Drugs Acting on Urogenital System | Animals | Pharmacology

After reading this article you will learn about the various drugs acting on urogenital system.

Diuretics:

These are drugs or agents that increase the volume of urine.

Indications:

(i) In the treatment of oedema due to cardiac failure.

(ii) Renal disease (Nephrotic syndrome)

(ii) Cirrhosis of the liver.

(iii) In the treatment of hypertension (thiazides)

Classification:

1. High efficacy diuretics:

(a) Mercurial diuretics:

(i) Mersalyl

(ii) Mercurophylline

(iii) Mercaptomerin

(iv) Chlormerodrin

(v) Mercurous chloride (calomel)

(b) High ceiling diuretics- (Loop diuredics) – Very potent Diuretics:

(i) Ethacrynic acid (Phenoxyacetic acid derivative)

(ii) Furosemide (Lasix®)

(iii) Bumetanide (3-amino benzoic acid derivative)

(iv) Piretamide

(v) Torsemide

2. Medium efficacy diuretics (Moderately Potent):

(a) Benzothiazides (Thiazides):

(i) Chlorothiazide

(ii) Hydrochlorothiazide

(iii) Polythiazide

(iv) Benzthiazide

(v) Cyclopenthiazide

(vi) Hydroflumethiazide

(vii) Bendroflumethiazide

(viii) Methyclothiazide

(ix) Trichlormethiazide

(b) Thiazide Like (related heterocyclics) agents:

(i) chlorthalidone

(ii) Xipamide

(iii) Metolazone

(iv) Indapamide

(v) Clopamide

(c) Polyvalent uricosuric diuretics:

(i) Tienilic acid (ticrynafen)

(ii) Indacrinone

3. Weak or adjunctive diuretics:

(a) Carbonic anhydrase inhibitors:

(i) Acetazolamide

(ii) Methazolamide

(iii) Ethoxazolamide

(iv) Dichlorphenamide

(v) Dorzolamide (Ophthalmic use)

(b) Potassium sparing diuretics:

(i) Aldosterone antagonist:

Spironolactone

(ii) Directly acting:

Triamterene

Amiloride

(c) Xanthine diuretics:

(i) Theophylline

(d) Osmotic diuretics:

(i) Mannitol

(ii) Isosorbide

(iii) Glycerine

(iv) Urea

(e) Acidifying or alkalinizing salts:

(i) Ammonium chloride

(ii) Pot. citrate

(iii) Pot. acetate

4. Combined diuretics:

(a) Combination with potassium e.g.

(i) Cyclopenthiazide + potassium

(ii) Furosemide + potassium

(iii) Bumetanide + potassium

(b) Combinations of thiazide or loop diuretics with potassium sparing diuretics:

(i) Hydrochlorothiazide + amiloride

(ii) Hydroclorothiazide + triamterene

(iii) Benzthiazide + triamterene

(iv) Hydroflumethiazide + spironolactone

(v) Furosemide + spironolactone

Mechanism of Actions of Diuretics:

A. Mercurials:

They liberate mercuric ion (Hg²⁺) which combines with sulphhydril groups of enzymes associated with transport system located in proximal and beginning of distal tubules. They primarily inhibit chloride reabsorption in ascending limb of Henle’s loop; also inhibit Na⁺-reabsorption from proximal and early distal tubule.

B. High ceiling diuretics: (Fig. 21.2)

1. Inhibit Na⁺– K⁺– 2Cl^– cotranoport acting at the luminal face of epithelial cells in ascending limb of Henle’s loop,

2. Also inhibit (Na⁺– Cl^–) cotransport at early distal tubule.

3. Increase renal blood flow → ↑ filtration rate (by giving i.v. ly)

4. ↑ excretion of Ca²⁺, Mg²⁺and K⁺.

5. ↑ excretion H⁺& NH³.

6. Furosemide and bumetanide are carbonic anhydrase (C.A) inhibitors (too weak)

7. ↑ reabsorption and ↓ excretion of uric acid from renal tubule (Like thiazides)

Adverse Effects:

(i) Metabolic alkalosis may be produced.

(ii) Hyperuricemia

(iii) Deafness (by Ethacrynic acid)

C. Benzothiadiazides (Thiazides) and Related Agents: (Fig. 21.3)

(i) block electro-neutral (Na⁺– Cl^–) cotransport in early distal tubule (DT).

(ii) inhibits Na⁺– reabsorption.

(iii) ↑ flow of urine through early DT → ↑ K⁺ secretion.

(iv) ↑ reabsorption and ↓/inhibit tubular excretion of urate → plasma urate concentration ↑.

