) Biosynhesis, storage and release of NT Acetyl co A+ Choline Ach
Choline acetyl transferase (choline acetylase

Cholinergic receptors: Nicotinic and Muscarinic Nicotinic:( Nicotine) ligand gated cation channels Muscarinic:(Muscarine) G-protein coupled receptors
94

Nicotinic
:occour peripherally at neurotransmitter junction, autonomic ganglia, adrenal medulla and also part of CNS Mediate fast excitatory synaptic transmission Two types : Nn and Nm Ligand gated ion channel receptor Response is always excitatory

95

 Muscarinic:occour on autonomic effector cells in heart, smooth muscles, exocrine glands and parts of CNS Belongs to GPCRs Response may be excitatory or inhibitory Receptor: 5, M1,M2, M3, M4 and M5 M1: ganglion cells of stomach and oesophagus M2: hear and smooth muscles M3: smooth muscles and secretory glands M4 and M5: CNS
96

 Other neurotransmitters: Non Adrenergic Non Cholinergic(NANC):adenosine, ATP, VIP(vaso active intestinal polypeptide), Neuropeptide y etc Neuromodulation: presynaptic and postsynaptic

97

Adrenergic agonists
I. Nonselective adrenergic receptor agonists: A. Catecholamines: adrenaline, noradrenaline, isoprenaline and dopamine B. Non catecholamines: amphetamine, ephedrine, pseudo ephedrine, phenylpropanolamine II. Selective adrenrgic agonists: A. Alpha 1 agonists: phenylephrine, methoxamine B. Alpha2 agonists:clonidine, xylazine,detomidine, medetomidine C: Beta 1 agonist: dobutamine D. Beta 2 agonists: clenbuterol, terbutaline, salbutamol, orciprenaline
98

 Mechanism: 1. Direct acting agonists: directly on alpha and beta receptors: adrebnaline, noradrenaline, methoxamine, salbutamol 2. Indirect acting agonists: amphetamine, tyramine 3. Mixed acting agonists: ephedrine, dopamine, metarminol etc
99

Adrenergic antagonists
I. Nonselective alpha receptor antagonists: A. Haloalkylamines/alkylating agents: phenoxybenzamine, dibenamine B. Imidazoline derivatives: tolazoline, phentolamine C. ergot alkaloids: ergotamine, dihydroergotamine D. Miscellaneous: 1. Neuroleptics: chlorpromazine, haloperidol 2. benzodioxan derivatives: piperoxane and dibozane 3. dibenzepine derivatives: azapetine

100

 II. Selective alpha adrenergic receptor antagonists: A. Selective alpha 1 antagonists: 1. Quinazoline derivatives: prazosin, terazosin, doxazocin 2. Indole derivatives:indoramine 3. Miscellaneous drugs:ketansarin, urapidil B.Selective alpha2 adrenergic antagonists: yohimbine, atipamezole
101

 Beta adrenergic receptor antagonists: I.Nonselective: propranolol. Nadolol, timolol, sotalol II. Selective: A.Selective B1 blockers: metaprolol, atenolol, esmolol B.Selective B2 blockers: butoxamine Mixed antagonists: Labetolol,dilevalol, carvedilol
102

 Cholinergic agonists(cholinomimetics): I. Direct acting A.Choline esters: acetylcholine, bethanechol, carbachol,,methacholine B.Cholinomimetic alkaloids: pilocarpine (Pilocarpus jaborandi ), arecoline (Areca catechu), muscarine, (from the mushroom Amanita muscaria) nicotine (Nicotiana tabacum) II.Indirect acting(Ch Esterase inhibitors) A.Reversible: neostigmine. Pyridostigmine, physostignine B.Irreversible: malathion, parathion, dichlorovos, sarin ,tabun etc
103

Anticholinergic drugs
Nonselectve: A. natural alkaloids: atropine, hyoscine B.Semisynthetic and synthetic: a. a.Mydriatics: homatropine, tropicamide, cyclopentonate b. antisecretory drugs: propantheline, glycopyrronium, dicyclomine, c. Antiparkinsons:nbenzhexol, procyclidine

104

II. Selective: A. M1 antagonists: pirenzepine, telenzipine B. M2: tripitramine, methoctromine C. M3: darifenacin, hexahydrosildifenidol

105

ANALGESICS: OPIODS AND NONSTEROIDAL ANTINFLAMMATORY AGENTS

Analgesics: Pharmacological agents OPIOIDS NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) CORTICOSTEROIDS

LOCAL ANAESTHETICS
lpha 2-AGONISTS KETAMINE, GABAPENTIN ETC.

