Anesthetic Drug Pharmacology Flashcards
Tranquilizers
drugs that reduce anxiety
Sedatives
drugs that produce sleep and reduce response to arousal
Analgesics
pain relievers
Induction agents
used to bring about a state of general anesthesia.
maintenance anesthetic agents
commonly inhalent anesthetics, but can also be injectable (also knowna s total intravenous anesthesia - TIVA)
Anticholinergics
Which receptors do they act on?
Where are the receptors located?
parasympatholytic drugs act on various muscarinic receptors found in the parasypathetic nervous system.
Receptors can be found in:
* the central nervous system
* salivary glands
* lungs
* sinoatrial and atrioventricular nodes of the myocardium
* smooth muscle of the GI tract
Pathophysiology of anticholinergics
Prevent the primary neurotransmitter, acetylcholine, from binding to their receptors, there by reducing the effects of the parasympathetic symptoms.
Common effects elicited by parasympathetic nerouvs system
- bradycardia
- bronchoconstriction
- tear and saliva production
- pupil constriction
- increased gastrointestinal motility
Two common anticholinergics
Atropine
glycopyrrolate
Physiologic effects of anticholinergics
- increase heart rate
- bronchodilation
- decreased tear and salive production
- pupil dilation
- decreased gastrointestinal motility
Potential side effects of anticholinergics
- arrhythmia
- sinus tachycardia
- increase in myocardial oxygen demand
- increase workload of the heart
- may thicken airway secretions
- Should not be used routinely used as part of premedication in most patients.
When to use anticholinergics with caution or avoid use
patients with hypertrophic cardiomyopathy
Pharmacokinetics of Aropine
Crosses the blood-rain and blood-placental barriers
quicker onset of action
metabolized by hydrolysis
excreted unchanged by kidneys in dogs
metabolized by renal esterase in cats
Peak effects of atropine can be seen within five minutes and duration of action is about 30 minutes
Pharmacokinetics of Glycopyrrolate
poorly lipid soluble
does not cross the blood-brain or blood-placental barriers
(use on pregnant patients if anticholingergics are required).
Rapidly cleared and excreted unchanged by the kidneys
Longer onset of action
peak effects at 5-7 minutes
duration of action 60-90 minutes.
Less likely to produce tachycardia
dose-dependent effects similar to atropine
Low doses - may see transient second degree AV block or worsening bradycardia.
Phenothiazines
tranquilizers that eert their effect on the central nervous system by blocking dopamine receptors.
Acepromazine
Drug glass
beneficial properties
Phenothiazine.
Also has antiemetic and potential antiarrhythmic effects.
Mild effects on vntilation and the rspiratory system.
Significantly reduces the amount of induction and maintenance anesthetic needed
Acepromazine disadvantages
Long duration >4 hours
no analgesic properties
inability to reverse
potent cardiovascular side-effects
- alpha - 1 adrenergic antagonist effects: vasodilation resulting in decreased cardiac afterload and systemic vascular resistence
- vasodilation - potential hypotension (especially when used with other vasodilating drugs - inhalant anesthetics), or in patients that are hypovolemic, dehydrated or in states of shock
promote hypothermia
temporarily decrease PCV
enlargement of spleen
Contraindications of acepromazine
Avoid in patients with liver dysfunction
Weak antihistamine properties therefore should e avoided prior to intradermal allergy skin testing.
Breed predispositions to Acepromazine
Some boxer dogs uniquely sensitive and have been reported to have profound cardiovascular depression and syncope
Australian shepherds, mini Australian shepherds, onghaired whippets, collies and several hearding breeds have genetic mutation to their P-glycoprotein pumps within their central nervous system. Known as multidrug-resistant-1 (MDR-1) gene mutation. Alters drug efflux from the central nervous system, resulting in prolonged drug effects.
Benzodiazepines
Class of tranquilizers that work by enhancing release of gamma-aminobutyric acid (GABA).
