Premedications, Sedatives, Tranquilizers Flashcards

Question

ACP, Assoc with Sz

Answer 1

● High-dose chlorpromazine altered EEG activity in epileptic dogs ○ Recent studies: ACP used in dogs with sz disorders does not lead to higher incidence ○ Some studies suggest it may be anticonvulsant (Tobias et al. 2006; McConnell et al. 2007).

Answer 2

● Considered a reliable sedative in dogs, cats, horses and cattle ● 0.05mg/kg IV in dogs - mild to moderate sedation in 10 min ○ Sedation scores elevated out to 80 min following 0.02mg/kg IV ● Long duration

Answer 3

● Associated with DECREASED perianesthetic morbidity and mortality in horses

Answer 4

● Some Boxer dogs have an exaggerated response (Brock, 1994) ○ Sedation and hypotension greater than expected ■ Possible syncopal episodes

Answer 5

● Dogs with increased vagal tone have been reported to have greater morbidity and mortality ○ Presumed adrenergic blocking effects

Answer 6

● May prevent the occurrence of halothane-induced malignant hypothermia in susceptible pigs (McGrath et al., 1981)

Answer 7

● Contraindicated in patients that are dehydrated, hypovolemic, bleeding, or in shock

Answer 8

■ Non-scheduled drug ■ No listed withdrawal times for dog, cat, horse ● Should not be used in horses intended for human consumption

Answer 9

■ Large volume of distribution ■ Highly protein bound ■ Time to effect: ● ~10-15 min following IV admin ● ~30 min after IM ■ Long acting ● Elimination half-life 3.1 hr (horse); 7.1 hr (dog) ■ Oral bioavailability (dogs): ~20%

Answer 10

Extensive hepatic metabolism

Answer 11

■ Yellow aqueous solution at 10 mg/ml and 5, 10, 25- mg tablets ■ Solution should be protected from light

Answer 12

0.01-0.05mg/kg IV, IM, SQ PO 0.5-2mg/kg

Answer 13

Horses: 0.01-0.05 Pigs: 0.03-0.2 Carrie: 0.01-0.1 Sheep, Goats: 0.05-0.1

Answer 14

1mg/kg IM or SQ

Answer 15

Butyrophenone Derivative ○ Used for sedation in swine and zoo/wildlife medicine ○ Classification: neuroleptic sedative

Answer 16

■ Antagonism of D2 (Gi/o) receptors in mesolimbic-mesocortical pathways in the brain ■ Less affinity for ɑ1-adrenergic receptors (Gq) ● Less hypotension than acepromazine Some D1 antagonism as weak

Answer 17

■ Swine for calming effects ■ Anesthetic adjunct and sedative in wildlife

Answer 18

varying levels of sedation ● Isolated reports on paradoxical excitement following IV admin to a horse

Answer 19

reduction in SVR from ɑ1-adrenergic receptor blockade (Gq) ● Decreased BP and possibly increased HR ● CV effects last longer than sedation

Answer 20

mild respiratory depression ● Enhanced when combined with other CNS depressants ● Some reports of increased resp rates in rats, horses, and pigs

Answer 21

muscle relaxation similar to ACP

Answer 22

decreased following administration ● Presumed secondary to vasodilation and splenic sequestration

Answer 23

■ Onset less than 10 min after IM injection ■ Peak effect seen ~30 min ■ Duration of action ~ 2-4 hrs in pigs ■ Biotransformed in the liver with 13% excretion in feces (pigs) ● Most drug eliminated within 16 hours

Answer 24

■ Nonscheduled drug ■ FARAD has no withdrawal times listed for azaperone in pigs ● Recommended 10-day withholding period prior to slaughter

Answer 25

■ Decreased ability to thermoregulate ■ Some dysphoric effects especially in patients with high levels of anxiety ● Extrapyramidal signs can be seen ■ Doses >1mg/kg IM may cause penile prolapse in boars ■ No antagonists, overdose tx focus on supportive care ■ May inhibit effect of dopamine on renal blood flow

Answer 26

■ 40 mg/ml, in a 100 ml multidose bottle ● Discard after 28 days

Answer 27

Swine: 0.4-2.2mg/kg IM Horses: 0.4-0.8 IM - IV admin not recommended (paradoxical excitation)

Answer 28

0.3mg/kg IM + xyla 1mg/kg IM

Answer 29

0.04mg/kg IM

Answer 30

50-120mg per elephant IM

Answer 31

○ Classified as Minor Tranquilizers ● Sedative-hypnotics due to ability to cause anxiolysis, sedation and sleep ● Sedation more reliable in neonates, geriatrics and ill patients

Answer 32

○ Benzodiazepine binding site located on the ɑ1, ɑ2 and 𝛾 subunits of 𝛾- Aminobutyric acid (GABA) receptor in cell membrane ● Synergistic effects with barbiturates, ethanol, etomidate and propofol (action at GABAA receptors) results in significant CNS depression ● Benzos enhance endogenous GABA binding to the receptor lack of direct agonist activity leads to wide safety margin (for CNS depression)

Answer 33

pentameric combination of homologous subunits with a central pore, spanning the cell membrane ■ GABA is the primary inhibitory neurotransmitter in the CNS ● Few receptor sites found outside the CNS, hence the minimal cardiopulmonary effects ■ Binding results in INC Chloride conductance and hyperpolarization of postsynaptic cell membranes

Answer 34

■ Location of ɑ1 and ɑ2 subunits on the receptor ■ Location of the receptor in the CNS ■ Specific drug affinity ■ Lipid solubility ■ Overall pharmacokinetics

