Veterinary · Para-clinical · also MSVE VPT-311
How drugs move through and act on the body, how species differ, and the drugs used on each organ system.
In the exams: ICAR AICE-JRF core group 07; ICAR AIEEA-PG 13 (Pharmacology & Toxicology); PRC 10%; Nepal NLEV 6 (with toxicology); China basic paper 15; BCSE 28-32 items (with physiology and toxicology); AVE Paper 1 at least 5
General and systemic veterinary pharmacology is the study of how drugs enter, move through, act on and leave the bodies of animals, and of the drugs used to treat disease of each organ system. General pharmacology covers the principles that apply to every drug: where drugs come from, pharmacokinetics (what the body does to the drug), pharmacodynamics (what the drug does to the body) and the reasons species respond differently. Systemic pharmacology applies those principles organ by organ: the autonomic nervous system, autacoids, the heart and vessels, the airways, the gut and rumen, the kidney and reproductive tract, the endocrine glands, inflammation and pain, and body fluids.
Veterinary pharmacology differs from human pharmacology in three ways that run through this manual. First, the patient may be a dog, a cat, a cow, a horse, a pig, a bird or a fish, and a drug that is safe in one may kill another: paracetamol in cats, ivermectin in Collies with the MDR1 mutation, lincosamides in horses and rabbits. Second, many patients are food animals, so every treatment decision carries a withdrawal period and a residue risk to people who eat meat, milk or eggs. Third, the law on which drugs may be used, and how, differs by country: the EU works through Regulation (EU) 2019/6 and the residue table in Regulation (EU) 37/2010, the USA through the Animal Medicinal Drug Use Clarification Act and 21 CFR 530, and other countries through their own regulators.
Examiners worldwide return to the same core. This manual is written to serve all of them.
A drug is any substance used to prevent, diagnose or treat disease, or to change a physiological function, in an animal. Drugs come from five broad sources. Plants gave the first drugs and still supply many: atropine from deadly nightshade (Atropa belladonna), digoxin and digitoxin from foxglove (Digitalis species), morphine and codeine from the opium poppy (Papaver somniferum), pilocarpine from Pilocarpus leaves, physostigmine from the Calabar bean (Physostigma venenosum), quinine from Cinchona bark, and ergot alkaloids from the fungus Claviceps purpurea growing on rye. Animals supply insulin (historically from pig and cattle pancreas), heparin (from pig intestinal mucosa), thyroid extract, and gonadotrophins such as equine chorionic gonadotrophin from the serum of pregnant mares. Minerals supply magnesium sulfate, kaolin, iron, copper and zinc salts, and calcium salts. Micro-organisms supply antibiotics: penicillin from Penicillium moulds, streptomycin from Streptomyces griseus, and the avermectins from Streptomyces avermitilis. Most modern drugs are synthetic or semi-synthetic, and a growing number are biotechnological, made by recombinant DNA technology, such as recombinant insulin and monoclonal antibodies.
Crude plant drugs work through chemically defined active principles. Alkaloids are nitrogen-containing bases, usually bitter, poorly soluble in water as the free base and soluble as salts; atropine, morphine, strychnine, nicotine and caffeine are alkaloids. Glycosides are a sugar (glycone) joined to a non-sugar (aglycone); the aglycone carries the activity. Cardiac glycosides of Digitalis act on the heart, anthraquinone glycosides of senna and aloe are purgatives, cyanogenic glycosides of sorghum and linseed release hydrogen cyanide, and saponins foam and are irritant. Tannins are astringent polyphenols that precipitate protein and were used as antidiarrhoeals. Volatile (essential) oils such as turpentine and eucalyptus oil are aromatic and carminative. Fixed oils such as linseed and castor oil are lubricant or purgative.
Every drug has three names: a chemical name describing its structure, a non-proprietary name (the International Nonproprietary Name, INN, used in pharmacopoeias and in this manual) and one or more proprietary trade names owned by manufacturers. Veterinary dosage forms reflect the species and the setting. Route governs speed and completeness of absorption: intravenous gives immediate and complete availability, intramuscular and subcutaneous give slower absorption that depends on blood flow and formulation, oral absorption is variable and subject to first-pass metabolism, and topical routes are intended for local action but may produce systemic effects and residues. In food animals the injection site matters: intramuscular injections damage muscle and can leave residues at the site longer than elsewhere, so many guidelines prefer the neck to the valuable hindquarter cuts. Extra-label use is regulated nationally: the EU cascade under Regulation (EU) 2019/6 steps from another species' or condition's authorised product, to a human product, to a compounded one; the US allows it under AMDUCA and 21 CFR 530 (chapter 6). Controlled drugs carry extra record-keeping duties everywhere.
Most drugs cross cell membranes by passive diffusion, moving down a concentration gradient through the lipid bilayer. The rate depends on lipid solubility, molecular size and the degree of ionisation. Weak acids and weak bases exist in ionised and un-ionised forms; only the un-ionised form diffuses readily. The Henderson-Hasselbalch equation gives the ratio. For a weak acid, log(ionised/un-ionised) = pH minus pKa; for a weak base, log(ionised/un-ionised) = pKa minus pH. An acid is mostly un-ionised in an acidic compartment and a base is mostly un-ionised in an alkaline one. When two compartments differ in pH, the drug accumulates on the side where it is more ionised, a process called ion trapping. This explains why weak bases concentrate in milk (pH about 6.5 to 6.8, lower than plasma at 7.4) and in the rumen (pH roughly 5.5 to 6.5 on typical diets), and why weak acids are excreted faster in alkaline urine. Absorption after oral dosing is also affected by gastric emptying, food, gut motility, formulation, and in ruminants by dilution in and degradation by the rumen.
Bioavailability (F) is the fraction of an administered dose that reaches the systemic circulation unchanged. It is 1 (100%) by definition for an intravenous dose. For any other route it is found by comparing the area under the plasma concentration-time curve (AUC) with that after intravenous dosing, corrected for dose: F = (AUC route / dose route) divided by (AUC IV / dose IV). Low oral bioavailability has two main causes: incomplete absorption and first-pass metabolism, in which drug absorbed from the gut passes through the portal vein and liver, and is partly metabolised, before reaching the systemic circulation. Drugs with a high hepatic extraction ratio, such as propranolol and lidocaine, have low oral bioavailability for this reason.
After absorption a drug distributes from plasma into interstitial fluid and cells. The rate depends on blood flow (brain, heart, liver and kidney first; muscle, skin and fat later), capillary permeability, lipid solubility and binding. Many drugs bind reversibly to plasma proteins: acidic drugs mainly to albumin, basic drugs also to alpha-1-acid glycoprotein. Only the unbound fraction is pharmacologically active, crosses membranes and is filtered at the glomerulus. Special barriers limit distribution. The blood-brain barrier, formed by tight junctions and efflux pumps such as P-glycoprotein, excludes polar drugs and P-glycoprotein substrates; this is why a defective MDR1 gene exposes the brain to ivermectin. The apparent volume of distribution (Vd) relates the amount in the body to the plasma concentration (Vd = amount / concentration). It is a proportionality constant, not an anatomical space. A Vd near 0.05 L/kg suggests confinement to plasma, about 0.2 to 0.3 L/kg to extracellular fluid, about 0.6 L/kg to total body water, and several L/kg or more indicates extensive tissue binding or sequestration.
