• glutamate is main excitatory receptor
• NMDA important in pain
• NMDA antagonists (ketamine, memantine) result in coma-like state

• located on some presynaptic termines (especially in pain, arousal)
• activation causes decreased Ca++ influx and decreased release of neurotransmitter
• causes analgesia, sedation
• examples:  xylazine, dexmedetomidine

• initially in high concentrations in central organs with high vascular perfusion (e.g. CNS)
• these drugs rapidly redistribute to other compartments, causing a decrease in blood concentration
• this may result in the animal waking up

• nociceptors:  primary afferents that respond to noxiouc stimuli; the first part of the pain pathway; may cause reflexes
• pain:  nociceptors combined with ascending APs that reach the thalamus/cortex; requires conscious perception

Peripheral

• inflammation (bradykinins, cytokines, PGs)
• PGs enhance nociception by lowering threshold of nociceptors

Central

• increased APs through pain pathways to brain
• modification of synapses in dorsal horn ("wind-up")
• decreased activity of descending inhibition

• releases enkephalins onto raphe magnus
• opioids affect mu, kappa, delta recptors
• often G-protein mediated (decreased adenylate cyclase)
• may inhibit or excite neurons

• releases serotonin onto inhibitory interneurons of substantia gelatinosa
• inhibits dorsal horn neurons (secondary afferents)

• often originates in motor cortex
• face is often affected resulting in twitching/blinking
• often limited to one side
• may spread to other areas of the brain resulting in generalized seizures

majority of the brain is affected.

usually brief and isolated.

may occur repeatedly (cluster seizures).

may become continuous (status epilepticus).

grand mal

• tonic-clonic
• major motor seizure
• rapid muscle contraction and relaxation
• many muscle groups involved

petit mal

• little motor involvement
• lose touch with surroundings
• rare in animals

• suppress nerve conduction
• stabilize neurons
• potentiate effects of inhibitory NT GABA

stabilization:  stop seizures as quickly as possible, protect from further damage

maintenance therapy:  prevent seizures at home

NOTE:  anticonvulsants DO NOT cure seizure disorders

diazepam

phenobarbital

bromide

clonazepam

gabapentin

levetiracetam

• class:  benzodiazepine
• MOA:  bind to sites on GABA receptors to increase the efficacy of endogenous GABA on GABA receptors
• net effect:  neuronal inhibition

• ideal for stabilization therapy:
• rapidly enters CNS (lipophilic)
• can administer IV, rectal, oral

• class:  barbiturate
• MOA:  increases efficacy of endogenous GABA on GABAa receptors
• use:  most commonly for chronic maintenance therapy; but also good second-line drug for acute seizures unresponsive to diazepam

metabolized by liver (CYP450)

half-life will shorten over time

increases clearance of other drugs metabolized by CYP450

• sedation
• polyphagia
• polydipsia
• polyuria
• side effects may subside over the first few weeks (tolerance, increased metabolism)
• increased liver enzymes without hepatotoxicity
• liver damage (increased ALP with increased bili)
• blood discrasias (rare)
• increased T4 metabolism
• increased corticosteroid metabolism

sodium bromide:  stabilization

• second/third line agent to stop seizures
• can be used in combo with phenobarb, diazepam
• given IV
• do not use KBr IV--can induce arrhythmias

potassium bromide:  maintenance

• may be used inc ombo with phenobarb
• PO
• high chloride diet can increase bromide elimination

polyphagia

behavior changes/sedation

bromism (bromide toxicity):  CNS depression, joint stiffness in rear limbs, coughing in cats

• class:  benzodiazepine
• effects similar to diazepam
• used as an alternative to diazepam in cats:  can be used for maintenance, not reported to cause heptotoxicity

• structural analog of GABA, MOA unknown
• anticonvulsant and analgesic effects
• may be used with other drugs for refractory seizures
• human liquid product contains xylitol
• adverse effects generally not a problem

