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Introduction to Pharmacology > Injectable and Dissociative Anesthetics > Flashcards

Injectable and Dissociative Anesthetics Flashcards

1
Q

What 4 things do animals experience under general anesthesia? What agents are most commonly used?

A
  1. unconsciousness
  2. hyporeflexia
  3. analgesia
  4. skeletal muscle relaxation

IV and inhaled agents that allow adequate surgical access to the operative site

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2
Q

What 4 classifications are anesthesias typically divided into?

A
  1. barbiturates (injectable)
  2. non-barbiturates (injectable)
  3. cyclohexylamines (dissociative)
  4. inhalants
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3
Q

What is the difference between anesthetic agonists and antagonists?

A

AGONIST: binds to and stimulates CNS (most anesthetics and adjuncts)

ANTAGONISTS: bind to and don’t stimulate CNS (reversal agents)

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4
Q

Why do we typically combine anesthetics?

A

no single agent provides all desirable properties both rapidly and safely
- maximizes benefits of each drug
- minimizes adverse effects (lower dose and concentration)
- allows anesthetist to produce CNS depression, immobilization, and pain relief appropriate for the patient and procedure

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5
Q

What are 2 major cautions that should be noted with combining anesthetics?

A
  1. don’t mix drugs in a single syringe unless they are compatible
  2. don’t administer a drug combination if a precipitate develops when the drugs are mixed
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6
Q

What is unique about the mechanism of action of injectable anesthetics?

A

exact mechanism is not known and no specific receptor has been identified

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7
Q

What argues against the existence of a single receptor for anesthetics?

A

chemically unrelated compounds are all able to produce anesthesia

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8
Q

What don’t anesthetics provide? How are they administered?

A

analgesia or muscle relaxation (pre-anesthetics!)

IV to effect based on patient (titration)

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9
Q

What are examples of barbiturates, non-barbiturates, and dissociative agents used as anesthetics?

A

BARBITURATES: Thiopental*, Methohexital, Pentobarbital, Phenobarbital

NON-BARBITURATES: Propofol, Etomidate, Alphaxalone

DISSOCIATIVE: Ketamine, Tiletamine

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10
Q

What are Barbiturates?

A

a group of sedative-hypnotic medications used for the treatment of seizures, preoperative anxiety, and inducing anesthesia (weak analgesic)
- controlled
- no reversal agent

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11
Q

What are the 3 classifications of Barbiturates based on duration of action? What are examples of each?

A
  1. ULTRA-SHORT: Thiopental, Methohexital - dogs cats, horses to induce general anesthesia
  2. SHORT: Pentobarbital - lab animals to induce general anesthesia and treat epilepsy
  3. LONG: Phenobarbital - anticonvulsant and sedative
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12
Q

What are the 2 classifications of Barbiturates based on chemical structure? How does the difference in structure affect each group?

A
  1. OXYBARBITURATES: Methohexital, Pentobarbital, Phenobarbital
  2. THIOBARBITURATES: Thiopental, Thiamylal
  • thiobarbiturates are more lipid soluble
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13
Q

How does lipid solubility of Barbiturates affect their pharmacokinetics?

A

high lipid solubility = quickly enter the CNS and depress its function with quick redistribution into other tissues (skeletal muscle and adipose tissue)

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14
Q

What affect do Barbiturates typically have on the respiratory system?

A
  • apnea
  • coughing
  • chest wall spasm
  • laryngospasm
  • bronchospasm
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15
Q

What is the mechanism of action of Barbiturates?

A

not fully understood - bind to GABA-gated Cl- channels resulting in hyperpolarization of neurons
- mimics inhibitory effects of GABA to cause CNS depression and loss of consciousness

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16
Q

When will the effects of Barbiturates terminate?

A

agents leave brain or are metabolized, excreted, or redistributed

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17
Q

Barbiturates are used for rapid anesthetic induction. What are 2 things do they allow for? How is thiopental and methohexital sustained during the procedure?

