Lecture 4 Injectable Anesthetics Anesthesiology

Front 1

Why are 5 clinical uses of injectable anesthetics?

Back 1

1) To induce a short period of chemical restraint
2) Maintenance of anesthesia
-Repeated bolus
-CRI
3) Induce anesthesia prior to inhalant anesthesia
-Typically faster, smoother, more controlled than inhalant induction
4) Component of "total intravenous anesthesia" TIVA protocol
-Combined w/ analgesics & muscle relaxants
5) Part of an inhalant anesthetic protocol
-Reduce inhalant anesthetic requirements

Front 2

What are the 7 injectable anesthetics available?

Back 2

1) Thiopental
2) Propofol
3) Dissociatives
-Ketamine
-Tiletamine (w/ zolazepam in telazol)
4) Etomidate
5) Alphaxalone
6) Neuroleptanalgesic combinations
7) Guaifenisen combinations

Front 3

What are the 4 routes of administration of injectable anesthetics? Most common?

Back 3

1) Oral (longer onset & duration)
2) SQ
3) IM*
4) IV*

Front 4

What is the definition of tranquilization?

Back 4

Calming, quieting, decrease anxiety, relaxed state
-Calms patient but can be aroused

Front 5

What is the definition of sedation?

Back 5

CNS depression, unaware of surroundings

Front 6

What are the effects of general anesthesia on the patient?

Back 6

Unconsciousness, analgesia, muscle relaxation
-Sensory, motor and autonomic reflexes depressed

Front 7

What are the 4 pros of injectable anesthetics?

Back 7

1) Simplicity
2) Availability of equipment
3) Cost
-Drugs
-Equipment
4) Rapid, controlled onset of effect

Front 8

What are the 4 cons of injectable anesthetics?

Back 8

1) Recovery dependent on metabolism &/ or redistribution of drug
2) Recovery may be
-Unpredictable
-Prolonged
-Rough
3) Recovery problems often worse as procedure duration lengthens
4) Depth may be difficult to control

Front 9

What are 4 problems associated with injectable anesthetics?

Back 9

1) Generally require IV access
-Not a disadvantage- generally advisable regardless of type of anesthesia
2) Some may cause pain on injection
3) Some understanding of PK/ PD modeling helpful
-What factors affect onset time, efficacy and recovery
4) Some require drug metabolism for recovery if multiple doses or CRIs are used
-Newer drugs tend towards shorter duration, more rapid recovery
-Inhalants only depend on ventilation for recovery

Front 10

What are 2 factors that affect the drug levels of injectable anesthetics in the brain?

Back 10

1) Rapid equilibration
2) Brain is highly perfused

Front 11

When does the anesthetic state occur from injectable anesthetics?

Back 11

When the blood level is sufficiently high
-one "circulation time" = 30-60 s =transit time from injection site through vasculature to effect site (brain)

Front 12

What are 4 factors influencing the drug effect of injectable anesthetics?

Back 12

1) Central compartment volume
2) Speed of injection
3) Cardiac output
4) Lean body mass vs fat body mass
-Lean body mass of fat dogs is often overestimated so overdose

Front 13

Is a drug with a higher or lower therapeutic index safer?

Back 13

The larger the number the safer the drug
"titrate to effect"

Front 14

Is ketamine or morphine safer? why?

Back 14

Morphine, higher therapeutic index

Front 15

What are 6 induction agents that we have available?

Back 15

1) Thiopental
2) Propofol
3) Etomidate
4) Ketamine
+ diazepam (Ketval)
+midazolam
+propofol
5) Telazol
-Tiletamine + zolazepam
6) Inhalants
-Mask
-Tank

Front 16

What are 5 things to consider when trying to decide on what induction agent to use?

Back 16

1) speed
-Fast?
-Slow?
2) Route available
-IM?
-IV?
-Inhalant
3) Duration of effect
-Minutes? hours?
4) Analgesia?
5) Cost?

Front 17

What are 2 dissociative anesthetics?

Back 17

1) Ketamine
2) Tiletamine
-With zolazepam in telazol

Front 18

What are the only currently available induction drugs that can be administered either IM or IV?

Back 18

Dissociative agents:
Ketamine & tiletamine
--Oral/ mucosal administration also possible

Front 19

Dissociative anesthetics are very important in what practices?

Back 19

Wildlife & exotic animal practice

Front 20

What are the effects of dissociative anesthetics?

