Exam 3 Flashcards
1
Q
What are the three primary medical reasons that NSAIDs are used in animals
A
analgesia, anti-inflammatory, antipyretic
2
Q
At what point in the nociceptive pathways do NSAIDs exert their predominant effect?
A
During the transduction phase, decreasing the sensitivity to nociception
3
Q
What are the clinical advantages of using NSAIDs in our patients?
A
Readily available (not controlled)
Effective for acute and chronic pain
Oral forms (easy to administer)
Long duration of action
Relatively inexpensive
NO CNS side effects (rare)
Fewer side effects than steroids
4
Q
What are risks of administering NSAIDS and glucocorticoids concurrently?
A
Increased likelihood of side effects
Increased chance of GI irritation (commonly dog)
5
Q
The anesthesia section of the VTH delays administration of an NSAID in a brachycephalic dog or cat undergoing surgery for approx 15-30 min after the patient is extubated. What is the reasoning for administering the NSAIDs
A
If the patient has an upper airways obstruction, they will be administered a rapid acting corticosteorid to decrease airways swelling. That is why you want to wait to give the NSAID
6
Q
What is the most common complication of NSAIDs in the dog?
A
GI side effects,
Anorexia, vomiting, diarrhea
gastritis, enteritis, gastric erosions/ulcers
7
Q
Should dogs be administered GI protectants prophylactically to prevent GI irritation when administered a course of NSAIDs?
A
No evidence that this actually works, just more money and drugs to give the dog
8
Q
What organ system is of most concern when giving an NSAID to the adult cat?
A
the kidney- tubular damage
9
Q
What are the two types of liver toxicity caused by NSAIDs
A
Intrinsic-dose dependent (e.g dog eats whole bottom of Rimadyl)
Idiosyncratic- we do not know, can occur
10
Q
Do dogs and cats need to have blood work before being administered an NSAID?
A
No easy answer, professional judgement is needed. No data, there is variation between every animal.
A complete physical exam and appropriate laboratory monitoring is needed (FDA)
11
Q
What are the potential downsides of requiring bloo work prior to administering an NSAID to one of our patients?
A
Expense of blood work may prevent some animals from receiving NSAIDs following surgery/trauma
12
Q
Is it appropriate to administer an NSAID to a dog or cat with mild elevations in liver enzymes?
A
it depends, up to your professional judgement
13
Q
NSAIDs are commonly administered in the perioperative period in dogs, cats, and horses. In dogs and cats is it preferable to administer NSAID before, during, or after surgery. If there is a preference what is your rational?
A
Potential for better pain control if given before surgery (quick procedures)
Potential for more side effects if given before surgery (e.g hypertension seen during long surgeries cannot be fixed if prostaglandin is blocked)-
14
Q
What are the pros and cons of using aspirin for chronic pain in dog?
A
Pros: inexpensive, readily available, effective
Cons: Higher risk of GI irritation/ulceration
15
Q
Why do NSAIDs fail to control pain in some patients
A
the pain is too severe necessitating the use of more than one type of analgesic (e.g opioids)
16
Q
What are commonly combined together to enhance postop analgesia?
A
opioid, NSAID, local anesthetic
17
Q
Why choose an NSAID over a corticosteroid for post-op pain control
A
NSAIDs have fewer side effects and do not affect the immune system
18
Q
How do NSAIDs work
A
inhibitors of cyclooxygenase (exception Galliprant)
Newer NSAIDs are COX-2 selective (COX-1 sparing)
*COX selectivity is dose dependent- all NSAIDs are non-selective COX inhibors at high doeses
Fixed doses (not a lot of dose manipulation)
19
Q
What is Galliprant (Grapiprant) ?
A
an NSAID that was developed to control pain and inflammation associated with OA in dogs
Highly selective for the EP4 receptor
Prostaglandin E2 is a product of cyclooxygenase enzymes
PGE2 targets four types of eicosanoid receptors EPI 1-4.
20
Q
How does grapiprant differ from a typical NSAID
A
it does not inhibit cyclooxygenase
It is an EP4 receptor antagonist
21
Q
Why do we use opioids in animals
A
*analgesia- primary for acute pain
Sedation in some patients (not primary effect)
22
Q
Why are clinically available opioids scheduled (controlled) by the DEA
A
Based on abuse potential
Acceptable medical use
Likelihood of causing dependence if abused
Politics of the times
23
Q
What are the components of addiction?
A
Addiction is a chronic relapsing disorder characterized by compulsive drug seeking and use despite adverse consequences
24
Q
How is the human opioid epidermic affecting veterinary medicine?
A
Vets are legally able to administer and prescribe opioids. Some states limit number of days they can be dispensed
Some states encourage or require use of PDMP
Some states are requiring vets to take CE on opioid use
25
According to the CDC, is the opioid epidermic control under control?
No
26
What guidance has the Colorado Board of Vet med provided vets regarding opioid epidemic
-Vet/Client Patient Relationship must be established, have to see the patient in person
-Verify and document need for opioids
-Dispense through an established pharmacy
27
How common is opioid addiction in veterinary patients?
It is not a problem
28
How does the development of tolerance affect the efficacy of the drug
Tolerance is biological phenomenon and is the most common response to the repetitive use of the same drug and can be defined as the decrease in effectiveness of a drug with its repeated administration
29
Can patients develop tolerance to the respiratory depressant effects of opioids? What about constipation?
Tolerance to respiratory depression (up to a point)
Tolerance to constipation: not typically- it can be managed
30
What is responsible for the development of tolerance to opioids
1) Pharmacokinetic tolerance - induced synthesis of hepatic microsomal enzymes
2) Pharmacodynamic tolerance- cellular adaptations such as changes in the number, affinity, and function of the receptors (activation of glutamate at NMDA receptor and stimulation of nitric oxide production)
31
Can animals become dependent on opioids?
Yes, physical dependence can occur with repeated use of opioids, as occurs with many medications
32
How can we avoid inducing withdrawl in a patient that has received opioids for several days?
Taper the opioid over time (1-2 days in most cases)
33
What are differences between general anesthesia and analgesia
Analgesia- loss of sensitivity to pain (it hurts less)
Anesthesia- total loss of sensation in: part of body (local or regional block) or in the whole body (general anesthesia)
34
What are the five components of general anesthesia?
Amnesia,
Hypnosis (loss of consciousness)
Hyporeflexia
Analgesia
Muscle relaxation
35
What are the two main opiate receptors that are targeted clinically?
Mu and Kappa receptors (g protein couple receptors part of the endogenous system of opiate receptors)
36
Endogenous opioid system
complex, anatomically widespread, and diverse system subserving multiple functions - including
sensory role (inhibiting responses to painful stimuli
Modulatory role in gastrointestinal, endocrine, and autonomic functions
Emotional role
Cognitive role in the modulation of learning and memory
37
What are endorphins
Endogenous opioid ligands (B-endorphins, enkephalins, dynoprhins, and nociceptin/orphanin FQ)
Definition: any chemical substances formed in the body (endogenous) that exhibits pharmacologically properties of morphine
Endorphins function at endogenous opiate receptors
38
What do endorphins do
Modulate numerous effects of the CNS
Stimulate mu receptors primarily and delta receptors to a lesser extent
Mediates analgesia (Beta endorphin is a potent analgesic)
39
What is the most potent endogenous opioid peptide mediating analgesia?
