Anethestic Drugs Flashcards
What effect does hypoalbuminemia have on anesthetic drugs
Decreases bound fraction of some drugs (increases free drug) which can result in changes in volume of distribution, plasma concentration, and drug effect (e.g. NSAIDs are tightly protein bound)
Which direction do opioids shift the CO2 response curve when given alone
When given alone, opioids shift the CO2 response curve to the right with little change in slope
What is the primary analgesic effect of tramadol
Metabolism of tramadol to M1 and M1 acts as a full mu opioid agonist
Analgesia via opioid and non-opioid (monoamine uptake inhibition) mechanisms
How is tramadol excreted
Excreted largely unchanged in the urine - no liver metabolism
Why is efficacy of tramadol weak in dogs
Dogs do not produce large amounts of M1 and studies show in humans that don’t form M1 from tramadol have little to no effect of the drug.
Fentanyl potency
100x more than morphine
Fentanyl pitfalls
More likely to cause apnea and bradycardia when given as a bonus compared to other opioids
Can cause wooden chest - chest wall rigidity
Remifentanil - what is it, metabolism, and benefit
Analogue of fentanyl
Metabolized by plasma esterases therefore it has a short half life.
Good if you want a patient to wake up quickly
Methadone potency
2x more than morphine
Why does methadone cause less excitation in cats
It is an NMDA antagonist
Buprenorphine potency
40x more potent than morphine
Buprenorphine advantages
Causes less ileus
Ceiling effect - not associated with increased analgesia but higher doses do cause longer duration
Advantages of Alfaxalone over propofol
Less decrease in cardiac output and apnea
Can be given IM
Alfaxalone MOA
Steroid anesthetic
Enhances GABA and glycine mediated CNS depression
Propofol MOA
Unrelated to steroid anesthetic
GABA agonist: Inhibits CNS
Disadvantages of propofol compared to Alfaxalone
Benzyl alcohol formulation shouldn’t be given repeatedly or in CRI to cats (can cause CNS toxicity - hyperesthesia and depression)
More likely to cause apnea
CV effects: Hypotension from vasodilation; decrease in SVR and CO
Propofol advantages
Appropriate for patients with liver failure - extrahepatic metabolism sites
Used to treat refractory status epilepticus and reduces ICP
Lipid solubility of morphine
Relatively low lipophilicity
Dopamine MOA
Stimulates endogenous norepinephrine from presynaptic storage sites at adrenergic receptors to cause sympathomimetic effect
Dopamine dosing and what receptors predominate
Low dose (1-2 mcg/kg/min) - dopamine and DA-2 receptors
Medium dose - B1 and B2 adrenergic receptors
High dose >10 mcg/kg/min - A1-adrenergic receptors
Effects of B1 and B2 adrenergic receptor stimulation by dopamine
Increases myocardial contractility, HR, CO, and coronary blood flow
Effects of A1-adrenergic receptor stimulation by dopamine
Increases SVR, pulmonary vascular resistance, venous return, and PCV (via splenic contraction)
MOA of vasopressin
Non-catecholamine vasopressin that acts on the peripheral vessels (V1a, V1b, and V) while decreasing cellular hyperpolarization and increasing intracellular calcium concentration
What is the MOA of doxapram and its effects on glottal gap
Analeptic (CNS stimulant) with central and peripheral effects. Increases activity of the respiratory nuclei of the medulla
When given to dogs with larpar: glottal gap area at inspiration was reduced and significantly greater during exhalation
What class of drugs are atropine and glycopyrrolate
Anticholinergics, parasympatholytics, antimuscarinics
Anticholinergics and GI motility and other GI effects
Dose required to decrease GI motility via blockade of M3 receptors is higher than that required to treat bradycardia
Decreases lower esophageal sphincter function which may lead to increased risk of gastroesophageal reflux
Atropine MOA
Does it cross the BBB
Anticholinergic- competitive, reversible antagonist of muscarinic receptors (M1- M5) inhibiting ACh release
Yes and blood placenta barrier
Can cause sedation
Glycopyrrolate and GI motility
Decreased for up to 30 minutes in dogs
Glycopyrrolate BBB and blood placenta barrier
Does not cross
Dobutamine MOA
Synthetic catecholamine
Primarily B1 adrenergic
Higher doses - B2 and A1 adrenergic receptors
Augments CO states associated with reduced myocardial function
Dobutamine effects
Limited effects on BP
Increases CO, HR, and SVR
Dexdormitor and its receptors
Mainly alpha 2 agonist with some peripheral alpha 1 agonist
What are the alpha 1 agonist effects of dexdormitor
Vasoconstriction, hypertension, arrhthmogenicity, and paradoxical excitation.
