Pharmacology Final Exam
Terms
undefined, object
copy deck
- barbiturates
-
phenobarbital
pentobarbital
methohexital
thiopental
thiamylal - alpha-2 agonists
-
xylazine
medetomidine
detomidine - benzodiazepines
-
diazepam
clonazepam
zolazepam
midazolam - dissociative anesthetics
-
ketamine
tiletamine - neuroleptics
-
phenothiazines: acepromazine, chlorpromazine
butyrophenones: droperidol - pure opioid agonists
-
morphine
hydromorphone (oxymorphone)
etorphine
codeine
dextromethorphan
methadone
carfentanil
sufentanil
fentanyl - pure opioid antagonists
-
naloxone
naltrexone
diprenorphine - mixed opioid agonists/antagonists
-
butorphanol
buprenorphine - miscellaneous opioids
-
loperamide
apomorphine - inhalational anesthesetics
-
halothane
isoflurane
sevoflurane
nitrous oxide - analeptics
-
doxapram
strychnine
theophylline
aminophylline
theobromine - local anesthetics
-
esters: cocaine, proparacaine
amides: lidocaine, bupivacaine, mepivacaine - anticonvulsants
-
phenobarbital
primidone
diazepam
clonazepam
potassium bromide
felbamate
gabapentin - phenobarbital
-
barbiturate
used to tx seizure disorders in dogs & cats; occasionally used as oral sedative - pentobarbital
-
barbiturate
sedative agent, drug of choice for tx of intractable seizures in dogs & cats d/t convulsant agents (ex. strychnine poisoning) or CNS toxins (ex. tetanus), major active ingredient in several euthanasia solutions
largely replaced by ultra-short acting barbiturates b/c of slow induction, long duration of action, inactivated primarily by metabolism (don't use w/ liver dz) - thiopental
-
barbiturate
ultra short acting
excellent IV induction agent in young, healthy animals, or alone for very short procedures - thiamylal
-
barbiturate
ultra short acting
no longer available in US; replaced by thiopental - methohexital
-
barbiturate
ultra-short acting anesthetic agent often used in sight hounds b/c it does not depend on redistribution to fat to reverse effect - etomidate
-
ultrashort acting, hypnotic non-barbiturate induction agent
excellent induction agent for patients w/ CV, respiratory, or liver dz
safe for use in sighthounds
depresses cortisol production
can't use in horses (excitement) - propofol: facts + pros
-
non-barbiturate sedative-hypnotic agent
used for induction &/or maintenance of anesthesia, to produce prolonged sedation of patients in ICU
pros: rapidly metabolized & redistributed --> very rapid recovery
does NOT accumulate in body w/ chronic dosing - barbiturates & lipid solubility
-
thiobarbiturate always more lipid soluble than oxybarbiturate
phenobarb<pentobarb<thiopental
as lipid solubility increases:
1. duration of action decreases
2. quicker onset
3. increased rate of distribution, metabolism
4. more hypnotic potency
5. more protein binding - barbiturates: metabolism & redistribution
-
renal excretion: if highly lipid soluble, completely reabsorbed --> metabolized in liver (caution w/ liver dz)
redistribution occurs if drug given rapidly (ex. IV), highly lipid soluble: drug goes to high flow organs 1st, then rapid reversal to muscle, adipose - clinical uses of barbiturates
-
induction
tx of seizures
to decrease ICP & tx cerebral edema
euthanasia - cons of barbiturates
-
NOT analgesic (HYPERalgesic at subanesthetic doses)
contraindicated w/ liver dz d/t metabolism, inc. free drug if hypoproteinemia is present
can't use thiobarbiturates in sighthounds
induce liver microsomal enzymes --> incr. metabolism of other drugs (phenobarb most potent)
given only IV or PO
w/ multiple dosing --> longer duration
no pharmalogical antagonist (phenobarb OD: give bicarb to alkaline urine --> increased rate of excretion of parent drug) - CV, resp. effects of barbiturates
-
brief hypotension, reflex tachycardia
transient resp. depression (+/- apnea)
arrhythmias, esp. in excited animals - clinical uses of alpha-2 agonists
-
preanesthetic agent
chemical restraint
selectivity: xylazine < detomidine < medetomidine
