Transcript LATG Pharmacology (Ch. 16)

LATG
Chapters 14 & 15
Pharmacology
Anesthesia
Pharmacology
• The science that deals with origin,
nature, chemistry, effects, and uses of
drugs
• includes pharmacokinetics,
pharmacodynamics,
pharmacotherapeutics, and toxicology
• drugs are good, but may be only one
factor
Modes of Drug Action
• Stimulation: increases the activity of cells
(doxapram)
• Depression: decrease cellular activity
(atropine)
• Irritation: leads to stimulation of activity (fleet
enemas)
• Replacement: synthetic substitutes (insulin or
synthroid)
• Chemotherapy: kill malignant tumor cells
(Taxol or Doxorubicin)
Drug Classification
• Classification systems: primary effect &
site of action
• Primary effect: unknown cause, but
drug may relieve clinical signs
• Site of action: organ specific drugs
Routes of Administration
• Enteral: drugs are delivered directly into GI
tract; slower absorption; wider safety
margin
– Oral & Rectal
– Oral: tablets, capsules, powders, solutions,
caplets, suspensions
– powders, solutions, or suspensions: mix with
food or require administration via stomach tube
– Rectal: suppositories or enemas
Routes of Administration
• Parenteral: without or around (par)
the intestines (enteral)
– IV, SC, ID, IM, IP, IC
– quickest route to get drug into animal & to
site of action
– other routes: Intra-articular; Subarachnoid
or Intrathecal, subconjunctival
– drugs given should be sterile,
nonirritating, and pyrogen-free
Routes of Administration
• Inhalation: directly into respiratory tract
– gas, vapor, fine mist or powder
– particles or droplets must be less than 5um
– most commonly used for anesthetic gases (i.e.
isoflurane)
– advantages: rapid absorption and elimination
– disadvantages: intubation, mask, or inhalation
chamber
Routes of Administration
• Topical: application to skin or external
membranes
– lotions, ointments, pastes, and
suspensions
– slowest rate of absorption
– advantages: high doses to local area
without systemic toxicity
– disadvantages: fur, dirt, bedding, licking
Dosage Forms
• Enteral forms: solutions, suspensions,
capsules, or tablets
• Solutions: water based, tinctures, spirits, fluid
extractions
• Suspensions: insoluble drugs
• Capsules: soluble in stomach or intestine
(time-release)
• Tablets: solid preparations (enteric coating)
Dosage Forms
• Parenteral forms: mixed or dissolved in
a sterile, pyrogen-free medium
• IV, IA, IC drugs: dissolved in water,
isotonic saline, or saline-dextrose
• Depot effect: drug dissolve slowly gives
a constant drug level
Therapeutic Use of Drugs
• Tolerance: decrease in response to
normal dose (e.g., NHP to ketamine)
• Sensitization: increase in response
(e.g., allergic reactions)
• Synergistic: two or more drug which
give an enhanced response (e.g.,
antibiotics)
• Potentiation: increased action by one
drug produced by another drug with
nonrelated action
Therapeutic Use of Drugs
• All drugs have a toxic effect if given in
excess
• Therapeutic Index or Margin of Safety
• TI = Toxic dose/Effective dose
Distribution and Elimination
• Distribution of drugs within the body varies
considerably
• Most drugs are inactivated by normal
metabolic processes
• Kidneys: primary route of excretion
• Other routes: bile, respiratory
• Metabolism: mostly occurs in the liver
Controlled Drugs
• Schedule III-V: less potential for abuse
(ketamine, butorphanol)
• Requires federal and state licenses
• Detailed records showing usage
• Facilities which use controlled drugs may be
inspected by DEA
• Must be stored behind at least two locked
doors
Controlled Drugs
• Potential for being abused or addictive
• Comprehensive Drug Abuse and Control Act:
lists control drugs and 5 schedules
• Schedule I: high potential for abuse; no
medical treatment, no safety (LSD, heroin)
• Schedule II: high potential for abuse, but
have medical uses (codeine, opium
derivatives, pentobarbital)
Dogs
• Parvovirus:
– acute disease of young dogs
– bloody diarrhea and severe panleukopenia