Beta endorphin, important role in injury and stress
40
What are enkephalins and dynorphin?
they are widely distributed throughout the CNS and serve multiple opioid functions
Dynorphin stimualtes the kappa receptor to mediate spinal analgesia, possibly dysphoria
41
How do opioids work?
Stimualte cascade of intracellular events (hyper-polarization of cell membranes, decrease in nociceptive neurotransmitter release, and inhibition of nociceptive (pain) pathways.
*exert pre- and post-synaptic effects on sensory neurons
GTP-intraelluar functions (inhibition of adenylyl cyclase activity, inhibition of sodium channels, activation of post-synaptic receptor activated K+ channels, suppression on voltage gated Ca2+ channels)
42
Why is pro-opiomelanocortin so important following an inury?
it is a precursor for ACTH, a-MSH, and b-LPH. The close association between b-endorphin and ACTH indicates an important role of endorphins in stress response
43
In general, are opioids more effective for acute or chronic pain?
acute pain, but they do have important roles in management of some chronic debilitating pain and cancer pain
44
What is opioid-induced hyperalgesia
increased amount of pain following discontinuation of opioids
not fully understood
withdrawl of exogenously admin opioids can result in long term potentiation of synaptic transmission between primary afferent neurons in the dorsal root ganglion and second order neuron.
45
What is a full opioid agonist?
affinity and activity at all the opioid receptors
maximum amount of analgesia (dose dependent)
Characterized as mu agonists
Ex: fentanyl, hydromorphone, methadone, morphine, heroin
46
What is a partial mi-agonist?
affinity primarily for mu receptor
partially binds, provides less analgesia that the full mu agonist
Ex: buprenorphine
47
What is an opioid agonist-antagonist?
agonist at the kappa receptor
antagonist at the mu receptor
Less analgesia than full mu agonist
Ex: Butorphanol, nalbuphine
48
What is naloxone?
high affinity for mu and kappa opiate receptors
exerts no activity at normal dosages
competetive antagonist
used to reverse effects of opioids
49
Why is affinity of an opioid to the opiate receptor important to know?
a drug's ability to bind to its receptor sites in the body affects the drug's duration of action (buprenorphine) affects drug interaction when opioids of different classes used
Clinical examples: buprenorphine after hydromorphone
50
Which opioid is difficult to reverse due to high binding affinity?
buprenorphine
51
What is the difference between opioid analgesic potency and efficacy?
potency directly related to the affinity of the drug for opiate receptor sites. Clinically used to determine the dose of a given opioid but does not indicate the ability of the drug to provide analgesia.
efficacy relates to the maximal effect that a drug can induce (analgesia)
52
What is an equi-analgesic dose of hydromorphone (potency 5) to morphine given at a dose of 0.5mg/kg
morphine at 0.5mg/kg is same as hydromorphone at 0.1mg/kg.
53
Is butorphanol (potency =5) more or less effective than morphine for the treatment of severe, acute pain in the dog?
Butorphanol is less effective than morphine
Butorphanol works primarily throug hthe kappa receptor and has a ceiling effect on analgesia
54
What are two reasons why butorphanol is not a great choice to treat severe pain in a dog?
1) It is an opioid agonist-antagonist (less analgesia and ceiling effect)
2) It has a short duration of action (0.5 - 2 hours)
55
How can the usefulness of butorphanol be improved for the treatment of acute pain in the dog or cat?
1) Combine it with other analgesic drugs (NSAIDs, alpha-2 agonists, local anesthetics)
2) Administer butorphanol as a continuous rate infusion (0.1-0.4 mg/kg/hour)
56
What factors influence the degree of analgesia provided by an opioid?
Degree of tissue trauma/pain
Central and peripheral sensitization
Acute vs chronic pain
Degree of concurrent fear, anxiety, stress
Route of administration
Dose and dosing interval
Other pain treatments administered
57
Are opioids good sedatives in dogs and cats?
sometimes, depends on age, presence of pain, health status
usually not good sedatives by themselves in young, healthy dogs and cats
58
What is meant by euphoria in a dog or cat administered an opioid?
Pleasant feeling with freedom from anxiety, distress, and pain
59
What is meant by dysphoria in a dog or cat administered an opioid?
unpleasant feeling in response to opioid analgesic
disoriented or disturbed behavior
dogs/cats may be restless. may be afraid, attempt to hide or escape, vocalize
dysphoria and pain can coexist
60
What are effects of opioids on respiratory function?
Respiratory depression
Reduction in responsiveness of the brainstem respiratory centers to CO2 (more CO2 needed to trigger breathe)
May affect respiratory rate, tidal volume, or both
Depress pontine and medullary centers involved in regulating respiratory rhymicity
61
How does the respiratory depressant effect of butorphanol compare to that of morphine?
Butorphanol is less of a respiratory depressant than morphine
Respiratory depression is dose dependent and butorphanol has a ceiling effect on respiratory depression
In severely compromised animals, sedation from butorphanol may not be tolerated
62
What is the difference between low dose fentanyl (as used in CCU) and high dose fentanyl (used in anesthesia) on respiratory depression?
Low dose (1-4mc/kg/hour) is well tolerated and will keep breathing
High dose (5-40mcg/kg/hour) causes dose-dependent respiratory depression and apnea
63
Are opioids used for cough suppression?
yes, directly depress the cough center in the medulla
cough suppression and respiratory depression are not directly linked
Antitussive agents do not necessarily depress respiration (butorphanol, hydrocodone)
64
What effect, if any, do opioids have on the GI motility in the horse?
Can slow GI motility, excessive doses can lead to ileus and colic
Butorphanol is associated with less GI slowing than MU agonists
65
Do opioids cause constipation in species other than horses?
Yes, opioids can caused constipation in most species. The constipating effects is serious issue when on chronic opioids
66
What opioid is most likely to induce vomiting in the dog or cat?
Morphine
Hydromorphone to a lesser extent
67
Is opioid-induced vomiting an advantage or disadvantage in dogs and cats?
depends on the patient and circumstance: sometimes we want our patient to empty their stomach before being induced to anesthesia (decreased risk of aspiration)
Sometimes we do not want our patient to vomit (e.g patient with brain tumor)
68
How can you prevent opioid induced vomiting in a dog or cat?
Select an opioid that is unlikely to cause vomiting: methadone, fentanyl, butorphanol, buprenorphine
Administer an anti-emetic (maropitant)
Administer the opioid IV rather than IM or SQ
69
How do high doses of hydromorphone affect body temperature in cats
All opioids can increase body temperature in the cat
High doses of hydromorphone may be more likely to increase body temperature in cat
Uncommon clinical side effect
70
Mechanism responsible for analgesia from tramadol
a synthetically dervied analgesic that has weak mu-opioid activity (M1 metabolite), inhibition of norepinephrine and serotonin re-uptake
Metabolism of tramadol in dogs appears to be variable (some dogs have little detectable MI and limited analgesic effect)
71
What is the controversy regarding the use of tramadol to treat pain in dogs?
Study found it wasnt effective for treatment of OA pain in dogs but found it had beneficial effects in cats with OA
72
How do you treat fentanyl induced bradycardia in a cat?
Due to result of increased vagal tone
Treat heart rate with atropine or glycopyrrolate
73
How do you treat opioid-induced excitement in a dog?