Metabolism, or biotransformation, converts lipid-soluble drugs into more polar compounds that the kidney and bile can excrete. Phase I reactions (oxidation, reduction and hydrolysis) introduce or expose a functional group. Oxidation is largely by the cytochrome P450 (CYP) enzymes of the smooth endoplasmic reticulum; hydrolysis is by esterases and amidases. Phase II reactions are conjugations: glucuronidation (by UDP-glucuronosyltransferases), sulfation, acetylation, glutathione conjugation, methylation and amino acid conjugation (glycine, and in some species other amino acids). Most metabolites are inactive, but some are active (prednisone is converted to prednisolone, enrofloxacin partly to ciprofloxacin, diazepam to desmethyldiazepam) and some are toxic (the reactive metabolite of paracetamol). Enzyme induction by repeated exposure to phenobarbital, rifampicin or some organochlorines increases metabolism of the inducer and of other drugs. Enzyme inhibition by chloramphenicol, ketoconazole, cimetidine and some fluoroquinolones slows metabolism and can cause toxicity from co-administered drugs such as theophylline. Metabolic capacity differs markedly by species, age and liver health.
The kidney is the main route of excretion for polar drugs and metabolites. Three processes act. Glomerular filtration passes the unbound drug. Active tubular secretion, by anion and cation transporters in the proximal tubule, can clear even bound drug; penicillins are secreted this way and probenecid competes with them. Passive tubular reabsorption returns lipid-soluble, un-ionised drug to the blood, so changing urine pH changes excretion: alkalinising urine speeds excretion of weak acids such as salicylate and phenobarbital. Herbivores normally produce alkaline urine and carnivores acidic urine, which affects the excretion of ionisable drugs. Biliary excretion carries larger, conjugated molecules into the gut; if gut bacteria remove the conjugate, the drug is reabsorbed and cycles through the liver again (enterohepatic recycling), prolonging its action. Drugs are also excreted in milk, which matters for residues and for suckling young; and, for volatile anaesthetics, through the lungs. Renal disease slows the excretion of drugs cleared by the kidney, such as aminoglycosides and digoxin, and doses or intervals must be adjusted.
In first-order kinetics, a constant fraction of the drug in the body is eliminated per unit time; the rate is proportional to concentration. Most drugs at therapeutic doses follow first-order kinetics. In zero-order kinetics a constant amount is eliminated per unit time, because the eliminating enzyme or transporter is saturated; ethanol is the classic example, and some drugs become zero-order at high doses. For a first-order drug in a one-compartment model, concentration falls exponentially: C = C0 multiplied by e to the power (-k t), where C0 is the concentration at time zero and k is the elimination rate constant (units: per hour). The elimination half-life (t1/2) is the time for the plasma concentration to fall by half: t1/2 = 0.693 / k. After one half-life 50% remains, after two 25%, after three 12.5%, after four 6.25%, and after five about 3%. For practical purposes a drug is regarded as eliminated after four to five half-lives, and the same number of half-lives is needed to reach steady state on repeated dosing. Many drugs show two phases after an intravenous bolus: a rapid distribution (alpha) phase and a slower elimination (beta) phase; this is the two-compartment model, and the terminal half-life is taken from the beta phase.
Clearance (CL) is the volume of plasma cleared of drug per unit time (for example mL/min/kg or L/h/kg). Total body clearance is the sum of renal, hepatic and other clearances. It can be measured as CL = F x dose / AUC. For a one-compartment drug, CL = k x Vd, and therefore t1/2 = 0.693 x Vd / CL. This equation shows that half-life is a dependent variable: it lengthens if volume of distribution rises (as in a dehydrated animal regaining fluid, or a lipophilic drug in an obese one) or if clearance falls (as in renal or hepatic failure).
A dosing regimen is the dose, route and interval. At steady state, the rate of drug in equals the rate of drug out, so the maintenance dose rate = CL x target steady-state concentration (Css) / F. For intermittent dosing, the average steady-state concentration is Css(avg) = F x dose / (CL x dosing interval). A loading dose fills the volume of distribution at once, so that the target concentration is reached without waiting four to five half-lives: loading dose = Vd x target concentration / F. When doses are repeated before the previous dose is fully eliminated, the drug accumulates. The accumulation ratio is R = 1 / (1 - e to the power (-k tau)), where tau is the dosing interval; if tau equals one half-life, R is 2, so steady-state peaks are twice the first-dose peak.
Example 1. A 20 kg dog receives 200 mg of a drug intravenously; the back-extrapolated plasma concentration C0 is 5 mg/L. Vd = 200 / 5 = 40 L, which is 2 L/kg. Example 2. A drug has k = 0.1155 per hour. t1/2 = 0.693 / 0.1155 = 6 hours. Example 3. Concentration is 40 mg/L at 2 hours and 10 mg/L at 6 hours. It has halved twice in 4 hours, so t1/2 = 2 hours. Example 4. A 500 kg horse needs a target concentration of 10 mg/L of a drug with Vd 0.7 L/kg given intravenously. Loading dose = 0.7 x 500 x 10 = 3,500 mg = 3.5 g. Example 5. A 30 kg dog needs a steady-state concentration of 5 micrograms/mL of a drug with clearance 2 mL/min/kg. Maintenance rate = 2 x 30 x 5 = 300 micrograms/min = 18 mg/h. The common errors are unit slips (mL versus L, minutes versus hours, micrograms versus milligrams), forgetting to multiply per-kilogram values by body weight, forgetting to divide by F for non-intravenous routes, and using the log10 slope without the 2.303 factor. Therapeutic drug monitoring, measuring plasma concentrations at defined times, is used in veterinary practice for drugs with a narrow therapeutic range and variable kinetics, such as phenobarbital, potassium bromide, digoxin and aminoglycosides.
Most drugs act by binding to a target: a receptor, an enzyme, an ion channel or a transporter. Receptors fall into four superfamilies. Ligand-gated ion channels (for example the nicotinic acetylcholine receptor and the GABA-A receptor) act within milliseconds. G-protein-coupled receptors (muscarinic, adrenergic, histamine, opioid and prostaglandin receptors) act in seconds through second messengers such as cyclic AMP, inositol trisphosphate and diacylglycerol. Kinase-linked receptors (insulin and many growth factor receptors) act over minutes to hours. Nuclear receptors (for steroid and thyroid hormones) regulate gene transcription and act over hours to days, which is why a single glucocorticoid dose has effects that outlast its plasma half-life.
