simasko Flashcards
(98 cards)
1
Q
nociception
A
neural response to painful stimuli
2
Q
nociceptors
A
nerve endings that detect pain with receptors that respond to heat, touch, pH and chemicals/neurotransmitters released during trauma or infection (prostaglandins, kinins, substance P)
3
Q
A-delta fibers
A
fast conducting they are responsible for “first” pain that is sharp and acute. they have discrete receptor fields making localizing the paineasier
4
Q
C fibers
A
slow conducting and are responsible for “second” pain that is dull, aching, burning or throbbing pain that is hard to localize
5
Q
hyperalgesia
A
exaggerated response to painful stimuli
6
Q
allodynia
A
a painful response is produced by a normal innocuous (non-painful) stimuli
7
Q
transduction
A
noxious stimuli are transduced into electrical signals
8
Q
transmitted
A
from electrical signal to spinal cord
9
Q
modulated
A
in spinal cord, signal modulated before being relayed
10
Q
projection
A
signal from spinal cord to the brain
11
Q
perception
A
signal in brain for processing and awareness
12
Q
opioid receptors
A
mu, delta, kappa
are g-protein coupled receptors
most opioid drugs act through the mu receptor
morphine acts on both mu and delta’
primarily inhibitory - couple through inhibition of cAMP, activation of K channals, closure of voltage-depend Ca channels
13
Q
affinity vs efficacy
A
affinity: bind to receptor
efficacy: ability to activate the receptor
14
Q
ex. of opioid drugs
A
naloxone, buprenorphine, morphine, etorphine
15
Q
mu receptors
A
activation causes analgesia, respiratory depression, decrease GI motility, sedation, euphoria, miosis/mydriasis (sp. dependent), nausea/vomiting (via CTZ) increase appetite, urinary retention, immunomodulation
most therapeutically used narcotic drugs (morphine and fentanyl)
16
Q
Kappa receptors
A
activation causes analgesia, decrease GI motility, increase appetite, sedation, miosis/mydriasis (species dependent), diuresis
ex. butorphanol
17
Q
delta receptors
A
activation causes analgesia, increase appetite, immunomodulation
selective delta agonists under development
18
Q
heterodimers
A
combined mu/delta
19
Q
analgesia
A
antinociception
decrease chronic dull pain> acute sharp pain
acts at multiple levels in pain pathway
20
Q
effects of opioid drugs (4 good, 6 bad/other)
A
analgesia
sedation/calming (dogs>cats)
euphoria (human drug addiction)
Antitussive (depression of laryngeal reflex)
gastrointestinal effecs (vomit,defecation, decreased GI motility - long term use, careful with colic)
respiratory depression
bradycardia
urinary retention
temperature effects (hypo- dogs, hyper-cats)
miosis/mydriasis
21
Q
opioids main cause of death
A
respiratory failure is normally the cause of death in narcotic overdose
decreases sensitivity of respiratory center in medulla oblongata to Co2
22
Q
opioid cardiovascular effects
A
bradycardia, likely due to opioid-induced medullary vagal stimulation
can increase cardiac output in horses
opioids can also cause hypotension due to vasodilation
23
Q
opioid temperature effects
A
- hypothermia - dogs, rabbit, guinea pigs
- hyperthermia - cats, also cattle, goats, horses (not seen with kappa drugs)
- panting (dogs after oxymorphone)
24
Q
opioid changes in pupils
A
miosis - pin point - dogs
mydriasis - cats, sheep horses
can last longer than analgesia so not an indication of pain relief
25
opioid neuroendocrine effects
```
increased vasopressin (antidiuretic hormone) release ->oliguria - reduced urine formation
decrease gonadotropin release
increase prolactin release
```
26
acute narcotic overdose
miosis in dogs, mydriasis in cats
respiratory depression ->failure
coma
therapy: opioid antagonists- naloxone and naltrexone, Supportive respiration
27
long term treatment with morphine
development of tolerance (except miosis and constipation, cross tolerance to other narcotic analgesicdrugs)
development of dependence (withdrawal if removed to quickly, restlessness, vocalization, aggression,vomiting, diarrhea)
28
opioid absorption
well absorbed orally, IM, subcue
| may have substantial first pass metabolism following oral administration (oral bio availability 5-20%)
29
opiod pharmacokinetic distribution
most very lipophilic with largevolume of distribution
most easily penetrate brain
can have significant accumulation in adipose tissue (fentanyl)
30
