Local anesthetics and inhalational general anes. + injectable gen. anesth. (barbiturates)

Question 1

What are local anesthetics?

Answer 1

Local anesthetics are drugs that when applied locally to nerve tissue (endings or fibers) cause reversible blockade of nerve impulse conduction.
The action is reversible.
Recovery of nerve conduction occurs spontaneously without evidence of structural damage to nerve cells or fibers.

Question 2

At effective conc. (depending upon the nerve and the area innervated), LA block transmission of:

Answer 2

• autonomic (autonomic nervous system blockade),
• somatic sensory (anesthesia), and
• somatic motor impulses (skeletal muscle paralysis).

Question 3

Describe the general chemical structure of LAs

Answer 3

The molecule consists of an unsaturated aromatic group linked by an intermediate chain to a tertiary amine end - a base (proton acceptor).

Question 4

What are the 2 distinct chemical groups of LA?

Answer 4

• Aminoesters - with an ester link between the aromatic and amine ends
  e.g., procaine, chloroprocaine, and tetracaine;
  – Aminoamides - with an amide link between the aromatic and amine ends
  e.g., lidocaine, mepivacaine, bupivacaine, and ropivacaine.

Question 5

It’s important for LAs to have a lipophylic-hydrophilic balance. Explain why lipophilic.

Answer 5

The aromatic ring and alkyl substitution to the aromatic ring or amine imparts lipophilic characteristics to the molecule.The lipophilic nature of the molecule affects the tendency of a compound to associate with membrane lipids (lipid solubility). – the more lipid soluble, the greater the potency!

Duration of action also increases with increased lipid solubility.
— dominance of aromatic ring substitution over amine substitution in determination of lipophilicity. Ex. procaine has greater amine substitution and tetracaine has greater aromatic substitution which makes it more potent + longer duration of action

Question 6

It’s important for LAs to have a lipophylic-hydrophilic balance. Explain why the hydrogen ion concentration is important.

Answer 6

LA - weak bases with pKa ~ 7.5-9 - the predominant form at phys. pH is
the ionized or cationic form
- important for activity at the receptor site,
-the uncharged base - important in the rapid penetration and diffusion
through biological membranes => so the amount present as an uncharged base strongly influences the onset of drug action and drug potency

A key function of the hydrophilic moiety is its affinity for the axoplasmic side of sodium channels in the nerve membrane. The intermediate chain serves to align the lipophilic amine group into the sodium channel.

Question 7

Describe the effect of LA+ protein binding

Answer 7

The degree to which local anesthetics bind to proteins influences their duration of action; greater binding relates to prolonged duration of action.
Amides have almost double the duration of action as esters do because of a higher % of protein binding.

Question 8

Describe the mechanism of action of LAs

Answer 8

The key target = sodium channels in the membrane of excitable cells.
• act at the voltage-gated Na channels in the nerve membrane to prevent
generation and propagation of nerve impulses or action potentials
• the LA enters the lipoprotein membrane and binds to a receptor site in the Na
channel to impede or prevent sodium ion movement.
-the drug basically inhibits channel conformational changes so the drug-bound channels fail to open—> rate of membrane depolarization slows down because there is prevention of achieving the membrane’s threshold potential —> action potential not propagates and nerve conduction is extinguished
• Local anesthetics also interact with the potassium channels but this is just additional and not important because it requires high concentrations of the drug, and blockade of conduction is not accompanied by any significant change in resting membrane potential either way.

Question 9

Describe absorption of LAs

Answer 9

The systemic absorption of LA is influenced by:
- the dosage (volume and conc.)- the higher the dose, the higher the systemic absorption and peak drug levels
- the site of injection (in a highly vascular area will be absorbed more rapidly and result in higher blood levels)
- presence of a vasoconstrictor (epinephrine tends to reduce systemic absorption by reducing local blood flow)
- physicochemical and pharmacological
properties of the drug
Many of these also influence duration of effect.