Sedate with acepromazine or dexmedetomidine
also could partially or completely reverse opioid (if not pain of procedure was performed yet_
74
What is a convenient and effective way for clients to administer buprenorphine to a cat
give it transmucosally- proved to be as effective as IV for bioavailability
75
Why is fentanyl administered as an IV infusion or transdermal patch
it has a short duration of action (approx 20 min into anesthesia)
IV infusion prolongs the effect
Transdermal patch- 3 days of analgesia
76
What are the potential consequences of morphine-induced histamine release?
Vasodilation and hypotension, especially under anesthesia- bronchoconstriction
if concerns use hydromorphone
If use morphine- SQ or IM
IV (low dose)
77
Heart rate in an anesthetized dog drops from 100 to 40bpm after IV administration of fentanyl. What can you do?
Administer atropine or glycopyrrolate
Dont give naloxone because dont want fully reversal
78
Are opioids used to treat pain in animals with a history of seizures. Why or why not
Yes, opioids do not lower the seizure threshold
exception overdoses
79
What are the effects of opioids on body temp?
Some patients can be hypothermic or hyperthermic
80
What are predominant cardiovascular effects of hydromorphone in the dog?
Bradycardia
81
Do opioids cause vasodilation
yes, under some circumstances histamine release
Morphine or meperidine
more likely in large IV doses
May be due to pain relieve and withdrawal of sympathetic tone
82
How could you completely reverse the effects of hydromorphone?
Naloxone
83
How could you completely reverse the effects of butorphanol
Naloxone (not complete reversal though
better at mu receptor) dose is not established
repeated doses or CRI may be needed
84
How can you partially reverse the effects of hydromorphone
Low dose of naloxone (102mcg/kg IV)
Buprenorphine
Butorphanol
Nalbuphine
85
What is the rationale for giving buprenorphine and meloicam to a cat following dental surgery?
Provide multi-modal analgesia
Buprenorphine and meloxicam have different mechanisms of actions
86
What is the mechanism of action of diazepam?
Enhance the effect of the inhibitory amino acid gamma-aminobutyric acid (GABA). The BZD receptor is a modulatory site of the GABAa receptor (regulates postsynaptic chloride channel gating, net result is an increase in the frequency of chloride ion channel opening)
87
How effective of a sedative in diazepam in young, healthy animals?
not effective in young, healthy, or excited animals
make animals harder to handle
88
Why is diazepam combined with xylazine and ketamine to induce anesthesia in the horse?
Diazepam and midazolam induce muscle relaxation. smooth induction (smoother transition to the ground, less rigidity of limbs, jaw, neck)
Prolong anesthesia (gives more time to finish procedure or transition to gas anesthesia)
89
Why is midazolam or diazepam used in anesthetic protocols in dogs and cats?
decrease dose of anesthetic induction drug
minimuze the effects on blood pressure
muscle relaxation (ketamine, etamidate)
frequently used in senior/geriatric patients
90
How do diazepam and midazolam differ? Is this clinically important
Midazolam is more potent than diazepam (does not appear to change the dose)
Midazolam is water soluble (diazepam is not) so it does not sting when administered IV and absorbed well from IM or SQ sites
91
Why do we administer flumazenil to a dog or cat?
If the patient had received midazolam or diazepam (Recovery is too slow), unsettled or strange behavior on recovery (disoriented, not able to focus, excited)
no down side to giving flumazenil
92
What is primary use of acepromazine
tranquilize and calm patients
tranquilizers act by depressing the hypothalmaus and the reticular activating system
tranquilized patients are calm/relaxed, awake and unconcerned with their surroundings, the patient can override drug effects with stimulation though
93
How are the effects of acepromazine antagonized?
there is no antagonist for acepromazine, just need to wait for it to go away, MoA involves multiple receptor sites, can last 4-6 hours, if you dont want to wait use dexmed and reverse with an a2 antagonist (atipamezole)
94
What effect does acepromazine have on clotting?
Decrease the number of platelets
Decrease release of ATP by platelets resulting in a decrease in aggregation
not a whole lot of literature about it but keep it in mind
95
What are the effects of acepromazine on the CV system?
alpha-adrenergic blocker
- vasodilation (hypotension, particularly under anesthesia, splenic enlargement and sequestrations of RBCs, Decrease packed cell volume)
-*Systemic hypotension (most important CV effect, dose dependent hypotension, treat with IV fluids)
96
Why does reflex tachycardia occur after administering acepromazine?
sympathetic response to decrease in blood pressure
mediated through the baroreceptors
97
How can you enhance the sedative effects of acepromazine in a dog or cat?
increase the dose of acepromazine
combine with an opioid
Combine with alpha-2 agonist like Dexmedetomidine
combine with an opioid and alpha-2 agonist (low dose of all)
98
Would you sedate an anxious dog with a history of seizures using acepromazine
acepromazine purported to decrease seizure threshold, but never documented
some data suggest that it does not lower the seizure threshold
99
What effect would high circulating concentrations of catecholamines have on acepromazine-induced hypotension?
acepromazine blocks a adrenergic receptors
epinephrine stimulates a-1, b1 and b2 adrenergic receptors so just b1 and b2 adrenergic receptors
100
What are the primary used of trazadone?
Anxiolytic- increasing the use of behavior issues (anxiety) in dogs
Decrease the dose of acepromazine and other premed drugs
used in human medicine as an anti-depressant and anxiolytic
101
How does trazadone work?
Serotonin receptor antagonist and reuptake inhibitor
Blocking the reuptake of serotonin increases the amount in the synpase leading to increase action of the post-synaptic 5HT1A receptors
also blocks post-synaptic 5HT2A and 5HT2C receptors (normally for insomnia, anxiety and sexual dysfunction)
102
What are two desirable effects of alpha-2 agonist?
1) Sedation- enhanced by concurrent opioid administeration, can be overridden with stimulation
2) Analgesia- different from acepromazine which has no analgesic effect
103
Does acepromazine have an analgesic effect?
NO
104
How do alpha-2 agonist exert their analgesic and sedative effects ?
Stimulation of pre and post synaptic a2 adrenoreceptors (G-protein linked receptors)
Stimulation of central alpha-2 adrenoreceptors decreases the release of norpinephrine-decreased sympathetic outflow
alpha-2 adrenoreceptor subtypes may play a role in specific effects observed with various alpha-2 agonists
105
What are the effects of alpha-2 agonists on the cardiovascular system?
Marked negative CV effects possible (dose and route dependent)
*Hypertension
*Bradycardia and bradyarrythmias
Xylazine sensitizes the myocardium to epinephrine-induced arrhythmias
*Decreased cardiac output
Hypotension (ony w general anesthesia)
106
What are the effects of alpha-2 agonists on the respiratory system?
Mild to moderate respiratory depression
depress respiratory center centrally- decrease sensitivity and increase threshold to CO2
May induce stridor and dyspnea in horses and brachycephalic dogs with upper airway obstruction
Sheep- Iv xylazine may induce pulmonary edema secondary to alterations in the alveolar capillary membrane
107
What are the advantages and disadvantages of giving atropine with an alpha-2 agonist
Advantages: Increase heart rate, blood pressure, cardiac output?