Affinity is the tendency of a drug to bind a receptor. Efficacy (intrinsic activity) is its ability, once bound, to produce a response. A full agonist has affinity and full efficacy. A partial agonist has affinity but produces less than the maximal response even at full occupancy, and can antagonise a full agonist; buprenorphine at the mu-opioid receptor is the veterinary example. An antagonist has affinity but no efficacy. A competitive (surmountable) antagonist shifts the agonist's log dose-response curve to the right in parallel, without lowering the maximum; atropine against acetylcholine at muscarinic receptors is the model. A non-competitive or irreversible antagonist lowers the maximum response. On a graded log dose-response curve, potency is the position on the dose axis, measured by the EC50 or ED50 (dose giving 50% of the maximal effect), and efficacy is the height of the plateau (Emax). A more potent drug is not necessarily more effective. Quantal dose-response curves plot the proportion of a population showing an all-or-none effect, and give the median effective dose (ED50) and median lethal dose (LD50).
The therapeutic index (TI) is LD50 / ED50 in animals (TD50 / ED50 when toxicity rather than death is the endpoint). A small TI means a narrow margin, as for digoxin, theophylline and aminoglycosides. The certain safety factor, LD1 / ED99, is a stricter measure because it compares the extremes of the two curves. Drugs given together may show additive effects (the combined effect equals the sum), synergism (greater than the sum, as with trimethoprim and a sulfonamide), potentiation (a drug with no effect of its own increases another's effect) or antagonism, which may be pharmacological (at the receptor), physiological (opposing effects through different receptors, like adrenaline against histamine in anaphylaxis), chemical (protamine neutralising heparin) or pharmacokinetic. Repeated exposure changes responses. Tolerance is a gradual loss of effect needing larger doses (opioids, nitrates). Tachyphylaxis is a rapid loss of effect over a few doses, often from depletion of mediators, as with indirectly acting sympathomimetics such as ephedrine. Adverse reactions are type A (dose-related extensions of known pharmacology, such as NSAID ulceration) or type B (idiosyncratic or immune, such as penicillin anaphylaxis); the MDR1 defect is the classic veterinary idiosyncrasy.
Species differ in body composition, gut anatomy, drug-metabolising enzymes, transporters and receptor sensitivity. The main metabolic gaps are: cats glucuronidate phenolic drugs poorly (UGT1A6 is a pseudogene), dogs lack N-acetylation, and pigs have weak sulfation of some phenols. Because cats glucuronidate phenolic drugs slowly, drugs that rely on glucuronidation have prolonged half-lives or toxic effects in cats. Paracetamol (acetaminophen) is the key example: with glucuronidation weak and sulfation quickly saturated, more drug is oxidised to a reactive metabolite that depletes glutathione and causes methaemoglobinaemia, Heinz body anaemia and facial and paw oedema. Paracetamol must never be given to cats. Aspirin has a much longer half-life in cats than in dogs, so if used at all it is given at long intervals. Cats also have a defective ABCG2 transporter at the blood-retina barrier, which is linked to retinal degeneration with high doses of some fluoroquinolones, notably enrofloxacin. Cats are sensitive to permethrin toxicity (covered in toxicology), to lidocaine-induced seizures at lower doses than dogs, and convert prednisone to prednisolone poorly, so prednisolone is preferred.
P-glycoprotein, encoded by the ABCB1 gene (also called MDR1), is an efflux pump in the blood-brain barrier, intestine, liver and kidney. A 4-base-pair deletion (ABCB1-1 delta) produces a non-functional protein. It is common in Collies and occurs in Australian Shepherds, Shetland Sheepdogs, Old English Sheepdogs, Long-haired Whippets, Silken Windhounds, McNabs, German Shepherds and herding-breed crosses. Homozygous affected dogs, and to a lesser degree heterozygotes, let P-glycoprotein substrates into the brain. Macrocyclic lactones such as ivermectin at the higher doses used for mange cause tremors, ataxia, blindness, coma and death (heartworm-preventive doses are generally tolerated); loperamide causes CNS depression; acepromazine and butorphanol produce deeper and longer sedation; and anticancer drugs such as vincristine, vinblastine and doxorubicin cause more severe myelosuppression. Dogs, lacking acetylation, handle sulfonamides by other routes and are prone to idiosyncratic sulfonamide reactions (keratoconjunctivitis sicca, polyarthritis, hepatopathy), especially in Dobermans.
The rumen dilutes oral drugs in a large volume (roughly 100 to 200 L in adult cattle), slows their absorption and exposes them to microbial degradation; some drugs, such as chloramphenicol, are inactivated there, and oral antibiotics can disrupt the microflora and cause indigestion. The rumen pH (about 5.5 to 6.5) traps weak bases given parenterally, which diffuse in and become ionised. In young calves the oesophageal (reticular) groove closes in response to suckling, diverting liquids to the abomasum; drugs given by bottle may bypass the rumen, while drenches can go either way. Oral bioavailability of many drugs in adult ruminants is low, so the parenteral route is usual. Cattle are far more sensitive to xylazine than horses and dogs, needing roughly one-tenth of the equine dose; goats are more sensitive still. Ruminant urine is alkaline, which speeds excretion of weak acids.
The horse is a hindgut fermenter with a large caecum and colon. Antimicrobials that disturb the hindgut flora, especially lincosamides (lincomycin, clindamycin) and, in some circumstances, oral macrolides and tetracyclines, can cause severe and fatal colitis; lincosamides are contraindicated in horses. Horses develop excitement with some opioids and are sensitive to the CNS effects of procaine released from procaine penicillin, especially if accidentally injected into a vessel. Phenylbutazone, widely used in horses, can cause right dorsal colitis and renal papillary necrosis, and in the EU a horse treated with it is permanently excluded from the food chain. Rabbits, guinea pigs, hamsters and chinchillas are likewise at risk of fatal dysbiosis and clostridial enterotoxaemia from oral lincosamides, penicillins, cephalosporins and macrolides. Fish are poikilotherms, so drug kinetics and withdrawal times depend on water temperature and are expressed in degree-days.
Neonates have immature hepatic enzymes, lower glomerular filtration, higher total body water and lower plasma albumin, so water-soluble drugs have larger volumes of distribution and many drugs have longer half-lives. Hepatic disease slows metabolism of high-extraction and CYP-dependent drugs; renal disease slows excretion of renally cleared drugs; hypoalbuminaemia raises the free fraction of bound drugs.