OPIOID ANALGESICS

History of Opioids
Opium is extracted from poppy seeds (Papaveer somniforum) Used for thousands of years to produce:
Euphoria Analgesia Sedation Relief from diarrhea Cough suppression

Terminology
opium is a Greek word meaning juice, or the exudate from the poppy opiate is a drug extracted from the exudate of the poppy opioid is a natural or synthetic drug that binds to opioid receptors producing agonist effects

 Morphine analogues. These are compounds closely related in structure to morphine and often synthesised from it. They may be Agonists (e.g. morphine, diamorphine [heroin] and codeine), Partial agonists (e.g. nalorphine and levallorphan) Mixed agonist-antagonisor weak partial agonist (buprenorphine) Antagonists (e.g. naloxone, naltrexone). Synthetic derivatives with structures unrelated to morphine: phenylpiperidine series (e.g. pethidine and fentanyl) methadone series (e.g. methadone and dextropropoxyphene) benzomorphan series (e.g. pentazocine and cyclazocine) semisynthetic thebaine derivatives (e.g. etorphine and buprenorphine

111

Pharmacological Effects
Sedation and anxiolysis
Drowsiness and lethargy Apathy Cognitive impairment Sense of tranquility

Depression of respiration
Main cause of death from opioid overdose Combination of opioids and alcohol is especially dangerous

Cough suppression
Opioids suppress the cough center in the brain

Pupillary constriction
pupillary constriction in the presence of analgesics is characteristic of opioid use

Pharmacological effects contd.

Nausea and vomiting
Stimulation of receptors in an area of the medulla called the chemoreceptor trigger zone causes nausea and vomiting Unpleasant side effect, but not life threatening

Gastrointestinal symptoms
Opioids relieve diarrhea as a result of their direct actions on the intestines

Other effects
Opioids can release histamines causing itching or more severe allergic reactions including bronchoconstriction Opioids can affect white blood cell function and immune function

Mechanism of action
Activation of peripheral nociceptive fibers causes release of substance P and other pain-signaling neurotransmitters from nerve terminals in the dorsal horn of the spinal cord

Release of pain-signaling neurotransmitters is regulated by endogenous endorphins or by exogenous opioid agonists by acting presynaptically to inhibit substance P release, causing analgesia

Primary Effect of Opioid Receptor Activation

Reduction or inhibition of neurotransmission, due largely to opioid-induced presynaptic inhibition of neurotransmitter release Involves changes in transmembrane ion conductance
Increase potassium conductance (hyperpolarization) Inactivation of calcium channels

Three Opioid Receptors

Mu Kappa
Delta epsilon Theta

Mu-Receptor: Two Types

Mu-1
Located outside spinal cord Responsible for central interpretation of pain

Mu-2
Located throughout CNS Responsible for respiratory depression, spinal analgesia, physical dependence, and euphoria

Mu and Kappa Receptor Activation

Response Analgesia Respiratory Depression Mu-1 Mu-2 Kappa

Euphoria
Dysphoria Decrease GI motility Physical Dependence

Mu and Kappa Receptors

DRUGS
Pure Agonists
AgonistAntagonist Pure Antagonists

MU
Agonist
Antagonist Antagonist

KAPPA
Agonist
Agonist Antagonist

120

AGONISTS
*Morphine *Heroin *Hydromorphone *Fentanyl *Codeine *

122

OPIOIDS
Morphine Oxymorphone Diamorphine[heroin] Codeine Nalorphine Levallorphan Pethidine (meperidine) Fentanyl Methadone Nalbuphine hydromorphone Dextropropoxyphene Pentazocine Cyclazocine Etorphine Buprenorphine Sufentanil, Methadone Butorphanol Alfentanil Carfentanil Remifenatnil Tramadol hydrochloride

Indications
Acute/chronic moderate to severe visceral pain In horses for various ailments, particularly to relieve acute pain of spasmodic colic. Combined with suitable tranquilliser as part of of neurolept analgesia for the restraint of animals(wild) To provide analgesia as part of a balanced anaesthetic technique Pentazocine as preanaesthetic in SA and horses Some opiates are also used for the antitussive (eg: codeine, hydrocodeine, hydrocodone, morphine) property and antidiarrhoeal (eg: loperamide, diphenoxylate, difenoxin) action.

Side effects

Severe respiratory depression Excitement (Transient, overstimulation of the CNS) In animals such as. cats, horses, cattle, sheep, goats, pigs Irregular effects in horses and ox, requiring higher analgesic dosage Nausea and vomition, constipation, sedation, allergy , respiratory depression Reversed by specific opioid antagonists such as Naloxone or Naltrexone together with the suitable symptomatic therapeutic agents like antiemetics, respiratory stimulants etc.