Question 10

Describe distribution of LAs

Answer 10

• Amide LA - widely distributed
• Distribution of ester LA in tissues is much more limited because have a very short plasma t 1/2 (within a few minutes due to rapid breakdown by plasma pseudocholinesterase)

Question 11

Describe elimination of ester LA

Answer 11

The esters are hydrolyzed primarily by plasma pseudocholinesterase
Cocaine is an atypical ester because it has significant hepatic metabolism and urinary excretion
— toxicity is inversely related to the rate of hydrolysis
— during pregnancy is decreased activity of pseudocholinesterase which prolongs clearance and increases potential for toxicity
– Products of hydrolysis - directly excreted by the kidney/undergo metabolic
transformation, PABA is a breakdown product (is the molecule responsible for allergies to ester LAs)

Question 12

Describe the elimination of amide LAs.

Answer 12

The amides largely undergo enzymatic degradation in the liver
– some plasma hydrolysis: prilocaine, etidocaine, and to a lesser extent lidocaine
— A common pathway is dealkylation primarily within the hepatic microsomes
-Clearance:prilocaine>etidocaine>lidocaine>mepiva/ropivacaine>
bupivacaine
Bupivacaine lasts 8 hours after administration.

Question 13

What are the clinically important properties of LAs?

Answer 13

anesthetic potency
speed of onset of action
duration of anesthetic action
differential sensitivity to anesthetic action

Question 14

What determines anesthetic potency? (LA)

Answer 14

-Lipid solubility - a primary determinant of intrinsic anesthetic potency.
The smaller and more lipophilic the molecule, the faster the rate of interaction with the sodium channel receptor.

-Potency is also highly dependent not only on intrinsic factors but also on anatomical and physiological factors

• Water solubility (hydrophilicity) is also important for diffusion to the site of
  local anesthetic action.

Question 15

Describe differential sensitivity to anesthetic action (LA)

Answer 15

Plasma cholinesterase activity is reduced with pregnancy
The spread and depth of epidural or spinal local anesthetic is also reported to
be greater in pregnant patients (ex. during a C-section)
• Reduce the dose of local anesthetics administered via this route in these patients.

Question 16

What influences the speed of onset of action? (LA)

Answer 16

The onset of LA action is related to the agent’s physicochemical properties and is also influenced by agent dose or concentration.
A larger number of molecules of the anesthetic in the region of the nerve facilitates more rapid action and prolongation of effect

Question 17

What affects the dose of the anesthetic agent? (LA)

Answer 17

Use of a greater volume of anesthetic or a more concentrated solution increases
the number of agent molecules in the region of the nerve - facilitates a more rapid anesthetic onset and increases the probability and duration of successful anesthesia.
– When injected in the epidural or intrathecal space, increased volume of local anesthetic solution will also influence the spread of the agent.

Question 18

Describe use of hyaluronidase with LA

Answer 18

• Addition of this mucolytic enzyme is thought to enhance the diffusion of local
anesthetic to the site of action (e.g., peripheral nerve).
• However, it may also enhance systemic absorption (and so toxicity) and is currently not felt to be cost-effective.

Question 19

Describe what influences duration of drug action (LA)

Answer 19

DRUG ACTION ON LOCAL BLOOD VESSELS
• All agents except cocaine tend to cause vasodilation in clinical doses - the duration of
block may be shorter.

-SITE OF INJECTION:
• Duration of action is inversely related to the absorption of the drug from the injection
site - generally independent of the agent used.
– the shortest duration of action - following intrathecal administration and
– the longest duration - following the peripheral nerve blocks (e.g., brachial plexus, sciatic) because the blood supply isn’t so dense here

-USE OF A VASOCONSTRICTOR:
• decreases local perfusion, delays the rate of vascular absorption, and therefore prolongs
anesthetic action.
– Epinephrine is most commonly added to the local anesthetic; phenylephrine and norepinephrine can be as well

Question 20

Indications and clinical uses of LA

Answer 20

LA are most often used to produce regional anesthesia.
• Regional anesthesia - a region of the body is affected as opposed to the entire body as with general anesthesia. The region affected may be very limited or broad in scope.
– topical (surface) anesthesia,
– local infiltration,
– peripheral nerve block (conduction block),
– intra-articular administration,
– intravenous block,
– epidural block, and spinal (subarachnoid) block.
• Some may also occasionally be used to provide analgesia, supplement actions of IV and inhalation anesthetics, and prevent or treat cardiac dysrhythmias.