A
  1. intubation - thiopental and methohexital
  2. used alone for short procedures
  • THIOPENTAL: with inhalation anesthetic
  • METHOHEXITAL: with repeated doses or continuous infusion
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18
Q

What 4 properties affect the potency, onset, and duration of action of Barbiturates?

A
  1. IONIZATION - non-ionized form makes for easier absorption
  2. PROTEIN BINDING - only unbound drug free of plasma proteins are able to have an effect
  3. LIPID SOLUBILITY - tendency of the drug to dissolve in fats, lipids, and oils
  4. REDISTRIBUTION - ability of blood to carry drug to brain and other tissues
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19
Q

How do ultra-short-acting barbiturates compare to short-acting and long-acting ones with respect to lipid solubility?

A

ULTRA-SHORT = high solubility (rapid tissue distribution)

SHORT = moderately soluble

LONG = low solubility

20
Q

Where are barbiturates most quickly distributed to? When will their effects begin/end?

A

vessel-rich tissues

  • begin = when drug reaches target tissue (brain)
  • end = drug leaves tissue when blood level drops, carrying drug to other tissues where it can be released and eliminated (animal recovers)
21
Q

What are the 5 steps to barbiturate redistribution?

A
  1. ultra-short-acting drug is given IV and travels to the brain, where it is able to cross the BBB quickly due to its high lipid solubility
  2. animal loses consciousness
  3. once the levels in the brain are higher than in the blood, the molecules will move back down the concentration gradient and re-enter circulation
  4. molecules redistribute to muscle, fat, and other body tissues, allowing the patient to recover
    5 drug is released from muscle and fat and eliminated from the body by liver metabolism and excretion in urine
22
Q

What are the 2 major pharmacological effects of barbiturates in the CNS?

A
  1. mild sedation to unconsciousness
  2. possible excitement at low doses (prolonged Stage 2 of anesthesia)
23
Q

What are the 3 major pharmacological effects of barbiturates in the cardiovascular system?

A
  1. cardiac depression
  2. increased cardiac sensitivity to epinephrine
  3. THIOPENTAL - cardiac arrhthymias
24
Q

What are the 3 major pharmacological effects of barbiturates in the respiratory system?

A
  1. decreased respiratory rate and tidal volume
  2. THIOPENTAL - brief apnea
  3. PENTOBARBITAL - shallow breaths
    - respiratory acidosis and poor tissue oxygenation
25
Q

What are 3 other pharmacological effects of barbiturates on other body systems?

A
  1. initial decreased motility in the GI tract followed by later increased motility
  2. sneezing, coughing, laryngospasm
  3. incomplete muscle relaxation
26
Q

What are common adverse effects of barbiturates in the cardiovascular and respiratory systems?

A

CV: cardiac arrhythmias (Thiopental), skipping a beat (bigeminy)

RESP: initial apnea, neonate respiratory depression in C-sections (dose- and administration-dependent)

27
Q

In what animals should barbiturates be used cautiously?

A
  • SIGHTHOUNDS (not enough muscle/fat for redistribution)
  • critically ill
  • hypoproteinemic
  • acidotic
28
Q

How can route of administration of barbiturates cause adverse effects?

A
  • not IV = tissue irritation and sloughs
  • intra-arterial = vasoconstriction, pain, tissue necrosis
29
Q

In what 3 situations can excitement during induction of barbiturate anesthesia happen? How can it be overcome?

A
  1. perivascular injection
  2. very slow rate of administration
  3. stage II excitement as a result of insufficient concentrations in the brain to induce stage III

administer more drugs

30
Q

What barbiturate can commonly cause excitement as the patient is recovering? What are common signs? How can this be overcome?

A

Pentobarbital

paddling and vocalization

administer IV Diazepam or pre-anesthetics

31
Q

What are 3 common barbiturate-drug interactions?

A
  1. enhances muscle relaxants
  2. increases hepatic enzyme activity, causing shorter duration of activity of drugs metabolized in the liver (opioids, diazepam)
  3. administration with chloramphenicol enhances the effect of pentobarbital and phenobarbital
32
Q

In what animals is Thiopental typically used? How should the dosage be adjusted in debilitated and heavily sedated animals?