(v) ↑ excretion of Mg²⁺ → hypomagnesemia and Iodide (I^–).

(vi) ↑ renal excretion of Ca²⁺.

1. In diabetes insipidus patients, thiazides actually decrease urine volume.

2. Thiazides may induce hyperglycemia and aggravate preexisting diabetes mellitus.

3. Thiazides are the diuretics of choice in the management of oedema due to mild to moderate congestive heart failure.

D. Carbonic Anhydrase (CA) Inhibitors: (Fig. 21.4)

(i) Inhibit cytoplasmic CA and thereby the reaction CO₂ + OH^– ⇌ HCO₃^– at Proximal convoluted Tubule. Na⁺ – H⁺ exchange mechanism is inhibited → H⁺ + HCO₃ – ⇌ H₂CO₃ ⇌ CO₂ + H₂O reaction in human is inhibited.

(ii) So, reabsorption (in the form of CO₂) of HCO₃– in proximal tubule is inhibited by 80%, half of which is reabsorbed in later parts and others excreted.

(iii) ↑ excretion of Na⁺& K⁺.

E. Spironolactone: (Fig. 21.5)

Aldosterone action:

Aldosterone enters into cytoplasm and binds with its receptors → enters into nucleus → binds with DNA → interfere with RNA and protein (enzyme) synthesis → ↑ reabsorption of Na⁺ and secretion of K⁺.

1. Spironolactone binds with aldosterone receptors competitively and only in presence of aldosterone, and inhibits (reverse) its action i.e. increase Na⁺ excretion and decrease K⁺ excretion.

2. Metabolites of spironolactone in Liver are canrenone and canrenoate which are interchangeable. Canrenone is active aldosterone antagonist.

3. Spironolactone increases Ca²⁺ excretion.

4. In high concentration, Spironolactone can inhibit aldosterone synthesis.

Salicylates may interfere with tubular secretion of canrenone and thereby de­crease effectiveness of spironolactone.

Toxicity:

hyperkalemia.

F. Pot. Sparing Diuretics-(Fig. 21.6):

1. Primarily inhibit electro genic entry of Na⁺ (Na⁺ per se) at late distal tubule and collecting duct. Na⁺concentration in lumen is increased → potential dif­ference between epithelial cells and lumen increased → K⁺ enters into the cells from lumen → H⁺ follows and thereby urine become slightly alkaline.

2. Amiloride is an inhibitor of Na⁺ – H⁺ exchange mechanism of proximal tubule and of Na⁺ – K⁺– ATPase.

3. Amiloride ↓ es excretion of Ca²⁺.

Toxicity: hyperkalemia

G. Osmotic Diuretics:

1. They are pharmacologically inert substances (e.g mannitol)

2. They act on the part of the nephron (proximal tubule, descending limb of the Henle’s loop and the collecting tubules) which is freely permeable to water,

3. They increase the amount of water with relatively small increase in Na⁺ excretion.

Clinical Uses:

(i) They are clinically used in raised intracranial pressure.

(ii) Intraocular pressure (glaucoma)

(iii) Prevention of acute renal failure

Dose- 20% solution i.v at the dose of 1-2 ml/kg b.w.

Unwanted Effects:

(i) Hyponatremia

(ii) Nausea and vomition

(iii) Transient expansion of extracellular fluid volume

H. Xanthines:

1. Increases renal blood flow → ↑ glomerular filtration rate.

2. f in the rate of excretion of Na⁺ and Cl^– with no significant effect on urinary acidification.

Urinary Acidifiers:

Urinary acidification enhances the excretion of basic substances by increasing their ionization in filtrate and diminish their passive reabsorption across the tubular wall. The usual urinary pH of dogs and cats is acidic (5.5-7.0) while that of horses, cattle, sheep and goats is alkaline (7.0-8.0). Acidification improves the antibacterial activity in urinary tract infections.

The examples of urinary acidifier, which are used in veterinary practice are listed below:

(i) Sodium Acid Phosphate:

Dose in dog: 150-300 mg orally thrice daily

(ii) Ascorbic Acid:

Dose in dog: 250 mg – 500 mg thrice daily orally

(iii) Methionine:

Dose in dog: 30 mg/kg b.w. twice daily orally

(iv) Chlorethamine:

Dose in dog: up to 90 mg depending on the size, thrice daily, orally

(v) Ammonium chloride:

Dose in dog: 200-500 mg, orally,

Cattle: 15 g, orally,

Sheep & Pig: 1-2 g, orally.