• suppresses seizure activity without altering normal neuronal excitability
• MOA unknown
• used for maintenace
• well-tolerated. few side effects
• does not undergo significant hepatic metabolism

local anesthetic, blocks sodium channels

not recommended for dogs/cats (toxicity, adverse effects)

may interfere with GABA metabolism

less use since development of gabapentin and levetiracetam

may use NMDA metabolism

effective for refractory seizures in dogs

generally well-tolerated

limited use in vet med (newer drug in human med)

may be used with other drugs

may inhibit neuronal sodium and calcium channels

glucocorticoids (cortisol):  zona fasciculata

mineralocorticoids (aldosterone):  zona glomerulosa

releases these in response to stress

genomic effects

• mediated by cytosolic glucocorticoid receptors
• slow changes in gene expression that alter cellular function

non-genomic effects

• mediated by cytosolic GC receptros and plasma membrane-bound GC receptors
• rapid nonspecific effects caused by interactions with cell membranes

• increased gluconeogenesis-->hyperglycemia
• increased insulin secretion-->insulin resistance
• increased protein breakdown
• increased lipolysis and redistribution of lipids

• increased vasoconstriction and cardiac contraction
• stimulates mineralocorticoid effects (salt/water retention)
• associated with hypertension (dogs) and congestive heart failure (cats)

• synthesis stimulated by ACTH, angiotensin II, increased extracellular K+
• increase in salt and water retention

bronchodilation (beta-2)

decreased histamine release (not just in the lungs)

physiologic levels:  maintain muscles

pharmacological levels:  muscle wasting

epidermal.dermal thinning

easy bruising, poor wound healing
poor-quality hair, alopecia

too little or too much-->decreased immune function

increased susceptibility to infection

• anti-inflammatory effects linked to immunosuppressive response
• effects are seen with pharmacological doses
• effects are dose-dependent
• profound at high doses
• does not address the underlying cause of inflammation
• inflammatory mediators suppressed
• white blood cell migration/function suppressed
• CMI suppressed

duration:  short

anti-inflammatory potency=1 (very mild)

mineralocorticoid potency=1 (very mild)

uses:  topical for pruritis and inflammation assoiciated with allergy

duration:  short (<12h)

anti-inflammatory potency=10

mineralocorticoid potency=125

uses:  systemic replacement of cortisol and aldosterone during adrenal insufficiency

duration:  intermediate (12-36h)

anti-inflammatory potency:  4

mineralocorticoid potency=0.8

uses:  systemically for long-term management fo allergy, chronic inflammation, and immunosuppression

duration:  intermediate (12-36h)

anti-inflammatory potency:  25

mineralocorticoid potency:  0

uses:  systemically to reduce inflammation in allergic reactions (contact allergic dermatitis and atopy)

duration:  long (36-72h)

anti-inflammatory potency:  25

mineralocorticoid potency:  0

uses:  systemically for immediate relief of hypersensitivity and septic shock, long term controll of allergy, immunosuppression

• at pharmacological doses, adrenocortical suppression can occur within weeks of daily GC therapy
• additional GC supplementation may be necessary during periods of stress
• cessation of GC therapy must be tapered to prevent hypoadrenocorticism
• can use alternate-day therapy to reduce long-term effects, but not always auitable

• used as diagnostic tool to test for primary/secondary adrenal insufficiency
• can be used to assess degree of HPA axis supression in patient receiving GCs

• adrenal steroid inhibitors
• cytotoxic to only zonae fasciculata and reticularis
• reduction in all adrenal steroids except aldosterone
• used to treat hyperadrenocorticism

anti-inflammatory

analgesia (mild to moderate)

antipyretic (used less commonly than in people)

peripheral:  block PG production and liberation of inflammatory mediators

• reduces chemical and mechanical nociceptor sensitization

• weak acids
• efficient enteral absorption
• food intake may minimize side-effects
• highly protein bound
• hepatic metabolism
• dosage adjustments needed for geriatrics and pediatrics

readily available, not controlled

oral forms (easy for owners)

long duration of action

relatively inexpensive

no CNS side-effects

fewer side-effects than steroids

tissue injury upregulates PG, which sensitizes nociceptors

decreasing PG production helps prevent this

• inhibit arachidonate cyclooxygenase and lipozygenase-->reduces expression of PGs, leukotrienes, thromboxanes

• COX-1:  constitutive isoforms associated with physiologic, GI, kidneys, CNS, coagulation function
• COX-2:  constitutive AND inducible isoform ssociated with inflammation, pain, fever
• most NSAIDs are COX-2 selective to minimize side-effects

