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21 Cards in this Set
- Front
- Back
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What are the clinical applications of α2 agonists?
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-they are widely used for chemical restraint and premedication in small and large animals
-while α2-agonists are considered more reliable sedatives, they also exert quite profound effects on other body systems and their use should be generally limited to the young healthy patient -α2 agonists have also been used as premedicants in a variety of anesthetic protocols -they produce a marked reduction in the requirement for both injectable & inhalation anesthetics and care is needed to ensure that overdose does not occur -they have proved popular in combination with the dissociative anesthetic ketamine -the muscle-relaxant properties of the α2-agonist counteract the rigidity that is a feature of ketamine anestheia and also promote a smooth recovery, while the sympathomimetic action of ketamine may moderate some of the unwanted cardiovascular effects -another factor contributing to popularity is these agents is the availability of specific α2-receptor antagonists |
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Where are α2 receptors located?
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-α2 receptors in medulla, in spinal cord, in the periphery (can be presynaptic or post synaptic)
-in the periphery on blood vessels -in spinal cord & brain, binding to receptors it is inhibitory -in blood the presynaptic receptor is inhibitory -post synaptic receptor is not inhibitory, when NA binds to α1 receptor get vasocontriction, if it binds to α2 receptor causes vasocontriction -β receptor causes vasodilation -have inhibitory effect on cardiovascular regulatory center |
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What is the mechanism of action of α2 agonists?
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-α2 adenoreceptors are found both centrally and peripherally in pre- and post-synaptic locations
-pre-synaptic α2-receptors are inhibitory and reduce release of the neurotransmitter noradrenaline -activation of postsynaptic α2-receptors triggers a sympathomimetic response more typical of α1-adrenoreceptor activation -the sedative, analgesic and muscle relaxant properties of α2-agonists are mediated at central α2-receptors -the primary mechanism involves a decrease in noradrenaline release and thereby inhibition of impulse transmission -sedation has been attributed to depression of neurons in the locus ceruleus, a region of the lower brainstem through which impulses are transmitted to the forebrain and limbic system |
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What cardiovascular effects do α2-agonists have?
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CARDIOVASCULAR EFFECTS:
•Blood pressure →Increase (phase 1) →Then decrease to normal or below (phase 2) (due to bradycardia & hypotension) • Bradycardia • Decreased cardiac output → Increased afterload → Coronary artery vasoconstriction • Muddy mucus membranes ✰BRADYCARDIA PHASE 1 -α2 agonist binds to α2 receptor on blood vessels and causes vasoconstriction because access to receptors in periphery is easier than in the CNS -that causes a baroreflex effect to medullary cardiovascular center → leads to a decrease in heart rate, consequence of SA node PHASE 2 -but then α2 agonist binds centrally, leads to direct inhibition of medullary cardiovascular center, means there is a further decrease in heart rate -getting profound bradycardia and blood pressure returns to normal or subnormal ✰HYPOTENSION -the hypotension is due to activation of the post synaptic α2 of vascular smooth muscle -the hypotension is caused by reduced norepinephrine release by the sympathetic nerve at the vascular smooth muscle -this is due to the decreased sympathetic outflow from the CNS as well as activation of presynaptic α2-receptors in the sympthetic terminal MUDDY MUCUS MEMBRANES: -in particular regions there is more α2 receptors than α1, ie. peripheral vessels & coronary vessels -in that situation, the α2 receptors agonist causes greater vasoconstriction -more worrying is the coronary vessels -reduce cardiovascular performance by decreasing HR and constricting vasocontriction -some clinicians give atropine to prevent decrease in HR, if you give atropine and stop barorefex, you might have a bigger increase in Mean Arterial Blood pressure because you have knocked out heart's ability to respond to blood pressure |
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What effects do they have on the CNS?
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• Sedation dose dependent
• Analgesia beware → ..shorter than sedation -the α2-receptos are located on the dorsal horn neurons of the spinal cord where they can inhibit the release of nociceptive neurotransmitters, for example, substance P and calcitonin gene-related peptide (CGRP) • Emesis → think cats! -activate the α2-receptors found in the chemoreceptor trigger zone • Muscle relaxation → greater in cows than horses -inhibit interneuronal transmission of impulses in the CNS |
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What are the renal effects of α2-agonists?
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-α2-agonists cause a diuresis, due to inhibition of renin release by juxtaglomerular cells
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What are the metabolic effects of α2-agonists?
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• Hyperglycaemia
– due to inhibition of insulin release • Inhibition of lipolysis as a result of stimulation of α2-receptors on fat cells • Impairment of temperature regulation for up to 24 hours post-administration • Kidneys diuresis – due to inhibition of renin release |
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What are the contraindications of α2-agonists?
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-heart disease, arterial hypotension and shock, renal or hepatic impairment, final trimester of pregnancy (α2-adonists have an oxyticic effect), epilepsy & ANY DEBILITATED ANIMAL!
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What are some warnings to keep in mind when using α2-agonists?
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-may engender a false sense of security
-an aggressive animal may appear sleepy, but can still react! -the effects of α2-agonists are additive with other CNS drugs, particularly anesthetics: barbiturate dose must be reduced by ONE HALF or more following α2-agonists -cattle are 10X more sensitive to these agents than horses, dogs & cats - the dose also has to be watched |
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What are some examples of α2-agonists?
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✰Xylazine - first α2-agonist developed and was widely used in horses, cattle, dogs & cats, now largely replace by agents below
✰Detomidine ("Dormosedan") and Romifidine ("Sedivet", less ataxia and longer sedation) in horses ✰Medetomidine ("Domitor") in dogs & cats - most potent of the α2-agonists |
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What are the clinical applications of phenothiazines?