Examples include:
diazepam
midazolam
alprazolam
zolazepam
Provide anxiolysis, mild to moderate skeletal muscle relaxation, amnesia and are effective anticonvulsants
minimal influence on the cardiovascular and respiratory systems
Reversible with flumazenil
Midazolam
benzodiazepine
water soluble
diazepam
not water soluble
light sensitive
should not be mixed with other agents other than ketamine
Disadvantage of benzodiaepines
Does not provide analgesia
does not provide consistent tranquilization.
Some patients may exhibit excitatory effects - dysphoria, disinhibition
When to avoid use of benzodiazepines
hepatic dysfunction
risk of human buse and addiction
CIV controlled
Opioids
cause profound analgesia and mild to moderate sedation
works predominantly by influencing mu and kappa opioid receptors within the central and peripheral nervous systems
neuroleptanalgesia
occurs when opioids are given in conjunction with a sedative or tranquilizer
profound central nervous system depression and potentially analgesia than when each drug class is given alone.
Side effects of opioids
panting in dogs, nausea and vomiting, dysphoria, hypothermia in dogs, hyperthermia in cats, ileus
can ocasionally cause excitement in some species such as cats in high doses
Mild effects of cardiovascular system
increase vagal tone–> results in bradycardia, but minimal effects to blood pressure, systemic vascular resistance and cardiac output unless high doses are used.
can cause respiratory depression
pharmacokinetics of opioids
metabolized by the liver –> use with caution in patients with hepatic dysfunction
Agonism of mu receptor can lead to decreased urine production
stimulation of the kappa receptor can incrase urine production due to release of antidiuretic hormone.
Full mu agonists
tend to be most likely to cause bradycardia and respiratory depression
morphine
hydromorphone
oxymorphone
methadone
fentanyl
remifentanil
What other receptor does Methadone block?
N-methyl-D-aspartate (NMDA)
Also inhibits norepinephrine and serotonin reuptake
partial mu agonist
drug that binds to and activates a receptor to produce a biological response that mimics the release of endogenous opioids in the body although the effect is not as robust as full mu agonists.
Buprenorphine only partial mu in vetmed.
Buprenorphine
Partial mu agonist.
High affinity for opioid receptor sites - longer duration of effect (8-12 hours) and difficult to reverse with naloxone
Will temporarily prevent full mu agonists from binding
slow onset time of 45-60 minutes
minimal sedation for most; significant bradycardia uncommon
CIII class
Butorphanol
agonist-antagonist
kappa receptor agonist
mu receptor antagonist
rapid onset of action but duration is short (<1hr)
Not as efficacious as full mu agonist or partial mu agonists
Provides mild to moderate sedation
CIV class
Alpha-2 Adrenergic agonists
Potent sedatives (sleep-producing), effective analgesic that also have muscle relaxant properties.
two drugs: dexmedetomidine and xylazine
mild effects on the respiratory system and ventilation at clinical doses
When administered at higher doses and in combination with other drugs, can cause respiratory depression.
Disadvantages: profound cardiovascular effects
What are the cardiovascular effects of alpha-2 adrenergic agonists?
reduced cardiac output
arrhythmias
increased cardiac afterload from increased systemic vascular resistance
increase in blood pressure
overall decrease in oxygen transport to tissues
Why are anticholinergics not recommnded to treat bradycardia from alpha-2 adrenergic agonists?
It will increase the myocardial work against increased systemic vascular resistence. Can result in greater hypertension.
Contraindications for alpha-2 agonists
Heart disease
patients with hepatic dysfunction
will also result in transient increase in blood glucose and urine output - therefore should be avoided in diabetic patients.
Propofol and Propofol 28
GABA agonist
exists preservative free - to be discarded after 6 hours of opening
with preservative - to be used for 28 days.
the preservative is toxic to cats
Advantages of propofol
short duration of action
smoothness of induction and recovery
minimal hangover effect
Can be used for TIVA
decreases cerebral blood flow and cerebral metabolic rate of oxygen consumption.
decreases intracranial pressure
pathophysiology of propofol
metabolized by the liver and by extrahepatic sites (more stable for patients with hepatic dysfunction)
disadvantages of propofol
respiratory depressant
profound cardiovascular effects:
* causes vasodilation and decreased cardiac output
* can lead to hypotension
* Heinz body enemia with repeated does in cats
* risk for allergic reaction
* ability to worsen or trigger pancreatitis beause of its fat emulsion
* pain on injection
* myoclonus (can be minimized with other drugs)
Dose of propofol
4-6mg/kg (titrated over 60-90 seconds)
Etomidate
propylene glycol-based imidazole derivative, used to induce general anesthesia.