A residue is any pharmacologically active substance, or its metabolites, remaining in meat, offal, milk, eggs, honey or fish after treatment. Residues matter because of direct toxicity (chloramphenicol can cause dose-independent aplastic anaemia in people), hypersensitivity (penicillin allergy), carcinogenicity (nitrofurans and nitroimidazoles), selection of antimicrobial resistance, inhibition of starter cultures in cheese and yoghurt manufacture, and loss of trade. Limits are derived from toxicology. Studies identify the no-observed-adverse-effect level (NOAEL); dividing by a safety factor (often 100, covering differences between animals and people and among people) gives the acceptable daily intake (ADI), the amount a person can ingest daily for life without appreciable risk, in mg per kg body weight per day. For antimicrobials a microbiological ADI, protecting the human gut flora, may be lower and then governs. The maximum residue limit (MRL) is the highest concentration of a marker residue legally permitted in a named food tissue, set so that a standard food basket does not exceed the ADI. The USA uses the term tolerance, published in 21 CFR 556.
In the EU, Regulation (EU) 470/2009 sets the procedure for establishing MRLs and Commission Regulation (EU) 37/2010 lists the outcome. Its Table 1 lists allowed substances with their MRLs (or states that no MRL is required) by species and tissue. Its Table 2 lists prohibited substances for which no MRL can be set, so they may not be given to food-producing animals: Aristolochia species, chloramphenicol, chloroform, chlorpromazine, colchicine, dapsone, dimetridazole, metronidazole, nitrofurans (including furazolidone) and ronidazole. A substance absent from Table 1 may not be used in food-producing animals at all. Separate EU legislation (Directive 96/22/EC) bans hormonal growth promoters and beta-agonists for growth promotion. Under Regulation (EU) 2019/6, when a veterinarian uses a product under the cascade in a food-producing species, the withdrawal period must be at least the longest label withdrawal period for that tissue multiplied by 1.5; if the product is not authorised for any food-producing species, the minimum is 28 days for meat and offal and 7 days for milk; for fish the period is expressed in degree-days. Horses are food animals in the EU unless their passport declares them not intended for slaughter; substances on the list of essential substances for equines carry a six-month withdrawal.
The US Animal Medicinal Drug Use Clarification Act (AMDUCA) of 1994, implemented in 21 CFR part 530, allows extra-label use of approved drugs by or under the order of a licensed veterinarian within a valid veterinarian-client-patient relationship, when the animal's health is threatened or suffering would result without treatment. It does not permit extra-label use in feed, and extra-label use in food animals must not produce a violative residue; the veterinarian must set a substantially extended withdrawal time, supported by scientific information, and ensure identification of treated animals. The Food Animal Residue Avoidance Databank (FARAD) advises on such withdrawal times. Section 530.41 lists drugs prohibited from extra-label use in food-producing animals. These include chloramphenicol, clenbuterol, diethylstilbestrol, dimetridazole, ipronidazole and other nitroimidazoles, furazolidone and nitrofurazone, fluoroquinolones, glycopeptides such as vancomycin, sulfonamides in lactating dairy cattle (other than approved uses of a few named sulfonamides), phenylbutazone in female dairy cattle 20 months of age or older, and certain extra-label uses of cephalosporins (other than cephapirin) in cattle, swine, chickens and turkeys. Antiviral adamantanes and neuraminidase inhibitors are prohibited extra-label in chickens, turkeys and ducks.
The withdrawal period (withholding time) is the minimum time between the last dose and slaughter, or collection of milk or eggs, for residues in all edible tissues to fall below the MRL. It is set from residue depletion studies: a marker residue is measured in the target tissue (often liver or kidney, or the injection site) over time, and a statistical tolerance limit is fitted; the EU commonly uses the 95th percentile with 95% confidence, and the US FDA the 99th percentile with 95% confidence. Because depletion is first-order, the time to fall from a concentration C0 to the MRL is t1/2 x log2(C0 / MRL); a safety margin is then added. Withdrawal periods are product-specific, not molecule-specific: the same molecule in a long-acting formulation, at a higher dose, by a different route, or in a sick or dehydrated animal may deplete more slowly. Common causes of violative residues are failure to observe the withdrawal period, poor treatment records, failure to identify treated animals, extra-label dosing without an extended withdrawal, injection-site residues, feeding waste milk from treated cows to calves destined for slaughter, and contamination of feed.
The autonomic nervous system has sympathetic and parasympathetic divisions, each with a preganglionic and a postganglionic neuron. Acetylcholine is the transmitter at all autonomic ganglia (nicotinic NN receptors), at parasympathetic neuroeffector junctions (muscarinic receptors), at sympathetic postganglionic fibres to sweat glands in most species (muscarinic), and at the adrenal medulla, which is innervated by preganglionic sympathetic fibres and releases adrenaline. Noradrenaline is the transmitter at most sympathetic postganglionic junctions. Muscarinic receptors M1 to M5 are G-protein-coupled; M2 dominates in the heart (slowing) and M3 in glands and smooth muscle. Adrenergic receptors are alpha-1 (vasoconstriction, mydriasis, urethral sphincter contraction), alpha-2 (presynaptic inhibition of noradrenaline release, sedation, analgesia, reduced insulin release), beta-1 (increased heart rate and contractility, renin release), beta-2 (bronchodilation, vasodilation in skeletal muscle, uterine relaxation, glycogenolysis) and beta-3 (lipolysis).
Direct-acting cholinomimetics include choline esters and alkaloids. Carbachol is resistant to cholinesterase and has both muscarinic and nicotinic actions; it was formerly used as a gut and rumen stimulant but is powerful and can cause severe side effects. Bethanechol is muscarinic-selective and resistant to cholinesterase; its main veterinary use is detrusor atony and urinary retention without obstruction. Anticholinesterases prevent breakdown of acetylcholine. Reversible agents include physostigmine (tertiary, crosses the blood-brain barrier), neostigmine and pyridostigmine (quaternary, do not). Neostigmine reverses non-depolarising neuromuscular block and pyridostigmine is used to treat acquired myasthenia gravis in dogs. Organophosphates bind cholinesterase irreversibly and carbamates reversibly; both cause cholinergic poisoning, treated with atropine and, for organophosphates, early oximes such as pralidoxime. Cholinergic signs are summarised by salivation, lacrimation, urination, defaecation, bronchoconstriction, bradycardia and miosis, with muscle tremors from nicotinic stimulation.
Atropine and hyoscine (scopolamine) are natural tertiary alkaloids that competitively block muscarinic receptors and enter the brain. Glycopyrrolate is a synthetic quaternary compound that does not cross the blood-brain barrier or placenta readily and has a longer duration. Uses include treatment of vagally mediated bradycardia, reduction of salivary and bronchial secretions, antidote to organophosphate and carbamate poisoning (where atropine is given to effect, often at high doses), mydriasis and cycloplegia for eye examination and uveitis (atropine, tropicamide), and relief of smooth muscle spasm (hyoscine butylbromide, used with an analgesic in equine spasmodic colic). Adverse effects are predictable: tachycardia, dry mouth, mydriasis, reduced gut motility, urinary retention, and in ruminants and horses ileus and tympany. Atropine is contraindicated in glaucoma because pupil dilation obstructs aqueous outflow.