Question 21

How lidocaine treat cardiac dysrhythmias?

Answer 21

It blocks sodium channels which blocks impulse conduction which blocks contraction of heart

Question 22

Why is lidocaine the most universal LA (is used most often)?

Answer 22

Became it is the only LA that can be administered in every way

Question 23

What are the adverse effects of LAs?

Answer 23

1. local - neural toxicity and skeletal muscle toxicity (↑ conc.)
2. systemic - due to elevated plasma concentration of LA, most specifically the
   free or unbound portion.
   – Generaly lower blood levels are
   required to cause CNS toxicity than
   to cause cardiovascular reactions
   (cardiovascular problems tend to be more life threatening and difficult to manage than CNS effects)

CNS side effects include first excitation and then depression.
Cardiovascular side effects include first hypertension and later hypotension.

Question 24

Describe the interactions of LAs

Answer 24

They vary: potentiation of CNS depressants, altered metabolism, altered protein binding, and enhancement of toxicity.
– Lidocaine’s potentiation of inhalation anesthetics is well documented with reduction of isoflurane requirements in cats, dogs and horses.
– Uremia is associated with alterations in protein binding.

Question 25

Name all the aminoester LAs

Answer 25

Cocaine hydrochloride 
Procaine hydrochloride
Chloroprocaine hydrochloride
Tetracaine hydrochloride
Benzocaine

Question 26

Describe cocaine hydrochloride

Answer 26

the 1st LA to be used clinically
no longer used in vet. practice due to its highly addictive nature (its use is
highly regulated).
Most importantly, it is the only LA that causes vasoconstriction and not vasodilation!!!!!!!!!

Question 27

Describe procaine hydrochloride

Answer 27

• still commonly used LA
• Two products of procaine degradation:
– PABA - no local anesthetic action; allergic reactions, and diethylaminoethanol a
part of anesthetic activity.
• The kidney excretes procaine and PABA,

Question 28

Describe procaine hydrochloride use and misuse

Answer 28

-I: 1-2%⊙ - infiltration and
2-4%⊙ - nerve block + Epinephrine to give a conc. of 1:100,000
- Procaine + penicillin G prolongs drug action (very slow absorption).
- CNS stimulant and analgesic actions have been used illegally in racing horses to improve their performance and/or to mask lameness during events. Due to a higher threshold for pain.

Question 29

Describe tetracaine hydrochloride and its use

Answer 29

-I: topical anesthesia of the eye, nose, and throat and for spinal anesthesia when both sensory and motor blockade are desired. Both a patch application system
and a gel preparation for percutaneous analgesia with favorable results are available

Question 30

Describe benzocaine’s use

Answer 30

I: -in dentistry (gums and buccal mucosa). - Cutaneous application; in wounds to
provide long-term analgesia.
- In a spray to anesthetize the larynx
- In fish, benzocaine induces sedation within 30 sec. after immersion. This permits weighing of the fish and injection of the calculated anesthetic doses of other anesthetic drugs.
• ADR: It has been reported to cause methemoglobinemia in some species (e.g., sheep), which may limit its widespread use.

Question 31

Describe lidocaine

Answer 31

• one of the most versatile and one of the most widely used of the LA in vet. medicine.
• an agent of choice for use with individuals sensitive to the ester-type agents (because no PABA produced)
• relatively quickly absorbed following injection - + vasoconstrictor

Question 32

Describe lidocaine use

Answer 32

I: for all forms of local anesthesia; in addition to its use as a LA, it is used intravenously as an antiarrhythmic agent and also as a supplement to general anesthesia. It decreases the requirement for inhalation and injectable anesthetics.

Question 33

Describe prilocaine hydrochloride and its use

Answer 33

pharmacological properties resemble those of lidocaine
• causes significantly less vasodilation and hence may be used without the
addition of epinephrine to prolong the duration of effect
• reported to be the least toxic of the amide LA and so best suited for IV
anesthesia.