• GI ulceration and intolerance is most common side-effect
• inhibit platelet aggregation
• inhibition of PG-mediated renal function (especially in patients with decreased renal blood flow)
• hepatocellular damage-->increased liver enzymes
• DO NOT USE WITH STEROIDS

COX-1 vs. COX-2 selectivity

prevalence of side-effects

half-life

oral vs. parenteral administration

platelet inhibition

species-specific side-effects

anesthesia decreases blood flow

PGs help maintain renal blood flow, but NSAIDs decrease PG production

can result in low renal perfusion and resulting damage

• Addiction describes behavioral syndromes that cause a patient to continue using a substance despite significant substance-related problems
• Physical dependence describes a biological phenomenon that results as an adaptation (tolerance) to continued use of a substance; it is produced by homeostatic mechanisms
• opioid dependence can occur in as little as 7 days

• a decrease in effectiveness of a drug with its repeated administration
• may involve many different mechanisms, including changes in metabolism, receptors, etc.
• cross-tolerance can develop between drugs with the same mechanism
• pseudotolerance is the need to increase medication because of disease progression or concurrent disease

• analgesia:  loss of sensitivity to pain (can range from mild to total loss of sensation
• anesthesia:  total loss of sensation in a body part (local) or whole body (general)
• general anesthesia ideally involves aamnesia, hypnosis, hyporeflexia, analgesia, and muscle relaxation

• sensory:  inhibiting responses to painful stimuli
• modulatory role in GI, endocrine, autonomic functions
• emotional role
• cognitive role in the modulation of learning and memory

mu

delta

kappa

clinical effects of opioids are primarily attributed to mu and kappa receptors

• pro-opiomelanocortin-derived peptides (most potent, beta-endorphin)
• pro-enkephalin-derived peptides
• pro-dynorphin-derived peptides

• opiates can bind presynaptically to decrease NT release in nociceptive neurons
• opiates can also bind postsynaptically to hyperpolarize the cell membrane
• bottom line:  opiates decrease transmission and perception of noxious stimuli

• affinity:  drug's ability to bind to its receptor sites in the body
• potency:  directly related to the affinity of the drug for opiate receptor sites; determines the dose of the drug
• efficacy:  measure of the maximal effect that a drug can induce

aka mu-agonists; has affinity and activity (maximal effect) at all of the opioid receptors

examples:  carfentanil, codeine, etorphine, fentanyl, hydromorphone, meperidine, methadone, morphine, oxymorphone, sufentanil

has a high affinity for mu opiate receptors, but exert no activity at normal doses (will have no effect on its own in normal animals, but can reverse effects of endogenous opioids)

examples:  naloxone, naltrexone, methylnaltrexone

has affinity for some opiate receptors, but only exerts partial activity (does not fully activate mu-receptors)

examples:  buprenorphine

has agonist activity at one opioid receptor and antagonist activity at another opioid receptor

results in lower efficacy with lower side effects

e.g. butorphanol is a mu-receptor antagonist and a kappa-receptor agonist

examples:  butorphanol, nalbuphine

• analgesia without loss of consciousness (threshold to pain is increased); response will be dependent on how much pain the patient is feeling
• euphoria
• dyphoria:  disoriented or disturbed behavior (more likely if animal is not in pain, but may occur if pain is present)
• sedation:  varies with species and drug; more effect if animal is in pain
• excitement:  especially with high doses in animals without pain; varies with drug given
• respiratory depression
• cough suppression:  depression of cough center in medulla; allows  ET tube to stay in trachea longer
• nausea/emesis:  varies between species and drug given; mu-agonists more likely to cause emesis
• miosis/mydriasis
• convulsions
• thermoregulation:  may induce hypothermia (dogs) or hyperthermia (cats); due to changes in serotonin release and resetting of thermoregulatory center in hypothalamus
• neuro-endocrine:  inhibits release of GnRH, CRF; increases release of ADH

bradycardia:  increase in vagal tone, decrease in sympathetic tone; can give anticholinergic to counteract effect