Urinary Alkalizers:

The urinary alkalizers are metabolized and cations are excreted with bicarbonate changing the urine pH to alkaline. Sodium bicarbonate is commonly used as urinary alkalizers in cattle and other animals.

Benefits:

(i) This increases the action of sulfonamides and streptomycin . Alkalinization is important during sulfonamide therapy because it prevents formation of crystals inside the ureter and kidney and thus minimise haematuria.

(ii) It helps in excretion of weak acids (e.g. aspirin, salicylates, barbiturates etc.)

Dose of Sodium Bicarbonate:

Cattle – 15-30 g, orally, thrice daily, or -1.5%-5%, sol., i.v. inj.

Dog – 500 mg to 1 g, orally thrice daily

Aphrodisiacs and Anaphrodisiacs:

Aphrodisiacs are drugs that increase sexual desire and libido; on the other hand, anaphrodisiacs decrease the sexual desire and libido in recipient animals. Use of aphrodisiac in veterinary practice is limited however, they are used in animals that refuse mating.

Classification:

(i) Non hormonal aphrodisiacs or those that act through nervous system e.g. yohimbine, strychnine.

(ii) Aphrodisiacs acting by irritating the urogenital system e.g. cantherides.

Urinary Antiseptics:

Urinary tract antiseptics inhibit microbial growth inside the kidney, bladder and urinary tract. They do not achieve desired concentration in plasma at safe recom­mended doses, therefore, their therapeutic use for combating systemic infections are not beneficial.

Common Urinary Tract Antiseptics:

The use of older drugs such as volatile oils and oleoresins (oils of sand wood) are not used in modern medicine. However, the synthetic methenamine and mandelic acid are still in use. Presently, the newer antibacterial such as nitrofurantoin, nitroxoline, quinolone derivatives (nalidixic acid and fluoroquinolones) are widely used.

Methenamine:

It acts well if the urine pH is below 5.5. In practice, especially in dog and cat it is given 15- 20 min after sodium acid phosphate administration. After decomposition it releases ammonia and formaldehyde exerts an antibacterial action.

Dose:

Oral dose for cattle, pig, sheep, goat, dog and cat is 50 mg/kg b.w.

Side Effects:

Methenamine is irritant to gastrointestinal tract and can produce vomition in dog and cat.

Contraindication:

Hepatic and renal insufficiency.

Nalidixic Acid:

Nalidixic acid is bactericidal to gram-negative bacteria.99% of E.Coli 98% of Proteus mirabilis and 75 to 97% of other Proteus species, 92% of Klebsiella, enterobacter and 80% of other coliform bacteria are sensitive to concentrations of 16 µg/ ml or even less than this. It is less active against gram-positive microorganisms. Acquired resistance to the drug is very common during therapy.

Pharmacokinetics:

It is absorbed readily and completely after oral adminis­tration in simple stomach animals. The plasma protein binding value is very high i.e. 93 to 97%. The urine contains very high amount of nalidixic acid and its metabolites. The Cp_max of nalidixic acid is comparatively higher (101.05 ± 3.25 µg/ml) in febrile goats as compared to normal one (49.91 ± 0.29 µg/ml) after single i.v, dose of 10 µg/kg b.w.

However, it has been reported that Cp_ther is maintained for a very brief period (2.5 hr). The t_1/2β in normal and febrile goals were 0.54 ± 0.03 and 0.77 ± 0.03 hour respectively. However, a 41.58% increase in Cp_max and prolonged t_1/2β value to the extent of 16.22, ± 2.95 hour in febrile probenecid treated goats has been reported.

Side Effects:

Nausea, vomiting, abdominal pain, photosensitivity, fever, thrombocytopenia, leucopenia and haemolytic anaemia.

Important:

Liver function tests and blood cell counts are advisable especially in dogs and cats if treatment is continued longer than 15 days. Large doses can cause convulsions in dogs and cats.

Preparations Available in Market:

(i) Tablets of 250, 500 and 1000 mg

(ii) Suspension (250 mg/5 ml)

Dose:

Dog – 15-50 mg/kg in divided doses.

Mandelic Acid:

Ammonium mandelate or calcium mandelate is an urinary an­tiseptic. It shows its antibacterial activity at low urinary pH (5.5). The therapy must not be prolonged for more than 15 days at a time because it is irritant to the urinary tract. If therapy is required for more than 15 days it should be discontinued and again be started after 7 days.

Dose:

(Calcium mandelate)

Dog and Cat: 250 mg/kg b.w. orally daily in divided doses for 4-7 days

Nitrofurantoin:

Nitrofurantoin is a synthetic furan derivative used especially for prevention and treatment of urinary tract infections.