Disadvantage: Increased myocardial work, cardiac output may not increase
108
What is vatinoxan? How does it work?
Peripheral alpha-2 adrenoreceptor antagonist
helps to maintain CO by preventing a-2 induced arterial vasoconstriction (medetomidine, dexmedetomidine)
Intensity and duration of alpha-2 agonist induced cardiovascular effects reduced by vatinoxan
109
What is Zenalpha
a combination of medetomidine and vatinoxan. Used for its sedative and analgesic effects while helping to maintain CO by preventing a-2 induced arterial vasoconstriction
110
How can you antagonize the effects of dexmedetomidine?
Atipamezole (alpha-2 antagonist)
111
What are the potential adverse effects of atipamezole
rapid awakening (poor recovery)
anxiety
pain
vasodilation with hypotension
Arrhythmias
CV collapse
112
What fold difference of atipamezole do you need to administer in order to get reversal of dexmedetomidine induced sedation
10 fold difference higher
113
What characterizations do the anesthetic induction drugs (thiopental, propofol, alfaxalone, ketamine, etomidate) have in common?
they are designed to induce unconsciousness rapidly (within 1 to 2 minute) induction should be free from excitement or struggling recovery should be smooth
adverse effects of the anesthetic induction drugs are dose-dependent
114
How is ketamine fundamentally different from thiopental, alfaxalone, or propofol in the induction of anesthesia?
Does not unifromly depress the CNS like the other drugs
does selective depression of regions of the CNS (particularly the medial thalamic nuclei and neocortex)
stimulation of the limbic system
stimulation of the sympathetic nervous system
Decrease in CNS neurotransmission
115
Why is it desirable to induce general anesthesia quickly with a drug like thiopental?
Thiopental is a prototypical anesthetic induction drug, still used in many countries
administered as a rapid IV bolus in young, healthy, or poorly sedated animals
Slow administration can lead to excitement and struggling
Administer slowly IV to sick or debilitated patients
116
What accounts for the end of unconsciousness with thiopental?
Dog: half-life is about 7 hours but anesthesia is maintained for approximately 15 minute after a single IV dose.
short duration of anesthesia is due to redistribution of the drug away from the CNS
Long half-life results in a residual or "hangover effect"
117
What is the effect of peri-vascular injection of thiopental?
tissue irritation or necrosis (ph: 11)
effect dependent on the volume of thiopental injected perivascular and concentration
tissue irritation due to alkaline pH of thiopental
118
What effect does alfazalone have on respiratory system?
Depression, decreased tidal volume, RR
apnea is possible
effects are dose dependent
119
What are the respiratory effects of propofol?
similar to the respiratory effects of thiopental and alfaxalone
Decreased RR, Vt, MV
apnea
effects are dose-dependent
120
What are the respiratory effects of ketamine?
less respiratory depression than thiopental, alfaxalone, or propofol
patient is likely to keep breathing IVt and RR decreased but less chance of apnea)
121
What are the respiratory effects of etomidate
mild depression of ventilation, possible short perioid of apnea but less than thiopental, alfaxalone, or propofol
122
What are the effects of ketamine on cardiovascular function?
generally stimulates the CV system
Increases heart rate
blood pressure maintained or moderately decreased
cardiac output may be maintained
but Stim effects dampened by other drugs
Ketamine may depress cardiovascular function in compromised patients
123
How does Ketamine increase heart rate and blood pressure?
Increases sympathetic output
Increases HR and BP an indirect effect
Compromised animals may have decreased HR and BP
124
What are the effects of propofol on cardiovascular function?
Hypotension- dependent on the dose and speed of injection, primarily due to vasodilation, may last longer than expected, can be treated with IV fluids
Not arrhthmogenic
125
What are the cardiovascular effects of alfaxalone?
Decreased cardiac output
Vasodilation and hypotension
Reflex tachycardia
Degree of vasodilation < propofol? (maybe)
126
What are the cardiovascular effcts of etomidate?
minimal depression of cardiovascular function, mild bradycardia in some patients, small to no drop in blood pressure, most sparing anesthetic induction drug on cardiovascular function
127
What are the differences between propofol and ketamine on the CNS function?
Propofol uniformly depresses CNS function- partially mediated through the GABAchannel
Ketamine depresses some parts of the brain and stimulates other parts
Induction is faster with propofol than ketamine
patients look awake during ketamine induction- tighter jaw tone, more active eye
128
Why is recovery from anesthesia in dogs so rapid with propofol
Propofol is quickly cleared by the liver as well as by extra-hepatic sites
In the liver: glucuronidation and sulfation inactivates it
metabolites primarily excreted in the urine
clearance is 10 times that of thiopental
129
Why is ketamine a poor choice to induce anesthesia in an animal with head trauma?
May increase cerebral blood flow and intracranial pressure
Ketamine stimulates parts of the brain (limbic system, SNS)
stimulation leads to increased CBF to meet metabolic demand
not a concern with normal patients
130
What is the effect of liver disease on the recovery from propofol?
Recovery may be slowed a little by liver disease
essentially propofol will still clear via extra-hepatic metabolism
131
What is the effect of a prolonged infusion of propofol on recovery in cats?
Prolonged recovery
Propofol metabolized by glucuronidation
Cats cant do this very well
Infusions <1 hour are recommended
132
What are the primary advantages of alfaxalone compared to other anesthetic induction drugs in dog and cat?
Alfaxalone induction is similar to propofol
Advantages:
IM or SQ
Vasodilation/hypotension may be < propofol
used in many small exotic species
Does not have the precautions of ketamine
Ex: spicy cat
133
What temporary endocrine abnormality is induced by etomidate?
can suppress the stress response
inhibits adrenocorticoid function for 2-3 hours in the dog
may require supplemental corticosteroid
134
When is etomidate used to induce general anesthesia in animals?
patients with heart failure
135
Which anesthetic induction drug should be used cautiously in a patient with glaucoma?
Ketamine - it increases the tone of extra-ocular muscles and increases intra-ocular pressure
136
What are analgesic properties of ketamine
induction of general anesthesia (analgesia)
suppression of activity in dorsal horn of spinal cord
inhibition of glutamate neurotransmission at the NMDA receptor
*Not adequate at analgesia
137
How can rough and prolonged recoveries from ketamine be avoided?
Keep the dose of ketamine be low
Large dose range clinically
combine with sedative/tranquilizing drugs (acepromazine, dexmedetomidine)
138
Which anesthetics are vapors?
Methoxyflurane, halothane, isoflurane, sevofurane
(Liquid at ambient temperature and pressure while gas exist in gaseous form at room temp and sea level
139
What is the relationship between anesthetic potency and lipid solubility?