Catecholamines are given intravenously or by infusion because they are destroyed by monoamine oxidase and catechol-O-methyltransferase. Adrenaline (epinephrine) acts on alpha and beta receptors and is the drug of choice in anaphylaxis and cardiac arrest. Noradrenaline is mainly alpha and beta-1, used as a vasopressor. Dobutamine is predominantly beta-1 and is used to support contractility during anaesthesia and in cardiogenic shock. Beta-2 agonists such as salbutamol (albuterol), terbutaline and clenbuterol are bronchodilators; clenbuterol is also a uterine relaxant used in some countries in cattle to delay parturition for obstetric intervention, but its illegal use as a repartitioning agent in meat animals has caused human poisoning, and extra-label use in food animals is prohibited in the USA. Alpha-1 agonists such as phenylephrine are vasoconstrictors; phenylpropanolamine, an indirect sympathomimetic, increases urethral sphincter tone in bitches with urethral sphincter mechanism incompetence. Alpha-2 agonists (xylazine, detomidine, romifidine, medetomidine, dexmedetomidine) are sedative-analgesics, discussed fully in neuropharmacology; they are reversed by atipamezole, yohimbine or tolazoline. Antagonists include phenoxybenzamine (irreversible alpha blocker, used for urethral spasm and phaeochromocytoma), prazosin (alpha-1), propranolol (non-selective beta blocker) and atenolol (beta-1 selective, used for tachyarrhythmias and hypertrophic cardiomyopathy in cats).
Autacoids are local hormones: substances formed in tissues that act near their site of release. They include histamine, serotonin (5-hydroxytryptamine), the eicosanoids (prostaglandins, thromboxanes and leukotrienes), kinins, angiotensin and platelet-activating factor. Histamine is stored in mast cells and basophils and released in type I hypersensitivity. Through H1 receptors it contracts bronchial and intestinal smooth muscle, increases capillary permeability and causes itch; through H2 receptors it stimulates gastric acid secretion; H1 antagonists (antihistamines) include older sedating drugs such as diphenhydramine, chlorphenamine and promethazine, and newer less sedating ones such as cetirizine and loratadine. Their veterinary uses include allergic reactions, pruritus (with modest efficacy in canine atopic dermatitis), and motion sickness. They do not reverse established anaphylaxis, for which adrenaline is required. H2 antagonists (cimetidine, ranitidine, famotidine) reduce gastric acid; cimetidine also inhibits cytochrome P450.
Serotonin (5-HT) is made from tryptophan in enterochromaffin cells, platelets and neurons. It acts on many receptor subtypes: 5-HT3 receptors in the chemoreceptor trigger zone and gut mediate vomiting, so 5-HT3 antagonists such as ondansetron are antiemetics; 5-HT4 agonists such as cisapride promote gut motility. Eicosanoids are made from arachidonic acid, released from membrane phospholipids by phospholipase A2 (which glucocorticoids inhibit indirectly). Cyclooxygenase (COX) converts arachidonic acid to prostaglandins and thromboxanes; lipoxygenase produces leukotrienes. Prostaglandin E2 mediates fever, pain sensitisation and inflammation and protects the gastric mucosa; prostacyclin (PGI2) is vasodilator and antiplatelet; thromboxane A2 causes platelet aggregation and vasoconstriction; prostaglandin F2-alpha is luteolytic in the cow, mare, ewe, sow and goat, and contracts uterine smooth muscle. Synthetic PGF2-alpha analogues (dinoprost, cloprostenol) are used to synchronise oestrus, treat persistent corpus luteum and pyometra, and induce parturition or abortion. They must not be given to pregnant animals unless termination is intended, and they are handled with care by women of child-bearing age and people with asthma, because skin absorption can cause abortion and bronchospasm. Misoprostol, a PGE1 analogue, protects the gastric mucosa against NSAID injury and is also abortifacient.
Non-steroidal anti-inflammatory drugs inhibit cyclooxygenase and so reduce prostaglandin synthesis, giving anti-inflammatory, analgesic and antipyretic effects. COX-1 is constitutive and supports gastric mucosal protection, renal blood flow when perfusion is threatened, and platelet thromboxane production. COX-2 is induced in inflammation but is also constitutive in kidney and some other tissues. Older drugs inhibit both isoforms: aspirin (irreversibly acetylates COX, so its antiplatelet effect lasts the life of the platelet), phenylbutazone, flunixin meglumine, ketoprofen, tolfenamic acid and metamizole (dipyrone). Drugs that are COX-2 preferential or selective include meloxicam, carprofen and the coxibs (firocoxib, robenacoxib, deracoxib, mavacoxib, cimicoxib). Paracetamol has analgesic and antipyretic but weak anti-inflammatory effects.
The principal adverse effects are gastrointestinal ulceration and perforation, renal injury (especially in dehydration, hypotension, anaesthesia or pre-existing renal disease, when kidney perfusion depends on prostaglandins), impaired platelet function, and idiosyncratic hepatotoxicity (reported with carprofen in dogs). Combining two NSAIDs, or an NSAID with a glucocorticoid, greatly increases gastrointestinal risk and should be avoided; when switching, a wash-out interval is commonly advised, though its length is not agreed. In cats, low glucuronidation lengthens the half-lives of many NSAIDs; meloxicam and robenacoxib are authorised for cats in many countries, with strict labels on duration, and paracetamol is never used. In horses, phenylbutazone is used for musculoskeletal pain and flunixin for visceral pain of colic and for its anti-endotoxic effect; phenylbutazone overdose causes right dorsal colitis, oral ulcers and renal papillary necrosis. In cattle, flunixin, meloxicam, ketoprofen and carprofen are authorised in various countries for mastitis, pneumonia and pain relief after procedures such as disbudding; flunixin given intramuscularly causes injection-site damage and residues, and some labels require the intravenous route. Diclofenac used in cattle in South Asia caused catastrophic declines of Gyps vultures that fed on treated carcasses, dying of renal failure and visceral gout; veterinary diclofenac was banned in India in 2006 and meloxicam has been promoted as a vulture-safe alternative.
Treatment aims to reduce congestion, improve forward flow and slow progression. Loop diuretics (furosemide, torasemide) inhibit the Na-K-2Cl co-transporter in the thick ascending loop of Henle and are the mainstay for pulmonary oedema; they cause hypokalaemia, hypochloraemic alkalosis, dehydration and azotaemia. Angiotensin-converting enzyme (ACE) inhibitors such as enalapril and benazepril reduce angiotensin II formation, causing vasodilation and reducing aldosterone. Spironolactone, an aldosterone antagonist, is a potassium-sparing diuretic used for its anti-remodelling effect. Pimobendan is an inodilator: it sensitises cardiac troponin C to calcium and inhibits phosphodiesterase III, increasing contractility and dilating vessels. In dogs with preclinical mitral valve disease and cardiomegaly (ACVIM stage B2), a large controlled trial showed that pimobendan delayed the onset of heart failure. Digoxin inhibits the Na-K-ATPase, raising intracellular calcium; it increases contractility weakly and slows AV conduction, so today it is used mainly to control ventricular rate in atrial fibrillation. It has a narrow therapeutic index, is excreted by the kidney, and its toxicity is increased by hypokalaemia; signs include anorexia, vomiting and arrhythmias.
