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VET 302 > Sedatives > Flashcards

Sedatives Flashcards

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1
Q

How do benzodiazepines cause CNS depression?

A

-GABA agonists
Utilize the GABA-controlled chloride channel to cause CNS depression.

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2
Q

GABA

A

Gamma amino butyric acid. Is the main inhibitory transmitter of the brain.
-Its main role is to reduce neuron excitability and promote a calming effect
-Activation of gaba receptors; have chloride channels on the outside- under normal conditions there is not alot of chloride.
-Open these channels and allow for chloride uptake in the neuron makes it even more negative
-therefore the neuron is “inhibited” because it is more difficult to activate due to its negative state
-associate these effects with CNS depression and sedation

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3
Q

What are the effects of benzodiazepines?

A

-Tranquillisation
-Disinhibition
-Centrally mediated skeletal muscle relaxation
-Anticonvulsant
-Antianxiety
Anterograde amnesia: difficulty to form memories

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4
Q

Analgesia

A

The term used for any level of pain relief

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5
Q

Hyperalgesia

A

To cause pain

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6
Q

Hypoalgesia

A

Decreasing amount of pain

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7
Q

What two benzodiazepines are of veterinary importance?

A

Diazepam
Midazolam

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8
Q

Diazepam “Pamlin” uses

A

-treatment of seizures
-combined with other drugs; higher dose of diazepam with ketamine to use as an anaesthetic
-sometimes used to relax the striated muscle component of the urethral sphincter

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9
Q

Diazepam methods of administration

A

-usually given IV
-good rectal absorption (good for dogs with anxiety)
-propylene glycol vehicle is not very water soluble–> can NOT spike into drip bags for IV CRI anticonvulsant therapy

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10
Q

Midazolam (Hyponovel)

A

-Water soluble, can be put in a IV drip bag
-Similar effects to diazepam
-more expensive $$$

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11
Q

Why is the timing of administration of the reversal agent of benzodiazepines critical?

A

-The reversal agent has a shorter DOA
-if the antagonist is given shortly after the agonist, the animal may relapse into sedation

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12
Q

What is the benzodiazepine antagonist?

A

Flumazenil
-almost never needed because of BZD safety
-$$$$

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13
Q

Potential side effects of BZD’s in cats?

A

-potential hepatic disease if chronic therapy is given

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14
Q

What are the two categories of neuroleptic drugs?

A

-Phenothiazines
-Butyrophenones

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15
Q

What are the two common neuroleptic drugs used in veterinary medicine

A

Phenothiazine: acepromazine

Butyrophenones: azaperone

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16
Q

How do neuroleptics work?

A

Dopamine antagonists

-can be antagonists at other receptors such as alpha-1 adrenergic receptors

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17
Q

What occurs when you antagonize dopamine receptors?

A

-sedation

-dopamine is used for brain reward pathways, motivation, and purposeful movements

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18
Q

Paraphimosis

A

-unable to retract penis into prepuce
-paralysis of penis retractor muscle

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19
Q

Priaprism

A

persistent erection

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20
Q

Why is acepromazine not recommended for geldings and stallions?

A

can cause
1) Paraphismosis
2) Priapism

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21
Q

Phenothiazines effects

A

-all mediated by dopamine
1)Sedation:
-sedative effect does not affect coordinated motor responses, so patients are easily aroused

2) Antiemetic
-prevents vomiting by blockade of domaine mediated chemoreceptor trigger zone

3) Analgesia- almost none

4)Hypotension:
remember it is a alpha-1 antagonist

5) Lowered hematocrit

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22
Q

Why does hypotension occur with phenothiazine (acepromazine)?

A

-alpha-1 antagonist
-peripheral vasodilation

*Note: have to be so careful with breeds that have high vagal tone; will get a much bigger drop in blood pressure

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23
Q
A
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24
Q

Why should you avoid taking blood from an anaesthetized patient that has acepromazine premed?

A

-lowers hematocrit
-splenic engorgement, spleen has blood with higher cellular fraction