duration: detomidine longest - effects of alpha-2 agonists
-
increases potency of other anasthetic drugs
sedation/hypnosis
analgesia
muscle relaxation - adverse effects of alpha-2 agonists
-
emesis
resp. depression
CV effects (vary b'twn drugs)
bloat
hyperglycemia
increased urine output
don't use xylazine during last mo. of pregnancy - CV effects of xylazine
-
transient hypertension followed by prolonged hypotension
bradycardia
arrhythmias - clinical uses of guaifenesin
- adjunct to anesthesia in horses (IV)
- effects of guaifenesin
-
sedation/hypnosis
analgesia
muscle relaxation
antipyretic
antitussive - pros & cons of guifenesin
-
pros: inc. potency of barbiturates
dec. hypertonicity assoc. w/ ketamine
little cardiopulmonary depression
cons: not very H2O soluble --> large vols. required
may hemolyze RBCs (esp. in cattle) - clinical uses of benzodiazepines
-
pre-anesthetic med (often w/ opioids)
tx of seizures (midazolam: neonatal seizures in foals)
tx anorexia in cats
tx fears & phobias - pros of benzodiazepines
-
dec. dose of other anesthetic drugs
muscle relaxant
weak resp. depression
minor CV effects - cons of benzodiazepines
-
cannot give IM (except midazolam)
weaker sedative/hypnotic effects than other meds
amnesia
can't give oral diazepam to cats --> idiopathic hepatic necrosis
avoid ending chronic tx abruptly
tolerance w/ chronic use
IV midazolam in cats --> profound tachycardia - pharmacokinetics of benzodiazepines
-
lipid soluble --> extensive redistribution when given IV
metabolism:
oxidative pathway --> many active metabolites
reductive path --> inactive compounds
midazolam: short duration d/t rapid metab & distribution - mechanism of action of benzodiazpines
- facilitates GABA by binding to site on GABA receptor --> inc. affinity of GABA for receptor & vice versa --> GABA produces inc. in chloride conductance
- flumazenil
-
benzodiazepine receptor antagonist
useful in sick animals, esp. cats, to speed up recovery from anesthesia - mechanism of action of barbiturates
-
low doses: facilitates GABA by binding to site on GABA receptor (separate site from benzos)
higher doses (anesthetic):
decreases presynaptic release of NTs
blocks postsynaptic action of excitatory NTs
GABA-mimetic effect - dissociative anesthetic state
-
eyes open
involuntary movements
vocalization
hallucinations
feel separated from body - physiological effects of dissociatives
-
analgesia (mostly somatic, less visceral)
sympathetic activation
hypertonicity (use w/ benzos, alpha-2s, or guaifenesin)
inc. ICP, IOP
convulsions (use w/ benzos)
apneustic breathing
retention of near normal pharyngeal & laryngeal reflexes - mechanism of acation of dissociatives
- noncompetitive antagonists of NMDA glutamate receptor --> inc. activity of layer V pyramidal output neurons (that release glutamate) --> disruption of thalamic & cerebral functions
- tiletamine
-
similar to ketamine, but longer duration of action
can only be bought mixed w/ benzo zolazepam = Telazol (recoveries may be prolonged & rough) - clinical uses of neuroleptics
-
chemical restraint
preanesthetic meds (dec. dose of other meds)
antiemetic - neuroleptic syndrome
-
sedation
tranquilization
dec. emotional behavior
dec. responsiveness to external stimuli
dec. spontaneous movement
NOT hypnotic
NO analgesia alone - adverse effects of neurolpetics
-
extrapyramidal effects: dyskinesia, dystonia, muscle tremors
higher doses --> catalepsy
hypotension
hypothermia
mild neg. inotropic effect
dec. seizure threshold
weak resp. depression, but can inc. resp. depression w/ other drugs - mechanism of action of neuroleptics
- antagonize dopaminergic, alpha-adrenergic, muscarinic, H1, certain serotonergic receptors
- phenothiazine neuroleptics: effects in horses
-
ace, chlorpromazine
can cause violent incoordination & excitement
penile prolapse & priapism - droperidol
-
butyrophenone neuroleptic
used in various preps in SA, swine