Back 20

-"Dissociation
-Catalepsy
-Increased EEG activity (seizure like activity)
-Breaks connection of lower brain stem from rest of brain

Front 21

What is a big downfall of telazol?

Back 21

Comes as a power have to mix it up and then once you do it has a limited shelf life

Front 22

What is the mechanism of action of dissociative agents?

Back 22

Exact mechanism unclear
-Interact w/ multiple receptors w/in CNS:
N-methyl-D-aspartate (NMDA) receptors (antagonize)
GABAalpha receptors
Opioid receptors
Monoaminergic receptors
Muscarinic receptors
-Analgesia & anesthetic effects may be mediated by different mechanisms

Front 23

What are NMDA receptors? What are the effects of NMDA antagonists?

Back 23

Pain pathway
Get animal wound up
NMDA antagonist--> analgesia

Front 24

What are 2 neurotransmitters that act on monoaminergic receptors?

Back 24

Norepinephrine
Dopamine

Front 25

What is the recovery from dissociative anesthetics like?

Back 25

Relatively rough, other drugs usually co-administered to improve quality

Front 26

Are the effects of dissociatives cumulative?

Back 26

Yes, cumulative effects occur w/ multiple doses or prolonged administration
-Telazol> ketamine
"GKX"

Front 27

What are the cardiovascular effects of dissociative anesthetics?

Back 27

Increased HR, CO, BP

Front 28

Why do dissociative anesthetics cause increased HR, CO & BP?

Back 28

-Indirect effect mediated thorugh increased sympathetic ouflow from CNS
-Direct myocardial depressant effects occasionally seen in highly stressed, debilitated patients

Front 29

What are the 2 respiratory effects of dissociative anesthetics (tiletamine, ketamine)?

Back 29

1) Mild respiratory depression
-apneustic ventilatory pattern occasionally seen
2) Tendency to retain protective airway reflexes
-Cough reflex
-Swallow reflex

Front 30

What are the 5 CNS effects of dissociative anesthetics?

Back 30

1) EEG activity resembles seizure activity
2) Increased intracranial pressure & cerebral metabolic rate
3) Increased intraocular pressure
-Increased tone of extraocular mm.
4) Muscular hypertonus, movement
5) Seizure-like activity
dogs> cats
Tigers & telazol

Front 31

What are 4 ways that the anesthetic state of dissociatives appears "different"?

Back 31

1) swallowing
2) Blinking
3) Lacrimation, salivation
4) Poor muscle relaxation
-DOESN'T mean crank up vaporizer otherwise dog goes too deep

Front 32

Dissociatives are almost always used in conjunction with other drugs, what are 4 of these other drugs?

Back 32

1) Benzodiazepines
2) Alpha2 adrenergic agonists
3) Acepromazine
4) Guaifenisen

Front 33

Why should you be really carefully giving dissociatives IM?

Back 33

They hurt on IM injection

Front 34

How are dissociatives metabolized/ excreted?

Back 34

Hepatic metabolism in most species
-Renal excretion of large % of administered dose unchanged in cats

Front 35

Renal excretion of dissociatives consist of a large % of administered dose unchanged in ________.

Back 35

Cats
-Renal disease/ obstruction could result in prolonged duration of effect

Front 36

What is the most common induction drug used in large animal medicine?

Back 36

Dissociatives
-Usually combined w/ diazepam, guaifenesin or propofol

Front 37

What is "GKX"?

Back 37

Guaifenesin/ ketamine/ xylazine

Front 38

What are 3 ultrashort acting barbiturates that are used as injectable anesthetics?

Back 38

1) *thiopental
2) Thiamylal
3) Methohexital

Front 39

What is a short acting barbiturate used as an injectable anesthetic?

Back 39

Pentobarbital
-short acting (hours)

Front 40

What is a long acting barbiturate?

Back 40

Phenobarbital

Front 41

What is phenobarbital used for? How is it administered

Back 41

Suppresses seizure activity
-Oral

Front 42

How long does it take for a full recovery from thiopental?

Back 42

Initial effect last 10-15 minutes but full recovery can take hours- "hangover"

Front 43

What causes the initial awakening from thiopental after 10-15 minutes seeing as the effects can last hours? What does complete recovery depend on?

Back 43

Initial awakening is due to redistribution
Complete recovery depends on metabolism
-With repeated administration, saturation of redistribution sites occur and then recovery depends on metabolism

Front 44

What is the mechanism of action of thiopental?