Question 34

Describe mepivacaine hydrochloride and its use

Answer 34

pharmacological properties are similar to those of lidocaine
• I: While its use in clinical practice is similar to that of lidocaine, mepivacaine is
not recommended for obstetrical anesthesia, because its actions are markedly
prolonged in the fetus.

Question 35

What is an eutectic mixture of lidocaine and prilocaine (EMLA)

Answer 35

consist of a 1:1 mixture available as a cream and a disk to produce dermal analgesia after topical application to intact skin.
I: a percutaneous analgesic prior to venipuncture in dogs, cats, rabbits and rats.

Question 36

Describe bupivacaine hydrochloride and its use

Answer 36

• is a long-acting local anesthetic (duration of action 3 - 8 hr).
• I: most commonly for regional and epidural nerve blocks and was the first local anesthetic agent to show significant separation of sensory and motor blockade,
making it the drug of choice for obstetrical anesthesia.

Question 37

Name the general anesthetics

Answer 37

• isoflurane (and halothane)
• nitrous oxide (N2O), methoxyflurane, enflurane
• sevoflurane, desflurane

(Halothane not available anymore in many countries, nitrous oxides not that potent so commonly mixed with isoflurane to decrease the concentration, sevoflurane commonly used for dogs, desflurane not used in vet med)

Question 38

What are the chemical characteristics of general anesthetics?

Answer 38

They are al liquid, organic compounds except for N2O which is an inorganic gas
They are either aliphatic hydrocarbons or ethers
• halogenation -> less reactive, more potent, nonflammable inhal. anesthetic
- CL and Br improve the potency
- F substituted for CL or Br improves the stability but reduces the potency and solubility
Halothane is a halogenated aliphatic hydrocarbon that is nonflammable and stable but can cause life-threatening cardiac arrhythmias (typical for hydrocarbons because don’t have oxygen)
• ether linkage - ↓incidence of cardiac arrhythmias
• fluorine ion - toxic to kidneys - if the parent compound is not resistant to metabolism (e.g., methoxyflurane, enflurane, sevoflurane)

Question 39

How are general anesthetics administered?

Answer 39

Administration requires a carrier gas that must include oxygen, a source of anesthetic, and a patient breathing circuit.
• very small animals (lab. rodents or small birds) - in a closed air-filled chamber cont. a cotton pledger saturated with liquid anesthetic
• larger animals or to provide more controlled delivery of anesthetic and O 2
- anesthetic machine - greatly improves the safety

Question 40

Describe solubility in blood and tissues and solubility in lipids. Describe the partition coefficients.

Answer 40

The kinetics of a drug in the body is determined by its:
– Solubility in blood and body tissues-primary factor in the rate of uptake and distribution within the body
—Solubility in lipids- strong relationship to anesthetic potency

Solubility - expressed as a partition coefficient (PC) - concentration ratio of an anesthetic in two solvent phases,e.g. blood and gas - describes the affinity/capacity of an anesthetic for one solvent phase relative to another
– Blood/Gas PC - a measure of the speed of anesthetic induction, recovery, and change of anesthetic levels: the lower the blood/gas PC, the more rapid the anesthetic induction or rate of change of anesthetic level in response to a stepwise change in anesthetic delivery.
– Oil/Gas PC - correlates directly with anesthetic potency, describes the capacity of lipids for anesthetic : the higher the oil/gas PC, the more potent the inhal. anesthetic is.

Question 41

Why is Paleveolar the most crucial?

Answer 41

the alveolar partial pressure (PA) of anesthetic - most crucial - a balance between anesthetic input (i.e., delivery to the alveoli) and loss (uptake by blood and body tissues) from the lungs
– A rapid rise in PA of anesthetic is associated with a rapid induction or change in anesthetic depth.