Meyer-Overton Rule:
anesthetic potency is correlated with lipid solubility (the more lipid soluble the agent, the more potent the anesthetic)- brain is full of lipids
140
What are the mechanisms of action of inhalant anesthetics
Alter intracellular functions of signaling proteins (including protein kinase C)
most likely target of volatile agents is the ion channel
Exert effects pre- and post- synaptic
inhibit neurotransmitter release and act post-synaptic to alter the response to neurotransmitters
*Dampen all neuronal activity of brain via ion channels*
141
MAC
minimum alveolar concentration (MAC) of anesthetic is a measure of potency
experimentally derived value and is the minimum alveolar concentration at 1 atmosphere that produces immobility in 50% of those patients or animals exposed to noxious stimuli
exhaled what measured- gives indication
142
What is saturated vapor pressure?
the maximum concentration of molecules in in the vapor state that can exsist for a given liquid at each temperature, unique for each volatile anesthetic
143
Why is the vapor pressure of inhalant anesthetic important?
it determines the type of vaporizer that is required to safety deliver the inhalant
Ex:
Isoflurane: Vapor pressure 252mmHg vaporize at sea level 33% while 39% at Colorado altitude. vaporizer needs to dilute out vapor so patient not given vapor dose of inhalant
144
How does the blood:gas solubility of an inhalant affect the rate of change of anesthesia?
determines how rapidly anesthetic saturates he blood and induces general anesthesia
Less soluble the anesthetic, the more rapid the partial pressure of anesthetic vapor reaches within the lungs and the more rapid anesthetic concentrations increase in the brain
Ex: methoxyflurane (slow), halothane, isoflurane, sevoflurane, desflurane (fast)
145
How is MAC used clinically
to compare different inhalant anesthetics
provide a general guide to vaporizer settings
*anesthetic potency increases as MAC decrease (lower the MAC, the greater the anesthetic potency)
146
What decreases MAC?
1) Other anesthetic/analgesic drugs used for premedicaton or induction: opioids, alpha-2 agonists, acepromazine, benzodiazepine
2) Decreased body temperature
3) Sick and/or debilitated
147
Why would you want a MAC reduction during general anesthesia?
A MAC reduction allows us to use a lower concentration of inhalant and maintain appropriate anesthetic depth
important approach to prevent induced hypotension
148
What are the effects of inhalants on cardiovascular function?
Dose dependent CV effects: depressed cardiac contractility
Decreased cardiac output
Vasodilation
May affect heart rate and rhythm
Hypotension
Depressed sympathetic outflow and obtunded cardiovascular reflexes
149
How do inhalant anesthetics affect heart function
Inhibit K+ and Ca2+ channels in the heart
Clinical result= dose dependent negative chronotropic and inotropic effects and arrhythmogenic effects
150
What are the effects of inhalants on respiratory function?
Depressed
Responsed to CO2 are blunted
Tidal volume and alveolar ventilation is decreased, minute ventilation is decreased, respiratory rate may increase or decrease
responses to increased CO2 are lost at deeper planes of anesthesia
overall: PaCO2 increased, PaO2 generally increased (delivered in 100% oxygen)
151
How are inhalants eliminated from the body?
primarily through respiration
all inhalants undergo metabolism to some extent ex: Methoxyflurane- 50% metabolite, isoflurane - 0.17%
152
What is the mechanism by which inhalant anesthetics can induce toxicity?
Metabolic byproducts: fluoride ions
Toxic byproducts: Compound A from sevoflurane and CO2 absorbents
Most common: decreased renal or hepatic blood flow during anesthesia
153
What are the differences between isoflurane and sevoflurane?
Very simular anesthetics
Sevoflurane has a lower vapor pressure (different vaporizer), Lower blood:gas solubility (faster), higher MAC (less potent- needs to run vaporizer higher), more metabolites, similar CV and resp effects
154
Which inhalant is the safest
no significant differences between isolfurane and sevoflurane
Some species/case advantages (ex: mice-sevoflurane)
155
Why do we use local anesthetics
facilitate performing a wide variety of minor and major surgeries (sedated animals)
Provide analgesia for invasive diagnostic procedures
Decrease the requirement for intraop opioids and lower inhalant doses
Provide analgesia in the immediate postop period
Provide multi-day analgesia
156
What are the advantages of local anesthetics
Advantages: Local anesthetics readily available
relatively safe drugs (dose-dependent)
Very effective at reducing or eliminating pain
many local blocks are relatively easy to do
Local anesthetics are affordable
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What are the disadvantages of local anesthetics
Disadvantages:
Local/regional blocks dont always work
Some blocks are time consuming to perform
Toxicity if over-dose
Motor block may complicate patient care
Local anesthetic may not last long enough (lidocaine)
Local anesthetics vasodilate
Possible CV effects with IV injection
158
What is the mechanism of action of local anesthetics
stabilize the membranes of excitable tissues (inhibit the transmission (conduction) of nerve pulses, selectivity to bind Na+ channels in the nerve membrane, Na+ channel blockers making the action potential not conducted)
159
What is the effect on inflammation on the efficacy of lidocaine
inflammation decreases efficacy of local anesthetics because inflammed tissues have a lower pH (more H+) prevents the local anesthetic from dissociating into the unionized form
160
How does the addition of epipinephrine affect the action of lidocaine
it will prolong the duration of action. Dilute concentration
decreases rate of absorption of lidocaine (because epi vasoconstricts)
161
What type of nerve fiber is likely to be affected first with a local anesthetic
Unmyelinated small fibers first
Sympathetic post-ganglionic, C fibers, pre-ganglionic autonomic
Delta fibers (pain)
Gamma fibers (muscle),
beta fibers (touch/pressure)
Alpha fibers (proprioception, somatic motor)
162
What local anesthetic does no vasodilate?
cocaine
163
How do local anesthetics exert an analgesic effect
Primarily block depolarization of A-Delta and C-fibers
nerves that are repetitively stimulated are more sensitive to local anesthetics than resting nerves
Also: bind Na+ and K+ channels in the SC
Binding of Ca2+ channels
Inhibitition of Substance P
Inhibit GABA uptake-potentiating Cl- channels
164
How are amide local anesthetics metabolized
Amide local anesthetics (lidocaine, bupivacaine, mepivacaine, and ropivacaine) are metabolized in the liver (microsomal enzymes)
Liver metabolism and hepatic blood flow affect the rate of metabolism
prolonged in patients with liver failure
165
Is bupivacaine or lidocaine a more toxic drug?
Bupivacaine is more toxic,
dissociates slowly from Na+ channels (longer lasting)
Difficult to resuscitate a patient with CV collapse from bupivacaine overdose because of tight binding, be careful calculating dose
166
What are the clinical signs of lidocaine toxicity?
1) CNS effects: Muscle twitching, seizures, depression, unconsciousness, coma, respiratory arrest
2) CV signs of toxicity: hypotension, decreased cardiac output, arrhythmias, CV collapse and cardiac arrest
167
How do you treat lidocaine toxicity?
Symptomatic treatment (IV fluids, O2 supp, intubate if needed and IPPV, Diazepam or midazolam for seizures, monitor closely)
168
How does systemic admin of lidocaine produce analgesia (IV)?
Several mechanisms
inhibition of spinal Na+ and K+ channels
Inhibition of NMDA receptors
Inhibition of glycine reuptake (inhibitory neurotransmitter)
169
What is Nocita and how does it differ from bupivacaine
Liposome encapsulated bupivacaine
Dosed at 5.3mg/kg Bupivacaine effect is approx 72 hours
Infiltrated at surgery site at the time of closure
170
What are the advantages of Nocita?
up to 3 days of analgesia
avoid the need to readminister local anesthetic
Decreases the need for postop opioids
171
What are the disadvantages of Nocita
infiltrated in the latter half of surgery, used in combination of other blocks (stays where you put it, wont diffuse)
Expensive
172
What is unique about grapiprant?
an NSAID that does not inhibit COX, EP4 antagonist, specific receptor for prostaglandins
173
What is the mechanism of action of diazepam?
it binds to specific site on GABA a receptors and increasing efficacy of GABA, increasing chloride ion conductance and hyperpolarizes the membranes
174
How can we avoid inducing withdrawal in a patient receiving opioids for several days
taper the opioids
175
What organ system is most concerning when giving an NSAID to an adult cat?