opioid pharmacokinetic metabolism/elimination
metabolized via hepatic cytochrome P450, conjugated via glucuronidation
conjugates are charged, filtered out by kidney
cats conjugate via sulfation
hal flife <2hr, longer in cats
effective chronic therapy requires constant infusion
31
morphine
(mu, kappa)
opium alkaloids
traditional, mild- severe pain, well tolerated in most species
can stimulate histamine release
can stimulate emesis
lasts up to 4 hours (use in surgeries/trauma)
32
Codein
mu receptor
opium alkaloid
less potent analgesic than morphine, often combo with acetaminophen *Do not use products containing acetaminophen in CATS
-useful as antitussive and antidiarrheal
33
hydromorphone
```
mu receptor agonist
semi/synthetic opioid drug
5-7x more potent than morphine, greater lipophilicity
used for pain
less histamine release than morphine
still have emesis and nausea, but less
```
34
etorphine
1000x potency of morphine, used as tranquilizer, mainly in zoos ( all receptors)
semi/synthetic opioid drug
all 3 receptors
full agonist with high efficacy for activating receptor
35
Fentanyl
```
100x more potent than morphine
mu receptor
semi/synthetic opioid drug
no histamine release
can cause excitation in horses
injectable, patch, transmucosal
```
36
buprenorphine
partial agonist at mu receptor, antagonist at kappa receptor
high affinity weak efficacy
treat mild to moderate pain
may help with withdrawal due to partial agonist action
longer duration of action
37
butorphanol
```
agonist at K receptor, mostly thought as antagonist at mu receptor
more limited analgesia
potency equal to morphine
mild-moderate pain
better tolerated than morphine in horses
```
38
tramadol
```
low affinity for mu (1/6000), agonist
act on non-opioid receptors (multimodal analgesia)
blocks NE and 5-HT reuptake
binds a2-adrenergic receptor
better oral availability than morphine
```
39
naloxone
opioid antagonist on all 3 receptors, effective for rabid opioid reversal
shorter duration than most agonists
antagonist, no efficacy to activate and blocks the effects of agonists
40
local anesthetics uses
to minimize or prevent pain
| often used to facilitate surgery (skin incisions, nerve/spinal block)
41
mechanism of action local anesthetics
reversible blockage of nerve impulse conduction by blocking voltage-dependent Na channels (primarily used in neurons)
block is on open channel (makes block use dependent)
42
local anesthetics - which sensations disappear first
pain followed by cold, warmth, touch, joint, deep pressure
| motor function can be maintained after all sensation is lost
43
local anesthetics chemistry
weak bases generally consisting of
1. lipophilic group
2. intermediate chain (ester or amide link)
3. hydrophilic group capable of ionization
44
local anesthetics classification: amino esters(one i)
cocaine, benzocaine, procaine, proparacaine
45
local anesthetics classification : amino amides (2 i's)
lidocaine, bupivacaine,
46
amino ester metabolism
hydrolyzed by plasmaesterases
| -can lead to formation of potential allergen
47
amino amides metabolism
biotransformed by liver enzymes (changes in hepatic funtion will impact metabolism)
-rarely evokes allergic reaction
48
amide link
| local anesthetics
amide link tends to be more stable than the ester link
- have longer half lives
- must be absorbed and transported to the liver to be metabolized vs ester are metabolized in the plasma
49
local anesthetics are weak bases
pKa's between 7.9-8.9
in tissue LA's dissociate to free ase
LA must be uncharged to cross the cell membrane and gain access to cell
*inflamed tissue is more acidic - thus LA's are LESS EFFECTIVE in inflamed tissue
50
Local anesthesia routes of administration
- surface anesthesia (sprayed in nose, dropped in eye)
- infiltration anesthesia (very localized)
- conduction anesthesia (nerve block)
- spinal anesthesia (epidural block)
51
local anesthesia adverse effects
| -dose related drug toxicity
1. CNS excitation (seizures)
2. Cardiac (decrease CO, may cause dysrhythmias)
3. Vascular dilation (hypotension)
4. apnea or respiratory depression
52
local anesthetic order of effects
1. analgesia
2. altered consciousness
3. muscle twitching and hypotension
4. myocardial depression and seizures
5. unconsciousness and apnea
6. Cardiovascular collapse and death
53
lidocaine (Xylocaine)
amino-amide