Answer 35

Benzene ring linked to 7 membraned diazepine ring

Answer 36

facilitate activity of GABA ● Results in sedation, muscle relaxation and anticonvulsant effects ● Diazepam and Midazolam

Answer 37

produce an effect opposite that of Agonists when bound to the receptor site ● Results in seizures and anxiety ● β-carbolines such as methyl-6,7-dimethoxyl-4-ethyl-β-carboline-3-carboxylate (DMCM)

Answer 38

have affinity for the receptor but little or no intrinsic activity ● Block the effects of both agonists and inverse agonists ● No antagonistic effect on other GABA agonists (propofol, ethanol, barbiturates) ● Flumazenil is only commercially available benzodiazepine antagonist in the US

Answer 39

exist but synthetic pathways remain unelucidated

Answer 40

● Anxiolysis ● Sedation ● Anticonvulsant actions ● Spinal-cord skeletal muscle relaxation ■ Not adequate for surgical procedures ■ Does not influence required doses of NMB drugs ● Anterograde amnesia (acquiring/encoding NEW information) ■ Amnestic potency greater than sedation

Answer 41

○ Minimal CV depression

Answer 42

○ May decrease respiratory rate, but rarely affect ventilation and oxygenation ● High doses can cause dose-dependent respiratory depression ■ Exaggerated when combined with other depressants or in debilitated patients

Answer 43

○ Effects on nondepolarizing neuromuscular antagonists are unclear ● In vitro cat muscle study should that benzos potentiate neuromuscular blockade (Driessen et al., 1987a)

Answer 44

● Liver metabolism but pathway (reduction, glucuronidation) differs based on drug and species ● Active metabolites: desmethyldiazepam, oxazepam, temazepam ● Following glucuronide conjugation - excreted in urine ■ Cats perform much slower ● Midazolam and Diazepam first undergo oxidation ■ Reduced metabolism if coadministered with cimetidine, erythromycin, isoniazid, ketoconazole, propranolol and valproic acid ■ Rifampin will INCrease metabolic rate

Answer 45

ataxia/disorientation, CNS depression or agitation, respiratory depression, weakness, tremors, vocalization, tachycardia, tachypnea, hypothermia

Answer 46

Administration of Flumazenil and supportive care

Answer 47

■ Schedule IV drugs (Diazepam, Midazolam and Lorazepam) ■ None of the benzodiazepines are intended for food producing animals, no established withdrawal times ■ No FDA veterinary approved products

Answer 48

standard against which all other benzodiazepines are measured Used as: ■ ● Anticonvulsant ● Mild sedative (small animal species) ● Adjunct to ketamine anesthesia

Answer 49

■ Poor water solubility ● Supplied for injection in a solution of organic solvent (propylene glycol and ethanol) ○ Large volumes or CRI admin should be used with caution due to hyperosmotic vehicle ○ Can lead to erratic absorption by any route other than IV ○ Can cause lysis of RBCs (greater in cats) ○ Risk of thrombophlebitis

Answer 50

■ pH of 6.6-6.9 ■ Viscid - potential pain with IV and IM administration ■ Light sensitive (photodegredation) ● Binds to plastics if exposed to light for long periods

Answer 51

■ Rapidly absorbed from GI tract (high bioavailability) ■ Metabolized by hepatic microsomal enzymes ● Oxidative pathway ● Repeated oral administration has been associated with severe life-threatening hepatic necrosis in cats (Center et al., 1996)

Answer 52

● Elimination half-life following IV administration is approx. 3.2 hours ● Active metabolites appear within 2 hours and eventually exceed diazepam concentrations ○ Nordiazepam (T1/2 3.6 hr) ○ Oxazepam (T1/2 5.7 hr) High protein binding, high volume of distribution

Answer 53

Breed differences: ○ Greyhounds have decreased terminal half-life (1 hr) following 0.5 mg/kg IV ➢ Oxazepam T1/2 6.3 hr

Answer 54

● High doses (5, 10 and 20 mg/kg) IV show a half-life of 5.5 hr ○ 50% quickly converted to nordiazepam (T1/2 of 21 hr)

Answer 55

● 0.05-0.4 mg/kg IV half-life 2.5-21.6 hr ○ Nordiazepam and oxazepam not detected in plasma but present in urine suggest rapid excretion ● Terminal half-life is unchanged during 1st 21 days of life** ○ Repeated doses should be given with caution in foals

Answer 56

■ Clinical doses result in minimal depression of ventilation, CO, and DO2 ■ HR, myocardial contractility, CO and ABP are effectively unchanged in dogs after IV admin of 0.5, 1.0 and 2.5 mg/kg ■ Blood gas values were unchanged in horses given 0.05-0.4mg/kg

Answer 57

■ Unreliable sedative but useful for muscle relaxation and anticonvulsant ■ Given with Ketamine to ameliorate central excitatory effects of cyclohexamines ● May not be required with additional premedications (ex. Opioids, ɑ2-adrenergic receptor agonists) ■ Use with propofol to reduce dose required for induction and minimize hemodynamic changes ■ Inhalant MAC is modestly reduced

Answer 58

■ Use as anticonvulsant: ● Higher doses used (0.5-1.0 mg/kg in dogs and cats, IV or rectally; 0.2mg/kg IV in horses) ● Care with repeat dosing due to active metabolites slow clearance (sedative but not anticonvulsant effects)

Answer 59

■ Caused a reduction in theta, delta, alpha, and beta-frequencies of the EEG of anesthetized dogs without any changes to CV parameters