Kidneys
176
What is a partial mu agonist and what is the clinically used drug?
buprenorphine, only partial activation of the mu receptor
177
When should you give flumazenil to animal
if you want to reverse a benzodiazepam
178
How can you enhance the sedative effects of acepromazine in a dog or cat?
1) Add Alpha-2 agonist
2) Add opioid
3) Increase dose
179
Why are NSAIDs used in animals
1) analgesia
2) anti-inflammatory
3) antipyretic
180
Which opioid is difficult to reverse due to high binding affinity
buprenorphine
181
What is the most common complication of NSAIDs in dogs
GI issues: nausea, vomitting, diarrhea, erosion, ulceration
182
How can you treat opioid-induced excitement in a dog
1) Alpha-2 agonist
2) Reverse opioid
183
How does ketamine increase heart rate and blood pressure
increases sympathetic tone (indirect effect)
184
How can you partially reverse the effects of hydromorphone
Low dose of naloxone (102mcg/kg IV)
Buprenorphine
Butorphanol
Nalbuphine
185
What is a clinically convenient way to administer buprenorphine to a cat
transmucosal
186
How do diazepam and midazolam differ?
midazolam is water soluble and can be given IM
187
What is primary use for acepromazine
sedation and tranquilization
188
How are the effects of acepromazine antagonized
they are not, no antagonist available
189
What are two desirable effects of alpha-2 agonist
sedation and analgesia
190
How can you completely reverse effects of buprenorphine
naloxone (high dose because it binds really tightly to mu receptor)
191
What are the main effects of acepromazine on the cardiovascular system
vasodilation leading to hypotension
192
What are some uses of NMJ blockers?
1) tracheal intubation
2) orthopedic manipulations (fractures)
3) Balanced anesthesia
4) Anytime that skeletal muscle paralysis is desired
193
Competetitive NMJ blockers
prevent motor end plate depolarization
initial muscle weakness followed by flaccid paralysis
194
What is Pancuronium used for?
it is a NMJ blocker
useful with tachycardia
long duration of 2-3 hours
195
How does renal disease influence pancuronium?
it increases the half life of its NMJ blocking
196
What NMJ blocker has a long duration of action
Pancuronium (2-3 hours)
197
What NMJ blocker has a short duration of action
Miracurium (15 minutes)
198
Rank the NMJ blockers on their duration of action
Pancuronium, Atracurium, Miracurium (shortest)
199
What NMJ blockers promote histamine release?
Succinylcholine, Atracurium and Miracurium
200
What NMJ blockers would you recommend for a patient with renal disease
Atracurium and Miraciurium (pancuronium's half life is increased with renal disease)
201
What increases the half life of Atracurium?
Hypothermia and acidosis because it is degraded spontaneously and hydrolysis by plasma esterases and renal elimination
202
How do you reverse NMJ blockers
acetylcholinesterase inhibitors (like physostigmine or neostigmine)
203
Name a depolarizing NMJ blocker
Succinylcholine
204
What are the competetive NMJ blockers?
Pancuronium, Atracurium, Miracurium
205
Succinylcholine
a depolarized NMJ blocker used clinically, essentially mimics ACh at the NMJ, rapid onset, some histamine release
206
How do you reverse succinylcholine
you cant
207
What is a side effect from succinylcholine
hyperkalemia from the release of intracellular potassium from skeletal muscles, avoid in presence of extensive soft tissue damage or burns
208
When should you use succinylcholine
short lived MNJ blockade (via depolarizing) such as facilitating tracheal intubation or wildlife immobilization
(immobilization without the CNS effect- not analgesic, and not dissociative)
209
Do you get CNS effects with succinylcholine
No
210
Potential problems with NMJ blockers
1) Unable to monitor the depth of anesthesia using muscular signs (ex: general and jaw tone)
2) Respiratory distress- make sure to monitor oxygenation and carbon dioxide levels
3) Toxicities via ganglionic blockade and histamine release leading to bronchospam, hypotension, bronchial and salviary secretion
4) Malignant hyperthemia: life threatening from excessive contracture and heat production from skeletal muscle initiated by release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle
211
How might you limit the histamine release from the NMJ blockers that release histamine ( succinylcholine, miracurium, atracurium)
Minimize with antihistamine treatment of diphenhydramine (Benedryl)
212
What NMJ blocker does not release histamine
Pancuronium
213
How can you treat malignant hyperthermia caused by NMJ blockade?
Dantrolene- a drug that limits SR Ca2+ release
also so supportive measures like rapid cooling and oxygen
214
What happens when you give a NMJ blocker IV?
paralysis to all skeletal muscles
215
Diuretic
agent that produces diuresis (Increased urine flow rate)
216
What are the major osmolytes being reabsorbed/secreted when making urine?
Reabsorbed: NaCl, Bicarbonate (HCO3-), Calcium (Ca2+)
Secreted: Hydrogen and Potassium
217
Why might you give a diuretic?
1) reduce extracellular fluid volume (Pulmonary congestion- CHF, fluid overload or ascites- CHF, liver disease)
2) Oliguric renal failure- pathogen: vasoconstriction leading to decreased blood flow and cellular ischemia/necrosis
3) Hypertension (systemic or excerise induced pulmonary hemorrhage)
4) Promote urinary excretion of selected agents/electrolytes (hypercalcemia)
218
Osmotic Diuretics
inhibits water reabsorption in the proximal tubule and thin loop by increasing the osmotic gradient in the lumen
Includes: Mannitol
219
Mannitol
an osmotic diuretic that functions to inhibit water reabsorption in the proximal tubule and thin loop by increasing the osmotic gradient in the lumen
Uses: Oliguric renal failure, cerebral edema, acute glaucoma
Dont use: if cant establish urine flow, or if there is intracranial bleeding
220
How does DM act as an osmotic diuretic
too much glucose infiltrate leads to water retained in the urine leading the clinical signs of PU/PD and causing dehydration
221
Carbonic Anhydrase inhibitors
promote reabsorption in the proximal tubule by increasing the retentions of bicarbonate reabsorption leading to increased retention of bicarb in urine (alkanization, blood acidifcation, and increasing H20 excretion)
ex: Acetazolamide
222
Acetazolamide
an CA inhibitor that inhibits bicarbo resportion leading to increased retention of bicarb in the urine, blood acidification, and increased H20 ecretion
Weak diuretic effect
Uses: treat metabolic alkalosis, glaucoma, altitude sickness
Side effects: may cause systemic acidosis through bicarb loss in urine. also hypokalemia due to H+/K+ exchange
223
What are some side effects of acetazolamide
may cause systemic acidosis and hypokalemia
224
Loop diuretics
inhibit NaCl resorption in the thick ascending limb of the loop of henle
induces urinary loss of NaCl and water, most commonly used
ex: Furosemide
225
Furosemide
most effective diuretic, most widely use in vet med
functions to inhibit NaCl resportion in the think ascending limb of loop of henle inducing urinary loss of NaCl and water
-also may cause hypokalemia and hypocalcemia
uses: oliguric renal, CHF, acute pulmonary hypertension, EIPH
226
Why is furosemide banned on the day of the race
because its diuretic effect can mask the presence of other drugs in urine
227
What can you use for EIPH in horses, commonly racehorses
Horses with EIPH commonly get epistaxis associated with impaired function from repeated capillary rupture and healing leads to scarring, decreased lung capacity
Treat with Furosemide: fluid loss- reduced blood pressure in the pulmonary circulation, bronchodilator effecr
228
Thiazide diuretics
act on the distal convoluted tubule to prevent the resorption of Na and Cl in the dital tibule by blocking the symporter leading to Na and Cl being retained in the filtrate
ex: chlorothiazide
229
Chlorothiazide
not as effective as loop diuretics but lead to Na, Cl being retained in the filtrate by blocking symporter in the distal tubule
use: treat nephrogenic diabetes inspidus, udder edema (cattle), and Ca2+ containing uroliths
230
What is furosemide used to treat?
