Pharmacology: CSHT & Propofol Overview

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Questions and Answers

What is the correct administration timing for Propofol injection?

Over 10-30 seconds

Over 1-2 minutes (correct)

Over 5-10 seconds

Over 30-60 seconds

How is context sensitive half-time (CSHT) affected by the duration of infusion?

It increases with longer infusion durations. (correct)

It remains constant regardless of infusion duration.

It decreases with longer infusion durations.

It is unaffected by infusion duration.

What leads to the accumulation of Fentanyl in the body during long infusions?

Small volume of distribution

Immediate clearance from fat

High rate of systemic clearance

Large volume of distribution (correct)

What is a characteristic of Remifentanil compared to Fentanyl?

Fast clearance from the body Signup and view all the answers

If the initial drug concentration is 10 units/ml and the half-time is 30 minutes, what will the concentration be after 60 minutes?

2.5 units/ml Signup and view all the answers

What is the main physiological mechanism implicated in the condition described, characterized by decreased dopamine neurotransmission?

Excitation of subcortical pathways Signup and view all the answers

Which anti-muscarinic drug is NOT suggested as a therapy for the described condition?

Atropine Signup and view all the answers

What is the primary composition of the macroemulsion preparation of Propofol?

Soybean oil and egg yolk Signup and view all the answers

Which formulation of Propofol is associated with less pain on injection?

Propofol-Lipuro VetTM Signup and view all the answers

What is a significant risk associated with the microemulsion formulation of Propofol?

Thrombophlebitis and injection site reactions Signup and view all the answers

What is the primary mechanism of recovery from single injection bolus of propofol?

Redistribution and metabolism Signup and view all the answers

Which population may accumulate propofol due to their lower glucuronidation capacity?

Cats Signup and view all the answers

What effect does propofol have on blood pressure?

Causes hypotension through venodilation Signup and view all the answers

What type of reaction can occur in cats with repeated propofol injections?

Phenolic toxicity leading to Heinz body production Signup and view all the answers

Which receptor does propofol primarily act on?

GABAA receptor Signup and view all the answers

What is a notable side effect of propofol when given in large doses via rapid IV injection?

Respiratory depression and apnoea Signup and view all the answers

How does propofol metabolism differ in greyhounds compared to other breeds?

Lower hydroxylation capacity leading to slower metabolism Signup and view all the answers

What is the primary reason propofol can cause pain during IV injection?

Macro-emulsion formulation Signup and view all the answers

What is a key effect of maintaining metabolic rate and perfusion coupling in neuroprotection?

Improvement in cerebral perfusion Signup and view all the answers

Which formulation of Propofol has a higher chance of causing Heinz body formation in cats?

Emulsion with preservative Signup and view all the answers

What is the typical dosage range for induction of general anesthesia in unpremedicated cats using Alfaxalone?

5 mg/kg Signup and view all the answers

Which phencyclidine derivative is considered the most potent and longest acting?

Phencyclidine Signup and view all the answers

What effect does the S(+) enantiomer of Ketamine have compared to the R(-) enantiomer?

More potent and less psychoactive Signup and view all the answers

What is the primary indication for using Alfaxalone at 0.05 - 0.2 mg/kg/min?

Infusion for total intravenous anesthesia (TIVA) Signup and view all the answers

What type of anesthesia does Ketamine primarily cause?

Dissociative anesthesia with profound analgesia Signup and view all the answers

Which factor influences the stability of Ketamine in solution?

Low pH levels Signup and view all the answers

What is the primary reason for administering Alfaxalone in lower doses when α2-agonists are used for premedication?

Decreases the amount of anesthetic needed Signup and view all the answers

Which option describes the primary site of action for Propofol?

Central nervous system Signup and view all the answers

What is the primary mechanism by which ketamine provides analgesia?

NMDA receptor antagonism Signup and view all the answers

Which of the following effects can ketamine induce in terms of respiratory function?

Post-induction apnea Signup and view all the answers

How does ketamine affect muscle tone?