Question 42

Describe the uptake of inhalation anesthetics

Answer 42

The aim is to achieve an adequate partial pressure (tension) of anesthetic in the brain to cause a desired level of anesthesia. (Partial pressure used instead of concentration because is a vapor)
• Movement of molecules of inhalation anesthetics occurs down partial pressure gradients gases move from regions of higher tension to those of lower tension until equilibrium is established.
- Pdelivered -> Pcircuit -> Pinspired -> Palveolar (some is expired) Parterial Pbrain
- when there’s a sufficient amount in the brain, the animal falls ‘asleep’.
-During recovery, molecules of anaesthetic diffuse from higher conc. (Brain) to lower conc. (Outside air). Therefore, everything depends on the concentration gradients. So during recovery, it occurs in the opposite direction from brain -> outside

Question 43

Describe recovery from inhalation anesthesia.

Answer 43

results from the elimination of anesthetic from the brain
– requires a decrease in alveolar anesthetic partial pressure (concentration), which
in turn fosters a decrease in arterial and then brain anesthetic p. pressure
• Factors accounting for recovery are the same as those for anesthetic induction - alveolar ventilation, CO, and especially agent solubility play prominent roles in recovery from inhalation anesthesia.
– The wash out of the less soluble anesthetics is high at first, then rapidly declines to a lower output level that continues to decrease but at a slower rate.
– The output with the more soluble agent is also high at first, but the magnitude of decrease in alveolar anesthetic concentration is less and only more gradually decreases with time.
So, the less soluble the quicker the onset of action and the quicker the recovery
• Recovery from desflurane and sevoflurane, is faster than with isoflurane and even more so than the older agents.

Question 44

What influences the duration of general anesthesia?

Answer 44

A greater reserve of a highly soluble agent such as methoxyflurane in the body after prolonged administration will cause its alveolar partial pressure to fall slower in comparison with less soluble agents such as isoflurane.

Question 45

Describe bio transformation of general anesthetics.

Answer 45

Rate of biotransformation is not important for recovery because a small amount is biotransformed and recovery is due to exhaling unchanged molecules via lungs.

Question 46

Adverse effects of inhalation anesthetics on the circulatory system.

Answer 46

• ↓arterial blood pressure, ↓cardiac output+contractility, stroke volume, heart rate, and/or rhythm of heartbeat.
– caused by direct myocardial depression by the inhaled anesthetic and decrease in sympathoadrenal activity
• ↑ in cerebral blood flow ↓ in blood flow to liver and kidneys
• Halothane may sensitize the heart to arrhythmogenic effects of catecholamines.

Question 47

Adverse effects of inhalation anesthetics on the respiratory system.

Answer 47

All depress alveolar ventilation - ↑PaCO2 in direct relation to anesthetic dose; 
• the normal stimulation to ventilation caused by ↑PaCO2 and/or a low arterial 
oxygen tension (PaO2 ) is reduced 
• Halothane, isoflurane, sevoflurane and desflurane - effective bronchodilators - relaxation of constricted bronchial muscles.

Question 48

Adverse effects of inhalation anesthetics on the liver, kidneys and muscle

Answer 48

LIVER
• reduction in hepatic blood flow/direct anesthetic agent toxicity halothane - hepatocellular injury
KIDNEYS
• ↓renal blood flow and glomerular filtration rate - small volumes of concentrated urine - a transient ↑ in serum urea nitrogen, creatinine, and inorganic phosphate - rapidly reversed after anesthesia.
-methoxyflurane - nephrotoxicity potential
-metabolism of halothane produces fluorine which is nephrotoxic
SKELETAL MUSCLE
• small amount of skeletal muscle relaxation
• enhance the muscle relaxation induced by the nondepolarizing
neuromuscular blocking drugs
• Malignant hyperthermia, a life-threatening pharmacogenetic myopathy, is
most commonly associated with halothane anesthesia.