oliguric renal, CHF, acute pulmonary hypertension, EIPH
231
What is used to treat nephrogenic diabetes insipidus
Chlorothiazide
232
What are the two K+ sparing diuretics
Spironolactone and Amiloride
233
What drug is a competitive aldosterone antagonist?
Spironolactone
234
What drug is a principal cell Na+ channel blockers
Amiloride
235
K+ sparing diuretics
help maintain electrolyte balance (K+) , unlike other diuretics by influencing aldosterone either by antagonism (Spironolactone) or blocking sodium channels of distal tubules (Amiloride) which aldosterone normally acts on to increase sodium, potassium channels, urine retention, and increased blood pressure, K+ excretion
236
What drug interaction can be prevented by giving K+ sparing diuretics like spironolactone and amiloride?
Digoxin is enhanced with hypokalemia and can lead to arrhythmias. patients on digoxin shouldnt be given diuretics
237
Spironolactone
Blocks aldosterone induced expression of multiple genes leading to mild diuresis with reduced potential for K+ loss
used in combination with loop diuretic to prevent hypokalemia, hypertension, treat hormonal acne in women
delayed onset of action and prolonged effect
238
Amiloride
an epithelial sodium channel blocker leading to an immediate but mild diuretic effect. used in combination with loop diuretics
239
Diabetes inspidus
lack of ADH leading to severe diuresis
240
Aquaretics
a class of diuretics that antagonize ADH/vasopressin V2 receptors in the kidney promoting solute free water clearance (no loss of Na+)
includes: Demeclocycline
241
Demeclocycline
an antibioitic that also antagonized the v2 receptor in the kidney leading to diuresis by diminishing responsiveness to ADH
Used to tx syndrome of inappropiate ADH production
effective in heart failure but not et approved
242
What dietary change can often increase the effectiveness of diuretics?
Restricting dietary NaCl
or add K+ to diet to decrease induced hypokalemia
243
What is an autacoid
a biological factor which act near the site of synthesis and have brief duration of action, act as local hormones essentially for diverse functions like modulating blood flow, regulating secretions, altering smooth muscle function, and participating in allergy, inflammation, and pain related processes
244
Derived from aa histidine, mast cells and basophils contain it and is released by exocytotic extrusion via IgE
Histamine
245
Mast cell degranulation results in
histamine to be released with other biologically active compounds like proteases, serotonin, phospholipid derivatives (prostaglandins and leukotrienes)
246
What histamine receptors are the most clinically relevant
H1: modulates smooth muscle function (vasodilation and bronchail contraction) and increase capillary permeability
H2: Stimulate gastric acid secretion
247
H1 antangonist
antihistamines that are specific to H1 receptors, function in varous allergic, anaphylactic, and other histamine related reactions, relax constricted bronchial smooth muscle, inhibit histamine vasodilation, decrease swelling and redness by decreasing capillary permeability, decrease itching
1st gen: Diphenhydramine, Chlorpheniramine, Dimenhydrinate, Promethazine
2nd gen: Loratadine
248
What does the swelling and redness of allergies come from
The H1 receptor increasing capillary permeability
249
How do 1st gen and 2nd gen H1 antagonist antihistamines differ
1st gen: unionized at physiological pH- able to enter the CNS often sedating
2nd gen: ionized at physiological pH, less enters the CNS and is less sedating
250
List the 4 1st generation H1 antagonists
1) Diphenhydramine (Benadryl)
2) Chlorpheniramine (Chlor-Trimeton)
3) Dimenhydrinate (Dramamine)
4) Promethazine (Phenergan)
251
What 1st generation H1 antagonist is not anti-muscarinic
chlorpheniramine
252
What is a 2nd generation H1 antagonist
Loratadine (Claratin)
253
What are the adverse effects of H1 antagonists?
1) CNS depression (lethargy, ataxia, sedation)
2) Antimuscarinic effects (dry mouth, urine retention, anti-sludge) - contraindicated in glaucoma
3) CNS stimulation- paradoxial or with high doses
254
Name an H2 antagonist
Famotidine (Pepcid)
255
What is the function of H2 antagonist like Famotidine?
Inhibiting gastric acid secretion by blocking H2 receptors on parietal cells in the gastric mucosa
Used in gastric, abomasal, and duodenal ulcers, drug-induced gastritis, reflux
256
Why might you use Famotidine?
reduce gastric acid secretion for gastric, abomasal, and duodenal ulcers, drug-induced gastritis, reflux
257
Derived from the amino acid tryptophan, found in platelets, neurons, and mostly in the GI tract
function to regulate gut motility, body temperature, sleep, mood, behavior, and pain
Serotonin
258
Ergot alkaloids
serotonin agonists from fungus on seeds, lead to cattle losses
259
Why might you use an SSRI
to increase serotonin levels leading to behavioral changes
Dogs: separation anxiety, compulsive behaviors, aggression
Cats: spraying, compulsive behaviors, aggression, psychogenic aopecia
260
What does angiotensin result in
Vasoconstriction and increase in blood pressure
261
What does bradykinin result in
vasodilation
262
Non-steroidal immunomodulators
drugs that suppress immune function via mechanisms distinct from corticosteroids
inhibit T cell activation, B cell activation, or both
often used when NSAIDs or corticosteroids fail
-Systemic disease (IMHA, IMTP, SLE)
-Dermatological Diseases (Pemphigus, Discoid Lupus)
263
Consequences of NSIMs
inappropiate autoimmune responses are blunted (good), normal immune responses are blunted (bad)
264
Calcineurin inhibitors
inhibits calcineurin an enzyme that activates T cells, leading to blockade of T cell proliferation and cell-mediated immunity
Cyclosporine and Tacrolimus
265
Cyclosporine
a calcineurin inhibitor that binds to cyclophilin leading to dephosphorylation of NFAT leading to decreased T cell activation and cell mediated immunity
Uses: IMHA, IBD, Immune mediated polyarthritis, atopic dermatitis, perianal fistulas (dogs), organ transplant regiments , keratoconjunctivitis sicca (KCS)
266
Tacrolimus
a calcineurin inhibotr that binds FKBPI2, an immunophilin involved with calcineuron function
Prevents dephosphorylation of NFAT leading to a decrease in T cell activation and cell mediated immunity
Minimal use in vet med
Topic administration for dermatoses in dogs
267
What drug is a Janus Kinase Inhibitor (JaK-1 and 3)
Oclacitinib (Apoquel)
268
Oclacitinib (Apoquel)
a JAK 1 and 3 inhibitor that decrease the effects of inflammatory cytokines made by lymphocytes as well as decreasing IL-31- directly involved in itch sensation
Use: manage chronic itching
side effects: Bone marrow suppression (increased risk of infection)
269
What drug is a monoclonal antibody against IL-31
Cytopoint
270
Cytopoint
a monoclonal antibody against IL-31, eliminating the itch sensation cytokine
SQ injection that last 4-6 weeks
minimal immunosuppression
used for atopic dermatitis in dogs
271
What are the cytotoxic alkylating agents?
