Lecture 8: Premed Drugs for the Anesthetic Px (Exam 2) Flashcards
Why do we premedicate
- Ease of handling px
- Lower dose of induction & maintenance drugs
- Pre- emptive analgesia
- Smoother recovery period
T/F: Many px are stressed in the hospital environment
True
What occurs if there is an effective premed
- Lower amount of drugs needed later
- Min alveolar concentration (MAC) sparing effect for inhalant anesthetics
What are the benefits of pre med
- Lower amount of drugs need later
- Synergistic effect from combo produces better results than a single drug
- Decreased cost b/c lower amount of induction & maintenance drug used
What is the theory of pre emptive or preventative analgesia
- Reduces the amount of anesthetics req to produce a surgical plane of anesthesia
- Stabilize the maintenance of anesthesia
- Reduces the amount of analgesics req intra-operatively & postoperatively
- Decreases overall px morbidity assoc w/ surgery& anesthesia
What is the preferred method for admin
IM or IV is preferred over SQ injection
When is IM usually used
Given in more anxious or fractious px to facilitate IV catheter placement
When is IV admin used
Px already has a catheter, the dose usually can be lowered due to more immediate onset & greater degree of effect
What are the commonly used drug classes for premed
- Anticholinergics
- Phenothiazines
- Alpha 2 agonists
- Benzodiazepines
- Opiods
Describe anticholinergics
- Not routinely included in pre med unless high vagal tone is currently suspected or a pediatric px
- Prefer to give them only as req during anesthesia
- High doses inhibit urinary & GI tract mobility (use cautiously in horses & cattle b/c colic & rumen stasis may occur)
Describe atropine
- Able to cross the blood brain barrier & placenta
- Limited ability of glycopyrrolate to cross
- Only one that causes pupil dilation (impairs vision & may lead to poor recovery in some species)
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What happens after giving anticholinergics as an IV injections
An initial increase in vagal tone may occur & a transient decreased heart rate or heart block can occur (this is followed by the expected increase in heart)
What occurs after an IV injection of atropine
- An initial increase in vagal tone may occur & a transient decreased heart rate or heart block can occur
- This is followed by the expected increase in heart rate
- It is recommend giving 1/2 atropine dose IV & the rest IM or SQ
What is a difference in glycopyrrolate
Less likely to cause an initial increase in vagal tone compared to atropine
What is the MOA of phenothiazines
Dopamine (D1 & D2) receptor antagoinist in the CNS
T/F: Acepromazine does relieve anxiety
False it just tranquilizes them
What is the most common phenothiazines
Acepromazine
What is the time peak effect of acepromazine
~ 15 min (IV) or ~ 30 min (IM)
What is the long lasting effects & reversal agent for acepromazine
- 4 to 8 H
- No reversal agents
What effect does acepromazine have that causes it to be avoided prior to skin testing for allergies
Antihistamine effect
T/F: Acepromazine alters thermoregulation (makes them cold)
True
How can acepromazine cause hypotension
- alpha 1 blockade which leads to vasodilation
- Giving epinephrine can cause a drop in BP b/c alpha receptors are blocked
In what situations should acepromazine not be used for
- Fractious or aggressive px or those w/ high anxiety
- Liver disease or portocaval shunts
- Valuable breeding stallions due to potential for paraphimosis (inability to retract penis)
- Von willebrand’s disease or other clotting disorders
- Shock or cardiovascular disease (reduced PCV due to splenic sequestration of RBCs)
Explain acepromazine in boxers & other short nosed breeds
- Spontaneous fainting or syncope may occur due to sinoatrial block caused by excessive vagal tone
- Use a low dose or another drug
What drugs are alpha 2 adrenoreceptor agonists
