CNS, A2 agonists, Opioids Flashcards
1
Q
What drug is used to treat malignant hyperthermia?
A
Dantrolene
- inhibits Ca2+ release from SER to cause muslce relaxation, does not generally affect respiratory muscles significantly.
2
Q
Which species is susceptible to Malignant hyperthermia?
A
Pigs- Belgian landrace
Dogs- Greyhounds
3
Q
What triggers Malignant hyperthermia? Name some clinical signs?
A
Halothane
- rapid sustained rise in body temp
- tachycardia, cyanosis, generalized muscle rigidity, cardiac arrhythmias are common clinical signs
- Acidosis, hyperkalemia, hyperphosphatemia, hypocalcemia from muscle-cell breakdown
- RHABDOMYOLYSIS
- Renal failure, DIC
4
Q
Name some centrally acting muscle relaxants?
A
Opioid agonists, Alpha 2 agonists, GABA agonists, General anesthetics.
- Guaifenesin (GG, GGE, Guailaxin)- Equines and cattle
- Methocarbamol (Robaxin-V) (dogs, catas, horses) oral or injectable.
5
Q
Guaifenesin is used at what percentage and why? What is the target and the duration of onset?
A
5% for IV infusion Because thrombophlebitis can be seen with over 10% and hemolysis can also be seen with even more than 10%. Cattle are more sensitive to this than horses.
- Depresses the nerve impulse at the internuncial neuron in the spinal cord
- Rapid onset at 2 mins and short duration 10-20 mins
6
Q
Clinical use of Guaifenesin
A
Anesthetic protocol to facilitate intubation, smooth anesthetic induction and recovery, and for anesthetic sparing effect
7
Q
What is in the triple drip?
A
GG + Alpha 2 agonist + ketamine
8
Q
Cautions with Guaifenesin?
A
Contraindicated use of physostigmine. Be cautious with other cholinesterase inhibitors neostigmine and edrophonium
9
Q
Methocarbamol is not typically used in anesthesia like GG, what is it typically used for?
A
Reduce muscle spasms.
- Supportive therapy for tremorgenic toxicoses like pyrethrins or strychnine. Urethral obstruction.
10
Q
Def of Tranquilizer
A
Neuroleptic, anxiolytic
patient relaxed aware of their surroundings
11
Q
Sedative definition
A
Induces a state characterized by CNS depression and drowsiness decreased awareness
12
Q
Hypnotic def?
A
SLEEP
13
Q
Narcotic?
A
Stupor bordering on general anesthesia. OPIUM.
14
Q
Local regional anesthesia definition
A
loss of sensation in a circumscribed body area
15
Q
General anesthesia definition?
A
drug induced unconsciousness characterized by controlled, reversible, depression of the CNS and analgesia. sensory, motor and autonomic reflexes are reduced
16
Q
Typically lipophilic drugs cross the BBB. T/F
A
True
17
Q
Ascending reticular activating system is involved in?
A
Consciousness
18
Q
Name excitatory receptors that when are suppressed cause depression of the CNS
A
Glutamate stimulated the NMDA receptor
ACH - neuronal nicotinic receptors
5HT3 seratonin- stimulates 5 HT receptors
19
Q
Which receptors can be mimicked to depress the CNS?
A
GABA
Glycine
20
Q
Surgery requires which of the following?
- Reduced consciousness
- Muscle relaxation
- Analgesia
- All of these?
- Only Muscle relaxation and Analgesia
A
All of them!
21
Q
Pheothiazines used primarily for ?
A
Sedation
22
Q
Drugs in the Phenothiazine class work on which receptors?
A
Dopamine receptor antagonists.
antagonism at histamine and muscarinic receptors
23
Q
Phenothiazines can be given A. IV B. IM C. SQ D. PO E. A and D F. All of them
A
All of them
24
Q
Pharmacologic effect of phenothiazine at the
CNS, ANS, Cardio, Resp., Skeletal, Analgesia?
A
CNS- Sedation, anti-emesis
ANS- Vasodilation => hypotension.
Cardio - Hypotension mostly with Acepromazine, bradycardia, boxers sensitive to Ace
Respiratory- at high doses respiratory depression
Skeletal? Moderate muscle relaxation
Analgesia? NONE IMPORTANT
25
Acepromazine is a Phenothiazine, but does it provide analgesia? Give me an adverse effect?