The Vaughan Williams scheme classifies antiarrhythmics. Class I drugs block sodium channels: Ia (quinidine, procainamide), Ib (lidocaine, mexiletine) and Ic (flecainide). Lidocaine given intravenously is the first choice for sustained ventricular tachycardia in dogs; cats are more susceptible to its neurotoxicity. Class II are beta-blockers (atenolol, propranolol, esmolol). Class III prolong the action potential (sotalol, amiodarone). Class IV are calcium-channel blockers (diltiazem, verapamil), used to slow ventricular rate in supraventricular tachycardias. Quinidine is used in horses to convert atrial fibrillation, with careful monitoring for toxicity. Bradyarrhythmias from high vagal tone respond to atropine or glycopyrrolate. Systemic hypertension in cats, usually secondary to chronic kidney disease or hyperthyroidism, is treated with amlodipine, a dihydropyridine calcium-channel blocker, or telmisartan, an angiotensin-receptor blocker. Cats with cardiomyopathy and an enlarged left atrium are at risk of aortic thromboembolism; clopidogrel, a P2Y12 antagonist, was shown in a controlled trial to be better than aspirin at preventing recurrence.
Respiratory drugs act on airway calibre, secretions, cough, and the drive to breathe. Bronchodilators relax bronchial smooth muscle. Beta-2 agonists (salbutamol by inhaler, terbutaline, clenbuterol in horses) are first-line for acute bronchospasm in feline asthma and equine asthma (recurrent airway obstruction). Methylxanthines (theophylline, aminophylline) inhibit phosphodiesterase and antagonise adenosine; they have a narrow margin, variable kinetics, and interactions with CYP inhibitors such as enrofloxacin and cimetidine. Antimuscarinics such as ipratropium (inhaled) or atropine (systemic, limited to one-off rescue in horses because of ileus and colic) relieve vagally mediated bronchoconstriction. Glucocorticoids, systemically or by inhaler (fluticasone, budesonide, beclomethasone), are the mainstay of chronic inflammation control in feline and equine asthma. Antitussives suppress unproductive cough: opioids such as butorphanol, codeine and hydrocodone act centrally. They are contraindicated when cough is productive, as in bacterial bronchopneumonia, because retained secretions worsen infection. Expectorants and mucolytics aid clearance: bromhexine increases the volume and lowers the viscosity of secretions; acetylcysteine breaks disulfide bonds in mucus (and is also the antidote to paracetamol). Doxapram is a respiratory stimulant acting on carotid chemoreceptors and the medulla, used to stimulate breathing in neonates after caesarean section or after anaesthesia; it does not replace ventilation.
Ruminatorics are drugs claimed to stimulate rumen motility. Historically, parasympathomimetics (carbachol, neostigmine), bitters (nux vomica, gentian and ginger) and volatile oils were used in rumen atony. The evidence for most traditional ruminatorics is weak; atony is usually secondary to a primary disease such as hypocalcaemia, pain, toxaemia or acidosis, so treatment of the cause (for example calcium in hypocalcaemia) is the effective ruminatoric. Bloat (ruminal tympany) is of two types. Frothy bloat, on legume pasture or high-grain diets, traps gas in a stable foam, and is treated with antifoaming agents that lower surface tension: poloxalene, dimethicone (a silicone), and vegetable or mineral oils; a stomach tube alone does not relieve it. Free-gas bloat, from oesophageal obstruction or impaired eructation, is relieved by passing a stomach tube or, in emergencies, by trocarisation. Rumen acidosis (grain overload, lactic acidosis) is treated by removing rumen contents in severe cases and by giving oral alkalinising antacids such as magnesium hydroxide or magnesium oxide to raise rumen pH, with intravenous sodium bicarbonate for systemic acidosis. Rumen alkalosis, as in urea (non-protein nitrogen) poisoning, is treated by drenching with dilute acetic acid (vinegar) and cold water, which lowers pH and traps ammonia as ammonium.
Antacids neutralise gastric acid. Systemic antacids such as sodium bicarbonate are absorbed and can cause metabolic alkalosis. Non-systemic antacids (aluminium hydroxide, magnesium hydroxide, calcium carbonate) are largely not absorbed; aluminium salts tend to constipate and magnesium salts to purge; aluminium hydroxide is also used as an intestinal phosphate binder in chronic kidney disease. Antisecretory drugs reduce acid production. H2-receptor antagonists (famotidine, ranitidine, cimetidine) block histamine at the parietal cell. Proton pump inhibitors (omeprazole, pantoprazole, esomeprazole) irreversibly inhibit the H-K-ATPase, are more effective acid suppressants than H2 antagonists, and are the drugs of choice for equine gastric ulcer syndrome and for significant gastric ulceration in dogs. Sucralfate, an aluminium salt of sucrose octasulfate, forms a protective barrier over ulcers in acid conditions; it can bind other drugs, so they are given apart. Misoprostol replaces protective prostaglandins and is used against NSAID-induced injury, but is contraindicated in pregnancy.
Emetics are used to remove recently ingested non-caustic poisons in dogs and cats. Apomorphine, a dopamine D2 agonist acting on the chemoreceptor trigger zone, is effective in dogs but less reliable in cats. Alpha-2 agonists (xylazine, dexmedetomidine) induce vomiting in cats. Hydrogen peroxide (3%) has been used in dogs but can cause gastritis and is not used in cats. Emesis is contraindicated after ingestion of corrosives or hydrocarbons, in animals that are unconscious, seizuring or with reduced gag reflex, and in species that cannot vomit reliably, such as horses, rabbits and rodents; ruminants regurgitate but do not vomit in the true sense. Antiemetics act on the pathways of vomiting. Maropitant blocks neurokinin-1 receptors for substance P in the vomiting centre, giving broad-spectrum control. Metoclopramide blocks D2 receptors in the trigger zone and is prokinetic in the upper gut. Ondansetron and dolasetron block 5-HT3 receptors.
Prokinetics increase coordinated gut movement. Metoclopramide acts on the stomach and proximal small intestine. Cisapride, a 5-HT4 agonist, acts throughout including the colon, and is used for feline megacolon. Erythromycin at low, sub-antimicrobial doses stimulates motilin receptors. Lidocaine infusion is used in horses with postoperative ileus. Laxatives and cathartics soften or speed faeces: bulk laxatives (bran, psyllium) retain water; lubricants (liquid paraffin, mineral oil) coat the ingesta and are used for large-colon impaction in horses, given by stomach tube because oral dosing risks aspiration pneumonia; osmotic agents include magnesium sulfate (a saline cathartic in large animals), lactulose (also used in hepatic encephalopathy, because colonic acidification traps ammonia) and polyethylene glycol; stimulant laxatives include bisacodyl and anthraquinones. Antidiarrhoeal therapy is mainly fluid and electrolyte replacement. Opioids such as loperamide reduce propulsive motility, but loperamide is dangerous in MDR1-defective dogs and should not be used where an invasive bacterial infection is suspected. Adsorbents (kaolin, activated charcoal, smectite) bind toxins; bismuth subsalicylate is antisecretory, but its salicylate content calls for caution in cats.