tachycardia:  with high enough doses to induce excitement

vasodilation:  generally a result of histamine release or result of pain relief

• effects primarily mediated through CNS
• reduction in responsiveness of brainstem respiratory centers to carbon dioxide
• depression is dose-dependent
• respiratory depressant effects are well-tolerated in animals, except in animals with preexisting respiratory disease
• respiration may be increased in certain animals if they become hyperthermic (panting)
• also causes release of histamine--> can cause bronchoconstriction rarely

relief of pain may improve immune function

but can also inhibit inflammatory response

• stimulation of vomiting
• stimulation of defecation followed by constipation
• decreases GI motility-->spasmogenic effect on smooth muscle
• morphine can induce contrction of the sphincter of Oddi-->inhibition of pancreatic secretion

morphine may result in urinary voiding reflex (tone of external sphincter increases)

may cause retention of urine for 24+ hours

• weak mu-opioid activity
• inhibition of norepinephrine and serotonin re-uptake
• not controlled
• adequate analgesia with fewer GI side effects than morphine

• examples:  naloxone, naltrexone
• primarily mu-receptor antagonists, also affect kappa receptors
• liver metabolism
• no effect in the absence of opioids
• rapid reversal of opioid effect
• opioid agonists may outlast naloxone-->re-narcotization
• can produce withdrawal from chronic users or animals that have been on sustained opioid use for several days

• fentanyl has higher potency (need lower dose)
• morphine induces vomiting and fentanyl may actually have anti-emetic properties (may be good or bad)
• morphine causes histamine release--can lead to bronchoconstriction
• morphine may cause urine retention

generally well-tolerated, but may cause problems in animals with preexisting respiratory conditions.

Respiratory depression will also be more profound when opioids are combined with other sedatives--monitor closely

morphine is likely to produce vomiting

fentanyl is unlikely to induce vomiting and may actually suppress vomiting

Resets the thermoregulatory center in the hypothalamus

may result in hypothermia (dogs) or hyperthermia (cats)

fentanyl is more potent

they are about the same efficacy

sedation/hypnosis (unconsciousness)

muscle relaxation

amnesia

anxiolytic

anticonvulsant

diazepam

midazolam

zolazepam (telazol)

rapid oral absorption

unpredictable IM/SQ absorption

highly lipophilic (insoluble in water)

metabolized by the liver

metabolites (some active) eliminated by kidneys

rapid IM/SQ absorption

water-soluble

3-4 times as potent as diazepam, but generally administered at the same dose

short lasting

metabolized by liver

metabolites are inactive

• hypnotic:  can induce unconsciousness
• sedative:  most profound in people>dogs>cats>horses; minimal to no calming in healthy animals but profound calming in sick/compromised animals
• anxiolytic:  not always effective, maay actually increase excitement
• anticonvulsant:  decrease seizure spread, increase seizure threshold
• skeletal muscle relaxation:  central depression of spinal reflexes; often combined with diazepam
• antegrade amnesia:  occurs in humans, but not animals

• minimal effect on cardio system
• propylene glycol base of diazepam can induce bradycardia, arrythmias, hypotension, but is uncommon
• minimal respiratory depression, but may induce apnea if administered in tosic doses or excessive doses to compromised animals

• diazepam increases appetite in cats and ruminants
• repeated administration of diazepam to cats may lead to liver failure
• paradoxicaal increase in anxiety and fear in some animals
• ataxia evident in large animals
• will reduce dose of thiopental or propofol required for induction, even if no calming effect is noted

• morphine more likely to cause vomiting
• morphine may cause histamine release

flumazenil

weak or no activity at GABAa receptor, high affinity binding, inhibits effects of benzodiazepine agonists

diazepam can sometimes induce a paradoxical increase in anxiety/fear in some animals.  If an animal is adversely reacting to diazepam, you could use flumazenil to reverse these effects

diazepam can cause ataxia in large animals; flumazenil could be used to reverse this

aacepromazine

chlorpromazine

promazine (not used in food animals)

• well absorbed from SQ, IM, IV
• absorbed from oral route, but must use high doses due to 1st pass metabolism
• chlorpromazine IM is very irritating to rabbits
• hepatic metabolism and urinary excretion
• no antagonist available