Drugs Acting on the Uterus:

Drugs acting on uterus can primarily affect the endometrium or myometrium. The most important drugs affecting endometrium are estrogens and progestins. Myometrium receives both sympathetic and parasympathetic innervation.

Autonomic drugs can affect its motility. However, directly acting drugs are more important and have more selective action. The responsiveness of mymoetrium to drugs is markedly affected by the hormonal and gestation status.

Oxytocics:

Oxytocics (ecbolics) are the drugs which stimulate contractions of the myometrium to promote rapid labour at term.

Abortifacients:

Abortifacients are the drugs which are able to induce parturition before full term. In other words, they are the agents which induce abortion.

There is overlap between ecbolics (oxytocics) and abortifacients, and the distinc­tion between them is in part dependent on use (at term or before term) rather than action; e.g. ergot is capable of inducing abortion if given during pregnancy. All ecbolics should be used with caution if the cervix is not fully dilated.

Classification of Drugs Acting on the Uterus:

A. Uterine Stimulants:

1. Posterior pituitary hormone:

(i) Oxytocin

2. Ergot alkaloids:

(i) Ergometrine (ergonovine)

(ii) Methylergometrine (methylergonovine)

3. Prostaglandins:

(i) PGE₂

(ii) PGF_2α

(iii) 15-methyl- PGF_2α (synthetic)

4. Miscellaneous:

(i) Quinine

(ii) Ethacridine

(iii) Cholinergic drugs

B. Ulterine Relaxants (Tocolytics):

1. Adrenergic agonists (selective β₂agonists):

(i) Salbutamol

(ii) Terbutaline

(iii) Ritodrine

(iv) Clenbuterol

(v) Isoxsuprine

2. Ca²⁺ – channel blockers:

(i) Nifedipine

3. Prostaglandin synthesis inhibitors:

(i) Aspirin

(ii) Ibuprofen

(iii) Other NSAIDS

4. Magnesium sulphate

5. Ethyl alcohol

6. Progesterone

7. Miscellaneous:

(i) Nitrites

(ii) Anticholinergics (Atropine)

(iii) Phenothiazines (Proquamazine)

(iv) General anaesthetics (specially halothane)

(v) Perphenazine (a major tranquillizer) and heroin were being used in earlier days.

Oxytocin, certain PG_S PGE₂& PGF_2α and some ergot alkaloids stimulate the smooth muscle of the uterus. Oxytocin is physiologically important at estrus in facili­tating sperm and zygote movement and at term in aiding parturition in most species. PG appears to be involved in natural parturition and its pharmacological use in dystocia or induced parturition is of great significance.

The autonomic nervous system has only minor influence on myometrial activity but does affect vasomotor control. The uterus, therefore, is independent of motor control by nervous system. Instead, it responds to humoral agents such as oxytocin and PG.

Myometrial response to oxytocin, PG, ergonovine and even the minor nervous system influences are very dependent on previous sensitization by estrogen or proges­terone. Estrogen, such as seen at estrous, increases spontaneous activity as well as responsiveness to oxytocic agents.

Progesterone, such as seen during diestrus or preg­nancy, decreases these responses. In most domestic species there is a prepartum de­cline in progesterone and a rise in estrogen, which facilitates myometrial response to these oxytocic agents.

Oxytocin:

Oxytocin is a Nano peptide synthesized in the supraoptic and para-ventricular nuclei of the hypothalamus within neurons that are distinct from those that contain ADH, then stored and released from the neurohypophysis.

Release of oxytocin is dependent on a signal from the nervous system. This could be reflexly induced by the fetus in the birth canal. Genital tract stimulation such as copulation is sufficient to cause oxytocin release to aid in propulsion of semen through the tract.

Pharmacological Effects:

1. Uterus:

Oxytocin stimulates both the frequency and force of contractile activ­ity in uterine smooth muscle. In low doses, full relaxation occurs in between contrac­tions; basal tone increases only in high doses.

Estrogens sensitize the uterus to oxytocin; its response is greatest when estrogen levels are high, such as during estrus or proestrus and late pregnancy; non pregnant uterus and that during early pregnancy (progester­one dominating time is rather resistant: sensitivity progressively increases in the third trimester; there is a sharp increase near term and quick fall during puerperium (the period or state of confinement after child birth).

Estrogen alone encourages spontaneous uterine motility, whereas progesterone alone depress it. During pregnancy or the luteal phase of the estrous cycle, both hormones are present but progesterone dominates. Likewise, during estrus and late pregnancy, estrogen dominates.