-versatile, widely used
2x as potent as procaine
- used in all forms
- rapid onset of action, short duration (60-120 min)
- metabolized by liver
- also used IV as an anti-arrhythmia agent
54
bupivacaine
Amino-amide
- widely used in vetmed
- one of the most potent and long lasting LA (5-8 hours) high lipid solubility
- slow onset (20-40 min for full nerve block)
- metabolized by liver
- used infiltration, nerve block, spinal and intrathecal
- greater risk of cardiac toxicity
55
Procaine (Novocain)
amino ester
non-irritating and quick onset
-brief period of anesthesia (can be lengthened with vasoconstrictors)
- rapidly hydrolyzed by pseudocholinesterases (watch for allergic reactions due to PABA)
- used in prep for Procaine Penicillin G (decrease pain associated with injection)
56
Proparacain
for diagnostic eye exams
| fast onset, short duration
57
mechanism of action of NSAIDs
inhibition of COX is primary action -> inhibition in everything after COX (PGI, PGE, PGF, TXA)
currently not thought to have any effect on leukotrienes
58
Main effects of COX and thus NSAIDs
- anti-inflammatory - (cox2)
- anti-pyretic (PG effect "set-point" for body temp in hypothalamus (Cox2,3))
- analgesia (cox2 sensitize pain fibers
- inhibit platelet aggregation (increase bleeding time, cox 1)
- reduced renal blood flow
- gastric ulceration
- interfere with parturition (PGF2 is needed for parturition)
59
NSAIDs and gastric ulceration
most frequent side effect,
PGI and PGE inhibit acid secretion adn stimulate mucous secretion (cox1)
ulceration causes 2ndary anemia due to gastric bleeding
60
salicylates; Aspirin
| NSAID
irreversible cyclooxygenase inhibitor (anticoagulant)
used in all species
tendency of gastric ulcer (potent on cox1)
can cause hepatic damage, detrimental to cartilage
inactivated via glucuronidation (T1/2 dogs: 3-9 hours, cats: 22-45 hours)
-acute CNS toxicity
61
pyrazolone: Phenylbutazone
| NSAID
equine - inexpensive, narrow therapeutic index
bone and joint pain and soft tissue pain
side effect includes blood disorders
t1/2 in cattle = 40 hours
drug can accumulate with multiple exposure
62
propionic acid derivatives: Carprofen (rimadyl)
| NSAID
```
dogs for osteoarthritis
relatively high selectivity for cox2 in canine
relatively high safety in dogs, not cats
inhibit PLA2 - unknown significance
liver metabolism (t1/2 ~ 8 hours)
hepatotoxicity can be limiting
```
63
propionic acid derivatives: Naproxen
| NSAID
horses
has been used in dogs but not recommended (renal/liver problems, long half life)
(aleve in humans, not recommended)
64
propionic acid derivatives: Ibuprofen
| NSAID
not recommended in dogs due to serious GI erosions
| most common reported NSAID toxicity in dogs, probably due to ease of access of clients
65
Nicotinic acid derivatives: Flunixin meglumine
| NSAID
horse for visceral indications like colic
approved for dog but tendency for GI side effects
might improve survival in dogs in septic shock
once a day administration, not recommended for more than 5 days
66
acetaminophen (tylenol)
analgesic and anti-pyretic but only weakly anti-inflammatory (not technically an NSAID)
potent COX3 inhibitor
not effective on platelets
low incidence of GI side-effects but propensity to hepatic damage
EXTREMELY TOXIC TO CATS (usually detoxified by glucuronidation)
67
Misoprostol
PDE1 analog that restores mucus secretion and inhibits acid secretion in the stomach
68
Cortisol
Natural GC in most mammals (except rodents). Has both GC and MC effects
half life about 90min
tissue effect 8-12 hours
69
Cortisone
GC with significant MC activity. Must be metabolically activated to cortisol so relative potency of 0.8 GC/MC
- T1/2 plasma = 30 min
- T1/2 tissue = 8-12 hours
70
Prednisone
more potent analog of cortisone (needs metabolic activation ability of cats and horses to do this has been questioned)
more GC selective than cortisol (GC=,MC=0.8)
T1/2 plasma = 60 min
T1/2 tissue = 12-36 hour
71
Prednisolone
more potent analog of cortisol. More GC selective than cortisol (GC=4, MC=0.8)
T1/2 plasma = 200 min
T1/2 tissue = 12-36 hours
72
Fludrocortisone
very selective for MC activity (GC = 10 MC=125)
T1/2 plasma = 200 min
T1/2 tissue = 8-12 hour
73
Dexamethasone
high potency GC analog. No MC activity. (GC=25, MC = 0)
Long duration of tissue action (T1/2= 36-54 hours)
T1/2 plasma ~200
74
Hyaluronate
