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Clinical Pharmacology
VM 609 Midterm
54
Veterinary Medicine
Professional
09/19/2012

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Term
Phenothiazines Drugs
Definition
acepromazine
promazine
chlorpromazine
anything ending in promazine
Term
Phenothiazines Mechanism of Action
Definition
given IV, IM, SQ, orally
induces sedation by depressing brain stem and neuronal signal transmission
inhibits dopamine release
Term
Phenothiazines Uses
Definition
anxiolytic
reduces concurrent administered anesthetic dose
provides no analgesia
interprets pain different
Term
Phenothiazines Side Effects
Definition
hypotension due to alpha-1 blockage
antiarrythmic due to secondary catecholamine release
acts centrally on CRTZ and vomition center to reduce nauseau and vomiting
lowers seizure threshold
large doses cause respiratory depression
mild muscle relaxation, delayed gastric emptying, decreased PCV and total protein due to splenic sequestration
increased plasma volume
decreased body temperature
decreased platelet aggregation
Term
Phenothiazines Metabolism
Definition
biotransformed in liver
metabolites excreted in urine for several days
as dose increases, hypotension increases not level of sedation
Term
Benzodiazepines Drugs
Definition
Diazepam
Midzolam
Zolazepam
Term
Benzodiazepines Mechanism of Action
Definition
binds receptor site and potentiates GABA
enhances chloride ion channel conductance
hyperpolarizes cell membranes
makes cell less excitable
reduces sympathetic output
Term
Benzodiazepines Side Effects
Definition
less CV side effects
paradoxical excitement or aggression in young healthy excited animals
Term
Benzodiazepines Metabolism
Definition
hepatic metabolism
renal and fecal excretion
Term
Diazepam
Definition
only soluble in propylene glycol
irritating to tissues
CV depressant/irritant
sedative effects varies among individuals
may stimulate appetite in cats/dogs
high doses may produce respiratory depression and decreased blood pressure
often combined with ketamine to allow for muscle relaxation during induction
used to treat seizuring
Term
Midazolam
Definition
2-5 times more potent than diazepam
well absorbed IM or SQ and doesn't need to be combined with propylene glycol
Term
Zolazepam
Definition
used in combination with tiletamine in Telazol for induction
prolonged rough recoveries
Term
Alpha 2 Agonist Drugs
Definition
xylazine
dexmedetomidine
detomidine
romifidine
Term
Alpha 2 Agonist Mechanism of Action
Definition
prejunctional inhibition of alpha 2 adrenergic receptors
decreased release of norepinephrine
causes sedation, decreased sympathetic activity, muscle relaxation, sedation, hypotension
Term
Alpha 2 Agonist Uses
Definition
decreases anxiety
chemical restraint
dependable sedation
potentiates effects of other drugs
provides analgesia
sedated animals can still move unexpectedly
Term
Alpha 2 Agonist Side Effects
Definition
initial transiet hypertension
followed by prolonged hypotension
bradycardia, secondary heart block, decreased cardiac output (up to 50-60%)
mild respiratory depression
increases blood glucose
decreased intestinal motility
increased urinary production through ADH antagonism at collecting ducts
increases uterine contraction
induces vomition
Term
Alpha 2 Agonist Receptor Specificity
Definition
Alpha2:Alpha1 ratio
Dexedetomidine 1620:1
Romifidine 340:1
Detomidine 260:1
Xylazine 160:1
Term
Xylazine
Definition
sedative, analgesia, muscle relaxation
onset 3-5 min IV
onset 5-15 min IM
sedation lasts longer than analgesia
tends to cause more vomition in small animals
no longer recommended for use in small animals with development of dexmedetomidine
Term
Dexmedetomidine
Definition
most potent alpha 2 agonist
causes marked ataxia in horses
reliable sedation
Term
Detomidine
Definition
used primarily in horses
can administer as CRI for standing procedures
Term
Romifidine
Definition
less ataxia for horses
approved for horses only
Term
Alpha 2 Antagonists Uses
Definition
used to reverse the sedative and cardiovascular effect of alpha 2 agonist
Term
Alpha 2 Antagonists Drugs
Definition
Atipamezole
Yohimbine
Tolazline
Term
Alpha 2 Antagonists Receptor Specificity
Definition
Atipamazole 8526:1
Yohimbine 40:1
Tolazoline 1:1
Term
Opioids Uses
Definition
pre, intra, and post operative analgesia
Term
Opioids Side Effects
Definition
may cause excitement in cats and horses at high doses (morphine)
differing concentrations and distribution of receptors in various regions of the brain
depends on temperature, pain, dose, route, timing
hypothermia
hyperthermia in cats
direct stimulation of CRTZ in medulla
inhibits coughing directly via medulla
improves mydriasis in cats, horses
miosis in dogs
dose dependent respiratory depression
minimal CV effects
bradycardia may occur
can cause histamine release causing vasodilation and hypotension
predisposes to ileus and constipation
may initially stimulate defecation in dogs