• have effects on multiple receptors (dopamine-2, alpha-1, alpha-2, cholinergic, histamine)
• affinity mostly for D1 receptors
• dopamine receptors are located pre- and post-synaptically
• increase rate of turnover of dopamine and NE
• block central and peripheral effects of catecholamines
• sedative action comes from depression of the brain stem and connections to the cerebral cortex

• mental calming (decreased response to external stimuli)--lots of species variation
• calming effect can be overridden by excitement/stress
• calming increased by concurrent administration of opioids or alpha-agonists
• anti-anxiety
• not analgesic
• decreased motor activity (Ace generally does not produce ataxia in horses)
• supression of sympathetic nervous system
• lower seizure threshold
• anti-emetic effect (blockade of dopamine)

• alpha-adrenergic blockade-->vasodilation
• systemic hypotension (dose-dependent)
• reflex tachycardia
• centrally mediated bradycardia (uncommon)
• anti-arrhythmic
• minimal respiratory depression

• ace blocks alpha-adrenergic receptos-
• epi stimulates beta receptors but cannot stimulate alpha-1 receptor since it is blocked with ace
• concurrent vasodilation from beta stimulation and alpha inhibition

baroreceptors sense phenothiazine-induced hypotension and cause tachycardia in response to the hypotension

can be blocked by opiates

• depressed thermoregulation
• anti-histaminic
• nictitating membrane prolapse
• erection and temporary or permanent prolapse of penis in stallions (dose-dependent, rare)
• inhibition of platelet function (decreased number and aggregation)

• used to produce mental calming, especially in dogs and horses
• not as effective in cats
• often used in conjunction with other drugs (especilly opiates) for sedation

• administration of IV fluids to combat systemic hypotension
• opiate administration to block reflex tachycardia
• exogenous heat sources to combat depressed thermoregulation

There is no antagonist, so there is no way to counteract ace CNS effects

You may have to keep the dog in hospital for a longer period of time for monitoring

Haloperidol, droperidol, azaperone (not used commonly in vet med except in pigs)

similar to phenothiazine

• IV, IM, SQ administration (SQ in horses may be irritating)
• duration of effect dependent on drug, dose, route of administration
• xylazine duration of effect not related to plasma half-life or elimination half-life
• hepatic metabolism (rapid for xylazine)
• duration of effect prolonged by general anesthesia

• stimulation of presynaptic a2-adrenoreceptors-->decreases release of NE-decreased sympathetic outflow
• also stimulation of alpha-1 receptors (depends on drug)-->general parasympathomimetic effect

• sedation:  may be profound, can be overridden, enhanced with opioid administration
• analgesia:  particularly for visceral pain, analgesia not antagonized by naloxone; enhanced by opioid administration
• muscle relaxation
• aggression, excitement (uncommon)

• negative effects greatest with IV administration
• hypertension (transient)
• bradycardia and brady-arrhythmia (central vagal effect)
• increased afterload
• xylazine sensitizes myocardium to epinephrine-induced arrhythmias
• decreased CO
• hypotension (decreased sympathetic output, decreased cardiac output)

• mild to moderate respiratory depression
• depresses central respiratory center--decreased sensitivity to carbon dioxide
• may induce stridor and dyspnea in horses and brachycephalic dogs with upper airway obstructions
• IV xylazine may induce pulmonary edema in sheep (aalterations to alveolar-capillary membrane

• emesis
• decreased GI motility
• depressed swallowing reflex
• suppression of insulin release
• inhibition of ADH release--diuresis
• hypothermia or hyperthermia
• ataxia
• aggression/agitation (rare)
• increased uterine tone in ruminants

• brachycephalic dogs
• animals with heart conditions

• Ace causes vasodilation and hypotension from alpha-adrenergic blockade
• xylazine can cause transient hypertension from alpha stimulation; hypotension is caused by decreased sympathetic output

causes decrease in GI motility

provides analgesia

• sedation
• analgesia, especially when used with opioids
• depresses swallowing reflex-->intubation

• stimulation of pre-synaaptic  alpha-2 receptors
• decreases epinephrine release-->decreased sympathetic output

• used to reverse excessive sedation induced by a2 agonists
• profound hypotension (alpha blockade)
• reflex tachycardia
• excitement/pain
• yohimbine, telazoline, atipamezole

• more selective for a2 than a1 adrenoreceptors
• enhances release of excitatory NTs (NE)
• may induce anxiety, pacing, panting in dogs, rouhg recoveries in any species