Diuretics increase urine output by reducing sodium reabsorption at different sites in the nephron. Osmotic diuretics (mannitol) are filtered and not reabsorbed, holding water in the tubule; they are used for cerebral oedema and to promote urine flow in oliguric acute kidney injury after rehydration, and are contraindicated in dehydration, anuria with fluid overload and pulmonary oedema. Loop diuretics (furosemide) are the most powerful. Thiazides (hydrochlorothiazide) act in the distal convoluted tubule and reduce urinary calcium excretion, which is useful in calcium oxalate urolithiasis. Potassium-sparing diuretics act in the collecting duct, either by blocking aldosterone (spironolactone) or epithelial sodium channels (amiloride). Urinary acidifiers such as ammonium chloride and DL-methionine lower urine pH, used to dissolve or prevent struvite stones, including prevention of urolithiasis in feedlot lambs and castrated male goats. Urinary alkalinisers such as potassium citrate and sodium bicarbonate raise pH, used in the management of calcium oxalate, urate and cystine stones. Allopurinol, a xanthine oxidase inhibitor, reduces uric acid formation in dogs with urate stones (notably Dalmatians), but with a high-purine diet it can cause xanthine stones.
Urinary incontinence from urethral sphincter mechanism incompetence in spayed bitches is treated with phenylpropanolamine (an alpha-agonist that increases urethral tone) or estriol (an oestrogen that sensitises urethral alpha receptors). Detrusor atony with a patent urethra is treated with bethanechol. Functional urethral obstruction is treated with alpha-1 antagonists (prazosin, phenoxybenzamine) for smooth muscle and with skeletal muscle relaxants for the striated external sphincter; oral diazepam is used with caution in cats because of rare idiosyncratic fatal hepatic necrosis. Drugs acting on the uterus are ecbolics, which contract it, and tocolytics, which relax it. Oxytocin causes uterine contraction and milk let-down; in dystocia it is used only when the cervix is dilated and there is no obstruction, and in the bitch small doses are preferred. PGF2-alpha analogues contract the uterus and lyse the corpus luteum, and are used in pyometra (open-cervix cases), for inducing parturition, and in oestrus synchronisation. Tocolytics include beta-2 agonists such as clenbuterol, authorised in some countries for cattle to delay parturition briefly or relax the uterus for obstetric manipulation.
Gonadotrophin-releasing hormone (GnRH) and its analogues (gonadorelin, buserelin, deslorelin) release LH and FSH; they induce ovulation, treat follicular cysts in cows, and in continuous release (deslorelin implants) suppress reproduction in male dogs. Human chorionic gonadotrophin has mainly LH-like activity and is used to induce ovulation and to treat cystic ovaries. Equine chorionic gonadotrophin, from the serum of pregnant mares, has both FSH- and LH-like activity in non-equine species and is used for superovulation and to stimulate follicle growth. Progestagens (progesterone in intravaginal devices, altrenogest in mares and gilts, norgestomet) suppress oestrus while in place, with synchronised oestrus after removal. A widely used cattle protocol, known as Ovsynch, gives GnRH on day 0, PGF2-alpha on day 7 and a second GnRH on day 9, followed by timed insemination about 16 to 20 hours later.
Glucocorticoids bind cytoplasmic receptors and alter gene transcription. They are anti-inflammatory (inducing lipocortin, which inhibits phospholipase A2, and reducing COX-2 and cytokine expression) and immunosuppressive at higher doses. Relative anti-inflammatory potency, taking hydrocortisone as 1, is about 4 for prednisolone and about 25 to 30 for dexamethasone and betamethasone; hydrocortisone and, to a lesser degree, prednisolone have mineralocorticoid activity, while dexamethasone has almost none. Short-acting drugs (hydrocortisone) suppress the hypothalamic-pituitary-adrenal axis for under 12 hours, intermediate ones (prednisolone, methylprednisolone) for 12 to 36 hours, and long-acting ones (dexamethasone, betamethasone) for over 48 hours. Long-term use causes iatrogenic hyperadrenocorticism and adrenal atrophy, so treatment is tapered rather than stopped abruptly. Other adverse effects include polyuria and polydipsia in dogs, gastrointestinal ulceration (especially with NSAIDs), delayed healing, infection, diabetes in cats, and laminitis in horses. In late pregnancy in cattle, sheep and horses, dexamethasone can induce parturition or abortion, with retained placenta common in cattle. Cats and horses convert prednisone to prednisolone poorly. Hyperadrenocorticism in dogs is treated with trilostane, which inhibits 3-beta-hydroxysteroid dehydrogenase, or mitotane, which destroys the zona fasciculata and reticularis. Hypoadrenocorticism (Addison's disease) is treated with a glucocorticoid plus a mineralocorticoid (desoxycorticosterone pivalate injection or oral fludrocortisone).
Diabetes mellitus in dogs resembles human type 1 and needs lifelong insulin. Cats usually have a type 2-like disease with insulin resistance and beta-cell toxicity from high glucose; with early control using insulin (often glargine or protamine zinc insulin) and a low-carbohydrate diet, many cats enter remission. Insulin preparations differ in onset and duration; porcine lente insulin is identical in sequence to canine insulin. Sulfonylureas such as glipizide stimulate insulin release and work only while beta cells function. Hypothyroidism in dogs is treated with levothyroxine (T4); dogs need a much higher dose per kilogram than people because they absorb less and clear it faster, and treatment is monitored by measuring post-pill T4. Hyperthyroidism in cats is treated with thioureylenes (methimazole, or carbimazole which is converted to methimazole), which block thyroid peroxidase; adverse effects include vomiting, facial pruritus and excoriation, hepatopathy, and blood dyscrasias such as thrombocytopenia and agranulocytosis. Treating hyperthyroidism can unmask chronic kidney disease by reducing glomerular filtration rate.
Total body water is about 60% of body weight in adult animals, more in neonates (often 70 to 80%) and less in fat or aged animals. About two-thirds is intracellular fluid (roughly 40% of body weight) and one-third extracellular fluid (roughly 20%), of which about a quarter is plasma (about 5% of body weight) and three-quarters interstitial fluid. Sodium is the main extracellular cation and determines extracellular volume; potassium is the main intracellular cation. Dehydration is estimated from history and examination. Losses under about 5% are not detectable clinically. At about 5 to 6%, skin elasticity is subtly reduced. At 6 to 8%, skin tenting is clearly delayed, mucous membranes are dry and capillary refill may be slightly prolonged. At 10 to 12%, the eyes are sunken, skin stays tented and signs of shock appear; beyond this, death is likely.