don't use in horses d/t bizarre rxns
shorter duration than phenothiazine neuroleptics
potent dopamine receptor antagonists --> more likely to produce extrapyramidal effects - mechanism of action of opioids & opiopeptins
- decrease release of substance P --> dec. transmission of nociceptive info
- species dependent effects of morphine
-
dogs, monkey, man: analgesia, sedation, euphoria, pupillary miosis
horses, cats, pigs, ruminants: analgesia, excitement, dysphoria, mydriasis (use low doses) - pros of morphine
-
valuable premed b/c dec. amt. of other drugs
antitussive
mild hypotension, bradycardia - cons of morphine
-
dose dependent resp. depression: CAUTION w/ lung dz, neonates
constipation, esp. w/ chronic use
emetic
SEVERE hypotension if in shock or w/ volume depletion - hydromorphone
-
pure opioid agonist
similar to morphine, but 5x more potent
less GI upset & vomiting than morphine in dogs - etorphine
-
pure opioid agonist
agonist at all receptors, 1000x more potent than morphine
used only to immobilize wild animals - codeine
-
pure opioid agonist
10x weaker than morphine
protected from 1st pass metabolism in liver --> converted to morphine
uses:
antitussive
w/ acetaminophen to relieve pain in dogs - dextromethorphan
-
pure opioid agonist
devoid of all opioid properties except ANTITUSSIVE effect - meperidine
-
pure opioid agonist (=Demerol)
effective analgesic, maintains much of potency when given PO
less constipating than morphine - methadone
-
pure opioid agonist
accumulates in body --> inc. duration of action w/ multiple doses
retains most analgesic potency when given orally
tolerance, dependence develop slowly
also NMBA glutamate antagonist --> dec. opioid dependence - carfentanil
-
pure opioid agonist
most potent of fentanil family (all are short acting, w/ rapid onset)
used to immobilize wild animals - sufentanil
-
pure opioid agonist
anesthetic adjunct in dogs - fentanyl
-
pure opioid agonist
anesthetic adjunct in dogs
patches: control of chronic pain (absorption can be unreliable) - naloxone
-
pure opioid antagonist
most commonly used opioid antagonist in vet med
parenteral use only (usually IV), slightly shorter acting than morphine - diprenorphine
-
pure opioid antagonist
parenteral only (usually IM)
used only to reverse etorphine-induced immobilization - naltrexone
-
pure opioid antagonist
uses:
control crib biting in horses
reverse carfentanil-induced immobilization
long duration of action
oral or parenteral use - butorphanol
-
mixed opioid agonist/antagonist
uses:
analgesic
antitussive
preanesthetic med
chemical restraint (w/ alpha-2 agonist)
popular in horses d/t low incidence of excitatory effects
weak resp. depression, less constipation - buprenorphine
-
mixed opioid agonist/antagonist
uses:
analgesic in dogs & cats
alternative to methadone for addicts
longer duration of action than torb, morphine
reverse w/ naloxone given PRIOR to buprenorphine
well tolerated in horses - loperamide
-
misc. opioid agent (=Immodium)
used to tx diarrhea
avoid repeated use --> constipation
can cause profound sedation in certain dog breeds (collies, Australian shepherds, etc.) - apomorphine
-
misc. opioid agents
strong dopaminergic agonist
emetic of choice in dogs
give conjunctivally (or SQ) - innovar
-
neuroleptanalgesic
= droperidol + fentanyl - midazolam + morphine
-
benzo/opioid combo
given IM as pre-med to dogs that can't be handled easily &/or are in pain
often given to cats as alternative to ketamine (ex. w/ intracranial mass, etc.) - diazepam + morphine
-
benzo/opioid combo
given IV as pre-med to calm depressed &/or sick dogs - neuroleptanalgesia
-
(+): sedation, dec. anxiety, intense analgesia, dec. movement, NO emesis, dec. dose of other drugs
(-): resp. depression, extrapyramidal effects, chest rigidity, change in autonomic fn - benzodiazepine/opioid combos
-
(+): sedation, dec. anxiety, intense analgesia, amnesia, minimal autonomic effects, NO extrapyramidal effects