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25
What are the clinically important effects of phenothiazines?
-produce sedation -Vasodilation -No analgesia -Paraphimosis/priaprism in male horses
26
What is the main use of acepromazine?
-as a pre-med
27
What do you have to watch for when dosing acepromazine?
-do not use the dog/cat doses written on the bottle because they are too high and do not provide a ceiling -careful in dogs with mutation of ABCB1 gene--> produces defective protein and issues with soluble vitamins in the brain. Makes them far more susceptible to toxicity and sedation can be exaggerated -white footed herding breeds
28
Azaperone "stresnil" indications
-a butyrophenone that is an effective tranquilizer in pigs -good for sows that attack piglets during farrowing
29
What is the major difference between butyrophenones and phenothiazines?
-less vasodilation due to less inadvertent a1-antagonism (butyrophenones)
30
Alpha-2 agonists, how do they work as sedatives?
decrease the central concentrations of noradrenaline -alpha-2 agonist binds to the alpha-2 receptor and induce the auto-regulatory inhibitory feedback mechanism to decrease the release of Nadr
31
What are the main effects of Nadr on the central nervous system?
-alertness -arousal -pain perception So, a-2 agonist will cause sedation and analgesia
32
CNS effects of A-2 agonists
-profound sedation, dose dependant -some A1 agonism which centrally can lead to arousal; should beware of back legs of cows and horses -level of sedation does not translate to its inability to kick out
33
What occurs when A2 agonists are given as an IV bolus vs. IM bolus?
-When given as an IV bolus they have a biphasic response: net result initial vasoconstriction, hypertension, and bradycardia -central α2 agonism decreases NAd and HR & ↓contractility (= ↓CO) & vasodilation (hypotension) -peripheral α2 agonism, overriding vasoconstriction reflex ↓HR Therefore, there will be a diminished peripheral effect but a persistent central effect meaning vasodilation and decreased HR prevail When given as a IM bolus -the biphasic response is not always seen -peripheral a2 effects are strongest when given as IV bolus, compared to IM because a2 mediated vasconstriction is occurring locally in the blood vessel wall
34
Why are A2 agonists rarely used for analgesic effects?
-due to significant sedation and decreased CVS -can be given epidurally to decrease sedation and CVS side effects
35
What are some off-target effects of A2 agonists
-central respiratory depression, can see cyanosis -GIT motility is decreased -reproductive: myometrial contractions abortion is possible in last trimester-- beware; xylazine can cause abortion in cattle
36
What animals display xylazine sensitivity
-Ruminants especially goats and brahmans, very sensitive to xylazine -About 10-fold more so than horses, dogs, cats etc. on a mg/kg basis
37
Medetomidine “domitor”
- common sedative used in small animal practice -given IV -profound sedation
38
What are the indications of medetomidine
-well suited to after hours stitch ups, x-rays, chemical restraint -when combined with other drugs (opioid) to decrease the dose of medetomidine needed
39
Atipamezole "antisedan"
highly effective and rapid antidote for (alpha-2 antagonists) -will wake the dog up when owner is waiting -do not give IV -shorter DOA than medetomidine, so if antidote given shortly after agonist, can relapse into sedation
40
Dexmedetomidine
medetomidine- racemic, it exists in two forms oDextromedetomidine, the better form that causes sedation and less cardiovascular effects
41
What can orotransmucosal dexmedetomidine be used for?
-behavioural modification -primarily used for reducing fear and anxiety
42
Xylazine indications
- common sedative in both equine and production animal practice Well suited to many procedures -After hours “stitch ups” -Small surgical procedures “eye enucleation” -X-rays -Chemical restraint (ocular examination) -Caesarean -Tubing a horse etc. Can be combined with other drugs ex. benzo and ket for equine intravenous general anaesthetic
43
Detomidine
-mainly used in horses -longer DOA than xylazine -high potency, efficacy, and concentration preparation -dormosedan gel (oromucosal preparation)
44
Romifidine
sedative used in horses -less ataxia and longer lasting than xylazine and detomidine
45
Yohimbine & 4-Aminopyridine
reversal agent The large animal a2 antagonists oDuration of action is shorter than the agonist- repeat doses may be needed
46
Yohimbine “Reverzine”
Used for xylazine reversal; less effective than atipamezole is for medetomidine - not usually used
47
4- Aminopyridine
+yohimbine= reverzine S.A Has CNS excitatory effects S.A. = small animal as 4-AP can be toxic to deer.
48
Guaifenesin indications
-used mainly in horses as "triple dip" for horses that won't stay down -can be used as a cough suppressant
49
Guaifenesin mechanism of action
-selectively blocks certain transmission at the spinal cord, brainstem, and subcortical areas -results in mild sedation and more moderate muscle relaxation
50
Methocarbamol “Robaxin” indications
muscle relaxant -can be used for small animal toxicity in cats -snail pellet toxicity
51
Discuss the applicability of flumazenil as an antidote for all GABA agonists.
Flumazenil is a benzodiazepine (BZ) antagonist and is therefore only suitable for reversing the effects of BZs. Other GABA agonists (e.g. barbiturates, propofol) bind to different areas on the chloride channel and so their actions are not significantly reversed by flumazenil.
52
What is the mechanism of action of opioids
The mechanism of action of opioids acts on the u,k, or Delta opioid receptors. Interferes with ascending and descending pain pathways. -interfere with pre-synaptic calcium channels and post-synaptic calcium channels -Reduced transmission of pain signals -Diminished pain perception -Slowed GI motility, respiratory depression, sedation
53
What are the main opioids to know?
-morphine -methadone -fentanyl -butorphanol -buprenorphine -Codeine -Pethidine -tramadol
54
List the effects / side-effects of opioids
-Analgesia -Drowsiness/Sedation Side effects: -hypothermia -respiratory depression -CVS effects -suppression of cough reflex (antitussive)
55
What is the antagonist for opioids
Naloxone
56
Discuss the relationship between CNS and GIT actions of the opioids
CNS: Pain relief (analgesia), sedation, euphoria (or dysphoria), respiratory depression GIT: Decreased motility → constipation (a classic opioid side effect)
57
Define the main classes of opioid drugs
u kappa delta
58
Discuss the relative amounts of pain relief provided by the opioids
Can provide (mild) to extreme analgesia--> fentanyl being the highest and coedine being the lowest Opioids are the strongest analgesic
59
Clinical indications of opioids
-providing analgesia for the procedure -reducing anaesthetic dose required to induce and maintain anaesthesia -provide less CVS depression than the alpha-2s and neuroleptic tranquilizers
60
U-receptor agonists- opioids
-Fentanyl -Methadone -Morphine -strongest pain killers Weak: opioids--> codeine, pethidine
61
Opioid mixed agonists
Butorphanol: very good sedative, weak analgesic -k agonist, weak u-antagonist Buprenorphine:long DOA up to 10hrs -partial u-agonist, weak k-antagonist

VET 302 (12 decks)

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