Question 49

Inhalation anesthetic use in veterinary medicine

Answer 49

• Isoflurane is the most popular in vet. med.
• Halothane use has declined and is not used in many countries
• Sevoflurane use is increasing
• Methoxyflurane was never widely used in large animals but can still (although increasingly less) be used in small animals
• Desflurane and Sevoflurane are the newest agents now approved

Question 50

Characterize halothane

Answer 50

• bronchodilator action – asthma patients
• ↓hepatic blood flow → mild transient form of hepatic dysfunction/halothane hepatitis often fatal
• causes some relaxation of skeletal muscle
• MALIGNANT HYPERTHERMIA – in pigs, characterized by muscle
rigidity, a rapid rise in body temperature, large consumption of O2 and
production of CO2. Death rapidly ensues in most cases unless very
aggressive therapy is instituted

Question 51

Characterize isoflurane

Answer 51

ether; isoflurane and enflurane - structural isomers
• probably the most commonly used inh. agent for dogs, cats, horses, birds!
• anticonvulsant effect
• less cerebral vasodilation than halothane - preferred for neurosurgery

Question 52

Characterize methoxyflurane

Answer 52

was a popular inhalation anesthetic for small companion and lab. animals
• Because of its extreme blood solubility, it was never widely advocated for use with large domestic species.
Is not used anymore because of its adverse effects

Question 53

Characterize enflurane

Answer 53

• The occurrence of motor hyperactivity such as twitching of the muscles of
the face and extremities
• epileptogenic nature - unique among the commonly used inhaled
anesthetics. Especially occurs in predisposed individuals so is not used anymore
• Malignant hyperthermia is induced in susceptible individuals

Question 54

Characterize desflurane

Answer 54

• It has a very low solubility in blood - greater precision of control over the maintenance of anesthesia and a very rapid emergence from anesthesia
Not licensed to be used actually

Question 55

Characterize sevoflurane

Answer 55

– Sevoflurane degrades to a compound known as Compound A (renal toxicity) that is lethal in 50% of animals

Question 56

All mentioned general inhalational anesthetics are…..

Answer 56

Liquids with low boiling points so that they can be inhaled as a vapor

Question 57

Characterize nitrous oxide

Answer 57

Also known as laughing gas
colorless, nonirritant, slightly sweet-smelling, nonflammable gas
• Many desirable properties: low blood solubility, limited cardiovascular and respiratory system depression, and minimal toxicity.
• not a potent anesthetic and under ambient conditions will not anesthetize a fit, healthy individual - necessary to use it in high inspired concentrations – max. 75% of the inspired breath
• it is used in conjunction (1:1) with an injectable and/or another inhalation anesthetic – as carrier gas!!!!!!!!!!
Combine usually with sevoflurane and isoflurane making the procedure cheaper

Question 58

Describe general injectable anesthetics

Answer 58

• Stages of anesthesia for CNS depressants are similar in a patient whether anesthetic is injected IV or administered by inhalation.
• possible to proceed more rapidly through induction with IV anesthetics
– a rapid course of induction is desirable to avoid excitement and struggling.
• No anesthetic agent producing ideal anesthesia under all circumstances.

Question 59

Name the general injectable anesthetics

Answer 59

• Barbiturates: thiopental, thiamylal, pentobarbital, methohexital,
• Propofol, etomidate
• Dissociative anesthetics: ketamine, tiletamine,
• Neurosteroids: alphaxalone, alphadolone,

Question 60

Name the indications for injectable anesthesia

Answer 60

-Induction of GA and intubation (IV injection of a short-acting anesthetic),
• animals that are difficult to restrain (IM injection),
• some minor procedures require only a short time,
• endoscopic upper and distal airway examination (larynx, trachea),
• large-animal surgical procedures (especially equine) - preventing the excitement stage is paramount for the animal’s safety as well as the medical personel,
• the capture and immobilization of wild life animals, and
• in situations where economy is the primary concern.

Question 61

Disadvantages of injectable anesthesia

Answer 61

• a large volume of distribution and wake up is associated with redistribution and then metabolism of the drug;
• the depth, or level, of anesthesia is less readily controlled;
• inj. anesthetic drug ceases to act only after it is metabolized and/or excreted
• Many injectable anesthetic agents as well as agents commonly used
concurrently - classified as controlled substances - restrictions

Active for 20-40 minutes so can just add more and prolong the action but no real control of the depth

Question 62

Characterize the barbiturates

Answer 62

• barbiturates - drugs derived from barbituric acid were shown to produce sleep and prevent seizures.
• Barbiturates are CNS depressants and can be used at increasing doses to
produce sedation-> hypnosis-> anesthesia->coma, and even death (euthanasia solutions)

Question 63

Name the indications for barbiturates

Answer 63

for rapid induction of general anesthesia, prevention and treatment of seizures, and euthanasia.