(-): resp. depression (easily reversed w/ opioid antagonist) - determinants of tension of gas in alveoli (FA)
-
rate of delivery of gas TO alveoli:
1. tension of anesthetic gas in inspired gas (FI)
2. minute volume
rate of removal of gas FROM alveoli:
1. cardiac output
2. blood solubility (Fblood)* - blood solubility & induction/recovery
-
LOW blood solubility:
fast induction & recovery
HIGH blood solubility: slow induction & recovery - effects of inhalational anesthetics
-
all produce dose dependent depression of respiration & MAP
minimal skeletal muscle relaxation
halothane is most potent (lowest MAC)
sevo has fastest induction/recovery (lowest max vapor conc.) - cons of halothane
-
hypotension d/t dec. myocardial contractility
arrhythmias
significant hepatic biotransformation (hepatotoxic metabolites)
alters Ca++ movements
1. intearctions w/ aminoglycoside Abs, Ca channel blockers --> severe CV depression
2. can produce malignant hyperthermia (esp. in pigs), caused by failure of Ca uptake in SR - dantrolene sodium
-
used to tx malignant hyperthermia
decreases Ca++ release from SR - sevoflurane
-
hypotension d/t vasodilation, esp. in muscle & skin (same w/ iso)
unstable in soda lime
excellent for sea turtles
expensive - nitrous oxide
-
used as adjunct to anesthesia in small animals b/c:
1. concentration & 2nd gas effects
2. decreases dose of primary anesthetic
3. mild stimulation of symp. nervous system
4. ANALGESIC
avoid conc. > 70-75%
do not give to patients w/ any condition where air is trapped in viscera --> will cause air pocket to expand (ex. pneumothorax) - concentration effect
-
only seen w/ high conc. of nitrous oxide
when higher conc. of anesthetic gas is inhaled, FA (& therefore Fblood), inc. at a slightly greater rate than if a lesser conc. were inhaled - 2nd gas effect
-
occurs when a 2nd gas (ex. 1% halothane) is inspired w/ 75% nitrous & 24% O2
conc. effect produced by 75% N2O not only concentrates O2, but also halothane --> inc. rate of movement of halothane from alveolar air to pulm. blood --> faster induction - uses of analeptics
-
used to reverse drug-induced CNS depression (esp. respiratory depression)
cause general CNS stimulation --> can result in convulsions - doxapram
-
most commonly used analeptic
used to stimulate respiration during or after gen. anesthesia, in newborns, in cases of cardiopulm. arrest
stimulates carotid & aortic chemoreceptors --> reflux stimulation of medullary resp. centers
short duration: 5-10 m.
excessive doses --> hypertension, hyperventilation, seizures (rare) - strychnine
-
analeptic; used as a pesticide
glycine receptor antagonist --> CNS stimulation
strychnine poisoning --> severe & extremely painful convulsions - theophylline
-
methylxanthine (weak analpetic)
used in tx of asthma, adjunct to digoxin to tx CHF (dilates coronary aa.) - aminophylline
-
methylxanthine (weak analpetic)
H2O sol. salt of theophylline (better oral absorption)
used in tx of asthma, adjunct to digoxin to tx CHF (dilates coronary aa.) - theobromine
-
methylxanthine (weak analpetic)
in chocolate - cocaine
-
local anesthetic (ester)
only one to cause vasoconstriction - proparacaine
-
local anesthetic (ester)
used to anesthetize cornea
lasts 15-30 m. - lidocaine
-
local anesthetic (amide)
most widely used local anesthetic
used to tx post-op ileus in horse
may cause local irritation & swelling, esp. in horse - bupivacaine
-
local anesthetic (amide)
useful for post-op analgesia
duration up to 8 hrs - mepivacaine
-
local anesthetic (amide)
most widely used local in horses b/c it causes little swelling & edema - mechanism of action of local anesthetics
- block initiation & propagation of AP by preventing voltage-dep. inc. in Na permeability that accompanies a small inc. in mem depolarization
- factors influencing sensitivity of nerves to blockade by local anesthetics
-
firing rate of nerve: resting Na channels least susceptible, then open channels, inactivated channels most susceptible