Answer 60

● In cats and goats ● MOA is unknown but may be associated with decreased inhibitions of serotonergic mechanisms ● Anorexia due to GI stasis should NOT be treated with diazepam as it slows gastric emptying

Answer 61

■ Highly water soluble ● At physiologic pH, diazepine ring closes and renders the drug lipid soluble and able to cross the BBB rapidly to causes central effects

Answer 62

■ Rapid absorption IM ● Bioavailability (dogs) greater than 90% ● Peak plasma concentrations in 15 min ■ Can also be absorbed intranasally ■ Rectal administration does not result in clinically useful plasma concentrations and cannot be recommended ■ Intranasal gel formulation ● 70.4% bioavail in dogs

Answer 63

■ Sensitive to light pH <4.0

Answer 64

■ High enteral bioavailability ● Affected by pH in GI tract ■ Elimination half-life - dose dependent kinetics ● dogs, admin 0.5mg/kg: 77 min ● Horses, 0.05mg/kg; 1.0 mg/kg: 216 min; 408 min (respectively) ■ Metabolized by hepatic microsomal enzymes

Answer 65

■ More potent than Diazepam but similar PD ■ CV effects are minor ● HR and CO decrease by 10-20% in dogs (0.25-1.0 mg/kg) ● Blood pressure may decrease as a result of central effects on vasomotor centers ■ Blood gas values are minimally affected ■ Effects on ventilation considered similar to diazepam

Answer 66

■ Unpredictable as sedative ● Dogs admin 0.5mg/kg display mild sedation, muscle relaxation or occasional agitation ● Cats show more excitement and agitation with less sedation as doses increase ● Ferrets, small mammals and birds sedate well (mild to moderate sedation) ■ Frequently administered with ketamine or propofol/alfaxalone (similar to diazepam) ■ Reduction in inhalant MAC noted ■ Can be used as anticonvulsant

Answer 67

○ Drug of choice for status epilepticus due to higher binding affinity to the benzodiazepine receptor and elevated brain concentrations ■ Therapeutic levels IV but not rectally ■ Unknown IM bioavailability

Answer 68

○ Supplied in propylene glycol ■ Pain on administration and hemolysis ○ Uncommonly used in vet med as sedative but oral bioavailability makes it suitable as an anxiolytic

Answer 69

○ Water-soluble ○ Available in US only in combination with tiletamine (Telazol) ■ Little clinical information exists on zolazepam alone ○ Metabolized at different rates in different species ■ Recovery time and smoothness may be different

Answer 70

○ Supplied with Tiletamine in powder ■ Reconstituted to 5 ml (50 mg zolazepam; 50 mg tiletamine)

Answer 71

○ Schedule III drug (Telazol) ■ Only FDA approved benzodiazepine for use in dogs and cats

Answer 72

○ Only antagonist available in the US ○ Specific and exclusive benzodiazepine competitive antagonist ■ High affinity for the benzodiazepine receptor site of GABAA Receptor ■ No agonist activity ○ Only binds and antagonizes the benzo binding site ■ No antagonism of other sedative-hypnotics (propofol, ethanol)

Answer 73

■ Reverses the EEG changes induced by benzos in dogs and horses ■ Use in the absence of benzodiazepines does not cause excitement

Answer 74

■ No direct effect on left ventricular function or coronary hemodynamics in humans ● In cats, antagonism of fall in blood pressure was observed

Answer 75

■ Reverses muscle relaxation

Answer 76

■ Tidal volume and minute ventilation are restored to normal ● Response curve of the respiratory center may still be depressed

Answer 77

reverses decrease in IOP seen after admin of benzos

Answer 78

■ Limited information in veterinary species ● Extensive metabolism by the liver in humans ● Metabolites excreted in urine (none appear to be active)

Answer 79

■ Rapid onset of active ● Rapid uptake, distribution ■ Human half-life 0.7-1.3 hours ● Time to reversal in dogs: 120+/-25 seconds IV; 310+/- 134 seconds IM ● Due to liver metabolism, liver disease can lengthen elimination ■ Multiple routes of admin: IV, IM, sublingual and rectal ■ High first-pass effect - oral route not recommended

Answer 80

■ Dogs: 0.01-0.04 mg/kg IV, IM, sublingual, endotracheal or rectal ● Repeated doses may be required ■ Horse: 0.01-0.02 mg/kg IV

Answer 81

○ Not a schedule drug ○ No withdrawal times have been formulation ○ There are no FDA approved veterinary products

Answer 82

● Provide sedation, analgesia, and muscle relaxation ● Can be reliably reversed with selective antagonists

Answer 83

● ɑ2-Adrenergic receptors are scattered throughout the body ○ Neural tissue ○ Most organs ○ Extra-synaptically in vascular tissue and platelets Why have variety of undesired effects

Answer 84

receptors are located in the cerebral cortex and brainstem ● Primary source of sedation and supraspinal analgesia ● Centrally mediated bradycardia and hypotension

Answer 85

receptors are located in the spinal cord and vascular endothelium ● Stimulation results in spinal analgesia, vasoconstriction and peripherally mediated bradycardia

Answer 86

receptors are located in the spinal cord ● Modulate spinal analgesia and thermoregulation (+/-)

Answer 87

receptors are thought to be similar to ɑ2a in function and distribution expressed in cattle