Crystalloids contain electrolytes and small solutes and distribute across the extracellular fluid; roughly three-quarters of an isotonic crystalloid leaves the vessels within an hour. Isotonic replacement fluids include 0.9% sodium chloride, which contains 154 mmol/L each of sodium and chloride, is mildly acidifying, and is chosen in hyperkalaemia with urethral obstruction or in hypochloraemic metabolic alkalosis from vomiting of stomach contents or abomasal displacement; and balanced solutions such as lactated Ringer's (Hartmann's), whose lactate is metabolised to bicarbonate, and acetate-based solutions. 5% dextrose in water is isotonic in the bag but becomes free water once the glucose is metabolised; it is used for free-water deficits and hypernatraemia, not for resuscitation. Hypertonic saline (7.2 to 7.5%) draws water from the interstitium and cells into the vessels and gives rapid, short-lived expansion of plasma volume at a small volume, typically about 4 to 5 mL/kg intravenously over a few minutes in hypovolaemic horses, cattle and small animals — confirm against the product label and your national formulary; in cattle it is followed by access to water or oral fluids. Colloids (plasma, albumin, and synthetic colloids such as hydroxyethyl starch) contain large molecules that stay longer in the vessels; the safety of synthetic starches has been questioned after human studies showed kidney injury, and their veterinary use is now debated.
A fluid plan adds three parts: the deficit, maintenance, and ongoing losses. The deficit in litres = percentage dehydration (as a decimal) x body weight in kg. A 400 kg cow estimated at 8% dehydrated has a deficit of 0.08 x 400 = 32 L; a 20 kg dog at 7% has 1.4 L. Maintenance requirements in adult dogs and cats are roughly 40 to 60 mL/kg/day, higher per kilogram in small patients and neonates and lower in large animals; formulas based on metabolic body weight are also used. Ongoing losses from vomiting, diarrhoea or polyuria are estimated and added. The deficit is usually replaced over 12 to 24 hours after shock has been treated with rapid boluses. Drip rate (drops/min) = volume (mL) x drop factor (drops/mL) / time (min): 1,000 mL over 8 hours through a 20 drops/mL set is 1,000 x 20 / 480 = about 42 drops/min. Potassium must not be infused faster than the widely taught ceiling of 0.5 mmol/kg/h — confirm against the product label and your national formulary — because rapid infusion causes cardiac arrhythmias and arrest. Patients are monitored by weight, packed cell volume and total protein, urine output, electrolytes and signs of overload such as chemosis, serous nasal discharge, tachypnoea and pulmonary crackles; cats and animals with heart disease are particularly prone to overload.
Diarrhoeic calves lose water, sodium, bicarbonate and potassium, and commonly develop metabolic acidosis with both hyperchloraemic and D-lactic components; depression, weak suckle and loss of the menace response suggest severe acidosis. Bicarbonate need (mmol) = base deficit (mmol/L) x body weight (kg) x a distribution factor, often taken as 0.3 in adults and 0.5 to 0.6 in neonatal calves because their extracellular fluid is larger. Isotonic sodium bicarbonate is 1.3% (about 155 mmol/L); 8.4% sodium bicarbonate contains 1 mmol/mL and is hypertonic. Oral rehydration solutions for calves contain sodium; glucose, which drives sodium and water absorption through the SGLT1 co-transporter; and an alkalinising agent (bicarbonate, acetate or propionate). Adult cattle with abomasal displacement or volvulus develop hypochloraemic, hypokalaemic metabolic alkalosis and need chloride-rich fluids.
A student uses this subject to explain why a drug works and to predict how it will behave in a new species. Build fluency with five equations (t1/2 = 0.693/k, Vd = dose/C0, CL = k x Vd, loading dose = Vd x C / F, deficit = % x kg) and practise them with units until they are automatic. Learn the species exceptions as mechanisms, not lists: cats glucuronidate poorly, MDR1 dogs lack P-glycoprotein, the rumen traps bases and dilutes drugs, horses have a fragile hindgut. For each organ system, be able to name one drug per class, its receptor or enzyme, one indication and one serious adverse effect. Read one national residue table so the idea of a prohibited substance becomes concrete.
A practitioner five years in makes the same decisions daily: which NSAID for an old dog with borderline kidneys, whether a Collie cross can have ivermectin, what fluid and rate for a vomiting cat, which drugs a dairy cow may receive and how long the milk is withheld. The core habits are to check the label and national formulary before every food-animal treatment, to record the product, batch, dose, route, animal identity and withdrawal date, to calculate the withdrawal under the cascade rule when going off-label, to genotype at-risk breeds, and to adjust doses for renal or hepatic disease. Keep a written fluid plan with deficit, maintenance, losses and a potassium ceiling, and reassess it every few hours.
A senior clinician or practice owner sets the rules others follow. That means writing practice protocols for NSAID use, antimicrobial stewardship and controlled drugs; deciding which products the practice stocks; training staff in dose calculation and fluid monitoring; auditing records for residue compliance before farm assurance or export inspections; reporting adverse reactions to the regulator; and handling residue violations with farmers and processors. Senior vets in government or industry sit on committees that set withdrawal periods, approve products and respond to events like the vulture decline caused by diclofenac. They must know how their country's rules compare with those of importers, since a legal growth promoter at home can block a shipment abroad.
A researcher with long field experience works on the open questions: population pharmacokinetics in sick rather than healthy animals, residue depletion in species and tissues with no data, the genetics of drug transporters and enzymes across breeds, PK/PD modelling to set antimicrobial doses that limit resistance, physiologically based models for withdrawal estimation (the approach used by FARAD and similar databanks), and environmental effects of veterinary drugs. Typical tasks are designing depletion studies with the statistical tolerance limits regulators accept, validating analytical methods for marker residues, and translating findings into label changes or national guidance. Such work needs fluency in both compartmental and non-compartmental analysis and in the regulatory frameworks of the EU, the USA and Codex.
This manual does not give drug doses except one standard value for hypertonic saline, because authorised doses differ by country, product and species; use your national formulary and product labels. It does not cover antimicrobial and antiparasitic chemotherapy, anaesthetics and CNS drugs, or toxicology in depth; those are separate subjects. Withdrawal periods for individual products are not listed, since they are product-specific and change. Exotic, avian, zoo and aquatic pharmacology is only touched on. National rules outside the EU and USA (for example India's FSSAI residue limits, Australia's APVMA and Codex MRL values for individual drugs) are named but not tabulated. Newer classes such as SGLT2 inhibitors in cats are not covered, as evidence is still accumulating.
Original practice questions written to the syllabus and pattern of the exams named in each question's examTags. They are not past papers and do not reproduce any board's questions.
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