Reflex bradycardia due to hypertension which leads eventually to hypotension
Side effects of dexdormitor
Hyperglycemia, diuresis, and respiratory depression
What are the consequences of giving an Anticholinergics with dexdormitor
Greater hypertension which increases the myocardial work
Gabapentin MOA
Structural analogue of GABA but does not interact with GABA, NMDA, or dopamine
Inhibits N-type voltage dependent neuronal calcium channels
Gabapentin excretion
By the kidneys
What was amantadines original use
Antiviral agent then for Parkinson’s, TBI and pain
Amantadine MOA
Dopamine agonist and NMDA agonist
Ketamine in terms of somatic pain and dosing
Subanesthetic doses of ketamine produce profound analgesia especially in situations of somatic pain
Can ketamine be given via an epidural
Yes
Ketamine side effects
Catatonic state Increases salivation, ICP and IOP
Eyes remain open and swallowing reflex is maintained
Produces mild sympathomimetic effect - increases myocardial work
What are the two categories of NMBAs and name an example of each
Depolarizing - Succinylcholine
Non-depolarizing - Atracurium
Atracurium duration of action
Dose dependent duration of action 5-30 minutes
Succinylcholine MOA and possible disadvantage
Mimics effects of acetylcholine
Initial depolarization of all skeletal muscle - looks like fasciculations
Trigger for malignant hyperthermia
Elimination of Atracurium
Degraded by Hofmann elimination - independent of liver and renal excretion
What is the TOF - train of four
In relation to NMBA
When 70% of receptors are occupied by a NMBA the twitches will fade beginning with the 4th, then the 3rd, then the 2nd then the 1st
NMBA reversals
Anticholinesterase
Edrophonium, neostigmine, and pyridostigmine
NMBA reversals MOA and side effects
Inhibit enzyme anticholinesterase increasing the concentration of ACh molecules at the neuromuscular junction
Can cause cholinergic crisis - SLUDD signs - give Anticholinergic to treat
Edrophonium MOA
Reversible inhibition of electrostatic attachment to the an ionic site and by H bonding at the esteratic site on acetylcholinesterase
Neostigmine and pyridostigmine MOA
Inhibit acetylcholinesterase by forming carbamyl-ester complex at the esteratic site of acetylcholinesterase
List opioids from least to most potent
Meperidine -> Morphine -> Methadone -> Hydromorphone -> oxymorphone -> buprenorphine -> fentanyl
Meperidine disadvantage
Causes severe histamine rerelease
When given with MAOI can cause serotonin syndrome
NSAIDs MOA
Arachidonic acid is the predominant fatty acid in animal cell membranes and biotransforms into eicosanoids. Prostanoids are eicosanoids metabolized by prostaglandins (PGD2, PGF2a, and PGE2), PGI, and TXA2. Arachidonic acid is acted upon by COX or LOX enzymes to form eicosanoids.
NSAIDS inhibit COX enzymes and alter the formation of prostanoids
COX - 1 (prostaglandin synthase-1): type of enzyme? Responsible for?
Constitutive enzyme
Responsible for normal physiologic function
COX -2 (prostaglandin synthase-2): type of enzyme? Responsible for?
Inducible enzyme
Usually unregulated (induced) by inflammation
May be unregulated during renal stress as a protective mechanism
GI stress - protective and healing.
Robenacoxib with or without food
Give fasted - cats absorption was 49% vs 10% when given with food. In dogs 84% absorption without food and 62% with food.
NSAIDs effects on the spinal cord
NSAIDs inhibit prostaglandin in both the peripheral and nervous systems (spine and brain)
NSAID GI toxicity
Direct irritation of the drug on the GI mucosa and prostaglandin inhibition
Inhibition of prostaglandins results in decreased cytoprotection, diminished blood flow, decreased synthesis of protective mucus, and inhibition of mucosal cell turnover and repair.
What type of drug is carprofen
Selective COX-2 inhibitor
Carprofen and phenobarbital
Animals on phenobarbital are more susceptible to hepatotoxicity
NSAIDs mechanism of renal injury
Prostaglandins modulate tone of blood vessels and regulate salt and water balance in the kidneys
COX 1 and COX 2 maintain renal blood blow and ion transport within the nephron
AKI from inhibition of renal prostaglandin synthesis
AKI is characterized by decreased renal perfusion, sodium, and fluid retention, decreased tubular function, and azotemia
Meloxicam in cats
Labeled for chronic use in cats outside of US
Give with food and when cats are euvolemic at a low dose 0.01-0.03 mg/kg/day
How do NSAIDs aid in treating OA
Canine chondrocyte cell cultures revealed that carprofen increases rate of PGAG synthesis which can be chondroprotective
Dual inhibitors (COX and lipoxygenase) may slow progression of OA
NSAIDs and liver injury
Idiosyncratic - carprofen and others
Intrinsic - aspirin and acetaminophen
Undergo extensive hepatic metabolism and the liver is exposed to high concentrations of the parent drug and its metabolites
Usually reversible with supportive care
Misoprostal type of drug and what its used for
Synthetic PGE analog that prevents and helps heal GI ulceration
Name four effects of PGE on the kidney
Maintains renal blood flow and ion transport within the nephron
Increases salt excretion and increases water excretion
Maintains water hemostasis and tubular function
Regulates the release of renin
Name 5 effects of PGE on the stomach
Maintains gastric mucosal layer
Quality of gastric mucous
Mucosal blood flow
Production of gastric acid
Bicarb secretion
Acetaminophen in cats and MOA of injury
Cats have a phase II/ acetaminophen metabolizing enzyme deficiency
acetaminophen is shunted to phase 1 enzymes which produce toxic oxygen radicals leading to methemoglobinemia and potentially hepatic necrosis
