Pharmacology of Injectable Drugs Flashcards
What are the advantages of injectable anaesthesia?
- Little equipment needed (syringes, needles, IV catheters)
- Usually, easy to administer
- Induction of anaesthesia can be rapid & smooth
- Possibly relatively cheap
- Limited environmental pollution (inhalants –> Greenhouse effect; plastics)
What are the disadvantages of injectable anaesthesia?
- Once given, retrieval is impossible
- The P must be weighed accurately to calculate the dose, esp in the smaller animals!
- Dose readjustment in sick/debilitated animals
- Some drugs have the potential for human abuse
- Risks of inadvertent self-administration
All drugs have the potential to cause…
apnoea, so be prepared for immediate intubation
propofol is what type of injectable anaesthetic?
non-barbiturate
What is the MoA of Propofol?
- GABA(alpha) receptor (beta subunit) –> slows down closure, activates directly
- indirectly potentiates activation of the channels
- direct in high amounts, will directly activate GABA
Propofol solubility
Insoluble in water
highly lipid solube
Propofol formulation contains…
10% soybean oil
2.25% glycerol
3.1.2% purified egg phosphatide
Great media for bacterial growth
If no preservatives are present in Propofol, how long is the vial good for?
24 hrs
Propoflo 28/PropoVet multidose uses what as a preservative?
benzyl alcohol, which can accumulate & be toxic
Do not use for TIVA
What is the propofol onset of action?
60-90 sec or faster
What is the duration of action of Propofol?
About 10-15 min of anaesthesia
Propofol is suitable for…
inductions & maintenance as CRI (preservative-free only)
Protein binding of propofol?
- Free fraction in plasma only 1.2-1.7%
- Binds to albumin/erythrocytes
- Low RBCs impacts dosage
- Free fraction in CSF 31%
Elimination of Propofol?
Exceeds hepatic blood flow
Extra-hepatic metabolisation sites –> kidneys, SI, lungs?
Metabolite: glucuronidation into non-active metabolites
Propofol has dose-dependent CV depression which causes what signs?
- vasodilation
- negative inotropic
- reduction of CO
- compensatory increase in HR abolished
Dose & rate dependent respiratory depression caused by Propofol causes what signs?
hypoventilation
apnoea
Propofol does not have
analgesic properties
What are the neuroprotective effects of Propofol?
Decreases ICP, cerebral metabolic rate (CMRO2), & cerebral perfusion pressure in P’s w/ high ICP
What is unique about propofol usage in cats?
- prolonged recoveries after repetitive boluses or long infusions
- feline hgb prone to oxidative injury by phenolic compounds which decrease PCV –> Heinz body anaemia if given several boluses over multiple days
- TIVA - difficult recovery
- Repeated or prolonged propofol anaesthesia leads to: anorexia, depression, D, facial oedema, delayed recovery
What patients indicate the use of propofol?
- C-sections
- Renal p’s
- Hepatic p’s
- TIVA
What are the patient contraindications of Propofol?
- hypovolaemia/shock
- heart failure
- diabetic hyperlipidaemia/pancreatitis?
- avoid repeated propofol/>30 min TIVA in cats
What are the main uses of Propofol?
- Sedation in SA
- induction of anaesthesia
- balanced anaesthesia
- maintenance (TIVA/PIVA)
Alfaxalone is what kind of anesthetic?
steroid
Alfaxalone is licensed in what species?
dogs, cats, rabbits, other wildlife
What route of admin is used with alfaxalone?
SQ, IM, IV
Alfaxalone solubility
insoluble in water
Alfaxan formulation does not have what side effects that were present in Saffan?
- no histamine release
- no perivascular necrosis
What is the mechanism of action of alfaxalone?
- increases Cl- conduction of cell –> inhibitory effect
- Works on Gaba(alpha)
What are the physico-chemical properties of Alfaxalone?
- colourless sln
- commercial prep 10 mg/ml
- does not irritate tissues
- does not promote bacterial growth
- 28-day shelf life in multidose formulation
Onset of action of Alfaxalone?
30-60 sec
Duration of action of Alfaxalone?
10 mins
Metabolism & excretion of Alfaxalone?
Phase I of liver via cytochrome p450
What are the effects of Alfaxalone?
- rapid loss of consciousness
- smooth induction
- good muscle relaxation
- duration of effect depending on dose/redosing
- resp depression/apnoea (dose/rate dependent)
- hypotension
- myoclonus & opisthotonus possible in recovery
Alfaxalone is suitable for use as CRI in…
CATS
What are the indications and clinical use of Alfaxalone?
- induction in small animal/rabbits/reptiles/birds
- slow titration to effect
- no analgesic effects
- use in C-sections
- TIVA
What are the main dissociatives used for injectable anaesthesia?