Acts through enhancement of the inhibitory neurotransmitter (GABA) and depresses the reticular formation of the brainstem causing hypnosis and unconsciousness
rapid acting; non-cumulative
Cardiovascular effects of etomidate
no changes to cardiac output, strole volume or myocardial contractility
no appreciable changes to heart rate or MAP
does not sensitize the heart to catecholamine-induced arrhythmias
do not influence the respiratory drive, but can have a brief period of apnea upon induction.
brief period of myoclonus
neurologic effects of etomidate
decreases cerebral blood flow and cerebral metabolic rate of oxygen consumption.
likely has anticonvulsant properties due to its interactions with GABA complex
Pharmacokinetics of etomidate
metabolized and distributed by the liver, heart, kidneys and spleen.
Rosses placental barrier but rapidly cleared
Side effects of etomidate
pain upon injection
inhibition of natural adrenocorticoid production
hemolysis of red blood cells
Ketamine
Dissociative drug
Analgesic effect by being a NMDA receptor antagonist
bronchodilator
breif analgesia properties
favorable cardiovascular and respiratory effects
CIII controlled
Is ketamine used in critical patients with hypovolemia and cardiopulmonary instability?
Ketamine is favorable for use in patients with hypovolemia and cardiopulmonary instability.
Ketamine can increase heart rate, cardiac output and blood pressure.
Ketamine can produce apneustic breathing patterin following administration.
Is ketamine reversible?
No
what are the pharmacokinetics of ketamine?
Can cause excitement - dysphoria, hallucinations, unpredictable behavior when given higher doses and without concurrent CNS depressing drugs.
Avoid in patients with hepatic dysfunction
It may increase intracranial pressure and cerebral metabolic oxygen consumption when used a lone, but not an issue when iven with other drugs such as benzodiazepines or propofol.
Increases intraocular pressure
My result in seizure like activity, but at other doses may be used to treat refractory seizures
Alfaxalone
neurosteroid produces a GABA-A agonist effect
Properties of alfaxalone
smooth inductiion of general anesthesia with minimial hangover
Less respiratory depressant than propofol
Less changes to blood pressure, cardiac output, and systemic vascular resistance.
Disadvantages of alfaxalone
Cost
6 hour shelf life once opened
potential for rocky anesthetic recoveries
Pharmacokinetics of alfaxalone
metabolized by the liver and eliminated by the kidney.
Inhalant anesthetics
Sevoflurane
isoflurane
desflurane
Minimum alveolar concentrations (MAC)
lowest concentration of inhalant needed to prevent gross motor response in 50% of patients when a painful stimulus is administered
MAC is a measure of drug potency. The more potent a volatile liquid, the lower the MAC
Blood-gas partition coefficient
ratio of concentration of a compound in a solvent to the concentration in anotehr solvent (e.g. alveoli) at equilibrium.
A measure of drug solubility and lipophilicity.
higher blood gas partition coefficients will have slower onset and recovery than agents with lower blood-gas partition coefficient
Factors that can decrease MAC
concurrent drug administration
hypothermia
severe hypotension
increased age
hypercapnia
pregnancy
severe hypoxemia
Factors that can increase MAC
drug use
hyperthermia
young age
Effects of inhalant anesthetics on cardiopulmonary systems
heart rate not usually affected
can cause vasodilation and decline in mean arterial blood pressure
Depresses cardiovascular system
Depression of respiratory drive is dose dependent
Effects of inhalent anesthetics on intracranial pressure
dose dependent increases in cerebral blood flow and intracranial pressure.
Effects of inhalant anesthetics on other body organs
Reduced blood flow to liver, kidneys and reduces glomerular filtration rate and urine output.
