Sedatives Flashcards
Why use premedication?
-relieve anxiety and stress in patient
-to smooth induction of anesthesia, maintenance phase of anesthesia, recovery from anesthesia
-Anesthetic sparing (reduce dose of induction and maintenance anesthetic agents and therefore reduce side effects)
-provide analgesia
-reduce muscle tone
Factors of an ideal premedication
-relieve fear and anxiety
-easily administered
-quick onset of action
-reasonable duration of action
-reversible
-predictable (dose)
-safe
-minimal side effects (cardio, resp)
-provide analgesia, muscle relaxation
-possibly provide amnesia
Pre-anesthetic medications
-Phenothiazines
-Butyrophenones
-alpha 2 agonists
- benzodiazepines- in some animals
-anticholinergics
-opioids
-ketamine
Phenothiazines, Butyrophenones, alpha 2 agonists, benzodiazepines (in some animals)
- sedation to calm animal and reduce anxiety
-anesthetic sparing effect
Anticholinergics
-prevent undesirable side effects (bradycardia)
Opioids, alpha 2 agonists, ketamine
-provide analgesia (pre-emptively)
Phenothiazines actions
-anti-adrenergic (alpha 1 block)
-antidopaminergic
-anticholinergic (muscarinic block)
-antihistaminic (H1 block)
-antiserotonergic (serotonin block)
-local anesthetic effects (clock ion channels)
-anti-arrhythmic
-no analgesia
-antithrombotic actions
Phenothiazines effects
-sedation
-hypotension
-hypothermia
-anti-emetic
-anti-arrhythmic
Phenothiazines chemical structure
-contain two benzene rings that are linked by a sulphur and nitrogen atom
-highly protein bound (more than 90%)
-lipophilic
-hepatic metabolism
Phenothiazines homeostasis control
-vasomotor control
-thermoregulation
-hormonal balance
-acid-base balance
-emesis
Phenothiazines mechanism of action
-Mediated by antidopaminergic actions in CNS (post-synaptic DA receptor blockage results in inhibition of dopamine release)
-results in mental calming effect
Overdose of phenothiazines
increased extra-pyramidal signs
**1mg is max dose ever
Phenothiazines cardio effects
Hypotension through vascular smooth muscle alpha 1 receptors
-not reversible
-duration is dose dependent (can last 8hrs)
-supportive management (fluid therapy and pressure support)
**avoid in volume depleted animals or when hemorrhage present
Phenothiazines respiratory effect
-reduce the sensitivity of the respiratory center to CO2
-slight reduction in RR
**overall, no change in blood gas
Phenothiazines thermoregulatory effect
Hypothermia can occur due to disruption of thermoregulation and cutaneous vasodilation
Phenothiazines anti-emetic effect
-positive; effects central chemoreceptor trigger zone
**effectiveness against opioids- need to give 15-20 mins prior
Phenothiazines anti-arrhythmic effect
-positive
-increases the concentration of EPI required to induce cardiac arrhythmias
Acepromazine (phenothiazine)
-common in vet med (cats, dogs, horses, rare in ruminants and exotics)
-30-40% anesthetic sparing
-mild sedation when used alone, no analgesia
-can be used in seizure animals
-can be used to control emergence delirium during recovery from anesthesia
-solution is yellow
-slow time to onset of effect
-dose dependent (duration and side effects)
What is Acepromazine (phenothiazine) given with commonly?
alpha 2 agonists, opioids
Acepromazine (phenothiazine) in horses
sometimes linked to penile prolapse
-will effect future breeding so avoid in stallions!
Benzodiazepines
-anticonvulsant, reduce amount of major anesthetic (anesthetic sparing), muscle relaxant
-avoid using alone in dogs, cats, horses because can cause excitement or aggressiveness
-combine with mu-opioids (IV or IM)
-good for very young, old, and very sick
-exotics
-no analgesia
-retrograde amnesia
Benzodiaepines chemical structure
-benzene rings fused to diazepine ring
- highly protein bound
Benzodiaepines absorption
-hepatic metabolism (oxidation and conjugation)
-well absorbed across mucous membrane
-significant first-pass metabolism= so need to increase dose
Benzodiaepines mechanism of action
Acts on specific benzodiazepine binding sites which are associated with GABA A Receptors. This enhances the affinity for and action of GABA (inhibitory neurotransmitter)
Results in depressed activity in reticular activating system and therefore anxiolysis and sedation (dose dependent)
Benzodiazepines acting on central GABA vs spinal cord
Central GABA: enhances activity= anti-convulsant effect
Spinal cord: depress internuncial neurotransmission= muscle relaxation
Benzodiaepines cardio effects
minimal
Benzodiaepines resp effects
-minimal
-can enhance respiratory depression caused by other anesthetic agents- due to a reduced ventilatory response to CO2 and slight relaxation of intercostal muscles
Benzodiaepines CNS effects
Overdose causes coma
Diazepam
-adheres to plastic syringes (takes 12 hrs), sensitive to light degradation
-propylene glycol carrier (pH 6.8) making it painful on IM and has unreliable absorption
-has mordiazepam (active metabolites)
Diazepam with pregnancy
Don’t use!
Diazepam will cross placenta, reach fetus
Midazolam structure at different ph
**Contains imidazole ring
-At pH less than 4, ring opens and compound is water soluble
-pH greater than 4, ring closes and compound is highly lipophilic
Midazolam administration
-can be administered IM, intranasal, transmucosal
-2-3x more potent than diazepam
-inactive metabolites
-popular in exotics
Flumazenil
-Benzodiazepine antagonist- binds to GABA A receptor
-no side effects, increases muscle tone to normal and improves ventilation
-useful in exotics
-30-60mins duration IV, IM
Trazodone
-behaviour modifier; decrease stress
-serotonin receptor antagonist and reuptake inhibitor (atypical antidepressant)
-oral admin may occur before visit
-can be combines with opioid
Gabapentin
-mechanism underlying anxiolytic properties is unclear
-has inhibitory effect on voltage gated Ca channels in neural tissue decreasing the release of glutamate within CNS
-oral admin before visit possible
What is gabapentin routinely used for?
-treatment of chronic pain
-epilepsy