Answer 88

○ Ɑ1-receptor action results in excitation and increased motor activity ○ The less selective for ɑ2-adrenergic receptors a drug is the more likely (in theory) that rigidity and paradoxical excitement might be noted ■ Arterial injection may also result in these effects so should be avoided* ○ Xylazine is the LEAST selective

Answer 89

Some a2 bind to/activate imidazole R detomidine, romifidine, medetomine, dexmedetome (tolazoline) NOT XYLAZINE

Answer 90

G-coupled proteins ○ When stimulated they inhibit adenyl cyclase activity -> decreased cAMP in the cell ○ Located both pre-and postsynaptically in the CNS Gi/o

Answer 91

Inhibition of platelet aggregation

Answer 92

CNS, binding leads to sedation, analgesia, muscle relaxation, and centrally mediated effects on heart rate and afterload (decreased sympathetic nervous system activity) ● Peripherally, increased SVR (afterload) is noted Dose dependent effects ○ Ceiling effect in some species (horses) - higher doses do not result in recumbency but increase duration of effect

Answer 93

● Occupancy of ɑ2-adrenergic receptors by agonist redacted NE release, may prevent occupancy of receptors ● In brainstem, binding at locus coeruleus, rostroventral lateral medulla (primary areas for sympathetic outflow from the CNS) cause sedation DT slowing of discharge frequency of tracts into the cortex.

Answer 94

● Rigidity, seizures, and/or excitement have been noted following accidental arterial injection of xylazine in horses

Answer 95

● Paradoxical excitement can result when the animal is fearful, excited, painful or otherwise stressed ○ High circulating catecholamine levels that medication can not overcome

Answer 96

● Binding at various points in nociceptive pathway --> analgesic effect ○ R isolated in dorsal horn of spinal cord, SC ○ Afferent input into dorsal horn from nociceptors in periphery continues but is MODULATED, DAMPENED by decrease in NE release (presynaptic inhibition) and occupancy of those receptors (postsynaptic inhibition), as well as decreased substance P release ○ Descending modulation of nociceptive input via locus ceruleus

Answer 97

○ Imadazoline-1 are associated with central blood pressure control ■ May contribute to CV effects ○ Imadazoline-2 binding may contribute to analgesic effects **Everyone but xylazine binds at imidazole R**

Answer 98

● ICP (dogs): unaffected with use of medetomidine ○ Modest increase in CPP (CPP = MAP - ICP) ● Other studies demonstrated a decrease in CBF with dexmedetomidine in dogs and rabbits ○ Decrease in ICP, decrease in DO2 ○ Care must be taken when considering ɑ2-adrenergic receptor agonists in patients with altered intracranial hemodynamics

Answer 99

often appear ‘muddy’ or pale blue/gray ○ Peripheral VC slows blood flow in periphery --> prolonged capillary transit time ■ Allows for a greater amount of deoxygenated hemoglobin present at end of capillary, > 5mg/dL threshold of observation of cyanosis

Answer 100

parameters generally maintained when using ɑ2-adrenergic receptor agonists alone ○ In conjunction with other sedatives, opioids, or anesthetics, values can be variable ■ Often indicative of Respiratory Depression

Answer 101

administration to patients with borderline respiratory function/CNS depression ○ Sheep are prone to hypoxemia with ɑ2-adrenergic receptor agonist administration* ■ Activation of pulmonary intravascular macrophages produce extensive damage to the capillary endothelium and alveolar type 1 cells ■ Pulmonary edema and secondary to pulmonary parenchymal damage ■ Treatment with antagonists will improve clinical signs but not eliminate or reverse damage

Answer 102

distribution of ɑ1- and ɑ2- adrenergic R in periphery --> wide variability in SVR, BP, HR and rhythm, and blood flow

Answer 103

■ Initial DT Baroreceptor (vagal)- mediated reflex due to high SVR ■ As SVR returns to normal, persistent bradycardia = decreased Central Sympathetic outflow ■ Antimuscarinic drugs are effective in increasing the HR early ● Severe hypertension can result ● May be less effective in later stages ○ Ephedrine may be more effective

Answer 104

usually decreased ○ Secondary to the reduction in HR in attempt to maintain physiological BP in face of increased SVR ○ Decrease in tissue blood flow is result ■ Not uniform: Skeletal muscle, adipose and other non-vital tissues reduced to greatest extent ○ Use of antimuscarinics to increase HR will not proportionally increase CO ■ Lead to hypertension, increased myocardial O2 consumption and arrhythmias with only marginal increase in CO.

Answer 105

○ First phase: activation of central ɑ2-adrenergic R reduce sympathetic outflow (decreased NE) ■ Negative inotropic, chronotropic, dromotropic effects on heart ● 1st, 2nd degree AV block ■ Peripheral VC - increased ABP --> BRR bradycardia ○ Second phase: decreased SVR but sustained low HR due to low NE ■ Hypotension and bradycardia

Answer 106

produce more sedation, analgesia, longer DOA but do not necessarily worsen cardiovascular response

Answer 107

associated with ɑ2-agonists, anticholinergics are likely DT increased myocardial workload (increased HR and afterload), oxygen consumption ○ Higher incidence with xylazine due to low ɑ2:ɑ1 ratio

Answer 108

● Diuresis by multiple mechanisms ○ Reduce production or release of ADH from pituitary ○ Inhibit actions of ADH on collecting tubules, enhance excretion of Na ○ Decreased Renin levels ● Decrease micturition pressure, bladder capacity, micturition volume and residual volume

Answer 109

● Motility in decreased ○ Large bowel more sensitive in dogs and horses ● Gastric emptying time delayed ● Used as emetics