Oxytocin can reinforce and further pro­mote uterine motility in the estrogen dominated uterus but is less able to stimulate progesterone dominated uterus. The increased contractility is restricted to the fundus and body; lower segment is not contracted, may even be relaxed at term.

Action of oxytocin is independent of innervation. There are specific oxytocin receptors which mediate the response. Their number increases markedly during later part of pregnancy. Oxytocin can also release PG_S in the uterus.

2. Mammary Gland:

Oxytocin contracts myoepithelium of mammary alveoli and forces milk into the bigger milk sinusoids leading to milk ejection reflex or milk letdown in the lactating animals.

3. CVS:

In large doses, oxytocin causes a marked but transient relaxation of vascular smooth muscle and thereby produces a marked but brief fall in BP, reflex tachycardia and flushing; but conventional doses used in obstetrics have no effect. By contrast, oxytocin is a powerful constrictor of umbilical arteries and veins.

Clinical Uses of Oxytocin:

(i) Induction of labour

(ii) Uterine inertia (when uterine contraction is feable and labour is not pro­gressing satisfactorily)

(iii) Postpartum haemorrhage and caesarean section (ergometrine, oxytocin)

(iv) To induce mid-trimester abortion in women (but not very effective)

(v) Mammary gland engorgement.

Dose:

USP units of oxytocin/animal, IV or IM

Prostaglandins:

In the female reproductive system, prostaglandins are found in the ovary, myometrium and menstrual fluid in concentrations that vary with the ovulatory cycle. Following coitus, accessable portions of the female reproductive track are also exposed to PG_S, which occur in high concentrations in seminal fluid. At term, and during labor (parturition) PG concentrations rise in amniotic fluid, umbilical cord blood and mater­nal blood.

Effect on Myometrium:

During the last two trimesters of pregnancy, the admin­istration of either PGE₂ or PGF_2α causes strong uterine contractions and can induce delivery of the fetus. As with oxytocin, the sensitivity of the uterus to PG increase as gestation progresses.

However, the changes are less pronounced, and PG_S are much more effective than is oxytocin in inducing contractions in the earlier months. The higher doses that are required to produce abortion in the first few weeks after conception result in serious systemic effects.

Clinical Uses:

1. Mid-trimester abortion in women.

2. Postpartum haemorrhage.

3. As cervical reopening agents to facilitate normal or induced labour.

4. To soften the cervix prior to performance of first trimester abortion by the method of dilatation and evacuation.

5. For expulsion of mummified fetus in animals.

6. For synchronization of estrous (PGF_2α).

Dose:

For synchronization – (PGF_2α).

Cattle – 30 mg, IM inj, twice, 10 days apart at any time of the estrous cycle. Estrous occur within 2-4 days after second inj of (PGF_2α).

Sheep & Goats – 10-15 mg, IM inj, single, on any day from 5-14 of the estrous cycle. Estrus comes within 1-3 days after injection.

Ergot and the Ergot Alkaloids:

Ergot is the product of a fungus (Claviceps purpurea) that grows upon the rye, millet and some other grains. Rye is the most susceptible crop.

Ergot alkaloids are tetracyclic indole-containing compounds which may be con­sidered as derivatives of Lysergic acid or 6- methylergoline (Fig. 21.2, 21.3, 21.4)

Only two ergot derivatives, ergometrine and methyl-ergometrine are used in obstetrics. Both have similar pharmacological property.

Pharmacological Effects:

1. Uterus:

They increase force, frequency and duration of contractions. At low doses contractions are phasic with normal relaxation in between, but only moderate increase in dose raises the basal tone; contracture occurs with high doses. Gravid uterus is more sensitive, specially at term and in early puerperium. Their stimulant action involves the lower segment also.

2. CVS:

They are much weaker vasoconstrictors than ergotamine and have low propensity to cause endothelial damage. Though, they can raise BP, this is not significant at therapeutic doses.

3. CNS:

No overt effects occur at usual doses. However, high doses produce complex actions, partial agonistic/antagonistic interaction with adrenergic, serotonergic and dopaminergic receptors in the brain.

4. GIT:

High doses can increase peristalsis. Methylergometrine is 1½ times more potent on uterus, but other actions are less marked. It has thus replaced ergometrine at many obstetric units.

Clinical Uses:

1. To control and prevent postpartum haemorrhage-These drugs are preferred over oxytocin because they produce sustained tonic contraction: perforating uterine arteries are compressed by the myometrial meshwork – bleeding stops).