- Xylazine
- Detomidine
- Romifidine
- Medetomidine
- Dexmedetomidine
Describe Alpha 2 adrenoreceptor agonists
- Class of sedative drugs
- Overall effect in the px is sedation, muscle relaxation, & analgesia
What drugs are considered alpha 2 adrenoreceptor agonists
- Xylazine
- Detomidine
- Romifidine
- Medetomidine
- Dexmedetomidine
Where are the alpha 2 receptors (transmembrane G-protein coupled receptors) located
On the pre & post synaptic sites on nerves & cell membranes in the brain, spinal cord, & periphery
What is the MOA of Alpha 2 adrenoreceptor agonists
- Produces CNS depression by stimulation of pre & postsynaptic alpha 2 adrenoreceptors in the CNS & periphery
- This decreases NE release & reduces ascending nociceptive input -> decrease in CNS sympathetic outflow & decrease in circulating catecholmines
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T/F: Alpha 2 adrenoreceptor agonist can have effects on alpha 1 receptors
True
How can alpha 2 adrenoreceptor agonists be given
- IV
- IM
- Buccally
- Epidural
What determines the amount of cardiovascular effect
the affinity ratio btw/ alpha 2 receptors and alpha 1 receptors due to alpha 1 stimulation
How can alpha 2 adrenoreceptor agonist be reversed
W/ the use of alpha 2 adrenoreceptors antagoinists like yohimbine, tolazoline, & atipamezole
Why do alpha 2 adrenoreceptor agonist cause bradycardia
- Increased systemic vascular resistance (SVR) in the periphery
- Decreased sympathetic tone due to decreased NE outflow in the CNS
What is more important Cardiac output or BP
Cardiac output
What alpha 2 adrenoreceptor agonists can increase cardiac sensitivity to catecholamine-induced arrhythmias during halothane anesthesia
Xylazine
What cause cardia out put to fall 30 - 50% when giving alpha 2 adrenoreceptor agonists
B/C of decreased hear rate & increased peripheral vascular effect
What are the behavioral effects of alpha 2 adrenoreceptor agonists
- Aggression after admin is reported in horses
- If px if very nervous or excited it may show an inadequate response, startle when touched or a loud noise occurs
What are the behavioral effects of alpha 2 adrenoreceptor agonists
- Aggression after admin in horses
- If the px is very nervous or excited it may show an inadequate response startled when touched or a loud noise
What are the respiratory effects of alpha 2 adrenoreceptor agonists
- Hypoventilation or apnea due to respiratory center depression
- Decrease sensitivity to increased PCO2 in the respiratory center
- Horses & brachycephalic animals are prone to stridor dyspnea from upper airway obstruction
- Sneezing/itchy nose noted occasionally in donkeys
What are the GI & renal effects of alpha 2 adrenoreceptor agonists
- Decreased gastric acid secretions & GI motility
- May cause vomiting in dogs & cats
- Swallowing reflex obtunded
- Excellent analgesic for treating GI Pain
- Suppresses insulin release which causes hyperglycemia & glucosuria
- Reduces hepatic BF & rate of metabolism
- Inhibits anti-diuretic hormone & increases the release of atrial natriuretic factors which causes diuresis w/ increased Na & water excretion
what is the onset of Xylazine
- Fast onset (1 to 5 min) but only last 20 to 40 min after IV injection
T/F: Xylazine may induce premature delivery cattle due to oxytocin like effects
True
Describe detomidine
- Given IM or IV
- Is a gel than can be given subligually to horses
- Typically used in large animals
- Onset of action is slightly longer than Xylazine
Describe Romifidine
- Concentration is 1%
- Effects last 45 to 90 mins (up to 2 hrs) after IV injection
- Generally though to produce less ataxia than xylazine (became popular for use in dentals & other standing procedure)
- No FDA approved form in the USA
Describe Dexmedetomidine
- Dextrorotarory isomer (the active optical enantiomer of medetomidine)
- Similar effect w/ a lower dose (less drug muse be metabolized by the liver)