• Otitis Externa:
– bacteria, yeast, ear mites (Otodectes cynotis)
– factors: dirt, trauma, hair, foreign bodies
– excess head shaking and odor
• Heartworms:
– Dirofilaria immitis; spread by mosquitos
– adults live in pulmonary artery, right artium, and
right ventricle
ANESTHESIA
Review dosage calculations using ratios and cross multiplication
Review the stages and planes of anesthesia
Stage 1 - narcosis, sedation, analgesia
Stage 2 - uninhibited response, delirium, excitement
Stage 3 - surgical stage
Plane 1 - loss of pain response
Plane 2 - surgical plane
Plane 3 - beginning of respiratory paralysis/pupil
dilation
Plane 4 - cyanosis, non-responsive pupils
Stage 4 - paralysis of brain respiratory centers
ANESTHESIA
Monitoring General Anesthesia
• Respiratory Pattern - rate, depth and character of the
respirations
Shallow, thoracic pattern = lightly anesthetized
Deep, abdominal pattern = deeply anesthetized
Pattern should be regular
• Monitored by observing flow valves, rebreathing bag,
observing chest movement, in-line flow meter
ANESTHESIA
Monitoring General Anesthesia
Mucous membrane color - The gums, lips, rectum/vulva
remain pink if the animal is receiving enough oxygen.
They turn blue if there is a lack of oxygen.
Capillary refill time - Measured by pressing on the gum
line until the color blanches and timing its return to normal
color when pressure is released. Normal is 2 seconds or
less. Longer times indicate a perfusion problem from
lowered cardiac output, increased vascular resistance, or
hypovolemia.
ANESTHESIA
Monitoring General Anesthesia
Pulse evaluation - Done on the
femoral or mandibular artery or the
heart itself. The strength and
character of the pulse vary with
anesthetic depth and blood pressure.
Blood pressure - Blood pressure can be measured
indirectly using a pressure cuff on the tail or leg and an
ultrasonic doppler flow detector. An arterial catheter can
be used for direct BP.
ANESTHESIA
Monitoring General Anesthesia
Body temperature - Anesthesia affects the brain’s heat
regulatory center, lowering the patient’s temperature. Loss
is minimized by using a heating pad, warm fluids, and
a heat lamp during recovery. Cooler temperatures slow the
metabolism of the anesthetic.
Eyes - Presence or absence of reflexes or nystagmus, and
size of the pupil indicate the level of anesthesia
ANESTHESIA
Monitoring General Anesthesia
Muscle tone - varies with type of anesthesia used. Ketamine
results in stiff, rigid muscles. Most other anesthetics result
in some degree of relaxation which is easily observed in
the larger species using jaw tone.
Reflexes - most common is the pedal or withdrawal reflex, anal reflex
also used. Both disappear as surgical plane reached. Laryngeal reflex
used to determine time to remove endotracheal tube
ANESTHESIA
Preanesthetics
• Preanesthetics include tranquilizers, analgesics, and
anticholinergics
• Tranquilizers - lower the animals apprehension and aid in
restraint for anesthetic induction
• Analgesics - work with the tranquilizer to lower the amount of
general anesthetic needed, increasing the safety margin. CAN
MASK THE ANESTHETIC STAGES.
• Anticholinergics - reduce secretions and raise heart rate
ANESTHESIA
Preanesthetics
• Anticholinergics - Atropine blocks acetylcholine
resulting in decreased secretions from salivary and
respiratory glands; blocks the vagal tone on the
heart, increasing the heart rate
• Tranquilizers - Phenothiazines reduce anxiety and
cause muscular relaxation. Note: These agents
cause peripheral vasodilation and hypotension.
• -Analgesics - Medetomidine, Xylazine provides some
anesthesia as well as analgesia and sedation. Often
used with ketamine.
ANESTHESIA
Injectable Anesthetics
• Pentobarbital - Not to be confused with
Phenobarbital. Long acting anesthetic that can be
given IV or IP. For IV administration, half the dose is
given quickly then titrated to the desired effect. No
reversal agent. Must be very deep for analgesia.