NOPE! Just Sedation. Hypotension! Boxers particularly sensitive to the cardio effects of ace. MDR1 ABC1 gene mutation dogs may have longer duration, careful with Stallions and their giant penis (paraphimosis predisposing to penile injury). AGRESSION. Extrapyramidal signs.
26
What are extrapyramidal signs?
Extrapyramidal system consists of axons that do not pass through the pyramidal system which initiates voluntary, discrete and learned movements. Extrapyramidal system is more responsible for postural antigravity muscle tone to keep you upright. Proximal extensor muscles. So the signs are stiffness, tremor, motor restlessness, tightening of facial muscles and opisthotonos (severe extensor rigidity)
27
Is Ace contraindicated in patients with seizures?
Nope... matter of opinion.. but it says on the label to not use in seizure patients.
28
Butyrophenones used as ____________ in human med. Not used in VET MED
antipsychotics
its a phenothiazine
29
Azaperone is used primarily in which species and for what?
Swine, reduces aggression
30
BAM is what?
Butorphanol-azaperone-medetomidine used for darting wild ungulates
31
Haloperidol is used to control feather picking behavior in birds? T/F
True
32
Benzodiazepines provide reliable sedation when alone in ruminants T/F?
True
But not typical with other species. Good muscle relaxants and anti seizure activity
33
What is the MOA with Benzodiazepines?
Potentiate GABA receptors
| When you say GABA think INHIBITION
34
Should diazepam be given IM?
Nope cause pain because the 40% propylene glycol.
35
Which benzodiazepine can be given IM?
Midazolam
36
Can cats be given oral diazepam? What about injectable?
NOPE. causes hepatic necrosis when given orally, you can still give it injectable
37
Which benzodiazepines gives the longest duration?
A. alprazolam
B. diazepam
C. Lorazepam
D. A and C
D.
38
Pharmacologic actions of Benzodiazepines
CNS: Mild sedation, Sedative-hypnotic effects
Good Skeletal muscle relaxation
Anticonvulsant
Aggression and Excitement in dogs,cats, horses, used with opioids, ketamine or tiletamine
Cardio: Minimal cardiac and respiratory effects seen at therapeutic doses, depression at larger doses
NO ANALGESIA
39
Diazepam is used in anesthetic premed, anticonvulsant and appetite stimulant?
YAsss
Not for chronic anti seizure
good for geriatric patients
given rectally (transmucosal absorption) in emergencies
AVOID ORAL DIAZEPAM IN CATS
40
Midazolam key importance?
can be given IM
| Same as diazepam
41
Alprazolam (xanax), can this be given orally in cats?
Longer duration of action, not associated with hepatic necrosis in cats orally. Used for outpatient management for non acute indications
42
Zolazepam/Tiletamine key words
only found in a fixed combo with tiletamine in product telazol, just recognize as a Benzodiazepine
43
What can you use to REVERSE diazepam?
Flumazenil
inverse agonist
only for overdosed patients
44
Do alpha 2 agonists provide analgesia?
Yes, along with muscle relaxation.
45
What is the MOA in A2 agonists?
Agonize alpha 2 adrenergic and non adrenergic receptors. Presynaptic receptors will inhibit release of NE thus decreasing sympathetic outflow.
- In the brain: it will cause sedation, vasomotor center causes vasodilation and bradycardia.
- in vascular endothelium causes vasoconstriction => reflex bradycardia
- Spinal cord = analgesia and muscle relaxation
46
Dangers of A2 agonists in humans?
Clonidine is used for hypertension in humans but not in vet meds. Vasodilation.
BUT humans can experience profound hypotension if they get exposed to vet alpha 2 agonist drugs.
47
Activation of Alpha 1 receptors can happen with Alpha 2 agonist drugs?
Yes.
48
Which drug is most selective for Alpha 2 receptors? Which is least?
