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Veterinary Pharmacology examples for MODA Lectures

Veterinary Pharmacology examples for MODA Lectures
Dr Clare Bryant.


Drug Interactions with Receptors and Ion Channels
Cats and dogs get diabetes mellitus.
Pharmacology of Peripheral Neural Transmission
Parasympathetic agents. Horses get paralytic ileus of the intestinal tract. Dogs can have bladder atony. Cats and dogs get myasthenia gravis as well as people. Competitive neuromuscular blocking agents are used in veterinary anaesthesia as well as human anaesthesia for thoracic surgery for example. This can be reversed using anti-cholinesterases, anti-muscarinics used are edrophonium or atropine. Note: some of the flea sprays contain organophosphorus compounds therefore neuromuscular blockade may be a problem in cats or dogs treated recently with one of these preparations. Cats, like humans, get laryngeospasm (spasm of the larynx leading to closure of the airway and potential asphyxiation) and succinyl choline (suxamethonium) can be used for intubation to prevent this (although local anaesthetics sprays are now generally used).
Muscarinic antagonists: Overdose of flea spray (some animals are very sensitive and show profound muscarinic effects). Emergency treatment, particularly due anaesthesia where severe bradycardia is common in horses and dogs. Acute treatment of chronic obstructive pulmonary diseases (asthma-like) in horses. Eye examinations of cats, dogs, horses. Cats, dogs and horses get peptic ulcers and hypermotility problems too!


Cardiovascular and Renal Pharmacology

Cats, dogs and horses get a range of dysrhythmias which need controlled usingsimilar anti-dysrhythmics that are used in humans, however animals don’t seem to get myocardial infarction or angina. The aetiology of these conditions in animals is not very clear, but is likely to involve myocardial damage or disease (heart failure, myocarditis, myopathies, valvular disease) due to other causes, genetic components, metabolic disorders and as complications of anaesthesia. Congestive heart failure is common in dogs (heart diseases (see above; sometimes genetic) or old age) and sometimes in cats
There is a similar classification for heart failure in animals as in people with similarprognostic indicators. Clot lysis is critical in cats (an emergency procedure) which get thrombo-emboli, usually at the ileac bifurcation leading to hind limb paresis and severe pain, as a consequence of any cardiac disease so all cats with cardiac disease should be on anti-clotting agents (which is tricky as 50% of cats are aspirin insensitive!). Renal disease is common in domestic animals particular cats (very  common) and dogs, less so in other species, but it does occur. Diuretics (loop and thiazide) are used a lot, potassium wasting occurs, gout does not! Glaucoma occurs and is treated in cats, dogs and horses. Osmotic diuresis is used in the treatment of head injury and removal of brain masses. Hypertension is rare in animals, but it occurs as a consequence of renal disease and anti-hypertensives are used to manage heart failure patients so understanding how these drugs work is important in veterinary medicine. Cats and dogs do not appear to get the cough associated with
elevation in bradykinin during treatment with ACE inhibitors. Centrally acting anti21 hypertensives of the alpha2-adrenoceptor class are potent hypertensives of the alpha2-adrenoceptor class are potent sedatives in all veterinary
species and the hypotensive effects viewed as an important side-effect! The
imidazolines are rumoured to less have sedative effects although a number of
imidazoline based compounds are the most potent of all veterinary sedatives
(medetomidine for example). Reserpine has been used to dope racehorses; similarly the other alpha2 compounds are likely candidates for doping of both racehorses and racing greyhounds.

Pharmacokinetics

It would be deeply useful to have PK parameters as figures that are per kg rather than for an 80kg man. This simple transformation would make PK applicable to medics and vets. Many of the PK differences between human and veterinary pharmacology reside in metabolism (phase I reactions are slower in cats, faster in dogs; phase II are reduced in carnivores compared to herbivores, particularly in cats who have a very limited glucuronidation capacity (1/3 of 100mg aspirin twice a week is ample and paracetamol is highly toxic)). Oral of administration of drugs to ruminants is fairly useless as drugs are usually broken down by rumenal bacteria. Oral drugs are of very limited use in the horse (apart from a few NSAIDs (phenylbutazone) and antibiotics
(trimethaprim-sulponamide mixes).

Inflammation and Immunosuppression
Anti-inflammatories: minor uses: lameness in cats, dogs, horses; major uses: injury (all species), pneumonia (ruminants), COPD (asthma-like allergic airway disease) horses, asthma in cats, auto-immune disease (primarily small animals), allergy, arthritis (old age not RA), anaphylaxis (drug induced, insect bites etc), treatment of shock and endotoxaemia (horses with colic primarily). Renal transplant in cats is sometimes performed (highly controversial!!!). As yet kinin inhibitors, LT antagonists and 5HT modulators have not reached the veterinary market.
Corticosteroids cause fewer problems in animals but iatrogenic Cushings, Addison's and diabetes mellitus do occur particularly in dogs (rarer in cats as they are more resistant to the effects of steroids). Histamine: released with insect stings (cats, dogs, horses), cats (asthma, allergic rhinitis) and horses (sweet itch due to insect bits in tail and mane). Horses (and to a lesser degree cats and dogs) get gastric and duodenal ulceration. There is possibly a bacterial link for horse gastric ulcers and they are treated very similarly to humans with ulcers. Horses get COPD but its aetiology is more like human asthma: COPD is a poor term for the horse disease and allergic airway disease would be better (its just general practitioners will use the term COPD and vet students will be familiar with it). Cat asthma occurs, but is rare and seems to be associated with inhaled allergens such as pollens. Note: a number of veterinary patients are passive smokers! Horses get shock (neonatal sepsis, endotoxaemia as
adults associated with colic) as do dogs and ruminants. Cats very rarely get this
disease syndrome. Autoimmune disease occurs in animals (for example Systemic Lupus Erythematosis, glomerulonephritis, diabetes mellitus) particular small animals.

Chemotherapy
Similar antibiotics are used in humans and animals although the trade names are different. Antibiotics are a huge market in veterinary as well as human medicine. Sulphonamide and trimethoprim are used in combination for the treatment of many conditions including skin diseases and urinary infections in cats and dogs. This antibiotic combination is very useful as its orally active in horses. Animals don’t get malaria, but do get infected with Leishmania and Entamoeba species as well as coccidiosis. Cats get feline AIDs, which is very similar to HIV. Influenza is an important disease in birds, pigs, horses (cats seem to be lethally susceptible to H5N1).
Herpes viruses cause important infection in horses and cats. Anti-viral treatment is fairly limited in veterinary species but will increasingly occur. Interferon gamma is available for treatment of cats and dogs with parvo-associated viral disease.
Anticancer treatment is increasingly important in cats, dogs and horses. Similar drugs are used except for hormonal treatments where prednisone is used, but tamoxifen is not (as yet), although mammary cancer is an important disease in cats and dogs.

Introduction to the Scientific Basis of Medicine
Dr Mark Holmes, a lecturer on this course and also a veterinary surgeon is very happy to provide advice on supervision for this course. The content of the course is very relevant to the future careers of all veterinary students but if specific examples are require Mark is happy to advise.
Dr Mark Holmes mah1@cam.ac.uk