Injectable Drugs Flashcards
What is the purpose of Injectable Agents?
To induce Anesthesia
What is the definition of Anesthesia?
- Without sensation, without pain
Includes NAP:
Narcosis
Analgesia and autonomic reflex suppression
Peripheral skeletal muscle relaxation/ immobilization
What is GABA, and where is it found?
Gamma-amino-butyric acid
- The main inhibitory transmitter present in the CNS
How many receptors does GABA have?
2
GABA a: receptor operated ion channel
GABA b: G-protein coupled receptor
All anesthetic agents seem to target and affect the _____ _______ somehow
GABA receptors
What happens when anesthetic drugs bind to the GABA receptors?
- Promote GABA release
- Assist GABA binding
- Promote greater channel open time to hyperpolarize excitatory channels and thus rate of excitatory firing
What are the most commonly used anesthetic injectable agents in small animal practice?
- Propofol
- Alfaxalone (especially in pediatric patients)
+ Ketamine
What is the mechanism of action of Propofol?
- Enhances the inhibitory effects of GABA at the GABA a receptor
note: higher doses of Propofol will improve the activity of glycine receptors and inhibit nicotinic Ach receptors (causing an inhibitory effect of the ANS, both PNS and ANS?)
What is the % protein binding, pH and pKa of Propofol?
% Protein binding: 95%
pH: 7.8
pKa: 11
Where in the body is Propofol metabolized and excreted?
Metabolized: liver (maybe the lungs too)
Excreted: urine and bile (can cause the urine to go green-yellow)
What are the risks associated with using Propofol in cats?
- Have longer recoveries (metabolism capabilities are reduced)
- Can cause Heinz body anemia (due to oxidative injury)
Can Propofol be used in the pregnant animal?
Yes, although Propofol does cross the placenta it is rapidly removed from fetal circulation
What are the effects of Propofol on the CNS?
- Hypnotic
- Depresses CNS activity
- NO ANALGESIA
- Anticonvulsant: used in seizure management
- Anti-oxidant and free-radical scavenging properties (similar to Vit E)
- Antiemetic effects too
-Reduces intracranial pressure: thus is favoured in head trauma patients
What are the effects of Propofol on the CVS?
- Vasodilation
- Hypotension: by resetting the baroreceptors in the aortic arch and carotid bodies, this means the body will NOT naturally compensate for the drop in BP and thus the BP remains low (e.g. HR and SV do not increase)
- Bradycardia
+/- Nitric oxide release leading to FURTHER vasodilation
What are the effects of Propofol on the Respiratory System?
- Central respiratory depression: can last several mins and may need manual ventilation
- Bronchodilation
- Inhibition of laryngeal reflexes
- Apnea post induction
- Transient cyanosis at induction
What are the effects of Propofol on the pancreas?
In human medicine it has been linked to pancreatitis, while this isnt noted in vet medicine very often, it is important to avoid Propofol in a patient with pre-existing pancreatitis
Why might Propofol be avoided for constant rate infusion in cats?
Due to the risk of Heinz body anemia (due to oxidative damage of feline red cells)
Which stage and plane of anesthesia is considered appropriate for most surgery?
Stage III, and trying to keep patient between planes 2 and 3 (moderate and deep)
What is the mechanism of action of Alfaxalone?
- It enhances the inhibitory effects of the neurotransmitter GABA at the GABA receptors
What is the % protein binding and pH of Alfaxalone?
% Protein binding: 17 - 50%
pH: 6.5 - 7.0
Where in the body is Alfaxalone metabolized and excreted?
Metabolized: liver
Excreted: urine and bile
What are the effects of Alfaxalone on the CNS?
- Rapid relaxation and induction
- Reduces Cerebral Metabolic Rate and Cerebral Blood Flow: similar to Propofol, but Propofol will always be 1st choice in head trauma patients with increased intra-cranial pressures
What are the effects of Alfaxalone on the CVS?
Fewer CVS effects than Propofol
- NO hypotension in healthy patients
- Mild tachycardia: as a response to mild vasodilation
What are the effects of Alfaxalone on the Respiratory System?
Minimal: only when injected slowly and appropriately: given over a 60 sec period
BUT, significant resp depression is seen in overdoses or given too quickly
Does Propofol and Alfaxalone provide analgesia?
No
Between Propofol and Alfaxalone, which is a better induction and maintenance agent for cats?
