ANSWERS

1. List 4 reasons for anaesthetic premedication.
   • To relax the patient, particularly during induction which may prove traumatic.
   • Pain relief.
   • Anaesthetic sparing effect.
   • Reduction of the undesirable side effects of anaesthesia such as salivation and vomiting.
2. List 5 drug classes often employed as premedicants.
   • Analgesics (pain relievers).
   • Hypnotics (arousable sleep inducing agents).
   • Parasympathetic antagonists (anticholinergic drugs; agents that oppose the effects of the parasympathetic nervous system).
   • Sedatives (calming agents that cause drowsiness).
   • Tranquillisers (calming agents that do not cause drowsiness).
3. As with general anaesthetic drugs, premedicants need to be chosen with care. The choice of drug and the dose rate should be selected in accordance with the requirements of the individual. List aspects to be considered with regard to premedication.
   • Age - age-related illnesses may mean that an animal is less able to metabolise certain drugs.
   • General condition - obese, dehydrated, malnourished and depressed patients all require extra vigilance.
   • Temperament - highly excitable terriers may prove resistant to drugs such as ACP.
   • Breed - some breeds may experience adverse effects with some premedicants; e.g. syncope (fainting) often occurs in Boxers given ACP.
   • Pain - pre-operative analgesia should be given if necessary; this also exerts an effect during surgery and the post-operative period.
   • Type of anaesthesia proposed - the length and complexity of surgery are also important in addition to choice of anaesthetic agent/s.
   • Post-operative requirements - an animal recovering from major surgery will need to be kept as calm and pain-free as possible during recovery, while a routine op such as a grass seed removal from the ear canal will require a patient to be up and about as soon as practicable.
   • Complications - these may include prolonged recoveries, adverse drug reactions, vomiting and pre-existing disease.
   • Pregnancy - certain drugs may cross the placenta causing adverse effects to the foetuses.
4. How is it possible to maximise the effects of sedatives or tranquillisers without increasing the drug dose?
   By keeping the patient calm and quiet; avoid excessive petting and stimulation. Cats should be kept out of the way of barking dogs. Each individual should be kennelled in a comfortable, secure cage spacious enough to allow the animal to stand up and turn around.
5. What is another name sometimes given to tranquillisers?
   Ataractic drugs.
6. One of the reasons for the administration of premedicants is to decrease anxiety in the patient. What group of compounds are lowered in order to achieve this effect?
   Catecholamines; including dopamine, adrenaline and noradrenaline. These stimulate the sympathetic nervous system.
7. What is a parasympathetic antagonist, and give 3 examples that may be used in veterinary practice?
   A parasympathetic antagonist is an agent that opposes the effects of the parasympathetic nervous system. These drugs are also known as anticholinergic or antimuscarinic agents. Common examples are:
   • Atropine sulphate (Atricare).
   • Glycopyrronium bromide (Glycopyrrolate).
   • Hyoscine (Scopolamine).
8. What are the advantageous properties of using parasympathetic antagonists as premedicant drugs?
   • Bronchodilation (reduces airway resistance).
   • Reduction of salivation.
   • Reduction of bronchial secretions.
   • Prevention of excessive vagal slowing of the heart (bradycardia as caused by acepromazine).
   • Prevention of the muscarinic effects of certain drugs.
9. List some disadvantageous properties of parasympathetic antagonists.
   • Increased metabolic rate.
   • Increased heart rate (hence contra-indicated in patients with pre-existing tachycardia).
   • Increased myocardial oxygen consumption.
   • Arrythmogenic properties (may cause bradyarrythmias or tachyarrythmias).
   • May cause gastrointestinal ileus (failure of peristalsis causing intestinal obstruction).
   • Possibility of peripheral airway collapse due to viscidification of bronchial secretions.
10. Acepromazine (ACP) is a commonly used example of the phenothiazine drug group. It is a popular drug due to its safety and does not cause coma if an overdose occurs. List 6 additional advantages of its use as a premedicant.
    • Tranquillising and sedative effects.
    • Anti-emetic properties (prevents nausea or sickness).
    • Spasmolytic properties (reduces discomfort from gastrointestinal spasm).
    • Antihistamine action (very weak).
    • Synergism (improves the effect of opioids).
    • Antiarrythmic in low doses.
11. Acepromazine (ACP) has several possible adverse side-effects. These are mainly due to the effect of ACP on the nerves that release noradrenaline causing adrenergic block. This may result in hypotension, excessive vagal tone and bradycardia. For these reasons it is undesirable to administer ACP to certain patients. In which animals is it undesirable to administer ACP and why?
    • Boxers - ACP may cause syncope (fainting) in Boxers who are exceedingly sensitive to this agent; other breeds may also prove particularly susceptible.
    • Hypovolaemic patients - ACP may cause a severe response including a dramatic fall in blood pressure and cardiovascular collapse.
12. List some further disadvantages of acepromazine, which whilst controllable and not necessarily life-threatening do require attention.
    • No analgesic properties (if pain relief is required, opioids are often administered as part of the premedication).
    • Hypothermia.
    • Poor muscle relaxation.
    • Long acting (4-6 hours) with a slow onset (peaks at 10-20 minutes).
    • Unpredictable (terriers and aggressive dogs are often resistant).
13. Acepromazine has both tranquillising and sedative properties. Given in very low doses, it tranquillises without sedation; whilst moderate doses promote moderate sedation (although not in resistant animals!). Why is it undesirable to administer high doses of acepromazine?
    The dose-response relationship of acepromazine for sedation levels out rapidly. This means that after a certain point, a higher dose will only increase the side- effects of the drug and not the level of sedation.