• Thiamylal, thiopental, methohexital - Ultrashort acting
(about 15 minutes) agents commonly used for
general gas anesthetic induction.
ANESTHESIA
Injectable Anesthetics
• Chloral hydrate - Used primarily as a
sedative/hypnotic due to poor analgesic properties.
Can cause profound depression of cardiovascular
and respiratory systems.
• Alpha-Chloralose - Poor analgesia and slow onset.
Used in physiological studies since there is little
effect on the cardiovascular and respiratory systems.
Primarily used as a sedative.
ANESTHESIA
Injectable Anesthetics
• Urethane (Ethyl Carbamate) - Long lasting
anesthetic. Has been associated with increased
tumor formation. Can cause intestinal irritation if
given IP. Usually used for long, terminal
experiments.
• Tricaine Methanesulfonate (MS-222) - A water
soluble anesthetic frequently used for fishes and
amphibians.
• Fentanyl/Droperidol (Innovar-Vet) - An opioid and
tranquilizer. Used for minor painful procedures.
ANESTHESIA
Injectable Anesthetics
• Ketamine HCl - A dissociative anesthetic. Administration results
in excessive muscular tone, very mild respiratory depression,
mild cardiac stimulation, salivation, adequate somatic but poor
visceral analgesia. May produce seizures in some animals.
Often used with xylazine for muscle relaxation and additional
analgesia.
ANESTHESIA
Inhalant Anesthetics
• Delivery and elimination occurs via the lungs = easy to adjust
level of anesthesia being administered.
• Supplied as a liquid that slowly evaporates at room temperature.
• Carrier gases (oxygen +/- nitrous oxide) enter vaporizer where
anesthetic gas vapor is added.
• Unused anesthetic gas and exhaled CO2 must be removed.
ANESTHESIA
Inhalant Anesthetics - Delivery Systems
• Chamber system - Clear plastic or glass
container with cotton soaked in anesthetic
placed in bottom and covered by mesh or
perforated floor. Animal placed on floor and
lid put on container. Anesthetic induction
can be observed through the container wall.
Once animal is removed, recovery begins.
• Open Drop system - Nose cone with
anesthetic soaked cotton used to maintain
animals induced above.
• Both systems must be used in a fume hood.
ANESTHESIA
Inhalant Anesthetics - Delivery Systems
• Rebreathing systems allows recirculation of carrier and
anesthetic gas and consist of a number of components
ANESTHESIA
Inhalant Anesthetics - Delivery Systems
• Vaporizer
– - Precision vaporizers are the most accurate
and most commonly used type today. It
automatically compensates for changes in
vapor pressure due to temperature.
– Copper kettle - older style that requires user
to adjust for temperature variations
– Wick-type - Used only with methoxyflurane
since delivery concentration determined by
liquid’s vapor pressure
ANESTHESIA
Inhalant Anesthetics - Delivery Systems
• Lime Canister - Soda lime (calcium
hydroxide or barium hydroxide) used to
absorb the carbon dioxide in the expired
air. A chemical indicator changes color
when the soda lime should be replaced.
• Compressed Oxygen - Supplied in tanks
available in a variety of sizes, green color
code, full tanks ~2200 psi indicated on
regulator pressure gauge, delivery
controlled by flowmeter (measured in l/m).
ANESTHESIA
Inhalant Anesthetics - Delivery Systems
• Tubing and rebreathing bag - Allow for
the one-way system to function.
Rebreathing bag expands/contracts
with each breath, should have a
capacity of about 6 times the patient’s
tidal volume.
• Pressure relief (Pop-off) valve Adjustable, used to fine-tune flow rate
so that the rebreathing bag stays about
2/3 full.
ANESTHESIA
Inhalant Anesthetics - Delivery Systems
• Scavenger systems - Used to remove the excess exhaled gases
= Waste Anesthetic Gas or WAG
– Most effective is direct exhaust to the outside via central
vacuum
– Activated charcoal canisters used on portable setups
• Leakage of anesthetic around tubing connections, around
endotracheal tube, and at machine connections can occur and
frequent equipment inspections should be performed.