Answer 110

○ Xylazine caused vomiting in up to 90% of cats and 30% of dogs ○ Theory: alpha2 agonists interact with the chemoreceptor zone located in area postrema to stimulate dopamine, NE ○ Can be antagonized by atipamezole

Answer 111

● Patients may be unable to control body temperature ○ Combination of CNS depression, reduction in motor activity (shivering) and loss of vasomotor control

Answer 112

**push for xylazine to become controlled, already is controlled in some states eg Florida** ○ Withdrawal times - Cattle 24 hour withholding time (milk) and 4 days for slaughter ■ Cervidae: not approved for use during hunting seasons ○ Veterinary approved products: ■ Approved for dog, cat, horse and deer ■ Rompun (20 and 100mg/ml), AnaSed (20 or 100mg/ml), Cervizine (300 mg/ml)

Answer 113

○ Withdrawal times - not approved for use in horses intended for human consumption ■ Extralabel use in cattle: 3 days meat, 72 hours milk ○ Veterinary approved products: ■ Approved for horses ■ Dormosedan 10 mg/ml injectable; Transmucosal gel 7.6 mg/ml

Answer 114

○ No published withdrawal times: Not approved in horses for human consumption ○ Veterinary approved products: ■ Sedivet 10 mg/ml

Answer 115

○ Not approved for use in food animals ○ Veterinary approved products: ■ Approved for use in dog ■ Domitor 1 mg/ml

Answer 116

○ Not approved for use in food animals ○ Veterinary approved products: ■ Approved for use in dogs and cats ■ Dexdomitor 0.1 and 0.5 mg/ml; Precedex (human) 4 or 100 mcg/ml

Answer 117

- Elimination Half-life: - Dog: 30 min (1.4mg/kg) - Cattle: 30 min (0.2 mg/kg) - Horse: 50 min (0.6 mg/kg) After IM admin, plasma levels peaked at 15 min; similar T1/2 after IV

Answer 118

Rapid onset if sedation and analgesia (horse): 5-10 min Duration: 30-60 min Poor sedation with SQ admin (reduced absorption with local VC)

Answer 119

Reflex bradycardia (persistent) Central effects outweigh peripheral Initial hypertension is brief - subsequent hypotension CO reduced up to 50% (dogs, horses) Linked to dec. HR BP decreased 20-30% SV is preserved with dec HR Bradyarrhythmias treated with anticholinergics when appropriate

Answer 120

Respiratory rate decreases, TV increases maintaining consistent minute ventilation PaO2, PaCO2, and pH are typically unchanged High doses can lead to decreased minute ventilation, physiologic dead space, and decrease delivery of O2 to tissues

Answer 121

Horses anesthetized with halothane showed dec PaO2 after admin of 0.5-1.0 mg/kg: likely due to V/Q mismatch due to altered CO and pulmonary vascular tone

Answer 122

PaO2 dec in Sheep due to pulmonary inflammation and edema (intravascular macrophages)

Answer 123

Can cause Salivation, emesis and reflux (cent ral effect); pretreatment with yohimbine limits GI motility, including rumen contractions reduced; reversible with antagonist administration Cecal and colonic motility decreases in horses Reduced intestinal blood flow

Answer 124

Increased urine production Decreased SG and osmolality Normal micturition reflexes are maintained Dec. uterine blood flow and tone (decreased O2 delivery); may impact fetus Cattle, sheep: oxytocin like effect on uterus with xyla, not detom * Controversial in pregnant cattle, esp early/late gestation --> premature birth, miscarriages

Answer 125

Dogs/Cats: short-term sedation and analgesia Premedication for induction Neuroleptanalgesia when combined with opioids Combined with ketamine IV for short surgical procedures Standing sedation/restraint in horses ‘Triple Drip’ or ‘GKX’ TIVA **Cattle require much lower doses (1/10 of equine dose)**

Answer 126

Goats > cattle > sheep Cattle > llamas > alpacas > horses

Answer 127

Branham's (anecdotally) > Herefords > Holsteins

Answer 128

Half-life Horses: 26 min (40mcg/kg IV); Median clearance of 37 min IM dose (horse) mean elimination half-life of 53 min Increased half-life and Volume of distribution with exercise Available as sublingual gel (some countries): mean bioavailability of 22% compared to 38.2% IM for same dose

Answer 129

achieved sedation

Answer 130

Rapid sedation, 5 min onset with IV dosing Duration: 1 hour Analgesia, sedation with 20 mcg/kg equipotent to 1.0 mg/kg xylazine but longer duration

Answer 131

Dose-dependent changes that dec with clearance Impaired systolic function with increases in left ventricular internal diameter CO decreased up to 50% Sig increase in MAP and SVR at 10-40 mcg/kg IV CRI dosing similar CV changes that persist with the duration of the CRI Decreased HR within 2 min Sinoatrial block or 2nd-degree block common

Answer 132

When admin alone: little impact on RR. Slight increase in PaCO2 with negligible changes in PaO2 O2 delivery decreased as CO decreases Pulmonary shunt fraction relatively unchanged with modest increases in V/Q

Answer 133

Potent analgesia for GI pain in horses Myoelectric activity, motility reduced Negative impact on GI blood flow

Answer 134

Increased flow Increased intrauterine pressure (sim to xylazine) Caution in pregnant mares Cattle, sheep: oxytocin like effect on uterus with xyla, not detom * Controversial in pregnant cattle, esp early/late gestation--> premature birth, miscarriages