• least specific of a2 antagonists
• potent H2-receptor agonist
• high doses cause hyperesthesia in cattle and seizures in llamas

barbiturates

ketamine

telazol

diazepam

midazolam

propofol

etomidaate

at low concentrations, barbiturates decrease the rate of dissociation of GABA from the GABAa receptor

at high concentrations, barbiturates directly activate the chloride-ion channel associated with the GABAa receptor

barbituraates may also inhibit the effects of excitatory NTs (glutamate, ACh)

acidosis causes more of the drug to be in unionized form and therefore more drug crosses the BBB.  This deepens the depth of sedation/anesthesia

opposite effect with alkalosis

the more alkaline the urine, the less barbiturates are reabsorbed from the tubules

• used widely for euthanasia
• induces unconsciousness before breathing/heart stops
• can cause transient excitement if given too slow
• oral, IP, IV (perivascular administration can induce tissue sloughing
• can be used as aanesthetic or anticonvulsant, but not common

• ultra-short acting barbiturate (15-20min), due to redistribution away from CNS
• alkaline formulations (sodium salts)
• half-life is 7 hours (can have prolonged DOA if administered multiple times)
• may induce excitement in young animals if administered too slow
• liver metbolism
• kidney elimination
• administer IV-can cause perivascular sloughing

• effects are dose-dependent
• apnea/hypoventilation (assisted ventilation often necessary)
• can sensitize myocardium to catecholamine-induced aarythmias
• CO and BP may increase, decrease, or not change

• selective depression of regions of the CNS
• stimulation of the limbic system
• stimulation of the sympathetic nervous system
• decreased CNS transmission
• inhibition of glutamate

cataleptic state of anesthesia

people feel dissociated/unaware of their environment

• most commonly used anesthetic induction drug used in vet med
• may be used in combination with a2-agonists or benzodiazepines to improve induction (ket-val)
• stimulates the sympathetic nervous system, leading to increases in heart rate and arterial BP (does not depress cardiovascular function as much as other drugs)

• induces muscle rigidity (can be minimized with diazepam)
• increases cerebral blood flow-->increase in intracranial pressure
• extra-ocular muscles stimulated to contract
• cardio-stimulation may be detrimental to some cardio conditions (hypertrophic cardiomyopaathy)
• can induce myocardial necrosis in cats (rare)
• ketamine and metabolites eliminated through kidney--renal disease may cause prolonged recoveries

• potential for rough recoveries, especially when used alone
• administration of sedative, analgesic, or tranquilizing drugs can improve recovery
• flash-backs occur in people

induces analgesia for superficial pain (blocks glutamate aat NMDA receptor)

has been used to prevent wind-up

• 1:1 combination of tiletaamine nd zolazepam (similar to ket-val)
• more potent than ket-val
• most side-effects more profound than ket-val
• maay have prolonged/rough recoveries (using smaller IV doses may help)

non-narcotic, non-barbiturate, rapid-acting anesthetic

highly soluble in lipid

formulation supports bacterial/fungal growth

• rapid penetration of BBB (highly lipophilic), rapid induction of anesthesia
• quickly cleared by liver and extra-hepatic sites
• inactivated in liver
• metabolites excreted in urine
• rapid clearance-->rapid, smooth recovery
• cats may have prolonged DOA if administered repeatedly (deficient in glucuronide synthetase)
• renal/liver disease does not appear to prolong recovery

• induction usually free from excitement, even when given slowly
• inductions improved if animal first receives premeds
• occasionally induces myoclonic contractions in older dogs during anesthesia (control with dizepam or thio)
• can be used as alternative to gas anesthetics
• less arrythmogenic than thio
• is not controlled
• expensive

• rapid boluses can induce respiratory depression and hypotension from vasodilation (can be decreased by administering loading dose of fluids and giving propofol slowly)

• non-opioid, non-barbiturate, sedative-hypnotic
• rapid redistribution
• DOA=5-10min
• metabaolism by liver hydrolysis (can be used with liver failure)
• used in dogs that are critically ill or have severe cardiovascular disease
• causes minimal cardio depression
• much safer than other induction drugs