Back 44

Activation of GABA receptor

Front 45

What is the mechanism of action of thiopental at low doses? What's the effect?

Back 45

Indirect; decrease rate of dissociation of GABA from the receptor
effect: sedative/ hypnotic

Front 46

What is the mechanism of action of thiopental at higher doses? Effect?

Back 46

Direct; activate the Cl- channel
Anesthetic effect

Front 47

What are 2 other sites that thiopental acts on other than GABA receptors?

Back 47

Glutamate
Acetylcholine

Front 48

What are the 3 cardiovascular effects of thiopental?

Back 48

1) Moderate hypotension
2) Arrhythmogenic
3) Splenic engorgement

Front 49

What are 4 things that contribute to the moderate hypotension experienced by animals given thiopental?

Back 49

1) Negative inotrope
2) Decrease sympathetic tone
3) Decrease CO
4) Dose dependent, additive w/ other sedatives/ anesthetics

Front 50

What are 2 types of arrhythmias that can result from thiopental use?

Back 50

1) Potentiate epinephrine induced arrhythmias
2) Bigeminy (classic arrhythmia)
-Normal beat followed by PVC, occuring in couplets

Front 51

What are 2 situations where you should be careful in using thiopental bc it causes splenic engorgement?

Back 51

Nephrosplenic entrapment
Splenic hemangiosarcoma
-Could rupture

Front 52

What are the respiratory effects of thiopental?

Back 52

Respiratory depression, apnea common- dose dependent

Front 53

What are 2 CNS effects of thiopental?

Back 53

1) Anticonvulsants (as are most barbiturates)
2) Decrease cerebral metabolic rate

Front 54

Does thiopental have an analgesic effect?

Back 54

No

Front 55

Why is thiopental not good to use in sighthounds?

Back 55

Recovery may be very prolonged
-Redistribution?
-Genetic metabolic defect?

Front 56

Why is thiopental very irritating to tissues if injected perivascularly? What is the result of perivascular injection?

Back 56

Solution is very basic (high pH)
Perivascular injection may result in sloughing of tissues

Front 57

What should you do if you inject thiopental perivascularly?

Back 57

The solution to pollution is dilution- infiltrate area w/ saline (or other balanced electrolyte solution)
-At least 5x injected volume
-Problems only occur if ignored

Front 58

How can you prevent perivascular injection of thiopental?

Back 58

Use properly placed IV catheter

Front 59

What is propofol solubilized in?

Back 59

Lipid emulsion
-White liquid

Front 60

Why does propofol have a short (6 hr) shelf life?

Back 60

Supports bacterial growth

Front 61

Why is propoflo 28 more convenient than propofol?

Back 61

28 day shelf life (VS 6hr) bc benzyl alcohol is used for preservative

Front 62

Why can't propoflo28 be used in cats?

Back 62

Benzyl alcohol is toxic to cats
-Benzyl alcohol= preservative

Front 63

What is the mechanism of action of propoflo?

Back 63

Acts on the GABA receptor
-Potentiates GABA activity
-Decreases cerebral metabolic rate

Front 64

Does propofol is thiopental have a quicker onset?

Back 64

Thiopental

Front 65

When an animal awakens from propofol, is the drug still present like with thiopental?

Back 65

No, rapid complete recovery
-Rapidly redistributed
-Rapidly metabolized
-Minimal if any "hangover"

Front 66

How is propofol eliminated?

Back 66

Rapidly metabolized
-Hepatic
-Extra-hepatic, lungs?

Front 67

Are the effects of propofol cumulative?

Back 67

No, so it is suitable for CRI

Front 68

What are the 3 cardiovascular effects of propofol?

Back 68

1) Dose dependent hypotension
-Vasodilation
2) Negative inotropic effect
-Greater than thiopental
3) Not arrhythmogenic

Front 69

What are the 2 respiratory effects of propofol?

Back 69

1) Apnea common
-Rate of administration related
2) Dose dependent respiratory depression

Front 70

What should you always have ready when anesthetizing an animal with propofol?

Back 70

Be ready to support ventilation bc apnea is common

Front 71

What are the 4 CNS effects of propofol
?

Back 71

1) Decreases intracranial pressure & cerebral metabolic rate
2) Decreases intraocular pressure
3) Anticonvulsant
4) Excitement of induction
-Rare
-Paddling, twitching, nystagmus, opisthotonus
-Decrease w/ premed

Front 72

Does propofol provide analgesia?