Answer 135

following IV administration of 80 mcg/kg fit a two-compartment model Elimination half-life was estimated at 138 min; clearance from plasma was 32 mL/min/kg

Answer 136

Profound sedation in horses at approx. 15 min following IV administration. Sedative effects noted up to 2 hours (longer lasting than xylazine and detomidine) IV and SQ (beagles; 20-120 mcg/kg) showed quick uptake and sedation effects Less ataxia noted than other ɑ2-agonists

Answer 137

Similar to other ɑ2-agonists Bradycardia noted after 80 mcg/kg dose in horses Second-degree AV block noted MAP increased 15% at 5 min, declining to below baseline by 60 min Significant decrease in Cardiac Index Similar dose-dependent effects in dogs:

Answer 138

Similar to other ɑ2-agonists with respect to intrauterine pressure Increased urine production Increased blood glucose concentrations

Answer 139

Labeled for use in horses *not intended for horses meant for human consumption Off label use in dogs/cats reported

Answer 140

Dexmedetomidine is dextrorotatory isomer of medetomidine

Answer 141

Medetomidine at 40 mcg/kg IV, dexmedetomidine at 20 mcg/kg IV produced peak sedation at 10-20 min Terminal half-lifes of 0.96, 0.78, 0.66 hr reported in dogs Cats: terminal half-life after 10 mcg/kg IV was 198 min

Answer 142

achieves similar sedation to IM with longer time to peak plasma concentrations

Answer 143

Admin of levomedetomidine produce no sedation or analgesia with faster clearance

Answer 144

Peak sedation (20-40 mcg/kg IV) was achieved at 10 min; peak analgesia at 20 min Medetom, Dexmed: similar impacts on ax requirements: Dose-dependent decreases in MAC Analgesia corresponds with sedation (onset, peak and duration)

Answer 145

Similar to other ɑ2-agonists Decreases in HR, CO (66% in in iso anesth dogs) Increased SVR Initial increase in ABP followed by hypotension Changes in left ventricular work and pulmonary vascular resistance; Coronary vasoconstriction balance with oxygen demand Contractility not significantly affected in dogs CO decreased in horses but returned to baseline after 30 min Blood flow directed to vital organs (heart, kidneys, liver, brain) Global oxygen requirements reduced

Answer 146

Plasma glucose concentrations increased Medetomidine at 20 (decreased), 40, 60 (increased) mcg/kg IV in pregnant dogs affected uterine motor activity Urine production increased

Answer 147

Medetomidine (without vatinoxan - see Zenalpha) only available for formulations for wildlife capture/restraint Dexmedetomidine primarily used in dogs and dogs, horses (CRI) Frequently used in conjunction with opioids Premedication for anesthesia Used as sole agent for imaging or with local anesthetic for minor surgical procedures Reversible (atipamezole

Answer 148

(Medetomidine (0.5mg/mL) and Vatinoxan Hydrochloride (10mg/mL)): Source: ZenalphaPackageInsert.pdf ● For IM injection in DOGS only, sedative and analgesic ● Medetomidine: racemic mixture containing the active enantiomer, dexmedetomidine ● Vatinoxan: peripherally selective alpha2-adrenoreceptor antagonist ○ Partially counteracts CV depressive effects of dexmedetomidine at peripheral alpha2-adrenoreceptors, preserves centrally mediated sedative, analgesic effects

Answer 149

Use as a sedative and analgesic in dogs to facilitate clinical examination, clinical procedures and minor surgical procedures ○ Not intended for use in cats

Answer 150

● Time to effect: 5-15 min ● Duration of effect: 38 min (avg) ● Reversal with IM atipamezole at the dose to reverse IM medetomidine ○ Reversal of sedation occurs at 5-10 min

Answer 151

○ Yohimbine and Tolazoline ■ Used in LA due to Xylazine use ○ Atipamezole ■ Has replaced others in small animal/exotic practice due to increase in highly-specific agonists (medetomidine/dexmedetomidine)

Answer 152

receptor ligands that are **competitive antagonists at ɑ2-receptors** ○ Varying degrees of antagonism at the ɑ1-receptor sites

Answer 153

● Should not be done without consideration of the potential of patient excitation, loss of analgesia and adverse CV effects (tachycardia and hypotension)

Answer 154

○ IV administration results in rapid vasodilation if patient still has high SVR ■ If vasodilation occurs without increase in HR and CO, severe hypotension results (transient but possibly not tolerated) ○ IV administration for ER purpose only Partial IV dose if no effect with IV - may rapidly result in recovery, wait until increase HR to minimize hypotension

Answer 155

○ **Highly specific ɑ2-receptor antagonist** ■ Does not bind 𝛽-adrenergic, 5-HT, histaminergic, muscarinic or dopaminergic receptors - decreases side effects ○ Approved for IM use in dogs ■ Off label in cats, horses an exotics ○ Label dose in mcg/m2 but most practitioners dose at equal volume to medetomidine/dexmedetomidine (50mcg/kg)

Answer 156

■ Nonscheduled ■ Not approved for use in food producing animals ■ Antisedan 5mg/ml

Answer 157

○ Indole alkaloid derived from bark of Pausinystalia yohimbe tree or the root of the Rauwolfia serpentina plant ○ Approved for dogs and cervidae ■ Used off label in cats, horse, cattle and exotics ○ Often administered 25% IV and rest IM to reduce side effects

Answer 158

○ Non-selective ɑ2-receptor antagonist ■ High doses activate ɑ1-adrenoreceptos, dopamine and serotonin receptors; inhibit monoamine oxidase production