Ketamine, Tiletamine (+ Zolazepam), Thiopental, Etomidate
What are the main features of dissociatives?
- dissociation btw thalamic & limbic system
- fxnl disorganisation of CNS
- analgesia, amnesia
- maintained reflexes
- catalepsy –> muscular rigidity
What is the MoA of Ketamine?
- NMDA antagonism
- Binds: opioid, cholinergic, adrengergic, GABA(A) receptors; Na+ channels
What are the physico-chemical properties of Ketamine
White crystalline powder
slns: 1, 5, 10%
preservative: benzethonium chloride
pH: 3.5-5.5 (pain on inj IM, esp in cats)
stable sln, protect from light/heat
What are the routes of admin of Ketamine
IV, IM, SQ, IP, transmucosal, epidural
What are the pharmacokinetics of ketamine?
- rapid distribution
- protein binding 50-60%
- rapid cross BBB (highly lipophilic)
What is the metabolism & excretion of ketamine?
Liver metabolism: ketamine (Active metabolite) –> norketamine (Active) –> inactive glucuronide metabolites –> excreted via kidney
What is unique about ketamine in cats and kidney dz?
- excrete some metabolite, metabolisation can stop at norketamine
- problems w/ kidneys –> prolonged duration of action = longer recovery
What are the CV effects of ketamine?
- reduced inotropism - direct effect on heart; critically ill patients, hypotension
- sympathetic stimulation: increased HR/MAP/CO/O2 consumption, if depleted of catecholamines, there is limited sympathetic stimulation
What are the CNS effects of ketamine
- does not appear to be asleep
- no response fom external stimuli
- increase in ICP (vasodilation & increase in BP)
- increase in CMRO
- Seizures?
What are the main resp system effects of ketamiine?
- minimal resp depression: maintains response to hypoxia & CO2, apneustic breathing pattern, transient apnoea if IV fast
- potentiates resp depression of other CNS depressants
- bronchial smooth muscle relaxation: bronchodilation, decreased airway resistance, clinical uses
- pharyngeal/laryngeal reflexes maintained: uncoordinated,** not protective, caution in upper airway exams/upper airway obstruction**
What are other effects of ketamine?
- pain at IM inj
- poor muscle relaxation
- central eye, increases IOP
- analgesia/anti-hyperalgesia
What are clinical uses & indications of ketamine?
- anaesthesia induction in every species; key in horse & wild/exotics
- peri-op analgesia/anti-hyperalgesia/ balanced anaesthesia: CRI for analgesia
- licensed in cattle
- to achieve IV access by giving IM inj
What are the contraindications of ketamine?
- HCM
- increased ICP
- increased IOP
- kidney dz in cats
What is the mechanis of action of Telazol/Zoletil?
- Zolazepam: Benzodiapine –> cannot remove tiletamine side effects (muscle rigidity/seizure-like manifestions), addition of alpha-2/opioids
- analgesia
- short shelf-life once reconstituted
What are the effects of Telazol/Zoletil (Tiletamine + Zolazepam)?
Onset: 60-90 sec IV, 2-10 min IM
other effects similar to ketamine
rough recoveries if redosing occurs in dogs/horses
Indications & clinical use of Tiletamine + Zolazepam
Induction of anaesthesia
Transport (wild/exotics)
Do NOT use in large felids
High doses of tiletamine + zolazepam can be used in what species?
cats for surgical anaesthesia
What is the mixture using Telazol for shelter medicine?
TTDex
Telazol
Torbugesic
Dexdomitor
Contraindications of Tiletamine + Zolazepam
- avoid in patients w/ head trauma/intracranial tumours
- avoid in intraocular globe procedures/open globe
- HCM
Thiopental is not
used anymore
Main effects of thiopental
- Rapid loss of consciousness
- Single bolus: 5-10 min anaesthesia
- Anti-epileptic, reduced ICP
- Marked resp depression
- Hypotension, reduced CO, vasodilation, arrhythmias
- Perivascular inj: tissue necrosis
- STRICTLY IV INJECTION
- High pH, can cause extreme perivascular necrosis
Thiopental uses
- Induction in CV stable patients
- Fast endotracheal intubation
- “lar-par” exam
- Patients w/ increased ICP
- Seizures
- Bolus when horse is “superficial”
- Induction in horses
What are the uses of etomidate?
- Cardiac dz (ex. DCM)
- CV unstable patients
- Neurologic patients (seizures, increased ICP)
What are the main characteristics of etomidate?
- CV stability
- minimal resp depression
- myoclonus, dystonia, tremor
- neuroprotective - decreases cerebral metabolic rate & ICP
- NOT an analgesic
- Adrenocortical suppression