Back 72

NO

Front 73

What is an "interesting phenomenom" seen with propofol use?

Back 73

Foreleg muscle rigidity- don't really know why it happens
-Minor problem

Front 74

What happens if you inject propofol perivascularly?

Back 74

Nothing, not irritating

Front 75

There has been conflicting literature relating what b/w RBCs and propofol?

Back 75

Heinz body anemia due to use over several days

Front 76

Is propofol a controlled drug?

Back 76

No, not currently

Front 77

Is etomidate used very commonly in anesthesia?

Back 77

No

Front 78

Why is etomidate non-cumulative?

Back 78

Rapidly metabolized and eliminated

Front 79

What are the cardiovascular effects of etomidate? respiratory effects?

Back 79

Minimal if any cardiovascular or respiratory depression

Front 80

When is etomidate the drug of choice for anesthesia?

Back 80

patients with a significant cardiovascular disorder
-Consider for patient w/ significant respiratory disease

Front 81

What are 6 reasons that we don't use etomidate ALL the time?

Back 81

1) Myoclonus
2) Regurgitation/ vomition at induction
3) Relatively rough induction/ recovery (if used alone)
-Almost always use premeds +/- a benzodiazepines at induction
4) Adrenocortical suppression
5) Hemolysis
-Highly osmolar solution
-May see hemoglobinuria
6) Expensive!

Front 82

Why don't we use alfaxan? What is aflaxan?

Back 82

Not available in the use
-Neuroactive steroid
-Modest cardiovascular effets
-Smooth induction, recovery
-Effective IM
-HR & BP similar to propofol

Front 83

When are inhalants a good idea for induction?

Back 83

Very young/very small patients
Birds, exotics, neonatal foals

Front 84

What are the 2 techniques for using inhalants for induction?

Back 84

1) Gradually increase agent concentration
2) "Pedal to the metal"
-His choice

Front 85

What are the 2 types of muscle relaxants?

Back 85

1) Central
2) Peripheral

Front 86

What are the 2 central acting muscle relaxants?

Back 86

1) Benzodiazepines
2) Guaifenesin

Front 87

What are 2 types of peripheral muscle relaxants?

Back 87

1) Depolarizing
2) Non-depolarizing

Front 88

What is a depolarizing peripheral muscle relaxant?

Back 88

Succinylcholine

Front 89

What is the primary non-depolarizing peripheral muscle relaxant used?

Back 89

Cisatracurium

Front 90

What is the mechanism of action of Guaifenisen?

Back 90

Central acting muscle relaxant- acts at internuncial neurons in spinal cord
- Modulate tonic muscle activity

Front 91

What are the 2 clinical uses of guaifenisen?

Back 91

1) Used to facilitate induction in large animals with ketamine or thiopental
-Produces smoother, quieter, induction & recovery
2) GKX or "triple drip"
-TIVA for large animal species
-Guaifenisen + ketamine + xylazine

Front 92

What happens if you inject guaifenisen perivascularly?

Back 92

Very irritating- can produce severe tissue damage/ necrosis

Front 93

What is the normal physiology of motor end plate?

Back 93

-Action potential initiates release of vesicles of Ach
-Ach attaches to nicotinic Ach receptor on motor end plate of skeletal muscle fiber
-Sufficient receptors occupied, ion channels open, Na+, Ca++ flow through channel and muscle contracts

Front 94

What is the mechanism of action of succinylcholine?

Back 94

Depolarizing neuromuscular blocker
-Occupies the nicotinic receptor site
-Produces depolarization of motor end plate
-Persists at receptor site, preventing further depolarization

Front 95

Are succinylcholines used very often in vet med?

Back 95

No, because only paralyses patient so can't operate on bc that's inhumane!

Front 96

What is the mechanism of action of non-depolarizing neuromuscular blockers?

Back 96

Large molecules that bind to nicotinic receptors
-Interfere w/ Ach binding
-Prevents depolarization

Front 97

How do you reverse neuromuscular blockade by non-depolarizing neuromuscular blockers?

Back 97

Acetylcholine esterase drugs
-Physostigmine, neostigmine, others
-Allow Ach to persist & compete for receptor sites at both muscarinic and nicotinic sites..

Front 98

What is a clinical use of non-depolarizing neuromuscular blockers?

Back 98

Ophthalmology

Front 99

True or false. In most cases the use of multiple drugs provides balanced anesthesia that's safer and smoother than only one drug.

Back 99

True