Answer 159

Non-selective a2 antagonist - variety of R effects ○ Potential to cause seizures at high dose due to GABAergic and NMDA-mediated pathways

Answer 160

■ Nonscheduled ■ Not approved for use in food producing animals ● Should not be used 30 days prior to hunting season ■ Yobine 2mg/ml; Antagonil 5 mg/ml

Answer 161

○ Synthetic imidazoline derivative ○ Non-selective ɑ-adrenergic receptor antagonist ■ Has histaminergic and cholinergic effects ■ Direct effects on vascular endothelium causing decreased SVR, vasodilation and increased venous capacitance

Answer 162

○ Reverses detomidine in the horse better than atipamezole ○ Can cause GI hypermotility, diarrhea, colic ○ Has been used to treat pulmonary hypertension in newborns ■ Reduce pulmonary vascular resistance and counteract the hypoxic pulmonary vasoconstriction reflex

Answer 163

○ Reverses detomidine in the horse better than atipamezole ○ Llamas appear to be more sensitive to side effects - recommended to give lower doses (2mg/kg IM) or avoid ○ Appears to be ineffective in Bears - not recommended

Answer 164

○ Regulatory: ■ Approved for use in horses ● Off label in cattle, camelids and exotics ■ Not approved for use in horses for human consumption

Answer 165

Derived from the Guaiacum genus of trees Centrally acting skeletal muscle relaxant with sedative properties Primarily co-administered IV with injectable anesthetic agents for induction, maintenance of GA in horses and ruminants Wide therapeutic origin (safety margin?)

Answer 166

moderately unknown Evidence suggests action in BS, subcortical regions, spinal cord (polysynaptic reflex inhibition) affected by interneuron depression --> sedation and muscle relaxation

Answer 167

* No change in HR, CO, CVP, or resp rate *~20% decrease in MAP *Hypotension, respiratory depression, and apneustic breathing pattern (~70-80% > than that required to induce recumbency in horses)

Answer 168

*Minute ventilation = maintained -Increased respiratory rate -Decreased tidal volume *Minimal changes in PaO2

Answer 169

Period of muscle spasm and mydriasis Loss of palpebral reflex then death after respiratory/cardiac arrest

Answer 170

Hepatic metabolism: Glucuronidation, Renal excretion Sex differentiation in elimination in ponies --More rapid elimination in females

Answer 171

--0.9% saline or 5% dextrose solution --Concentration dependent risk of hemolysis **Unrelated to speed of injection **Hemolysis in horse with [ ] > 15% solution **Hemolysis in cattle with [ ] > 5% Intravascular thrombus formation is also related with concentration > 7% (Increased risk of thrombus)

Answer 172

Drug is prone to precipitate out of solution when stored below 22 degrees C Reversed with heating (immersion in a warm water)

Answer 173

1. Risk of IV thrombus at concentrations >7% 2. Hemolysis in horses >15%, cattle >5% 3. Perivascular injection - tissue necrosis 4. Urticaria

Answer 174

* Serotonin reuptake inhibitor, serotonin R antagonist o Atypical antidepressant o Used to facilitate low stress handling, --> signs of anxiety in hospitalized dogs

Answer 175

No cholinergic effects moderate antihistaminergic activity antagonist of post-synaptic alpha1 adrenergic R

Answer 176

o Dogs: bioavail after PO admin, variation in time to maximal plasma concentration o PK data not available in cats

Answer 177

* Humans: cytochrome enzyme CYP2D6 involved in metabolism of trazodone o Caution when Rxing with SSRIs that inhibit CYP2D6 o When given over weeks, produces anxiolytic properties similar to diazepam o ER formula now available = Oleptro, has not been evaluated in animals

Answer 178

Droperidol - not used anymore DT behavior effects Haloperidol Azaperone

Answer 179

Highly protein bound so hypoalbuminemia will change unbound fraction, enhance clinical effects *Both diazepam, Midazolam >95-97% (primarily to albumin)

Answer 180

- Likely site of sedation, most abundance - 60% in brain

Answer 181

-anxiolytic effects -more restricted expression vs a1, principally in hippocampus, amygdala

Answer 182

Positive - benzodiazepines Negative - flumazenil

Answer 183

premed of dogs with PO trazodone at 8mg/kg 2h prior to anesthesia induction had significant isoflurane MAC-sparing effect (decrease 17±12%)

Answer 184

trazodone 9-12mg/kg vs placebo 90’ prior to veterinary clinic, trazodone dogs had lower dog stress scores (assessed by owners for PE, video analysis). No meaningful differences in other behavioral or physiologic outcomes, including serum cortisol concentrations single dose prior to transport reduced signs of stress prior to veterinary visits in dogs

Answer 185

* Structural analog of GABA; anticonvulsant used for tx of neuropathic and chronic pain, refractory sz, sedative effects , does not interact with GABA R to produce analgesia

Answer 186

Do not appear to interact with GABA, NMDA or dopamine receptors Inhibition of N-type voltage-dependent neuronal calcium channels Inhibition --> decreased Ca2+ influx into neurons, in turn decrease release of range of excitatory and inhibitory NTs altering channel trafficking and stimulating movement of channels away from the neuronal cell membranes

Answer 187

binding to N-type Ca channels in DRG, results in modulation of GABA R and may decrease release of excitatory NTs (eg substance P, glutamate) thus decrease central sensitization, may also act as NMDA R antag (decrease neuropathic pain including allodynia, hyperalgesia)