• expensive
• rough inductions in excitable animals (opioid generally administered as pre-med, diazepam given concurrently)
• burns while being injected (dminster with IV fluids)
• may induce myoclonus (use diazepam with it)
• suppresses stress response (dexamethasone should be administered in severely compromised animals)

respiratory depression (less with ketamine)

hypoventilation, apnea

Thio works to depress the whole CNS, resulting in unconsciousness

ketamine selectively depresses regions of the CNS, resulting in dissociation

etomidate inhibits adrenocorticoid function and suppresses the stress response

may need to give exogenous steroids (e.g. dexamethasone) to severely compromised animals

gas exists in gaseous form at room temperature with sea-level pressure

vapor is a liquid at room temperature/pressure

• produce unconsciousness, hyporeflexia, muscle relaxation, amnesia, analgesia during a procedure
• provide greater flexibility than injected anesthetics
• level of consciousness can be changed rapidly
• rapid recovery
• commonly eliminated through respiratory system
• delivered with oxygen-->decreased risk of hypoxemia

• non-polar molecules
• potency is correlated with lipid solubility (more lipid soluble, more potent--Meyer-Overton Rule)
• alter intracellular functions of signaling proteins, including protein kinase C
• may involve changing how lipid membranes function
• exert pre- and post-synaptic effects
• enhance inhibitory post-synaptic channel activity (GABA, glycine)
• inhibit excitatory synaptic channel activity (nACh, serotonin, glutamate)
• inhibit NT release and alter response to NTs
• inhibition of K+ and Ca++ channels--cardio effects

non-irritating and free of disagreeable odors

induces pleasant anesthetic induction

rapid, smooth recoveries

eaasily control depth of aanesthesia

minimal side-effects, particularly cardiopulmonary

non-toxic, minimal residual effects

not explosive

inexpensive

lipid solubility

vapor pressure

blood:gas solubility

minimum alveolar concentration

side effects

metabolism

• the pressure that vapor molecules exert when liquid and gas phases are in equilibrium
• saturate vapor pressure is the maximum concentration of molecules in vapor staate that can exist for a given liquid aat each temperature
• vapor pressure determines the type of vaporizer that is required to safely administer inhalant
• methoxyflurane can be administered without a precision vaporizer because it will not reach high vaporized concentrations
• vapor pressure continuum:

methoxyflurane<<<halothane<isoflurane

<sevoflurane<desfulrane

• determines how rapidly an anesthetic saturates the blood and induces general anesthesia
• less soluble-->more rapid induction

<--blood:gas solubility

methoxyflurane>>>halothane>isoflurane>

sevoflurane>desflurane

-->faster induction/recovery

• measure of potency
• minimum alveolar concentration that produces immobility in 50% of patients exposed to noxious stimuli
• lower MAC=higher potency
• affected by other drugs and body temperature (hypothermia lowers MAC)

methoxyflurane<halothane<isoflurane<sevoflurane

<desflurane

• all volatile inhalant anesthetics my induce cardio depression at anesthetic doses
• depressed cardiac contractility
• decreased CO
• vasodilation
• heart rate/rhythm effects
• hypotension
• depressed sympathetic outflow nad obtunded cardiovascular reflexes
• effects are dose-dependent
• isoflurane noted for cardio stability, especially when compared with halothane
• sevoflurane causes less sympathoaadrenal response

• respiration depressed by all inhalants
• tidal volume decreased
• alveolar ventilation decreased
• respiratory rate may increase to compensate for decreased tidal volume
• repiratory rate may decrease
• responses to increased CO2 lost at deeper planes of anesthesia
• isoflurane is more potent respiratory depressant than halothane
• sevoflurane may be even more of a respiratory depressant than isoflurane

• eliminated primarily through respiration, but there is always some metabolism
• % anesthetic recovered as metabolite:

methoxyflurane>>halothane>>sevoflurane

>isoflurane>desflurane

• methoxyflurane induces renal failure in humans (production of fluoride ions); dogs are somewhat resistant
• sevoflurane undergoes limited hepatic biotransformation
• sevoflurane may interact with CO2 absorbents, yielding nephrotoxic haloalkanes--should not be used in closed circle rebreathing systems

hypothermia lowers MAC

animals often become hypothermic under anesthesia-->you may have to turn down gas to get same effect during a procedure