Tramadol hydrochloride
Centrally acting analgesic with opioid, monoaminergic, (monoamine reuptake inhibitor) and local anesthetic effects. Approved for acute or chronic mild to moderate pain relief in dogs and cats. Can be combined with other classes of analgesics including steroids, NSAIDs, NMDA antagonists, and gabapentin to allow a lower dose of both drugs Should not be combined with tricyclic antidepressants (TCA; eg: clomipramine), selective serotonin reuptake inhibitors ( SSRIs; eg: fluoxetine) or monoamine oxidase inhibitors (MAOI; eg: selegiline ) due to the risk of serotonin syndrome.

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

Most widely prescribed drugs in the treatment of pain and inflammation in many conditions. The advantages over opioids No immunosuppressive and metabolic side effects associated with corticosteroids. Devoid of sedation, hypotension, bradycardia and respiratory depression Long acting analgesia for mild to moderately painful conditions, Analgesic, antipyretic and antiinflammatory actions Not controlled substances

NSAIDS.. contd

Drawbacks Potencywise : lesser than opioids .with their effect on visceral pain considered to be poor. Other potential adverse effcets: gastric, hepatic and renal

NSAIDS.. contd Mechanism of action Inhibition of cyclo-oxygenase (COX) enzyme(s) which leads to a decrease in the synthesis of various prostaglandins and thromboxanes May also inhibit phospholipase A enzyme; major mechanism for effects of glucocorticoids on prostaglandin production. Few agents like ketoprofen and tepoxalin inhibit lipooxygenase enzyme involved in leukotrienes synthesis, in addition to cyclooxygenase inhibition

NSAIDS.. contd
COX-1 Virtually all tissues of the body Catalyzes the formation of constitutive PG, which mediate a variety of normal physiologic effects including hemostasis, GI mucosal protection, and protection of the kidney from hypotensive insult. COX-2 Activated in damaged and inflamed tissues and catalyzes the formation of inducible PG, including PGE2, associated with intensifying the inflammatory response Involved in thermoregulation and the pain response to injury. COX-3 In brain, involved with central pain relief

NSAIDS.. contd Most are nonselective COX inhibitors, with COX 1 inhibition ratio being highest Meloxicam, nimesulide, etodolac and aceclofenac are considered as preferential COX-2 inhibitors. The newer Coxib class of selective COX-2 inhibitors includes rofecoxib, celecoxib, valdecoxib, parecoxib, deracoxicb, etoricoxib, firocoxib, lumiracoxib Paracetamol (acetaminophen) is a selective COX-3 inhibitor with only analgesic and antipyretic actions, devoid of anti-inflammatory action

NSAIDS.. contd
Pharmacological Effects Antipyretic, analgesic, and anti-inflammatory properties. ( acetaminophen: no antiinflammatory) Less potent analgesics than opioids Potent antithrombotic and antiendotoxic poroprties (few) Reduce the effect of endotoxaemia by inhibiting the production of eicosanoids and thromboxanes, which are responsible for many of the clinical manifestations of endotoxaemia such as changes in cardiovascular output (vasoconstriction, followed by vasodilation), and renal bl;ood flow, fever, ileus, leucopenia and a tendency to develop coagulaopathies. It is most common secondary to ischemic gastrointestinal injury or metritis. Flunixin, phenyl butazone, ketoprofen and meloxicam are the most effective

NSAIDS.. contd

Indications Pain resulting from musculoskeletal injury either due to trauma or surgery As adjunctive therapy to antimicrobial treatment in acute respiratory diseases in cattle. Antiendotoxic to reduce endotoxaemia( eg: flunixin, phenyl butazone) Antithrombotic (eg: aspirin) to prevent thrombosis.

NSAIDS.. contd Side /Adverse effects Cellulitis, thrombophlebitis and tissue necrosis Gastric ulceration Renal toxicity Haematological effects : Bleeding, thrombocytopenia, haemolytic anaemia and agranulocytosis Hepatotoxicity CNS (behavioural disturbances, seizure precipitaion) Skin (rashes, pruritus) manifestations

Acetaminophen Little ulcerogenic potential No effect on platelets or bleeding time. More effective in inhibiting COX-3, in the brain rather than in the periphery. Dose-dependent adverse effects include depression, vomiting, and methemoglobinemia Use in cats is contraindicated due to a lack of glucuronosyl transferase and the potential for hemolytic anemia and centrilobular hepatic necrosis.