A

small animals and horses

give to effect - dose reduction

33
Q

Methohexital is very similar to Thiopental. What makes it different?

A

higher in lipid solubility, making it useful in unfasted animals and greyhounds/other sighthounds

34
Q

In what animals is Pentobarbital most commonly used in? Why has usage decreased?

A

lab animals to treat status epilepticus (IV) and preform euthanasia

  • narrow margin of safety
  • replaced by propofol
35
Q

What is the most commonly used anesthetic in vet med? How quickly is it able to act? In what cases is it best?

A

Propofol (non-barbiturate)

ultra-short acting (highly lipophilic)

outpatient cases —> onset is smooth and rapid
- small animals, small ruminants, exotic animals, neonates of all species

36
Q

What is the mechanism of action of Propofol? What are some major benefits to its use over barbiturates?

A

activates GABAa receptors (similar to barbiturates)

  • onset = 30-60 secs
  • complete and quicker recovery
  • safe to use in animals with head trauma or increased intracranial pressure
37
Q

Why should Propofol be used cautiously in cats?

A

cats may not tolerate prolonged infusion well

38
Q

Why does Propofol have poor storage characteristics?

A

available in an egg lectin, glycerin, soybean oil aqueous solution which can support bacterial growth, making aseptic technique necessary
- discard unused drug within 6 hr of opening
- 3 year shelf life if unopened
- more expensive than ketamine, diazepam, and thiopental

39
Q

What are the pharmacological effects of Propofol on the CNS, cardiovascular system, and respiratory system?

A

CNS: dose-dependent depression, poor to no analgesia, euphoric feelings

CV: cardiac depressant, transient hypotension

RESP: depressant with possible apnea

40
Q

What are 6 other pharmacological effects of Propofol?

A
  1. twitching during induction (dogs)
  2. muscle relaxation
  3. safe in animals with liver or kidney disease
  4. appetite stimulant as low doses
  5. antiemetic
  6. decreases intraocular and intracranial pressure
41
Q

What are possible adverse effects of Propofol in the CNS, cardiovascular system, and respiratory system?

A

CNS: transient excitement and muscle tremors on induction, paddling, muscle twitching, nystagmus, opisthotonus (resembling seizures)

CV: hypotension

RESP: apnea with rapid injection of high doses

42
Q

What are 2 other possible adverse effects of Propofol? Specifically in cats?

A
  1. seizure-like signs (treat with diazepam)
  2. pain with injection (no perivascular injection tissue damage)

with multiple doses: anemia, diarrhea, anorexia, blindness, aggression, prolonged recovery, death

43
Q

What is Etomidate? When is it commonly used?

A

sedative, hypnotic non-barbiturate of ultra-short duration with a high margin of safety

as an alternative to thiopental and propofol, specifically in animals with preexisting cardia dysfunction, head trauma, or critical illness

44
Q

What is the mechanism of action of Etomidate? What are 2 possible adverse effects?

A

binds to GABA receptor and allosterically enhances the affinity of GABA to its receptor

  1. pain and hemolysis on IV injection
  2. may inhibit myocardial contractility
45
Q

What pharmacological effects does Etomidate have on the CNS, cardiovascular system, and respiratory system? What effect does it have on hormones?

A

CNS: decreases cerebral blood flow, metabolic rate, and oxygen consumption

CV and RESP: minimal depression

  • inhibits adrenal steroidogenesis reducing the normal increase in plasma cortisol levels during anesthesia and surgery
46
Q

What is Alphaxalone? What is it mechanism of action?

A

synthetic neuroactive steroid wih rapid, short-acting general anesthetic effects

GABAa receptor agonist

47
Q

What are 3 common situations when Alphaxalone is used? What are 3 possible adverse effects?

A
  1. short procedures
  2. induction of anesthesia and transition to an inhalant
  3. used as a constituent of anesthetic drug mixtures
    - dogs and cats

~ respiratory depression when given with other sedatives and anesthetics
~ apnea
~ animals tend to become irritated during recovery

Introduction to Pharmacology (39 decks)

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