- Quick onset after IV admin ( 1 to 3 mins) & IM admin (5 to 10 min)
- Transmucosal takes longer (30 to 60 mins)
- Effects last 90 to 120 mins
- Reversed w/ atipamezole
Describe Medetomidine
- Trade name is Domitor (precursor to dexdomitor)
- Onset in about 10 mins after IM injection (faster if IV)
- Analgesia lasts about 30 mins but sedation can last up to 2 H
- Reversed w/ atipamezole
- Phased out & replaced w/ dexmedetomidine
Describe Zenalpha
- Newer drug
- Mix of medetomidine + vatinoxan
- IM use in dogs only
- Key points: Procedural sedation, short onset (5 to 15min), short duration (30 to 45 min), & CV stability/parameters maintained @ more acceptable levels
- Can be combined w/ other drugs (but reduce the label dose by 50%)
- Can use atipamezole IM to reverse side effects
What is the use of yohimbine
Reverse xylazine
What should be avoided when using tolazoline
The use in camelids
Describe atipamezole
- Alpha 2 antagonists
- Higher alpa 2: alpha 1 selectivity
- Reversal of medetomidine & dexmedetomidine
- The concentration of atipamezole was formulated so that the volume of injectate is the same (mL for mL) as the dose of dexmedetomidine (.5mg/mL) given
- Always given IM
- Effects seen w/in 5 mins
What are the uses of benzodiazepines
- Muscle relaxants
- Anti-anxiety effects
- Treatment of active seizures
- Used during anesthesia
What is the MOA of benzodiazepines
Enhances the activity of the CNS inhibitory neurotransmitter gamma-aminobuyric acid (GABA) by binding to a specific site on the GABA A receptor which opens chloride channels & hyperpolarizes the membrane
Describe benzodiazepines
- Reduces sympathetic output, minimal sedation, muscle relaxation, & antiseizure effect
- Min cardiovascular & respiratory effects
- No analgesia
Describe diazepam
- Must be formulated in propylene glycol to make drug soluble
- Rapid IV admin can cause bradycardia, hypotension, or apnea
- Metabolized in liver & duration of action in 1 to 4 H
- Increases appetite
- Paradoxical excitement & aggression can occur
- Water insoluble so dont give IM (poor absorption & painful)
Describe midazolam
- Water soluble (IM, IV, of via MM)
- More potent than diazepam
- Metabokized in the liver but metabolizes are inactive, so shorter acting w/ less risk of accumulation
- Better choice in sick, debilitated or older px
- Paradoxical excitement & aggression can occur
What is used to reverse benzodiazepines
Flumazenil
Who should not be given flumazenil
Epileptic px
What is the MOA of opiods
- Reversible combo w/ one or more receptors (mu, kappa, delta) in the brain & spinal cord
- Coupled to G-protein receptors that ultimately decreased conductance through calcium channels & open inward K+ channels which causes hyperpolarization of membranes & decreased propagation of action potentials
Where are opioids metabolized
- In the liver
- The metabolites of some drugs have analgesic properties
What are the CNS effect of opioids
- Sedation
- Euphoria
- Dysphoria
What are the respiratory effects of opioids
- Depression of the respiratory center response to hypercapnia & hypoxemia
- Cough suppression
- Panting
What is the main cardiovascular effect of opioids
Bradycardia
What are the GI effects of opioids
- Vomiting
- Defecation
- Salivation
- Decreased gastric emptying time
- ileus
(miosis/mydriasis) occurs in cats while (miosis/mydriasis) occurs in dogs when given opioids
- Cats = mydriasis (enlarged pupils)
- Dogs = Miosis (dilated pupils)
What are some other effects of opioids
- Increased urethral sphincter tone
- Inhibition of voiding
- Disruption of thermoregulation (dose-related)
describe morphine
- High affinity for mu receptors but some affinity for delta & kappa
- Hydrophilic compared to other opioids (longer duration of action the lipophilic opioids)
- Can cause histamine release & subsequent hypotension when given IV (less efficacious in cats)
- Duration is 4 to 6 H