Cyclophopshamide
Chlorambucil
272
What is the mechanism of action of cyclophosphamide and Chlorambucil
Nitrogen mustard that adds alkyl groups to damage DNA of T, B, and other rapidly dividing cells of the bone marrow
273
What cells are cyclophosphamide and Chlorambucil toxic to?
T and B cells
274
Cyclophosphamide
a cytotoxic alkylating agent that is potent to T, B, and other rapdily dividing cells in the bone marrow
Uses: anti-neoplastic and immunosuppression (IMT, SLE, rheumatoid arthritis, pemphigus, IMHA)
Toxicity: Bone marrow suppression, nausea, vomiting, diarrhea, alopecia, Sterile hemorrhagic cystitis
275
Sterile hemorrhagic cystitis
seen in cyclophosphamide toxicity primarily in dogs
due to accumulation of acrolein that damages bladder epithelium. Minimize with glucocorticouds/diuretics and MESNA to bind the toxin
276
Chlorambucil
a cytotoxic alkylating agent that is potent to T, B, and other rapdily dividing cells in the bone marrow
Uses: substrate for cyclophosphamide and often immune mediated skin diseases in cats like pemphigus
Toxicity: less toxic than cyclophosphamide but not as effective
277
What are the cytotoxic inhibitors of purine synthesis
Azathioprine and Mycophenolate mofetil
278
Azathioprine
a cytotoxic inhibitor of purine synthesis disrupting T and B cell proliferation
primarily in dogs for immunosuppression, IBD, immune mediated skin disease, IMHA
Uses: often with corticosteroids so both can be given at lower doses and limits the adverse effects
Toxicity: Major- immunosuppression and bone marrow supression (especially in cats)
Minor: GI distress, anorexia, pancreatitis, hepatotoxicity
279
Mycophenolate mofetil
a cytotoxic inhibitor of purine synthesis disrupting T and B cell proliferation, used as an alternative to azathioprine
Uses: similar to azathioprine- IBD in dogs, organ transplant regiments, immuosuppression, IMHA, immune mediated skin diseases
Potentially useful in cats but still use with caution
Limited Vet med use
280
What results in increased pain?
Peripherally: activation of nociceptors via TRPV1 (heat), TRPA1 (pressure), and TRPM8 (cold) via inflammaion (prostaglandins, bradykinin, cytokines, and lipids
Centrally: Increased action potentials through pain pathways to the brain (modification of synapses in dorsal horn- windup leading to increased pain perception, decreased activity of descending inhibition)
281
Where is aldosterone produced
zona glomerulosa under ACTH, angiotensin II, and increased extracellular K+
282
Why is aldosterone produced
to increase salt and water retention
283
Where is glucocorticoid produced
in the zona fasciculata of the adrenal cortex under CRH from hypothalmus and ACTH from anterior pituitary
284
What are the 8 effects of glucocorticoids
1) Metabolism (increased gluconeogensis, increased insulin secretion, increased protein breakdown, increase lypolysis)
2) Cardiovascular (increased adrenergic and angiotensin signaling, increased vasoconstriction and cardiac contraction, CV effects associated with hypertension and CHF)
3) Respiratory effects Bronchodilation and B2 receptor expression, decreases histamine release
4) Skeletal muscle effects: maintains muscles but can waste at high amounts
5) Integumentary skin effects: epidermal and dermal thinning, easily bruiing, poor wound healing, poor quality hair, alopecia
6) Immunological skin effects: easy bruising, poor wound healing, epidermal and dermal thinning, alopecia
7) Water and Electrolyte balance: Polyuria and Polydypsia from inhibiting ADH
8) Gastrointestinal effects: possible ulceration from increased HCl and pepsin
9) Anti-inflammatory at pharmacologically high doses- primarily cell mediated immunity more than humoral immunity
285
What 3 ways do different glucocorticoids differ?
1) Ant-inflammatory potency
2) Duration of action
3) Mineralocorticoid activity
286
Hydrocortisone (cortisol)
Short duration (<12 hours)
Anti-inflammatory and mineralocorticoid potency=1
Uses: topically for pruritus and inflammation associated with allergy
287
Fludrocortisone
Short duration of <12 hours
Anti-inflammatory potency of 10
Mineralcorticoid potency of 125
Uses: Systemically for cortisol and aldosterone replacement during adrenal insufficiency (Hypoadrenocorticism- Addisons)
288
inactive pro-drug that gets metabolized to prednisolone
intermediate duration (12-36 hours)
Anti-iflammatory potency of 4
Mineralocorticoid potency of 0.8
Used for long term allergy management, chronic inflammation like arthritis, immunosuppression (autoimmune)
Prednisone
289
Give for Cats/horses or hepatic failure as they have less prednisolone conversion
intermediate duration (12-36 hours)
Anti-iflammatory potency of 4
Mineralocorticoid potency of 0.8
Used for long term allergy management, chronic inflammation like arthritis, immunosuppression (autoimmune)
Methylprednisolone
290
long duration (36-72 hours)
Anti-inflammatory potency of 25
A mineralocorticoid Potency of 0
Used systemically for immediate relief of hypersensitivity and septic shock, long term control of allergy, and immunosuppression
Dexamethasone
291
What is mitotane used for
it eliminates of decreases the availability of adrenal steroids
cytotoxic to the zonae fasciculata and reticularis
reduces all adrenal steroids except for aldosterone
Used for Hyperadrenocorticism or steroid-secreting adrenal tumors
292
How can you get iatrogenic hypoadrenocorticism
adrenocortical suppression can occur a few weeks of glucocorticoid therapy
Additional supplementation may be necessary during periods of stress,
tapering to wean animal off of the steroid, based on GC involved, dose, duration of therapy, stress level, etc.
293
what does COX 1 produce?
PGE2 (Vasodilation, sensitization of nociceptors, GI protection via mucous production)
Thromboxane A2 (Platelet aggregation and vasoconstriction resulting in enhanced coagulation and clot formation
294
Does COX 1 have constitutive or inducble expression?
constitutive
295
What does COX 2 produce?
1) PGE2 (Vasodilation, sensitization of nociceptors, GI protection via mucous production)
2) PGI2: produced in endothelial cells, causes vasodilation, inhibits platelet aggregation
296
How do NSAIDs produce an analgesic effect?
by inhibiting prostaglandin synthesis and decreasing nociceptor activity
297
COX-2 selective drugs
fewer GI effects than non-selective NSAIDs but not safer for kidneys.
have a procoagulant effect through losing PGI2
298