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-Acepromazine is the drug most commonly used and is licensed for use in the dog and cat in most countries
-it is used to facilitate the handling or restraint of patients and if often employed as a premedicant prior to general anesthesia -low doses of acepromazine have a general calming effect -increasing the dose will induce a degree of sedation which is more apparent in dogs than cats -however, the dose response curve reaches a plateau, after which further increases in dose simply prolong the duration of actions and increases the incidence of adverse effects -DO NOT POSSES ANALGESIC ACTIVITY -must be combines with an analgesic, usually an opioid, if sedation is to be achieved in painful patients -the antiemetic effects of phenothiazines are of benefit in such combinations -phenothiazines are considered to be anti-arrhythmic and will protect the myocardium against adrenaline induced fibrillation |
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What is the mechanism of action of phenothiazines?
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-the sedative and anti-emetic actions of phenothiazines are due to antagonism of dopamine, primarily at D2 receptors
-additional side effects of phenothiazines can be attributed to their activity at other receptors, including α1-adrenergic receptors, H1-histaminergic receptors and muscarinic cholinergic receptors |
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What are the adverse effects of phenothiazines on the central nervous system?
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-since dopamine is also important in motor control, high doses of phenothiazines may cause extrapyramidal signs such as restlessness, rigidity, tremor and even catalepsy
-an additional central effect is the modification of thermoregulatory mechanisms at the level of the hypothalamus, which may lead to hypothermia -this effect is compounded by peripheral vasodilation and is particularly significant in small patients with large surface area to volume ratios |
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What are the adverse effects of phenothiazines on the cardiovascular system?
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-the main cardiovascular effects of phenothiazines such as acepromazine , is peripheral vasodilation and a consequent fall in blood pressure
-this effect is mediated predominantly through α1-adrenergic blockade; however, depression of central vasomotor centers and a direct action on vascular smooth muscle may also contribute -the hypotension is well tolerated in healthy animals -marked hypotension has also been described in excessively fearful dogs -in such cases it is hypothesized that α1-adrenergic blockade prevents the usual vasopressor action of circulating adrenaline, thereby unmasking β2-mediated vasodilation in skeletal muscle and leading to so-called orthostatic hypotension |
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What other effects do phenothiazines have?
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-causes a fall in hematocrit that is most likely due sequestration of red blood cells in sites such as the liver and spleen
-inhibit adenosine uptake into neurons which is believed to be important in the anxiolytic properties of phenothiazines -emesis is suppressed because phenothiazines block dopamine receptors of the chemoreceptor trigger zone -phenothiazine derivatives also possess weak anti-muscarinic actions and antihistaminic (H1) sedative actions |
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What are the adverse reactions and warnings for phenothiazines?
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-acepromazine should NOT be used in shocked or debilitated animals due to its hypotensive properties (not recommended in equine colic)
-CNS seizure threshold may be lowerd by acepromazine hence it shold not be used in epileptics or when performing myelograms -phenothiazines will potentiate the effects of barbiturate anaesthetics |
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What are examples of phenothiazines?
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-acepromazine is the most commonly used
-it is more potent than promazine or chlorpromazine -prochlorperazine (stemetil) is a piperazine derivative of phenothizine that has antiemetic properties greater than those of the non-piperazines -in addition the sedative, respiratory, and hypotensive effects are lower than hose of the non-piperazines |
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What are the clinical applications of benzodiazepines?
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-do not induce reliable sedation in normal healthy animals and, indeed, their anxiolytic action may increase excitement and render patients more difficult to handle
-however, in very young, very old and critically ill patients benzodiaepines may produce effective sedation and their relative lack of adverse effects is an advantage in such 'high risk' groups -they have also been sed to calm distressed or restless patients in the postoperative period -LACK ANALGESIC ACTIVITY -benzodiazepines may be used to induce general anesthesia in combination with other agents, tpically the dissociative anesthetics -the anticonvlsant and muscle relaxant properties of the benzodiazepines counteract some of the less desirable effects of the dissociative drugs, reducing muscle tone and decreasing the incidence of seizures -benzodiazepines may be used specifically for their anticonvulsant action and diazepam is a drug of choice in the treatment of status epilepticus -the ability to relax skeletal muscles may also have specific indications such as the treatment of tetanus and relief of urethral spasm -benzodiazepines with stimulate appetite in a number of species and is used in anorexic cats (Diazepam) |
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What is the mechanism of action of benzodiazepines?
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-the sedative and anticonvulsant properties of the benzodiazepines have been attributed to the potentiation of the inhibitory neurotransmitter GABA at GABAa receptors
-these receptors are linked to chloride channels, opening of which causes hyperpolarization and a reduction in membrane excitability -benzodiazepines combine with a regulatory site on the GABAa receptor, thereby facilitating the binding of GABA and enhancing its effect *minimal cardiorespiratory effects |
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What are the principle effects of benzodiazepines?
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-they are hypnotic (promoting sleep), sedative (reducing arosal), anxiolytic, anticonvulsant, skeletal muscle relaxant and amnesic
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What are the effects of butyrophenone derivatives? What is an example?
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-not widely used
-produce reduced motor activity and catalepsy due to a blockade of the central effects of dopamine and noradrenaline -an example is droperidol used in combination with fentanyl (opiod) in the neuroeptanalgeic "Innovar-Vet" -azoperone ("Stresnil") is used in pigs to reduce population stress and fighting when litters are mixed, to prevent sows from hurting their young at farrowing, and reduce aggression in boars etc. |