Induces involuntary muscle contractions Signup and view all the answers

What is the primary reason for caution when administering ketamine to cats?

Inability to metabolize norketamine further Signup and view all the answers

What kind of agents are barbiturates derived from?

Barbituric acid Signup and view all the answers

Which classification of barbiturates has the shortest duration of action?

Ultra-short acting Signup and view all the answers

What type of barbiturate is thiopental classified as?

Thiobarbiturate Signup and view all the answers

What is norketamine and what is its activity compared to ketamine?

An active metabolite of ketamine with 20-30% activity Signup and view all the answers

What effect does ketamine have on the cardiovascular system?

Increases sympathetic nervous system output Signup and view all the answers

Which characteristic distinguishes oxybarbiturates from thiobarbiturates?

Less lipid soluble and less protein binding Signup and view all the answers

What is the effect of ketamine on intracranial pressure?

Increases intracranial pressure Signup and view all the answers

Which of the following is a potential immunosuppressive effect of ketamine?

Reduction of cytokine production Signup and view all the answers

What happens to the elimination of barbiturates classified as oxybarbiturates?

Excreted unchanged in urine Signup and view all the answers

Which condition may lead to abnormal cardiovascular responses when administering ketamine?

Hyperthyroidism Signup and view all the answers

Study Notes

Context Sensitive Half-Time (CSHT)

CSHT is the time it takes for a drug concentration to fall by 50% after a continuous infusion is stopped.
CSHT is influenced by the duration of the infusion, meaning the longer the infusion, the longer the drug effect persists.
CSHT is influenced by the volume of distribution and the rate of systemic clearance of the drug.
Drugs with a large volume of distribution have a smaller volume in the central compartment, resulting in longer CSHT (accumulation, such as fentanyl).
Drugs with a rapid clearance have a shorter CSHT, leading to faster elimination from the body (such as remifentanil).

Propofol

Propofol is a general anesthetic available as a macroemulsion or microemulsion.
The macroemulsion is a lipid-based formulation available in two forms: with preservative (benzyl alcohol, PropofloTM) and without preservative (Propofol-Lipuro VetTM).
The formulation with preservative should be avoided for continuous rate infusions (CRIs) due to potential for benzyl alcohol toxicity, particularly in cats.
The microemulsion is a lipid-free (aqueous) nano-droplet formulation (PropoclearTM). This formulation was withdrawn from the market due to pain on injection, thrombophlebitis, and injection site reactions, potentially caused by rapid release of propofol from the nano-droplets.
Propofol has a high lipid solubility and is an agonist at GABA A receptors.
It is metabolized rapidly in the liver, lungs, kidneys, and gastrointestinal tract via glucuronidation and hydroxylation.
Cats may accumulate propofol due to their lower glucuronidation capacity (slower metabolism).
Greyhounds have a lower hydroxylation capacity, also leading to slower metabolism.
Propofol can cause urine coloration (green) due to excretion of phenolic metabolites.
Propofol is not an analgesic and can cause hypotension due to negative inotropy and venodilation.
It also depresses the baroreceptor reflex, potentially leading to bradycardia in response to hypotension.
Propofol can induce apnoea following a rapid intravenous (IV) injection, and it also depresses chemoreceptor function (decreased sensitivity to low blood oxygen and high blood carbon dioxide).
Despite the effects on respiratory depression, propofol can provide neuroprotection by maintaining cerebral metabolic rate and perfusion coupling, which reduces electroencephalogram abnormalities.

Alfaxalone

Alfaxalone is a general anesthetic available as a solution, administered intravenously (IV).
It is a potent GABA A receptor agonist, acting primarily on the central nervous system (CNS).
Alfaxalone is metabolized primarily in the liver but also to a lesser extent in extra-hepatic tissues.
Alfaxalone does not accumulate in cats.
Alfaxalone preserves the baroreceptor reflex, unlike propofol.
In cats, high doses of alfaxalone may be administered, but caution is needed because they may accumulate the drug.