2. After caesarian section/instrumental delivery- to prevent uterine atony.

3. To ensure normal involution.

Doses of Ergometrine:

Ergometrine maleate (As tablet or by injection IM)

Horse and Cattle 10-20 mg

Sheep, Goats, Pigs – 0.5 – 1 mg

Dogs – 0.2 – 1 mg

Cats – 0.07 -0.2 mg

Fluid and Blood Therapy:

General Considerations:

1. Fluid compartments of the body:

(a) Total Body Water (45-75% of body weight).

1. Extracellular Fluid:

Fluid in the body outside the cell.

(a) Plasma (about 4% of body weight):

It comprises fluid of the intravascular space.

(b) Interstitial (about 15% of body weight):

Comprises all fluid not in the vascular system or within the cell.

2. Intracellular (about 50% of the body weight):

Includes all water within the cell.

2. Electrolyte:

(a) Extracellular:

1. Cations:

(a) Na⁺ – main cation – primary function is in maintenance of osmotic pressure and thus a certain volume of water.

2. Anions:

(a) Cl^– -also serves as a function of osmolality, also important component of certain tissues such as ovaries, testes, gastric and intestinal mucosa.

(b) HCO₃^– – very important in the blood buffering system

(b) Intracellular:

1. Cations:

(a) K⁺ plays a similar role as Na⁺, in addition important in conduction mechanism.

2. Anions:

(a) PO₄⁼ and Protein are important as intracellular buffers

3. Transport of Fluid:

(a) Occurs between various compartments due to a number of factors.

1. Osmotic pressure

2. Hydrostatic pressure

3. Diffusion

4. Concentration gradients

(b) Loss of fluid in one compartment reflects changes in others which may be opposite.

4. H⁺ ion concentration:

(a) Determines the pH

(b) Various disease states alter this and tend to either decrease or increase H⁺ ion concentration.

1. Acidosis – increased H⁺ ion decreases pH of blood

(a) Respiratory acidosis – due to respiratory changes or accumulated H₂ CO₃.

(b) Metabolic acidosis – non-respiratory in nature.

2. Alkalosis – decreased H⁺ ion increases pH of blood

(a) Respiratory alkalosis – due to respiratory changes

(b) Metabolic alkalosis – non-respiratory in nature.

5. Changes that result in either body water deficits or excesses quite often result in alterations in electrolyte and H⁺ ion concentration.

6. Sources of body water:

(a) Oral drinking – most important source regulated by thirst centre in brain

(b) Through food.

(c) Through oxidative processes.

1. Only source left when animal is unable to eat or drink.

7. Sources of water loss:

(a) Urine -most important

1. Kidney vastly important regulator in water conservation in addition to electrolyte and H⁺ ion

(b) Faeces

(c) Lungs – Insensible loss

(d) Skin – important in dog and horse. Large amounts of water can be lost by these routes in hot weather.

Dehydration:

1. Definition – loss of body water

2. Causes – will occur in any condition where water intake is less than water output.

(a) Water depletion

(b) Salt depletion

(c) Vomiting

(d) Diarrhoea

(e) Obstructive disease of GI tract

(f) Sweating

(g) Hyperventilation

(h) Renal dysfunction

(i) Diabetes insipidus

3. Signs:

(a) Weight loss

1. Generally fatal if 15% lost

(b) Loss of skin turgor and elasticity.

1. Pinch skin and it won’t retract back as fast.

2. More marked with loss in extracellular compartment.

(c) Dry mucous membranes:

(d) Sunken eyeballs

(e) Faeces firm and dry.

(f) Decreased urine output.

(g) Hemoconcentration.

(h) As dehydration becomes more marked.

1. Fall in blood pressure

2. Increased heart and respiratory rate.

3. Anuria.

4. Shock.

5. Coma and death.

Water Depletion:

Results in:

1. Greatest fluid loss in intracellular compartment

(a) Some loss in extracellular but not as marked.

2. Some loss of electrolyte, primarily Na⁺ and Cl^– with a little K⁺.

3. Causes.

(a) Faulty drinking devices.

(b) Overzealous diuretic therapy

(c) Diabetes insipidus

4. Signs of dehydration

(a) Skin turgor not as marked even though very marked cellular dehydration

5. Prognosis

(a) Will depend on severity

6. Treatment

(a) In mild cases

1. Oral water supplementation with salt

(b) In more advanced

1. 5% glucose solution intravenously (10-30 cc/kg body weight over a 12 hour period)

2. Supplement with oral water and salt

Salt Depletion:

1. Result in marked loss within the plasma and interstitial compartments. Very little in the intracellular.

2. Causes:

(a) Restriction of salt

(b) Sweating or hyperventilating without adequate salt intake

(c) Renal disease

(d) Overzealous diuretic treatment

3. Signs:

(a) Dehydration signs all marked

4. Prognosis:

(a) Will depend on severity

5. Treatment:

(a) In mild dehydration, oral supplementation; if able, intravenous isotonic saline.