ANESTHESIA
Inhalant Anesthetics - Delivery Systems
• Non-rebreathing systems - used for animals weighing ~ 7kg or
less. Their tidal volume is too small to use the rebreathing
systems so they use equipment that provides linear flow through
the animal and then out to the scavenging device. This set-up
produces large amounts of WAG.
ANESTHESIA
Inhalant Anesthetics
• Vapor pressure - the higher the vapor pressure of a
liquid, the quicker it will evaporate at a given
temperature. The reason halothane and isoflurane
can’t be used in the open drop system but
methoxyflurane can is due to the differences in vapor
pressure.
• Tissue solubility - the greater the solubility of the gas
in tissue, the slower the induction and the longer the
recovery. Less soluble anesthetics are more potent.
ANESTHESIA
Inhalant Anesthetics
• Diethyl Ether - highly flammable and explosive and
must be used in explosion proof hoods. High tissue
solubility = slow induction and recovery
• Chloroform - NOT TO BE USED IN ANIMAL
FACILITIES. Can be highly toxic to mice, has low
margin of safety, is a known carcinogen.
ANESTHESIA
Inhalant Anesthetics
• Methoxyflurane - Low vapor pressure and
high tissue solubility = safe. Can use wicktype vaporizers. Provides some analgesia
after anesthetic recovery
• Halothane - Common veterinary inhalant
anesthetic. High vapor pressure and low
tissue solubility - use only precision
vaporizers. Has been associated with
cardiac arrhythmias.
• Isoflurane - Similar to halothane but no
cardiac problems.
ANESTHESIA
Inhalant Anesthetics
• Nitrous Oxide - Like oxygen, nitrous exists in a gaseous state at
room temperature and is supplied in (blue) tanks. Under
pressure it becomes a liquid. Tank pressure remains even
(~800 psi) until there is no more liquid, then it decreases as the
remaining gas is used.
• Nitrous is combined with oxygen and should make up 50-80% of
the carrier gas combination to be effective. Low tissue solubility
= rapid onset and recovery.
• Discontinue nitrous several minutes before oxygen
ANESTHESIA
Neuromuscular Blockers
• ALWAYS USED IN CONJUCTION WITH GENERAL
ANESTHESIA AND APPROPRIATE MONITORING
• gallamine, pancuronium, succinylcholine
• These agents cause paralysis of the voluntary
skeletal muscles and, at higher doses, the
diaphragm. Usually used with a ventilator. They
provide NO analgesia.
• Indications: fractures, dislocations, laparotomies
• Use BP, HR, mucous membrane color and capillary
refill time to monitor anesthetic depth
Analgesics
• NSAIDs - act by inhibiting prostaglandin synthesis,
good for inflammation but not good for pain. Oral
delivery.
-Aspirin and Acetaminophen have limited use.
- flunixin, ketoprofen, and carprofen
• Opioids
– Morphine provides sedation and analgesia. May also cause
vomiting and defecation, cardiac and respiratory depression.
Can see tremors/convulsions in mice and cats.
– Meperidine, Oxymorphone, Pentazocine, Buprenorphine
Postanesthesia
and Emergency Care
• Drugs to keep on hand for
emergencies:
– Apomorphine - induces
vomiting
– Atropine sulfate - increases
heart rate
– Calcium gluconate strengthens myocardium
contractions
– Chlorpromazine tranquilizer
– Dexamethasone - steroid for
shock/anaphylaxis
– Doxapram - stimulates
breathing
– Epinephrine HCl - for
asystole
– Heparin - dissolves blood
clots
– Lactated Ringer’s increases blood volume
– Morphine HCl - analgesia
– Pentobarbital - anesthesia
– Pitocin - stimulates uterus
– Sodium bicarbonate acidosis
– Normal saline - increases
blood volume
– Isoproterenol - stimulates
heart
Postanesthesia
and Emergency Care
• Evaluation of patients should include behavioral
observations and a complete physical examination
• Emergencies can usually be prevented by careful
attention to the patient before, during, and after the
anesthetic administration
• Technicians should work with the veterinarians both
to avoid problems from occurring and to learn from
those that do occur to prevent them from happening
again.