Neuromuscular blocking agents
classifications
depolzarizing
non-depolarizatin
does not have any anesthetic, sedative, anti-anxiety or analgesic effects
Depolarizaing neuromuscular blocking agents
Act as Ach receptor agonists in that they bind to the AcH receptors and generate an action potential.
Because depolarization agents are not metabolized by acetylcholinesterase, the binding of this drug to the receptor is prolonged, resulting in extended depolarization of the muscle endplate. As the muscle relaxant continues to bind to the acH receptor, the endplate cannot repolarize, resulting in muscle relaxation
Non-depolarizing neuromuscular blocking agents
competitive receptor antagonists - bind to acetylcholine receptors but do not induce ion channel openings and block acetylcholine from binding resulting in muscle relaxation
neuromuscular blocking agents pathophysiology
alter the binding of acetylcholine to the nicotinic receptors, resulting in skeletal and respiratory muscle paralysis
Succinylcholine
classification and side-effects
depolarizing neuromuscular blocker
side-effects: muscle soreness, hyperkalemia, malignant hyperthermia, increased intracranial pressure
no reversal agent
non-depolzaring neuromuscular blocking agents
atracurium, cisatracurium, pancuronium, vecuronium, rocuronium
each has different duration of effect and side effect
inihibiting non-depolarizing neuromuscular blocking agents
Non-depolarizing neuromuscular blocking agents can be antagonised by acetylcholinesterase inhibitors such as edrophonium or neostigmine
use of acetylcholinesterase inhibitors
avoid residual neuromuscular blockade and critical respiratory events such as hypoxemia and aspiration during anestehsia recovery
Reversal agents result in acetylcholine release at both niotinic and muscarinic sites
Side effects of acetylcholinesterase inhibitors
bradycardia
bronchoconstriction
nausea
vomiting
diarrhea
abdominal cramping
rarely cardiac arrest
Atropine = drug of choice to treat adverse effects from AcH inhibitors
Types of opioids: agonist
The opioid drug binds to the receptor producing maximum stimulation at the receptor
Types of opioids: partial agonist
The opioid drug binds to the receptor but produces only weak stimulation - has a ceiling effect
Types of opioids: Agonist/antagonist
have agonist or partial agonist activity at one or more types of opioid receptors and have the ability to antagonize the effects of an agonist at one or more types of opioid receptors
Types of opioids: Antaonist
The opioid drug binds to the receptor producing no stimulation but effectively blocks the receptor to the other opioids
Types of opioids: NMDA antagonist
Inhibits the action of N-methyl-D-aspartate receptors. Helps decrease wind up pain.
Opioid receptors: Mu receptors
Analgesia, euphoria, sedation, respiratory depression, constipation.
Opioid receptors: Delta receptors:
hallucinogenic effects and decreased gastrointestinal secretions
Opioid receptors: Kappa receptors:
dysphoria via reduction in dopamine release
What are the four phases of pain pathway?
Transduction: the processes by which tissue-damaging stimuli activate nerve endings
Transmission: the relay function by which the message is carried from the site of tissue injury to the brain regions underlying perception.
Modulation: neural process that acts specifically to reduce activity in the transmission system.
Perception: the subjective awareness produced by sensory signals.
Pain Pathway interventions: Nociception
Can be in inhibited by local anesthetics, opioids and NSAIDS
Pain Pathway intervention: Transmission along peripheral nerve
inhibited by local anesthetics and alpha 2 agonists
Pain pathway interventions: spinal cord sensitization
inhibited by opioids, NSAIDS, NMDA antagonists, alpha 2 agonists and local anesthetics
Pain pathway interventions: conscious perception
Inhibited general anesthetics, opioids and alpha agonists.
Effects of opioids: Sedation
CNS depression or excitement (in cats)
Effects of opioids: termoregulation
hypothermia mostly, but come can show hyperthermia in cats.
Effects of opioids: chemoreceptor trigger zones
can see nausea and vomiting. Seen more commonly with morphine.
Effects of opioids: depression of coughing reflex
used as an antitussive
e.g. codeine or butorphanol
Effects of opioids: mydriasis or miosis
Depending on CNS depression or stimulation.