Adjuvant analgesic drugscontd

Gabapentin A newer anticonvulsant Used in dogs and cats for the treatment of chronic pain, particularly of neuropathic origin and also used in chronic arthritic pain and pain associated with malignancy. Most effective when combined with other types of analgesic agents, NSAIDs, permitting the use of lower doses. Side effects are mild sedation and ataxia. Care to be taken in animals with decreased liver or renal function. It should not be discontinued abruptly because withdrawal may precipitate seizures or rebound pain. The dosage should be decreased over the course of two to three weeks. The commercially available human liquid-product contains xylitol, which can be hepatotoxic in dogs.

Other Antiinflammatories
CHRONDROPROTECTIVE COMPOUNDS Heparinoids: Polysulfated glycosaminoglycan and Pentosan polysulfate sodium Sodium hyaluronate: Chondroitin and glucosamine Dimethyl sulfoxide (dimethyl sulphoxide, DMSO):

Antiseborrheic agents

Sulfur Seborrheic dermatitis and primary seborrhea sicca and oleosa. keratolytic. antibacterialpossible antifungal action of sulfur nota good degreasing agent and is therefore not as drying as other antiseborrheic agents.

Antimicrobial agents
Benzoyl peroxide superficial and deeppyodermas follicular flushing activity, in demodicosis prominent degreasing activity choice for patients with greasy or oily skin. at concentrations of 23%

Chlorhexidine
greater efficacy for bacterial infections, particularly Staphylococcus spp, than for yeast or dermatophyte concentrations between 0.5% and 3%. Shampoos containing combinations of chlorhexidine and miconazole Others fusidic acid polymixin Neomycin

Topical corticosteroids: Mild: e.g. hydrocortisone prednisolone, dexamethasone Moderate: e.g. betamethasone valerate triamcinolone acetonide fluocinolone acetonoide. potent: e.g. betamethasone dipropionate betamethasone valerate, diflorasone diacetate; Very potent: e.g. clobetasol propionate, halobetasol propionate,, betamethasone

PHARMACOLOGY OF GLUCOCORTICOIDS

ANATOMY Adrenal Anatomy: small, triangular glands loosely attached to the kidneys divided into two morphologically and distinct regions : adrenal cortex (outer) , adrenal medulla (inner)

Hormones of the Adrenal Medulla : Adrenaline (epinephrine ) , noradrenaline (norepinephrine)

Hormones produced by the adrenal cortex corticosteroids.-glucocorticoids an dmineral corticoids

Steroid Preparations

Short-acting
(duration of action < 12 hours) Cortisone and hydrocortisone Intermediate-acting duration of action 1236 hours); Prednisone, prednisolone, prednisolone sodium succinate, methylprednisolone, methylprednisolone acetate, and triamcinolone Long-acting (duration of action > 36 hours) Dexamethasone, betamethasone, and fluocinolone

Pulse therapy: parenteral administration of supra pharma. doses of short acting steroids for shorter periods of time
Short term therapy: ( <2weeks) Use short acting steroids Administer in divide doses ,BID Used till the condition is controlled (4-7days) Discontinue therwapy once the condition is controlled Long term therapy Starting as above for 2 weeks, then bring the dosage to the lowest possible single dose per day. Giving other adj. therapy: antihistaminics, NSAIDS to keep steroid dose as low as possible. Gradual withdrawl by tapering the dose, in order to avoid iatrogenic hypoadrenocortisism.

Principles of GC therapy..contd
Tapering the dose and gradually withdrawing before stopping therapy to avoid iatrogenic hypoadrenocortisism. The antiinflammtory effect is palliative and routine use in inflammatory conditions should be avoided

Short/Intermediate acting GC : more flexible dosing schedules, potent GC effects, lesser suppression of HPAA and less GIT irritation.

Clinical Indications of GCs

Adrenocortical insufficiency (acute,chronic) Addisons disease In acute adrenocortical insufficiency, a rapidly acting parenteral corticosteroid with the most mineralocorticoid effect available RelativeMC: most to the least potency is hydrocortisone > prednisolone/prednisone > methylprednisolone > dexamethasone

Clinical Ind. of GCscontd

Allergic disorders Dexamethasone injection, methylprednisolone acetate inj. Susp.,methylprednisolone tablets prednisolone sodium succinate, triamcinolone acetonide inj. table suspension and triamcinolone tablets Allergic : such as bee stings, drug allergy, pruritic dermatoses and allergic lung (rhinitis, astma) and GI diseases.