(b) In severe dehydration, hypertonic saline solution will result in a more clinical improvement

1. Supplemented with oral water

2. 5% saline commonly used

(a) 6 ml/Kg body weight, dose divided in Quarter for each infusion.

3. In severe dehydration, isotonic saline may also cause oedema.

Fluid and Electrolyte loss from Gl tract:

1. Vomiting:

(a) Greatest loss of H⁺ ion and Cl^– plus water.

1. Some loss of Na⁺ and K⁺

2. Results in a metabolic alkalosis with a hypochloremia

(b) Occurs commonly in dog, cat and pig

(c) Ruminants and horses rarely vomit

1. Cattle sometimes vomit on grass silage

2. A penetrating foreign object near the ruminoreticular fold or cardia may cause vomition.

(d) Treatment

1. Correct primary cause

2. Parenteral fluid and electrolyte

(a) Won’t retain oral fluid

(b) Use a fluid to replace electrolyte lost

1. NaCl quite good

2. NH₄ CI

2. Diarrhoea:

(a) Loss of water, Na⁺, K⁺ and HCO₃^–

1. Some loss of Cl^–

(b) Acidosis is present because of excessive bicarbonate loss

1. Acidosis is mild to severe, depending on the severity and somewhat the age of the animal

2. In young calves acidosis is quite severe

(a) Dehydration is also more severe in young animals.

1. Faster water turnover

2. Have larger interstitial compartment and less intracellular space than adult

(a) Water not as well conserved

(c) Treatment:

1. Anti-diarrhoeal therapy

2. Parenteral fluids

(a) Sodium lactate

(b) Lactated Ringer’s

3. Oral fluids may be of value if gut motility slowed down

3. Obstructive Diseases of Bowel:

(a) Etiology:

1. Foreign bodies

2. Faecal masses

3. Adhessive bands

4. Intussusception

5. Volvulus

6. Torsion

7. Strangulation

8. Ileus

(b) Site of obstruction affect on pattern

1. In general, higher the obstruction the quicker death results

2. High obstruction

(a) Causes vomition in species that vomit

1. Results in Hypochloremic alkalosis

(b) In ruminants and horses, even though vomition doesn’t occur, have build up of fluid and electrolyte in stomachs and compartments, so it is effec­tively lost.

1. Results in Hypochloremic alkalosis

3. Low obstruction

(a) will tend to develop alkalosis.

(b) In some cases little change may be seen.

(c) Type of obstruction

1. The obstructions producing occlusion of blood supply result in a much more rapid course.

(d) Treatment

1. Correct underlying cause

2. Parenteral fluids patterned to replace the major constituents lost.

(a) NaCl/NH₄Cl – For high obstruction

(b) Lactated Ringer’s – in low obstruction

Route of Administration:

1. Oral:

(a) This route is often neglected

(b) Can administer large amounts of fluids quite rapidly. In addition electro­lytes can be given quite safely.

(c) Can not use in vomition or obstruction

1. May aggravate diarrhoea

(d) Rate of absorption is slow

2. Intravenous:

(a) Immediate results – used where treatment has to be prompt

(b) Can not administer as rapidly as the oral route.

(c) Danger of over-hydration, pulmonary edema and cardiac failure

(d) Generally solutions should be isotonic unless otherwise indicated

3. Subcutaneous:

(a) Can give fairly large amounts of fluids quite rapidly.

(b) Rate of absorption slower than IV but faster than oral.

1. Can increase rate of absorption by greater diffusion with administra­tion of hyaluronidase.

(c) Solutions should be isotonic or hypotonic

l. Hypertonic solutions will draw water and cause further dehydration.

4. Intra-peritoneal:

(a) Fairly large volumes may be administered quite rapidly.

(b) Rate of absorption quite rapid.

(c) Can not use irritating fluids.

(d) Contraindicated in peritonitis

1. May also introduce infection

(e) Should use isotonic solutions

1. Hypertonic solutions will draw water.

5. Intramuscular and intra-pleural not often used.

Dosage of Fluids:

1. Dependent on estimated loss:

(a) Use a fluid to replace those ions lost.

(b) 10-30 cc/kg up to 60-100 cc/kg body weight.