pH of body fluids & pKa of local anesthetic: uncharged mols penetrate mem, but CHARGED mols bind receptors (if pH dec. d/t inflammation --> more drug needed to block)
anatomical structure of nerve: small diameter n. easier to block - local anesthetics: determinants of absorption from site of administration
-
dosage
site of injection: absorbed more quickly in highly vascular area
extent of tissue binding: keeps drug at site of admin --> inc. duration of action
concurrent admin of vasoconstricting substances: locals are vasodilators & usually sold w/ vasoconstrictor (ex. epi); vasoconstriction --> inc. efficacy b/c systemic absorption is decreased d/t low blood flow - metabolism of local anesthetics
-
esters: shorter half life d/t rapid hydrolysis by plasma & liver cholinesterases
amides: hydrolyzed by liver microsomal enzymes (DO NOT USE w/ liver dz) - systemic effects of cocaine
-
restlessness, euphoria --> tremors --> convulsions
vasoconstriction, hypertension, arrhythmias - systemic effects of local anesthetics (except cocaine)
-
only w/ HIGH plasma levels:
marked hypotension d/t dec. cardiac contractility --> dec. CO & vasodilation by dec. symp. tone - mechanisms of action of seizures
-
seizure focus activated, seizure discharge from focal area may synchronize w/ other neurons & propagate to surrounding areas of brain
dec. GABA activity & inc. glutamate activity important - 3 ways anticonvulsants inhibit seizures
-
1. dec. excessive discharge of seizure focus
2. inc. seizure threshold required for discharge
3. dec. spread of discharge to surrounding neurons
most drugs work by 2 & 3 - tx for chronic seizures in dogs & cats
-
Dogs:
1. phenobarb
2. phenobarb + KBr
3. KBr alone
Cats:
1. phenobarb
2. benzodiazepine
3. third level drugs - when to start tx for seizures
-
> 1 seizure/month
very intense seizures w/ breathing difficulties
clusters of seizures - pros of phenobarbital for tx of seizures
-
effective against wide spectrum of epilepsies
inexpensive
relatively non-toxic
easy to measure blood levels
relatively little sedation - cons of phenobarbital for tx of seizures
-
polyphagia --> wt. gain
PU/PD
hepatotoxicity
w/ chronic use:
altered bone metabolism
inc. metabolism of other drugs using liver microsomal enzymes
blood dyscrasias
inc. liver enzymes - mechanism of action of phenobarb for tx seizures
-
inc. seizure threshold, dec. spread of discharge d/t facilitation of GABA, then also inhibition of glutamate
at higher doses, may dec. Ca flux across neuronal mem - primidone
-
anticonvulsant (dogs only)
congener of phenobarb
more expensive, more hepatotoxic, quite sedative intially
it & 2 metabs all anti-convulsant - benzodiazepines to tx seizures
-
orally ineffective in dogs
tolerance to anticonvulsant properties can develop over time
most potent elevator of seizure threshold: facilitates GABA
diazepam: used in cats that are refractory to phenobarb (don't give orally)
clonazepam: not metab. by liver microsomal enzymes (no active metabolites), longer half life, doesn't cause hepatic necrosis - cons of potassium bromide
-
vomiting
pancreatitis (rare)
takes ~1 mo. to reach therapeutical plasma levels
in emergency, would have to give large loading dose --> potentially cardiotoxic (can use sodium bromide IV instead) - third level drugs used to tx seizures
-
felbamate (dogs)
gabapentin (dogs, cats) - tx of status epilepticus
-
1. IV diazepam (2-3 doses if needed)
2. IV phenobarbital
3. if still seizing, IV pentobarbital to produce anesthesia (or IV propofol)
if seizures result of strychnine poisoning: tx of choice is anesthetic dose of IV pentobarbital - cons of propofol
-
-some pain w/ IV administration
-can damage tissue if given extravascularly
-apnea common after administration
-dose dependent vasodilation --> dec. MAP (do NOT use in hypotensive patients)
-cats: chronic admin can cause oxidative injury to RBCs