Alfaxalone: not metabolized by glucoronidation, and no Heinz body anemia seen
What is the mechanism of action of Ketamine?
- Antagonist of NMDA receptors
Binds to the receptor and prevents Ca++ from entering the cell, thus excitatory function is limited
What is the % protein binding and pH of Ketamine?
% Protein binding: 50%
pH: 3.5 - 5.5
note: so acidic, it will sting upon IM or SQ injection
Where in the body is Ketamine metabolized and excreted?
Metabolized: liver
Excreted: urine
Can Ketamine be used in dogs and cats with renal dysfunction?
Dogs with renal dysfunction: Yes, due to excretion as an inactive metabolite
Cats with renal dysfunction: No, due to excretion as an ACTIVE metabolite
What are the effects of Ketamine on the CNS?
- Dissociative anesthesia
Superficial sleep, amnesia + Analgesia
May appear ‘awake’ but immobile and unaware of surroundings: eyes wide open- must lube
Palpebral, laryngeal and eye reflexes are maintained - Can induce seizure-like activity
- Increases Cerebral Metabolic Rate and Cerebral Blood Flow
What are the effects of Ketamine on the CVS?
- Increase HR and BP: this can increase intracranial pressure
Why must Ketamine never be used for induction of Moribund patients?
- Causes a direct negative inotropy on the heart + vasodilation, which WILL kill your patient
What are the effects of Ketamine on the Respiratory System?
- Mild, transient decrease in ventilatory rate and tidal volume
- Apnea
- Increased salivation and respiratory secretions
- Bronchodilation: good for asthmatic patients
What is Tiletamine, and what species is it used for?
Tiletamine is an analogue of Ketamine: thus has similar pharmacology
Used in darts for wildlife (except Tigers!)
What are the differences between the S(+) and R(-) enantiomers of Ketamine?
- S(+) is 3-4x more potent that R(-)
- S(+) is 2x longer in action than R(-)
- S(+) provides more analgesia than R(-)
- S(+) provides less dysphoria R(-)
note: in human medicine you can get pure S(+) Ketamine, however this is VERY expensive
note: in vet medicine, we use a Ketamine that has BOTH S(+) and R(-), making it more affordable
What are the most commonly used Barbituates used in vet medicine?
Thiobarbiturates: thiopentone, thiamylal = short acting
Oxybarbiturates: pentobarbital, phenobarbital = long acting
What is the mechanism of action of Thiopentone?
- Binds to GABA receptor
- Enhances inhibtory effects of GABA by increasing the binding of GABA and benzodiazepines, and allowing a longer opening time for Cl- ions and the cell becomes hyperpolarized and impulse transmission is slowed down
- This is used as an induction agent, as it produces unconsciousness through gradual depression of the CNS
What is the pH and pKa of Thiopentone?
pH: 11 - 12 (HIGHLY alkaline): must never be administered any other way except IV
pKa: 7.6
Where in the body is Thiopentone metabolized and excreted?
- Metabolized: liver
- Excreted: urine
What are the effects of Thiopentone on the CNS, CVS, RS and Kidneys?
CNS:
Hypnosis
Reduced metabolic rate and oxygen consumption: thus reducing cerebral blood flow and intracranial pressure
CVS:
Vasodilation + Hypotension
Tachycardia as a compensatory mechanism
Arrythmias
RS:
Depression: Intubation is required
Kidneys:
Decreases renal blood flow
What are the uses of Thiopentone?
- Emergency management of gross movement during horse anesthesia
- Control of convulsions
- Neurosurgical patients: due to the profound decrease in intracranial pressure
What is the use of Pentobarbitone?
Euthanasia solution
What are the effects of Pentobarbitone on the CNS, CVS, and RS?
CNS: loss of consciousness + anticonvulsant
CVS: hypotension and tachycardia
RS: depression
What is the use of Etomidate?
Alternative to thiopental or propofol for anesthetic induction in small animals, especially in patients with:
- Preexisting cardiac dysfunction: minimal effects on the CVS
- Head trauma
- That are critically ill
note: may be used for immersion anesthesia in certain exotics e.g. frogs
What are the risks or cautions associated with Etomidate?
- Decreases Hypothalmic pituitary axis, thus inhibiting the conversion of cholesterol to cortisol, thus risking the patient to develop addisons disease
- Can cause histamine release
- Can cause paddling of the limbs during induction