14. In addition to acepromazine, list 3 other phenothiazines used in veterinary practice.
    • Chlorpromazine (Largactil).
    • Promazine (Sparine).
    • Trimeprazine (Vallergan).
15. Opioids (narcotic analgesics) are often used in conjunction with other drugs such as acepromazine in order to provide a synergistic combination of analgesia and sedation. Why must the same degree of care be given to patients administered with this drug combination as for general anaesthesia?
    Profound sedation is achieved, and respiratory depression may occur. The patient should be intubated and a supply of oxygen must be available for such cases. Commercially prepared drug combinations of this kind are called neuroleptanalgesics. Hypnorm is a common example used in veterinary practice.
16. What legislations control the use of opioid analgesics?
    The Misuse of Drugs Act 1971 and the Misuse of Drugs Regulations 1985. Opioid analgesics are classified as Schedule 2 drugs; by law they must be kept in a locked receptacle and each use recorded in a controlled drug register.
    Opioid analgesics are covered more fully in Revision Module 4 - Understanding the Use of Analgesic Drugs.
17. Butyrophenones are similar in behaviour to phenothiazines, but none are licensed for veterinary use. Drugs such as droperidol and fluanisone are however available in commercial neuroleptanalgesic mixtures. What advantages exist in the use of such combinations?
    • Synergism - lower doses of sedative and analgesic may therefore be used, thus reducing side-effects.
    • Butyrophenones have a potent action in reducing opiate-induced vomiting.
18. What is the name of the common commercial neuroleptanalgesic used very successfully in rabbits and guineapigs?
    Hypnorm.
19. Give 2 advantages of Hypnorm as a premedicant drug.
    • Deep sedation.
    • Excellent analgesia.
20. In which cases would the administration of Hypnorm be contraindicated and why?
    • Animals with respiratory disease - Hypnorm produces variable respiratory depression.
    • Animals with advanced renal and liver failure - Hypnorm is not easily metabolised by such patients.
21. What is the name of the narcotic antagonist that reverses the effects of Hypnorm?
    Naloxone (Narcan).
    Naloxone may also be used to reverse the effects of Immobilon.
22. Give 2 examples of alpha agonists commonly used in veterinary practice.
    • Xylazine.
    • Medetomidine (Domitor).
23. What is the name of the drug used to antagonise the effects of medetomidine (Domitor), and why is its use desirable?
    Atipamezol (Antisedan). The use of atipamezol is advantageous since the prolonged effect of medetomidine may predispose the patient to hypothermia and hypostatic pneumonia.
    If a painful procedure is carried out, it may be advisable to withold the use of atipamazole, or provide pain relief with another analgesic since the animal may be in considerable discomfort if aroused early.
24. High doses of alpha agonists produce basal narcosis; describe this condition.
    Basal narcosis is defined as a state of unconsciousness produced prior to anaesthesia.
25. In addition to basal narcosis, list 4 other advantages of the alpha agonists.
    • Profound, dose dependent sedation.
    • Prolonged circulation time which accelerates the uptake of volatile anaesthetic agents; thus producing a marked drug sparing effect.
    • Muscle relaxation; Ketamine (a popular dissociative agent) causes muscle rigidity when used alone and is therefore often used in combination with an alpha agonist to ease this stiffness.
      Remember though that muscle relaxation is not always advantageous; this may result in respiratory obstruction in brachycephalic breeds.
    • Visceral analgesia.
26. List 6 disadvantages of alpha agonists.
    • Cardiovascular depression (hypertension, hypotension, bradycardia and hypoventilation result).
    • Respiratory depression (pallid mucous membranes and apnoeic pauses are not uncommon).
    • Emetic effect; always undesirable in an unconscious animal due to the risk of inhalation pneumonia and asphyxia.
    • Impaired thermoregulation.
    • Reduced or abolished gut motility; therefore unsuitable for use in barium contrast radiography of the digestive tract.
    • Aerophagia (excessive swallowing of air); therefore not recommended in breeds predisposed to gastric dilation.
27. The benzodiazepines which include diazepam (Valium) and midazolam are often used in premedication due to their muscle relaxant effects and tranquillising properties. Give 2 other important advantages of these drugs.
    • Safety - high therapeutic indices mean that overdose is uncommon.
    • Drug sparing effect - particularly after oral administration.
28. List 2 other uses of diazepam in addition to premedication.
    • Anticonvulsant - used in the treatment of epilepsy.
    • Appetite stimulant - may be used in partially anorexic cats to improve the desire to eat.
29. List 4 disadvantages of diazepam.
    • Painful upon injection (unless diazemuls is used intravenously).
    • Risk of thrombophlebitis.
    • Unpredictable effects - diazepam may stimulate rather than sedate, causing ataxia and often violent struggles.
    • Drug formulation - diazepam binds to polyvinyl chloride (the material of which plastic syringes are usually made); use drawn up preparations immediately or syringes of an alternative material.
30. What is the name of the most common benzodiazepine antagonist?
    Flumazenil.
31. Finally, a word about the commercial neuroleptanalgesic "Immobilon". This powerful drug combination produces deep sedation, hypnosis and profound analgesia, however it also results in severe respiratory depression. What species is very susceptible to Immobilon and what precautions should be taken if it is used?
    Immobilon is VERY dangerous to man. It must never be used unless an antagonist is available (Naloxone = Narcan or diprenorphine = Revivon). Self injection may prove fatal if the effects are not reversed, and it must be appreciated that self absorption through cuts or mucous membranes can also be lethal. Utmost care should be taken when disposing of used needles and syringes.