• both lipophilic and hydrophilic groups on molecule
• weaak bases
• drug binding on cytoplasmic side of sodium channel
• infected tissues have low pH-->decreased efficacy of local anesthetic

• absorption depends on vascularity of tissue injected
• epinephrine can decrease raate of absorption (increases DOA at a specific site)
• distribution--rapid uptake by many organs
• amide (lidocaine) anesthetics metbaolized by liver
• ester (procaine) anesthetics metabolized by plasma esterases
• excreted in urine
• liver metabolism and blood flow contribute to DOA

• stabilize membranes of excitable tissue--inhibit transmission of nerve impulses
• Na+ channel blockers
• can bind to Na channels in open/activated state to prevent them from returning to resting state
• conduction blockade related to size of nerve, amount of myelination, frequency of activity
• small, sensory, frequently-used fibers more susceptible to locals
• molecule must be in uncharged state to cross lipid membrane; if there is excess H+ in an area, molecule will retain + charge and not be able to cross membrane

allergic reaction

• rare
• esters more likely to cause than amides
• metabolism of ester drugs causes reaction

systemic toxicity (overdose)

• rare
• usually due to accidental IV injection or administration of excessive dose
• results in CNS and cardio system dysfunction
• CNS signs seen first:  muscular twitching, seizures, depression, unconsciousness, coma, respiratory arrest
• cardio signs seen second: decreased myocardial contractility, decreased rate of conduction, alterations in vascular tone
• with bupivicaine, neuro and cardio signs will show up much closer together

amide:  lidocaine, mepivicaine, bupivicaine

esters:  procaine

efficacy is decreased

inflammation causes increased concentrations of H+ in an area, preventing dissociation of anesthetic and inability to cross lipid membrane

reduces parasite numbers

wide therapeutic index

does not require multiple administrations

easily administered

no residues in food animal tissues

changes in:

animal

parasite

dosage

route

• avermectins:  ivermectin, eprinomectin, doramectin, selamectin
• milbemycins:  moxidectin, milbemycin oxime
• spinosad

• flaccid paralysis for avermectins, milbemycins
• binds to glutamate-gated Cl- channels
• potentiates GABA-mediated neurotransmission
• spastic paralysis for spinosads:  cholinomimetic

• depends on route of administration
• highly lipophilic--prolonged withdraawal times
• moxidectin and eprinomectin have no milk withdrawal time
• excreted in feces via bile; excreted relaatively unchanged

• least toxic parasiticide
• p-glycoprotein drug efflux transporter:  collies with ABCB1 defect may be susceptible to CNS toxicity due to drug buildup
• dogs that are heterozygous can be safely given HWP doses, but not higher doses

broad

nematodes

some cestodes:  Moniezia benedeni

some trematodes:  Fasciola hepatica

giardia (off-label)

albendazole

oxibendazole

fenbendazole

oxfendazole

febantel

mebendazole

cambendazole

binds to dimeric tubulin fusion proteins--disrupts cell division

inhibits fumarate reductase--blocks mitochondrial function

• poorly absorbed
• oral
• enterohepatic recycling occurs
• withdrawal
• excreted in feces via bile

levamisole

tetramisole

• low margin of saafety
• rapid absorption (generally oral, can be topical)
• metabolized quickly
• excreted in urine

cholinomimetic:  spastic paralysis

inhibits fumarate reductase:  blocks mitochondria

pyrantel tartrate (well-absorbed)

pyrantel pamoate (poorly absorbed)

morantel (ruminants)

• usually given orally
• ruminant morantel no milk withdrawal time
• excreted in urine

cestodes

trematodes

epsiprantel

praziquantel

instantaneous contraction and paaralysis

vacuolization of integument

• MOA unknown
• topical (domodex)
• collar/spray/dip/topical:  ticks, mites, lice
• DO NOT use on cats!!
• owners must be careful if they are on MAOIs

inhibits GABA-regulated chloride channels

fleas/ticks in dogs/cats

binds to ACh receptor sites

fleas will bite host until compound takes effect

methoprene, pyriproxyfen, fenoxycarb:  ovicidal, juvenile hormone analog

lufenuron (Program):  inhibits chitin synthesis