Clinical Ind. of GCscontd

Ocular and Aural Inflammtion(otitis externa) Important drug therapy for suppressing inflammation in eye and ears Topical steroids are used for conditions of the anterior chamber systemic steroids for posterior chamber Contraindicated in viral infections, fulminant bacterial infections, fungal infections, injuries (ulcers) and glaucoma

Clinical Ind. of GCscontd

Musculoskeletal Inflammation indicated for reduction of pain, inflammation, and swelling in cond. of musculoskeletal disorders osteoarthritis, bursitis, tendonitis, immune mediated rheumatoid arthritis, myositis; should be used in conjunction with therapies that target the underlying cause

Clinical Ind. of GCscontd

Adjunct therapy of cardiogenic ,hemorrhagic shock

The primary treatment-adm. of large volumes of crystalloid solutions. High doses of GC may aid in reversing some of the effects when administered in conjunction with IV fluids The rapidly acting ones dexamethasone sodium phosphate and prednisolone sodium succinate Short-acting soluble steroids such as the succinate esters Routinely used in the treatment of circulatory shock. When given IV in the early stages of shock, GC and aggressive fluid therapy may improve hemodynamics and survival rates

Clinical Ind. of GCscontd

Adjunct therapy of septic shock (endotoxemia) Use of GC is controversial primary treatmentantimicrobial therapy and supportive parenteral fluid therapy High doses of a rapidly acting GC, preferably of short duration, should be given in conjunction with fluid and electrolyte therapy within a short period of time, possibly less than 1 hour, after the onset of sepsis

Clinical Ind. of GCscontd

As immunosuppressive in immune mediated haematopoietic and skin diseases immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated neutropenia Dexamethasone, prednisolone, and prednisone immune mediated skin diseases like Systemic lupus erythematus, pemphigus complexus. Primary underlying causes should be ruled out to be certain therapy is appropriate. Myasthenia gravis. Dogs and cats that do not respond well to anticholinesterase treatment maybe considered candidates for corticosteroid therapy. initially given GC at anti-inflammatory doses, which may be increased to immunosuppressive levels over a 1-2 week period

Clinical Ind. of GCscontd

Termination of pregnancy/ Induction of abortion

Dexamethasone injection is used in the induction of abortion

Generally administered after the 100th to 150th day of gestation, when prostaglandins administered alone are no longer effective usually administered in conjunction with a prostaglandin Risk of fetal mummification, retained placentas, metritis, or dystocia

Clinical Ind. of GCscontd

Induction of Parturition Dexamethasone,betamethasone and flumethasone In conj. with a prostaglandin in order to produce a predictable response time. In cattle, retained placentas are a common sequale even when GC are administered with prostaglandin Parturition may be induced in the last few weeks of gestation to speed the onset of lactation or to control timing of parturition Involves much less risk to the fetus than earlier termination of pregnancy. Administration of GC more than 1 month before expected gestation leads to poor neonatal survival

Clinical Ind. of GCscontd

Intervertebral disc disease Dexamethasone, flumethasone injection supportive therapy in intervertebral disk disease (Hansen type:1;disk syndrome). Methylprednisolone, prednisolone, or prednisone, administered at an anti-inflammatory dosage, may be a more appropriate choice of therapy in many cases However, acute paralysis due to intervertebral disk disease is an emergency usually requiring surgery and/or higher anti-inflammatory dosages of GCs

Clinical Ind. of GCscontd

Ketosis in Cattle Dexamethasone,flumethasone,isoflupredone acetate,prednisolone acetate administered with IV glucose solutions For secondary bovine ketosis, GC should be used concurrently with other therapies for underlying disease, including local and systemic antibacterials to treat primary bacterial infections A significant decrease in milk production

DRUGS ACTING ON SKIN

Ethyl lactate
mild superficial bacterial infections in normal to dry skin. Conflicting results arereported from various studies: some show it to be as effective as benzoyl peroxide, others that it is no more effective than water.

Triclosan
antibacterial ingredient in some shampoos used for seborrheic disorders and may be helpful in preventing infections of seborrheic skin.

Emollients
fats such as lanolin, hydrocarbonssuch as paraffi n, petrolatum and mineral oil, humectants such as carboxylic acid and lactic acid oilssuch as olive, cottonseed, corn, almond, peanut and coconut oil. added to shampoos as vehicles and for their local effects in softening and protecting the skin.

Moisturizing agents
Urea, glycerin and propylene glycol protection and moisturizing of the skin. Essential fatty acids and colloidal oatmeal.

Mupirocin
is an antibacterial agent G+ve localized bacterial infections \effi cacious in the treatment of felin acne, even when Malassezia spp rather than bacteria

Tacrolimus
immunomodulator synthesized for canine atopic dermatitis, perianal fi stula and discoid lupus erythematosus. It is also used for other immune-mediated

Antipruritic agents
Hydrocortisone antihistamines aloe vera extracts