Effects of opioids: respiratory depression
Dose dependent
Can also be due to decreased respiratory responsiveness to chemoreceptors in the brainstem.
Help respiratory function depending on the case (e.g. thoracotomy)
Effects of opioids: cardiovascular system
Bradycardia but responsive to anticholinergics
Morphine can cause rapid histamine release and can cause vasodilation and hypotension if given IV
Generally though, opioids have minimal effects on cardiac output, cardiac rhythm.
Effects of opioids: GI system
defecation and bowel movements, but can also lead to constipation (especially long term)
Morphine
Full opioid agonist that works on Mu, Kappa and Delta receptors.
Natural narcotic
Duration: 3-4 hours
Use with caution when giving IV because of histamine release
poor lipid solubility so in epidural space 12-24 hours.
Fentanyl
Pure mu agonist, with 100x potency compared to morphine.
Fast onset (approx 5 minutes) and short duration of action (approx 30 minutes) - makes it ideal for CRI
Common effects include apnea and bradycardia (monitor HR and RR) with high doses
Lipid soluble therefore can be administered as patches. 24 hours in dogs and 12 hours in cats for full effect. Last up to 72 hours.
Methadone
Synthetic mu agonist with 1.5x the potency of morphine.
Duration of time is 2-4 hours
Can give TM in cats
Can cause more dysphoria but less likely to vomit
More affinity to NMDA and alpha 2 adrenergic receptors so can help with wind-up pain.
Oxymorphone
Synthetic mu opioid and 10x the potency of morphine.
Less likely to make patients vomit
Good for patients with respiratory considerations because less likely to cause any panting.
Hydromorphone
Less to cause panting
Remifentanyl
50x potency of morphine
Faster acting than Fentanyl
Unique because it is metabolized by non specific plasma
Independent in kidney and liver metabolism.
Buprenorphine
Semisynthetic partial mu agonist with partial to no effect on Kappa receptor.
Higher affinity for mu receptors, so can displace morphine if administered at the same time, but cannot elicit maximum clinical response therefore only used to treat mild to moderate pain.
Duration 6-12 hours depending on dose and route of administration.
Butorphanol
Agonist/antagonist
good sedation when used in conjunction with acepromazine or benzodiazepine.
Works at Kappa receptors - 5x potency at kappa receptor than morphine
Antagonizes mu receptor.
Also has antitussive properties.
Naloxone
Mu antagonist
higher affinity to mu receptors
reverses opioids
duration of action 20-40 minutes
Onset within 1 minute
Quick onset - naloxone should be titrated to effect to avoid adverse effects
May need additional doses
Theoretically PVC can be seen
Can be used to reverse agonist and agonist/antagonist drugs but will not reverse buprenorphine.
Ketamine
NMDA antagonist
increase HR/BP due to indirect stimulation of cardiovascular system
Increases intracranial pressure
Cats increase sensitivity - hallucinaations, ataxia, hyperflexia (administer with muscle relaxant)
Good somatic analgesia but poor visceral analgesia
Local anesthetics pathophysiology
Reversibly bind to sodium channels and block impulse in nerve conduction
Sensation disappear in the order of: pain, cold, warmth, touch, deep pressure
Sensory blockade will usually persist longer than motor blockade
Meditomidine, dexmeditomidine, xylazine
Alpha 2 agonist
sedation and hypnosis, analgesia and muscle relaxation.
Metabolized in liver and excreted by kidneys
Cardiovascular effects - spike in arterial blood pressure and reflex bradycardia - can see dysrhythmias
Can see pale mucous membranes
emesis in cats
Contraindicated in cardiac cases, renal failure and obstructed urinary tracts as it tends to lead to increase urine output
Lidocaine vs bupivicaine
Lidocaine duration of effect is 1-2 hours
Bupivicaine is cardiotoxic should not be delivered IV, duration 2-6 hours
Diazepam/ketamine
can cause cardiopulmonary depression
Prolonged effects in patients with hepatic or renal dysfunction
Cardiovascular effects include:
- tachycardia
- increased blood pressure
- increased cardiac output
- increased myocardial oxygen consumption
Good analgesic properties
muscle relaxant