Question 64

Name the types of barbiturates and their common use

Answer 64

Oxybarbiturates:
1. Phenobarbital- anticonvulsant
2. Pentobarbital- anaesthesia/euthanasia
3. Methohexital- anaesthesia 
Thiobarbiturates:
1. Thiopental- anaesthesia
2. Thiamylal- anesthesia

Question 65

Describe the chemical aspect of barbiturates

Answer 65

• substituting sulfur (thio) for oxygen (oxy), at position 2 - ↑lipid solubility
(thiobarbiturates vs. oxybarbiturates)

Question 66

Describe the physiological effects of barbiturates in general

Answer 66

-The major action of barbiturates is to depress the CNS

• Effects upon other systems become important as toxic limitations to use

Question 67

Describe the effect of barbiturates on the CNS

Answer 67

Depress:
– the cortex of the brain and probably the thalamus.
– motor areas of the brain - used to control convulsive seizures
– sensory areas and induce anesthesia
• barbiturates are the most potent known depressants of cerebral O2 consumption
- as much as a 55% decrease in oxygen consumption may occur
• depress the reticular activating system (RAS), which controls arousal and inhibits the development or spread of epileptiform activity

Question 68

Describe the effect of barbiturates on the cardiovascular system

Answer 68

• In healthy dogs - ↓ in stroke volume and contractility and ↑heart rate and systemic vascular resistance
• in compromised dogs - exaggerated cardiovascular depression

Question 69

Describe the effect of barbiturates on the muscles

Answer 69

Good relaxation of skeletal muscle

Question 70

Describe analgesia effects of barbiturates

Answer 70

Do not provide analgesia

Question 71

Describe the absorption + distribution of barbiturates

Answer 71

• absorbed readily from the GIT; after IV injection – rapid brain distribution
• distributed more or less generally throughout the body.
• Thiobarbiturates - thiopental, a highly lipid soluble drug, passes readily through the BBB - rapid induction of general anesthesia, then redistributes to the moderately perfused body tissues (such as muscle) - ↓ the brain concentration - allows to regain consciousness - further redistribution to adipose tissue - complete recovery
• Since sighthounds (e.g., Greyhounds) - lower percentage of adipose tissue, their complete recovery from the thiobarbiturates is delayed
Thiobarbiturates should be not be administered multiple times because have a cumulative effect

Question 72

Describe the bio transformation and excretion of barbiturates

Answer 72

• eliminated by renal excretion in urine and/or metabolized principally by the hepatic microsomal enzyme system (P450).
– Greyhounds are deficient in oxidative enzymes → awakening may be >8 hr. Thiobarbiturates
should not be used in greyhounds!!!!!

Question 73

Effect of barbiturates on sighthounds

Answer 73

Sight hounds: lean breeds with small fat stores (e.g., whippet, Irish wolfhounds) - exaggerated effect to barbiturates,increased risk of prolonged duration of action/overdose.
– Greyhounds: In addition - deficient in oxidative enzymes - extremely prolonged recoveries from thiobarbiturates.

Question 74

What species can barbiturates be used in?

Answer 74

Dogs, ruminants, horses, birds, rabbits, reptiles

Question 75

Describe thiopental sodium

Answer 75

the most com. used ultra short-acting thiobarbiturate

• In ~40% dogs - arrhythmogenic effect

Question 76

Describe pentobarbital sodium

Answer 76

a short-acting oxybarbiturate
• current use is primarily as a euthanasia solution and for anesthesia in laboratory rodents.
• long duration of action - for long-term anticonvulsant treatment

Question 77

Describe phenobarbital sodium

Answer 77

It is a long-acting oxybarbyturate

• primary use is as an anticonvulsant or for long-term sedation

Question 78

Describe methohexital sodium

Answer 78

ultrashort-acting oxybarbiturate

• for dogs and cats