Dexmedetomidine is most selective 1600: 1
| Xylazine is only 160:1
49
Pharmacokinetics of alpha 2 agonists
Given IV or IM
avoid intra arterial injections (horses intracaratid injections causes seizures)
Absorption SQ is poor
CRI or epidurally used
Detomidine gel for horses (transmucosal fomulation)
Wide distribution CNS and placenta
Metabolized in liver, excreted in urine
50
Pharmacologic effects of alpha 2 agonists
- CNS
- Cardio
- Resp
CNS: Sedation, analgesia and centrally mediated muscle relaxation, Emesis (CRTZ; Chemoreceptor trigger Zone), Xylazine used as an emetic drug in cats
Cardio: Biphasic responses, CO decreased 30-50%; initial peripheral phase consists of vasocontriction which can cause reflex bradycardia. AV block, arrhythmia related to high vagal tone can be seen. DON'T USE ANTICHOLINERGICS SUCH AS ATROPINE. Later central phase decreased sympathetic flow, vasodilation without compensatory rise in heart rate, and can lead to hypotension.
-Resp: Centrally mediated decrease in respiratory rate, but mild, except in sheep which can lead to pulmonary edema
51
Xylazine is used in many species. List the animals from most sensitive to least.
A. Swine, Equines, small animals, Ruminants
B. Ruminants, small animals, Equines, swine
C. Small animals, Ruminants, Equine, Swine
B.
52
Dexmedetomidine is used in large animals only. T/F
False,
| Commonly used in small animals. highly specific for A2 receptors
53
Detomidine & Romifidine are used for large animal and more suitable for standing procedures? T/F
True. Used in equine and cattle
Detomidine is available as sublingual gel for horses Dormosedan Gel
Less sedation so it can be used for standing procedures.
54
Alpha 2 Antagonists are used to reverse the effects of A2 agonists. Reversal will not reverse the analgesic effect. T/F
F.
| ALL EFFECTS INCLUDING ANALGESIA
55
Which antagonist is most selective? Which antagonist is least? Which would you use for Xylazine?
Atipamezole 8526: 1 reverses dexmedetomidine
Yohimbine 40 : 1 xylazine
Tolazoline
56
Opioid def?
agonist at opioid receptors anything that can be displaced by naloxone
57
Opiates:
Natural occurringa drugs alkaloids extracted from opium
58
Narcosis
stupor bordering on general anesthesia .. used to be induced with opium
59
Natural opiates def?
alkaloids from the seed pods of opium (papaver somniferum eg. Morphine)
60
Semisynthetic opioids Def.
Substitution of chemical radicals in the place of hydrogen atoms at the hydroxyl positions of morphine - eg. oxymorphone, hydromorhone, apomorphine
61
Synthetic opioids def?
Completely manufactured in a lab, eg. Fentanyl, carfentanyl, butorphanol
62
Opioids are very good analgesics and provide varying degrees of sedation? T/F
True
63
What is Neuroleptanalgesia?
Opioid with a (alpha 2 agonist, benzodiazepines, phenothiazines) synergistic effect is seen resulting in a very good sedation
64
Opioids are considered controlled substances by the DEA. DEA scheduling goes from I to V with lower numbers for lower abuse potential? T/F
```
FALSE.
Schedule I : heroin (OH lordy)
Schedule II: Morphine
Schedule III: Buprenorphine
Schedule IV: Butorphanol
Schedule V: Robitussin with codeine
```
65
MOA of opioids
G protein coupled and activation of them cause reduced adenylate cyclase increased K+ efflux and decreased calcium Ca ++ influx leading to hyper-polarization of neuronal cells making them less responsive
66
Mu and kappa are most clinically important, what are the main effects?
sedation and analgesia
- mu : beta endorphisn, endomorphins
- k : dynorphins
67
Pharmacokinetics of opioids
Given IV, IM SC poor oral bioavailability
68
Why is morphine not typically given IV?
causes histamine release
69
Butorphanol and hydrocodone are given PO as what?
antitussives
70
Buprenorphine is used as an oral transmucosal in cats? T/F
True
| Sublingual/ buccal
71
Fentanyl is used as single IV injections, IV CRI, or transdermal?
truth is all of the above
72
In cats sulfation will occur with morphine instead of glucuronidation and morphine will be metabolized to morphine 3 sulfate?
Yasss
73
Pharmacological actions with opioids in Dogs and monkeys, humans/
CNS depression, decreased motor activity, hypothermia and miosis
74
CNS effects in Cats, horses, and ruminants may show?
CNS excitement dysphoria, increased locomotor activity, hyperthermia, and mydriasis
75
Opioids cause coughing and vomiting?
yesLess common to see emesis when patients have more pain.