a natural polysaccharide found in cartilage. Also contributes to synovial fluid viscosity
75
Polysulfated glycosaminoglycans
a mix of natural mucopoly-saccharides found in cartilage
76
DMSO
A solvent that easily penetrates the skin. Beneficial action appears to be scavenging free radicals, but also a vasodilator. Has other uses. Will "carry" impurities across the epithelia
77
Iatanoprost
Ocular Drug - glaucoma
Synthetic PGF analog that is used to treat glaucoma. causes a rapid decrease in intraocular pressure (IOP) by increasing uveoscleral outflow and by other mechanisms not fully understood. used for dogs, not effective in cats or horses
78
Timolol
ocular drug - glaucoma
non-selective B-blocker used to treat glaucoma, lowers intraocular pressure by decreasing aqueous humor fluid formation through a direct action on the ciliary epithelium. careful if respiratory or heart disease is present
dogs and cats
less side effects than parasympathomimetics
79
Demecarium
ocular drug - glaucoma - topical parasympathomimetic
Acetylcholinesterase inhibitor used in the prevention of glaucoma in the normotensive eye in primary glaucoma patients. Improves fluid drainage by contracting the ciliary muscle via increasing cholinergic tone
increase tear formation, side effects: diarrhea, urination, miosis, bradycardia, salivation, lacrimation, emisis, dyspnea
80
Pilocarpine
ocular drug - glaucoma
| Direct acting muscarinic agonst that lowers intraocular pressure. Contracts ciliary muscle to improve fluid drainage
81
Epinephrine
ocular drug - glaucoma
topical sympathomimetic
A mixed a- avDB- agonist used in glaucoma to decrease fluid formation. action thought to be mediated by a-receptor action to decrease cAMP levels in ciliary epithelium vasoconstriction of blood vessels leading to the ciliary epithelium
weak effect
82
Dorzolamide
ocular drug - glaucoma
a carbonic anhydrase inhibitor used to treat glaucoma because it reduces fluid formation by the biliary epithelium
side effects: systemic acidosis, GI upset, panting, hypokalemia (cats)
83
mannitol or glycerin
ocular drug - glaucoma
- systemic osmolites that draw fluid out of the eye and thereby decrease intraocular pressure. used in acute glaucoma when there is no response to topical medication
84
Atropine
eye surgery
classic muscarinic blocker (antagonist) - produces profound long acting mydriasis and causes paralysis of the ciliary muscle. (8h initial then days of effects)
decreases tear formation, can increase IOP in cats
85
Phenylephrine
ocular drug - glaucoma
a-adrenergic agonist used as a pre-treatment in eye surgery because it augments the mydriasis produced by muscarinic antagonists and also causes vasoconstriction (reduces bleeding)
86
Tropicamide
eye exams
muscarinic antagonist used for eye exams, produces a strong mydriasis that lasts 2-6 hours (shorter acting than atropine)
-can precipitate acute congestive glaucoma
87
Cyclosporine
```
Keratoconjunctivitis sicca (dry eye)
an immunosuppressive drug that specifically interferes with activation of lymphocytes. It is used to treat KCS in dogs. Also has poorly understood direct lacrimostimulant action
```
88
M3 agonists and eye
accommodation for near vision (squeeze ciliary muscle)
miosis (pinpoint)
tears
increase drainage
89
M3 antagonist and eye
```
profound mydriasis (dilated) (predominately action is parasympathetic)
may precipitate acute pressure increase
```
90
B-agonsts and eye
increase fluid formation
91
B antagonists and eye
decrease fluid formation
92
a-agonists and eye
relatively weak mydriasis (a1)
| decrease fluid formation (a2-direct, a1- indirect)
93
PGF2a and eye
increase fluid drainage
94
glaucoma
excessive increase in intraocular pressure (IOP)
| left untreated will cause blindness
95
prednisolone or dexamethasone
topical corticoid
used for inflammation of conjunctiva, sclera, conrea, anterior chamber
-inhibit wound repair, can worsen corneal ulceration, should not be used if viral infection present
96
muscarinic antagonists in eye
used cautiously to treat uveitis, prevent synechia and ciliary spasm pain
(atropine, tropicamide)
97
topical tetracycline
conjuntivitis in cats
chlamydia and mycoplasma
antibiotics
98
neomycin/polymixin/bacitracin
antibiotic
| treats infections, triple combo, broad spectrum, little resistance develops. serious systemic toxicity
