Clinical uses Benzodiazepines are used in pediatric, geriatric or debilitated dogs and cats that may also show signs of CNS depression. DIAZEPAM VERSUS MIDAZOLAM While both drugs act very similarly, there are some advantages of using midazolam over diazepam. These advantages are: ● Shorter acting than diazepam. ● Can be given IM.
not cause seizures. They will exacerbate any form of CNS depression. XYLAZINE Xylazine causes sedation, bradycardia, and in small animals, it causes emesis. This drug is commonly used to induce vomiting in cats. Xylazine also increases urine production for up to 5 hours, so it not recommended to use for cats who have a urinary blockage. Since xylazine increase myometrial tone, it may cause abortion in pregnant animals. DEXMEDETOMIDINE Dexmedetomidine causes dose-related deep sedation in both dogs and cats. It causes prolonged and severe bradycardia. Their respiratory rate will usually drop, too. Dexmedetomidine is dosed based on body surface area and not a mg/kg dosage. ALPHA 2 RECEPTOR ANTAGONIST All Alpha 2 agonists can be easily reversed. The common drug used for reversal is: ● Atipamazole . Atipamazole is used to reverse dexmedetomidine. The full reversal takes about 4 to 5 minutes after IM administration. It is not recommended for IV use as it can cause sudden cardiovascular changes on reversal. The dosage used to reverse dexmedetomidine is an equal volume of atipamezole as you used for sedation with dexmedetomidine. Atipamazole can also be used to reverse xylazine. ● Yohimbine . This medication can be used to reverse xylazine. It is very hard to acquire in the US due to a drug shortage currently. OPIOIDS These are the most commonly used opioids in small animal medicine: ● Full agonist : Commonly used full agonists are morphine, methadone, hydromorphone, fentanyl. Full µ agonists are used for the first-line analgesia when intense pain is anticipated to occur in very invasive surgery. ● Partial agonist : A commonly used partial agonist is buprenorphine. This drug does have a ceiling effect where, despite the increase in the dosage of drug, you will not see any more effect on the patient. ● Mixed Agonist/antagonist : These drugs are full or partial agonists at one receptor and partial agonist or antagonist at another. The most commonly used mixed agonist/antagonist is butorphanol.
● No pain on injection. ● Can be given as a CRI. ● No active metabolites. Benzodiazepine reversal
Flumazenil is the main reversal agent for Diazepam and Midazolam. This drug produces a rapid and smooth reversal. Flumazenil does have a very short duration of action, so it may be necessary to administer multiple dosages in order to fully reverse Benzodiazepines. ALPHA 2 AGONIST While there are many drugs that fit in this category, these are the most commonly used drugs in dogs and cats: ● Xylazine. ● Dexmedetomidine. The effects of alpha 2 drugs on the body CNS effects : This class of drugs causes sedation, analgesia, bradycardia, emesis, and a decrease ADH secretion, causing an increase in urine production. Peripheral effects : This class of drug causes smooth muscle constriction, a decrease GI motility, a decrease in insulin secretion which causes hyperglycemia, stimulated myometrial contractions of the uterus. Cardiovascular effects : Alpha 2s cause a biphasic effect. At first, they cause an initial peripheral vasoconstriction causing an increase in blood pressures, induced by a short-lived bradycardia reflex. Respiratory effects : Mild respiratory depression occurs at low to moderate dosages. At high dosages, a more noticeable respiratory depression will occur. Alpha 2 agonists are contraindicated in any patient with cardiovascular, respiratory, hepatic, and renal diseases. CNS disease is another likely contraindication even though it does
PHARMACOLOGY OF OPIOID RECEPTORS
Opioid receptors are referred to as, δ , κ , and µ. The activation of the µ (Mu) receptor causes analgesia, euphoria, sedation, respiratory depression, bradycardia, and gastrointestinal stasis. Useful properties of opioids Opioids cause many very useful properties that can be used in small animal medicine. These are the most common reasons that opioids are included in many sedation protocols: ● Profound drug and dose-dependent analgesia. There are opioid receptors that are located throughout the body. They are mainly concentrated in the central and peripheral nervous systems but are also found on the articular surfaces and in the skin. Unwanted effect of opioids Opioids are a great addition to your anesthetic plan, but there are some unwanted effects that you must consider. These are: ● Causes respiratory depression. ● Decreases GI motility and can cause constipation from prolonged use. ● Can induce vomiting when used for pre-medication. ● Causes bradycardia by enhancing vagal tone throughout central actions and by direct action on the sinoatrial (SA) node. This can be prevented or treated by giving an anticholinergic drug such as atropine.
Activation of the κ (kappa) receptor results in sedation and some degree of analgesia. Activation of the δ (delta) receptor will result in some dress of analgesia and respiratory depression.
● Lack detrimental cardiovascular effects. ● Anesthetic – sparing effect. By giving opioids, you can decrease the dosage of other anesthetic drugs that you would need. ● Antitussive effects. ● Opioid antagonists are widely available to treat any overdosage or to quickly reverse once the procedure is complete. ● At extremely high dosages, dogs will become sedated and cats usually become excited. ● Decrease efficacy following repeated administrations. ● Causes a histamine release, especially when given IV. This may lead to vasodilation and hypotension. In patients with allergic airway, conditions may cause bronchoconstriction. ● Causes urinary retention due to dysfunction of the detrusor muscle in the bladder. This is more commonly seen after epidural injection but can occur after systemic use. ● Causes Mydriasis in cats and Myosis in dogs.
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