Ketamine

Ketamine is an anesthetic that induces dissociative anaesthesia characterized by profound analgesia, light sleep, amnesia, catatonia, poor muscle relaxation, hypersensitivity to noise, active cranial nerve reflexes, and transient convulsive-like activity.
It is a racemic mixture of two enantiomers, S(+) and R(-), with the S(+) enantiomer being more potent and less psychoactive.
It is a basic drug and only stable in solution at a low pH, promoting a high proportion of the ionized form, which is less lipid soluble.
However, at body pH (7.4), the non-ionized form is favored, leading to high lipid solubility and rapid membrane crossing.
Ketamine's action onset is slow (1 to 2 minutes) because it promotes dissociative effects rather than unconsciousness.
Ketamine is metabolized via cytochrome P450 to an active metabolite, norketamine, which has 20-30% of ketamine's activity (10% in cats).
Dogs and horses further metabolize norketamine, but cats do not, so norketamine accumulates, potentially leading to prolonged recovery times.
Ketamine is an NMDA antagonist at spinal, supraspinal, and peripheral sites of action, facilitating analgesia.
This antagonism also contributes to anti-hyperalgesic effects by reducing the chances of CNS hypersensitization.
Ketamine can prevent tolerance to opioids and opioid-induced hyperalgesia.
Ketamine has cardiovascular effects, such as increased sympathetic nervous system (SNS) output.
It also possesses direct negative inotropic and vasodilator properties.
In animals with hyperthyroidism or phaeochromocytomas, it may induce arrhythmias.
Ketamine has minimal respiratory depression but may induce post-induction apnoea.
While maintaining ventilatory response to carbon dioxide (CO2), Ketamine also maintains hypoxic pulmonary vasoconstriction.
Ketamine causes irregular breathing patterns (apneustic breathing) and has bronchodilator properties.

Ketamine (cont.)

Ketamine increases intracranial pressure due to increased cerebral blood flow (CBF) but also has neuroprotective properties due to calcium channel and NMDA blockade.
Ketamine can be given intrathecally for nerve blocks requiring preservative-free solutions.
Ketamine may increase intraocular pressure due to increased contraction of extraocular muscles.
Ketamine has anti-inflammatory and immune system effects; it suppresses natural killer cells, reducing oxidative stress and phagocytosis by neutrophils and macrophages.
- It also reduces nuclear transcription factor-Kβ, blunts tumor necrosis factor α, and reduces cytokine production.
Ketamine's immuno-modulatory effects can impair natural killer cells, promoting tumor metastasis.

Ketamine (mechanism of action)

Ketamine is a non-competitive antagonist of the NMDA receptor.
It also antagonizes non-NMDA glutamate receptors.
It has µ-antagonism, κ-agonism, and δ-agonism.
Ketamine is a GABAA receptor antagonist and inhibits re-uptake of serotonin and norepinephrine.
It also has local anesthetic-like activity by blocking sodium channels.

Barbiturates

Barbiturates are derived from barbituric acid.
They are classified according to their duration of action:
- Long-acting (8-12 hours): phenobarbital.
- Short-acting (45-90 minutes): pentobarbital.
- Ultra-short acting (5-15 minutes): thiopental.
Barbiturates are also classified based on the oxygen position at the C2 position:
- Oxybarbiturates: Oxygen at C2 position (less lipid soluble, less protein binding, excreted unchanged)
- Thiobarbiturates: Sulfur at C2 position (more lipid soluble, higher protein binding, liver metabolism required)
Thiopental, a thiobarbituate, is a yellow powder in a vial containing sodium carbonate and nitrogen.
Sodium carbonate increases the pH, making the drug more water soluble.
Nitrogen helps prevent a decrease in pH, which would reduce the drug's water solubility.

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Description

This quiz explores the concepts of Context Sensitive Half-Time (CSHT) in relation to drug pharmacokinetics and provides insight into the formulation of Propofol as a general anesthetic. Understand how factors like infusion duration, volume of distribution, and systemic clearance affect drug concentration and elimination. Test your knowledge on the implications of different Propofol formulations.