may cause urinary retention
Term
Opioids Mechanism of Action
Definition
acts as agonist on specific receptors
modulates inhibitory/excitatory effects of CNS
mu receptors- supraspinal analgesia, euphoria, sedation, respiratory depression, bradycardia, increased GI transit time, hypothermia, physical dependence
kappa- spinal analgesia, sedation, meiosis
sigma- spinal analgesia, respiratory depression
Term
Opioids Pure Agonist
Definition
produces max biological response
binds mu receptor
gives best analgesia
Term
Opioids Partial Agonist
Definition
produces sub-maximal response at mu receptor
Term
Opioids Mixed Agonist-Antagonist
Definition
have divergent activities on different receptors
agonist at kappa and sigma receptors
antagonist at mu receptors
Term
Opioids Antagonist
Definition
competitively reverses effects of agonists by preventing their binding
Term
Morphine
Definition
full agonist at mu, kappa, sigma
cross BBB slower than synthetic opioids
single dose provides analgesia for 3-4 hours
high first pass effect orally
causes release of histamine
reduces MAC
can give IV, IM, SC, edidural
receptors in synovial and cornea
Term
Hydromorphone
Definition
full agonist
more lipid soluble
2-4 hour duration
see panting in dogs
less vomiting
CRI administration
Term
Oxymorphone
Definition
synthetic full agonist
Term
Methadone
Definition
synethetic mu opoid
NMDA antagonist
useful for chronic pain
excellent oral absorption in humans
high potency and extended duration of action
Term
Fentanyl
Definition
short-acting synthetic mu agonist
short onset and short duration
redistribution terminates clinical effect
metabolized by liver
excellent for CV
if given IV, significant bradycardia and respiratory depression
can be given CRI with inhalant anesthetics or as induction agent
transdermal patch
Term
Buprenorphine
Definition
partial mu agonist
binds tightly and dissociates slowly
delayed but long duration of action
ceiling effect
difficult to antagonize
can place in buccal pouch of cats and absorbed transmucosally
Term
Butorphanol
Definition
synthetic agonist-antagonist opioid
minimal sedation and analgesia
short term
can be used to antagonize mu agonists
Term
Naloxone
Definition
pure opioid antagonist
blocks both mu and kappa receptors
short duration
patients can rencarcotize
occasional excitement
Term
Remifentanyl
Definition
analog of fentanyl
does not need functioning liver or kidneys to work
metabolized by plasma esterases
shortest acting
Term
Guaifenesin
Definition
centrally acting muscle relaxation
used in large animal anesthesia
irritating to tissues
don't give perivascularly
Term
Anticholinergics Drugs
Definition
Atropine
Glycopyrrolate
Term
Anticholinergics Mechanism of Action
Definition
parasympatholytic
blocks effects of parasympathetic sysmte
antagonizes effects of Ach at postganglionic muscarinic receptors
does not block nicotinic receptors
muscarinic receptors at CNS, SA and AV nodes, glands vascular endothelium, smooth muscle
Term
Intravenous Anesthetic Agenst
Definition
barbiturates
propofol
etomidate
dissociatives
opioids
Term
Propofol Side Effects
Definition
delirium free recoveries
can't rapidly bolus
no preservatives so need to use within 8 hours after opening vial
decreses intracranial and cerebral perfusion presures
reduces cerebral metabolic demand for oxygen
favored for neurologic disease associated with increased intracranial pressure
hypotension
strong dose dependent respiratory depressant
provides no analgesia
phenol can cause oxidative injury to cat RBC's with repeated use (Heinz Body Anemia)
Term
Propofol Metabolism
Definition
hepatic and extrahepatic metabolism
Term
Etomidate
Definition
imidazole
single injection suppresses adrenal steroidogensis for several hours
minimal CV depression
propylene glycol irritation
can cause myoclonus at induction
Term
Dissociatives Mechanism of Action
Definition
interruption of ascending signals the parts of the brain responsible for unconscious and conscious function
good for somatic analgesia but not visceral
Term
Dissociatives Side Effects
Definition
eyes open with slow nystagmic gaze
increases muscle tone, spontaneous muscle movement
salivation, lacrimation, occasionally seizures
stimulates sympathetic NS
direct myocardial depressant
minimal respiratory depression
Term
Dissociatives Metabolism
Definition
50% excreted by kidneys unchanged in cats
metabolized in liver
Term
Ketamine
Definition
NMDA receptor antagonist
Term
Ketamine Side Effects
Definition
avoid use in seizures or increased intracranial pressure
hepatic dysfunction
cardiac disease
muscle rigidity or seizures
emerging delirium and hallucinations are common - need to smooth out with acepromazine, benzodiazepam, opioids, alpha 2 agonist
Term
Ketamine Uses
Definition
induction agent
CRI for chronic neuropathic or somatic pain
Term
Telazol
Definition
dissociative
tiletamine and zolazepam 1:1
used as darting agent in exotics
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