76
Panting can be seen in dogs with lower dosages of opioids?
yes
77
Cardiovascular effects of opioids?
Bradycardia and vasodilation, increased intracranial pressure
78
GI effects with opioids?
Decreased. can lead to delayed gastric emptying, ileus, colic and constipation with chronic use.
79
Urinary tract effects with opioids
Mu agonists will cause increased sphincter tone and suppression of detrusor muscle leading to urinary retention. Stimulation of ADH hormone may decrease urine production. Kappa agonists may inhibit ADH and increase urine production.
80
Full mu agonists are weak or strong?
Binds to the receptor and elicits a full response. STRONGER
81
all opioids are Dea Schedule III? T/F?
False
Schedule II
82
Morphine what is the onset and how long does it last.
Rapid onset 5-15 mins and lasts several hours.
Natural opioid used for premed and perioperative pain, less lipophilic than other opioids which make it popular for epidurals can provide analgesia for up to 24 hours. Higher incidence fo vomiting than other mu agonists.
83
Hydromorphone and Oxymorphone general characteristics
Semisynthetic opioids onset and duration similar to morphine. Cause LESS histamine release and can be used IV or IM as preanesthetic or for peri operative analgesia. Cause less emesis, oxymorphone is more expensive.
84
Fentanyl gen characteristics
Synthetic opioid more potent and lipophilic than morphine and is typically dosed in micrograms
-Rapid onset ( 1 min) short duration of action ~ 30 mins. Typically only used IV CRI or as transdermal outpatient
dont cut the patches
85
Carfentanil / etrophine HCl are these natural?
Synthetic opioids are VERY potent 4000-1000 morphine only used in zoo and wild animal immobilization. Can kill people, need to be a specialize vet. Naltrexone, diprenorphine or naloxone must be on hand` when these are used. Carfentanil is a mu agonist, and etorphine is mixed mu, kappa and delta receptors.
86
Methadone is a mu agonist, what is the receptor that it antagonizes?
NMDA receptor has efffects on re uptake of NE and serotonin which contribute to its analgesic effects. more common in the UK/ Aussie than North America
87
Meperidine
Less potent than morphine, very short acting, less histamine release. not used much in vet med.
88
Partial mixed agonists have a lower ceiling analgesic effect compared full mu agonists? T/F?
True
89
Buprenorphine general characteristics. is it synthetic or natural? DEA class number?
Semisynthetic opioid partial mu agonist Schedule III. Slower onset 45 mins longer duration up to 8 hrs in cats. used IV, IM SC, oral transmucosal good for the oral pH in cats.
90
Butorphanol is a synthetic mixed agonist what is the schedule number
Schedule IV.
Used as analgesia and antitussive. Used more in equine. Visceral pain (abdominal organs) not so great with muscles and joints. Given IV, IM, SC, or PO. Antagonist effects at mu receptors it is used to reverse full mu agonists and will reduce dysphoria, cardiorespiratory depression without completely reversing the analgesia.
91
Full antagonists block any agonists from acting, you will see reversal of effect. Will it reduce analgesia?
yes
92
Naloxone
Competitive mu antagonist that will also cause antagonism at the kappa and delta receptors typically used to reverse opioid induced respiratory and or cardiovascular depression in patients who have received a full mu agonist.
93
Naltrexone/Diprenorphine reverse what drug specifically?
carfentanil and etorphine. Naltrexone has longer duration of action than naloxone
94
Methylnaltrexone
Used in humans. Does not cross BBB can be used to counter some of the peripheral issues associated with opioid use.
95
Hydrocodone
Semisynthetic opioid used orally in dogs as an antitussive. Only labeled for humans, and often formulated with homatropine or acetaminophen to reduce human abuse potential.DEA schedule II drug.
96
Apomorphine
Most effective emetic in canines through stimulation of dopamine D2 like receotpros in the CRTZ.
97
Loperamine Imodium
antidiarrheals
98
tramadol
weak mu agonist, used orally for analgesia in small animals, may lower seizure threshold and should be avoided in epileptic patients. Caution with patients who are on MAO or other SSRI. DEA schedule IV drug
99
Dantrolene is a direct acting drug that targets the muscle. What is the receptor and what is the MOA?
Ryanodine receptor antagonist. It communicates the arriving action potential on the post synaptic muscle membrane to the smooth ER to release calcium and facilitate muscle contraction.