- Dose dependent MAC sparing effect
Describe hydromorphone
- 5 to 10x more potent than morphine (can use less & get the same effects as morphine)
- Semi-synthetic pure mu agonist w/ similar properties to morphine
- Dose dep analgesia
- Duration: 4 to 6 hours (for acute surgical pain, lasts about 3 to 4 H)
- Hypothermia is reported in cats
- Less likely to vomit if given IV
How much more potent is fentanyl compared to morphine
100x
Describe fentanyl
- Synthetic pure mu agonist
- Fast onset (1 to 2 mins)
- Short duration (~ 30 mins)
- Lipophilic
- Can come in a transdermal patch
What is unique about remifentanil
It is metabolized by nonspecific esterases that occur in the body (mainly skeletal muscle). This leads to a clinical advatage of extremely rapid clearance that is not dependent on liver or kidney fxn
Describe remifentanil
- Half as potent as fentanyl
- Is metabolized by nonspecific esterases in the body (extremely rapid clearance that is not dep on the liver or kidney)
- Req a CRI b/c of rapid clearance
- Recovery ~ 3 to 7 min after discontinuation of CRI
Describe methadone
- Synthetic pure mu agonist
- Similar potency to morphine but causes less sedation & more dysphoria
- least likely of u-agonist opioids to cause vomiting
- NMDA receptor antagonist & serotonin reuptake inhibitor which could improve analgesia & help prevent dev of tolerance
- Duration: 2 to 6 H
- Very expensive & not currently in the US
Describe Butorphanol
- Mixed opioid agonist-antagonist (agonist @ kappa receptor & partial mu receptor agonist or mu antagonist)
- Used for mild to mod visceral pain, not effective for severe or ortho/dental pain
- Mild sedation & anti-tussive effects; less resp depression than pure mu agonists
- Duration of analgesia is 30 min to 2 H
- Can be used to reverse sedative or respiratory effect of pure mu agonists
Describe buprenorphine
- Partial mu agonist & an antagonist @ kappa receptors
- Not adequate for severe pain
- Higher receptor affinity & can displace pure mu agonist (makes it difficult to antagonize)
- Long duration of action (4 to 8 H, maybe 12) but slower onset of abt 30 M to an hour after IV
- Can be given IV, IM, SQ, or via oral transmucosal route (for cats)
How does buprenorphine cause a similar to full mu agonist
It must occupy a higher # of receptors
Describe SIMBADOL
- For SQ injectable use in cats for 24 H duration of surgical pain control
- Buprenorphine injection
- FDA approved for cats
- Up to 3 once daily SQ doses for a total of 72 H
Describe Transdermal buprenorphine (zorbium)
- FDA approved
- Postop pain control up to 4 days in cats
- Administered transdermally
- Risk of accidental exposure
What are some opioid antagonists
- Naloxone
- Nalmefene
- Nalorphine & diprenorphine
- Naltrexone
Describe Naloxone
- Used to reverse pure mu & mixed agonist/antagonists b/c it has a high affinity for mu & kappa receptors but no intrinsic activity
- Rapid onset & lasts 30 to 60 mins
What is neuroleptanalgesia
- A state of CNS depression & analgestia produced by the combo of a tranquilizer or sedative & analgesic drug
- Useful or pre med or short med or surgical procedures
- Bradycardia & respiratory depression can occur
- Px may or may not remain conscious
T/F: Cost & availability of drugs fluctuate in vet med
True
What are some examples of neuroleptanalgesia
- Acepromazine + opioid
- Benzodiazepine + opioid
- Alpha agonist + opioid
- For dental or standing procedure in horse
Fill out chart on slide 64
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What should be considered for anesthesia of obese px
- Opioids & propofol may depress ventilation or cause apnea, so monitor ETCO2, arterial blood gases, & be ready to provide ventilation
- Avoid alpha 2 agonists if possible due to cardiovascular depression
- Continue oxygen in recovery & keep intubated until px can maintain airway
- Reduce vol of drugs given via epidural route