Answer 188

short HL, frequent dosing, 10-20mg/kg PO BID-TID

Answer 189

o Used to successfully improve CS in case series with CKCS with Chiari malformation, syringomyelia o Prospective clinical trial: gabapentin vs gelatin capsule placebo in dogs undergoing thoracic limb amp did not identify advantage of gabapentin in management of postop pain o Prospective clinical trial: gabapentin (10mg/kg PO BID) as adjunctive analgesic agent resulting in non-significant reduction in pain scores compared to placebo for hemilaminectomy * Dose of gabapentin should be tailored to individual animal’s response, as is performed in humans, vs adhering to rigid dosing o 3 cases of neuropathic pain: successful management with gabapentin or amitriptyline o Maximal plasma concentrations achieved within 2h

Answer 190

o Pregabalin: better bioavail, longer duration of action – BID dosing vs TID

Answer 191

6 healthy dogs received 20mg/kg gabapentin PO 2’ prior to ax Mean +/- SD MAC isoflurane 0.91+/- 0.26% vs with gabapentin 0.71 +/- 0.26%, mean reduction in MAC of isoflurane = 20 +/- 14% without any effect on hemodynamic variables/vital parameters

Answer 192

o Increase in thermal threshold did not occur when admin orally at 5, 10 or 30mg/kg, doses resulted in plasma concentrations greater than those assoc with analgesia in humans * Sedation not assoc with any dose * **Not able to show MAC-sparing effect of gabapentin on isofluran**e despite achieving plasma drug concentrations almost double those reported to be effective in people

Answer 193

o PO bioavailability: 16% horses (no metabolites in equine plasma) vs 80% in dogs o Frequency of drinking increased, standing at rest decreased, sedation scored as mild to moderate in all horses for 1h following IV injection at 20mg/kg o No metabolites found in plasma  majority of drug excreted unchanged in urine o SEDATION o Maximal plasma concentrations achieved within 2h o Suggested dosing: 4mg/kg PO Q8hr

Answer 194

gabapentin did not improve subjective or objective measurements of lameness in horses with chronic thoracic limb MSK pain

Answer 195

o Gabapentin vs G+meloxicam vs M alone: did not result in significant differences in groups undergoing dehorning or compared with placebo in plasma cortisol concentrations, eye temp * Mechanical nociceptive threshold equivocal * Average daily weight gain greater in G+M * Plasma levels > threshold assoc with analgesia in people * Peak plasma concentrations not appreciated until 7h post administration

Answer 196

o Adult cattle: 8 hr to achieve maximal plasma concentrations when admin orally, concentrations in milk took over 3d to drop below detection levels

Answer 197

* Dogs: ~30-35% of administered dose undergoes hepatic metabolism, unchanged drug excreted by kidney

Answer 198

* Sedation seen in dogs, horses; NOT cats, cattle

Answer 199

o Pregabalin * Schedule V * o Gabapentin * Not controlled * Off label use

Answer 200

-0.3mg/kg IV: 5 compartment model, high inter individual variability in plasma of 1-hydroxymidazolam concentrations - low clearance, persisteted in plasma longer than parent drug -Elimination HL ~80min, clearance rate ~12ml/kg Midaz did not result in clinically significant changes in physiologic variables

Answer 201

People: active metabolite, high plasma concentrations assoc with sedation Animals: unknown

Answer 202

MED at 5mcg/kg followed by 2.5mcg/kg/hr produced less sedation than DET at 10mcg/kg IV followed by 6mcg/kg/hr

Answer 203

Two-compartment model best described mean plasma concentration weakly correlated with nociceptive thresholds. Sedative effects significant at 0.08mg/kg+0.03mg/kg/hr until 160' but variable, not correlated to plasma concentration and weakly correlated to nociceptive thresholds. Romifidine elicited marked antinociceptive effect. Romifidine-induced antinociception appeared with delayed onset, lasted longer than sedation after dc admin.

Answer 204

o 3x more potent, 2x more affinity for BZD site, >sedative effect

Answer 205

o Principle metabolite (1-hydroxymidazolam) has approx. half the activity o Conjugated then excreted by kidneys o Cimetidine, erythromycin, ca channel blockers, antifungal inhibit cytochrome p450 and produce  CNS depression

Answer 206

o Neuro: decreased CMRO2 , CBF – acceptable for ICP concerns

Answer 207

o Resp: dose dependent decreases in hypoxic drive; in healthy volunteers no decrease except with synergisms of opioid

Answer 208

o Crosses the placenta but less than for other benzos

Answer 209

substantia gelatinosa

Answer 210

cerebral cortex, brainstem, platelets  Major sedative effect  Supraspinal analgesia  Centrally mediated bradycardia and hypotension  Gi  low AC  low cAMP  low Ca conductance, alter postsynaptic K conductance  NE from presynaptic terminal --> decreased transmission (i.e. sedation)  Brainstem (locus coeruleus, rostroventral lateral medulla) – low discharge frequency of tracts into cortex

Answer 211

– spinal cord – dorsal root ganglia, vascular endothelium  Spinal analgesia  Vasoconstriction and peripherally mediated reflex bradycardia  CV biphasic response * Phase 1: Peripheral o α2B and α1 activation in vascular endothelium = vasoconstriction o Baroreceptor mediated reflex bradycardia * Phase 2: Central o Central VD; HR remains same or bradycardia persists o Central α2A R activation – low symp outflow (low NE),  parasympathetic tone o Negative inotropic, chronotropic, dromotropic o Peripheral vasodilation * Due to differences in central and peripheral response