(c) Generally isotonic -iso-osmotic solutions are used.

1. Hypertonic solutions are used where severe loss of sodium.

(d) Where water alone is indicated administer 5% glucose

(e) In cases of over-hydration, administer hypertonic saline.

Whole Blood Therapy:

1. Indications:

(a) Shock

(b) Anemia

(c) Specific blood clotting deficiencies

(d) Specific diseases

2. Calculation of dosage:

(a) Hemoglobin method:

1. 18 kg dog has a total blood volume

(a) @88 ml/kg – 18 x 88 = 1584 ml Total Blood volume (T.B.V.)

(b) Normal Hb value 16 gm.%

2. Therefore 1584 cc/16 gm.% = 99 ml/1gm% Hb

3. Example: Same animal is anemic and has a measured 4 gm.% Hb. To raise the Hb value to 75% of normal or 75 x 16 = 12 would require an additional 12-4 = 8 gm. Hb or 8 x 99ml = 792 ml blood.

(b) RBC Method:

1. 150 lb. animal

(a) 150 x 40ml/lb = 6,000ml T.B.V

2. Animal has normally 6,000,000 RBC/mm³, or 6 x 10⁹ RBC/ml blood.

3. So 6,000,000/6,000 = 1,000 RBC/mm³/ml blood

4. If you then have an anemic animal with a measured 3,000,000 RBC/ mm³ you need 6,000, 000-3,00,000 = 3,000,000 to return to normal value.

So, administer 3,000,000/1,000 = 3,000 ml blood to raise blood count to 6,000,000 RBC/mm³

(c) Some administer 6-8 ml/lb body weight and then evaluate clinical picture.

3. Complications:

(a) Circulatory overload

1. Administration too rapidly and too large an amount.

2. Very anemic and toxic animals can not tolerate large or rapid amounts.

(b) Phlebitis at injection site

(c) Urticarial and allergic reactions

1. Fairly common.

2. Seen following sensitization especially with repeated transfusions,

(d) Transfusion reactions

1. Important in dog and horse.

(a) Should cross match if animals are valuable.

2. One transfusion generally does not have any reaction,

(e) Transmission of disease

1. Blood parasites.

(f) Administration of grossly contaminated blood.

1. Poor collection method and storage.

(g) Miscellaneous

1. Pyrogenic reactions

2. K⁺ excess

3. Administration of blood clots

4. Administration of air emboli

4. Collection of blood:

(a) Donor:

1. Select a young (3-6 yrs. of age), healthy donor free from any apparent acute or chronic infectious disease.

(a) Exposure to a variety of diseases at an early age will result in donor that may well be utilized as a source against specific diseases (calf scours, etc.).

2. If animal has a temperature rise at the time of collection do not collect.

3. May draw 10-15% of estimated blood volume without complications.

(a) Give animal a chance to regenerate (4-6 weeks rest).

4. Often practitioners have several herds from which blood can be donated. So a source is always available and thus storage problems are minimal.

(a) Small animal practitioners may keep several donor dogs and cats in their kennels.

(b) Abbatoir

(b) Collection procedure

1. For storage – must use strict aseptic technique and sterile equipment.

2. Anticoagulants

(a) Storage:

1. ACD (Acid Citrate Dextrose) solution.

Na citrate – 25 gm.

Citric acid – 8 gm.

Anhydrous dextrose – 24.5 gm.

Distilled Water – up to 1000 ml

Dose:

15 ml of ACD solution per 100 ml blood.

2. Na citrate sol.:

Sod. Citrate – 2.5 g

NaCl – 0.9 g

Distilled water – 100 ml

Use 1 ml for 9 ml blood for direct transfusion.

4. Heparin sodium – 400-600 units/100 ml blood.

5. Na oxalate

(c) Collection apparatus:

1. Gallon plastic bottles

2. 2 liter Fenwall apparatus with adapted vacuum bulb.

3. 1 liter commercial vacuum bottles with anticoagulant^

4. 100cc, 300cc, 500cc commercial bottles.

5. Gravity flow collection.

5. Storage:

(a) 35-37° F best, 40-42° F quite good

(b) Can store for 15-21 days.

1. Too much hemolysis after this time.

2. Can harvest plasma.

(c) Allow blood to cool down slowly before refrigeration; otherwise too much hemolysis may occur. Administer refrigerated blood directly with­out warming (again hemolysis may be found on warming).

6. Plasma:

(a) Harvested from sterile, collected blood under aseptic techniques.

(b) Can be stored up to 3 yrs. at room temperature if it is sterile.

(c) Usually dextrose is added.