They change to zero-order kinetics.
'e' is a mathematical constant and the base of the natural logarithm, approximately equal to 2.71828.
The theoretical volume into which a drug must disperse to produce the measured plasma concentration.
From a log concentration–time graph using the formula Vd = Dose/c0.
Lipid solubility and an indicator of potency.
They are based on several assumptions about tissue blood flow and drug metabolism.
Anaesthesia is achieved when sufficient agent dissolves into a neuronal lipid membrane.
137 bar.
Higher lipid solubility allows fentanyl to better penetrate tissues, resulting in a higher Vd.
The theoretical volume into which a drug must disperse to produce the measured plasma concentration.
Cheap, long shelf life, water soluble, painless on injection, safe for intra-arterial injection, rapid onset and offset time, no excitation or emergence phenomena, no accumulation following infusion, no interaction with other drugs.
Induction of anaesthesia.
Drugs with a small volume of distribution, rapid metabolism (with no active metabolites), high clearance, and short context-sensitive half-times (CSHT) are ideal.
The therapeutic dose of some drugs is close to the plasma concentration at which metabolic enzymes become saturated, leading to increased drug availability with small increases in dosing.
It is linear between 20% and 80% response, allowing for better prediction of effective doses.
An infusion system where the target concentration of the agent in the plasma or effect site can be chosen.
It starts to fall as the drug is metabolized and excreted.
The rate of change in plasma concentration per unit time, represented by the slope of the line.
Class of drug, mechanism of action, presentation, uses, dose, systemic effects, side effects, pharmacokinetics, and interactions.
It represents the substrate concentration at which the reaction velocity is half of V max.
Approximately five half-lives or three time constants.
It means the drug does not build up in the body, reducing the risk of prolonged effects.
The elimination rate constant, k.
The volume of plasma completely cleared of a substance per unit time.
The dose of a drug required to produce a response of a given magnitude.
80%.
When inhalational agents are unavailable, difficult to administer, contraindicated, or to reduce post-operative nausea and staff exposure.
Non-competitive antagonist at NMDA receptor.
Kidney and liver.
Increases noradrenaline and adrenaline release, HR, CO, BP, and cardiac O2 consumption.
The time taken for the plasma concentration of a substance to reduce to half its original value.
It increases the duration of opening of GABA Cl– channels in the CNS, causing hyperpolarization and neuronal inhibition.
Using the equations t½ = 0.693 × Vd/Cl, t½ = 0.693/k, or t½ = 0.693 τ.
The mechanism is uncertain but may involve potentiation of GABA A receptors and action at cannabinoid receptors.
Because plasma drug concentrations decline due to multiple factors, including distribution, metabolism, and excretion.
It includes a central compartment (C1 - plasma), an intermediately well-perfused peripheral compartment (C2 - tissues like muscle), and a poorly perfused peripheral compartment (C3 - tissues like fat).
282 minutes.
It undergoes hepatic metabolism mainly to inactive glucuronide, with renal excretion, and liver/renal dysfunction has little effect on its metabolism.
0.3 mg/kg.
log(a) - log(b).
-log(a).
The velocity of reaction [V] over substrate concentration [S].
More receptors are stimulated, increasing the response.
There are proportionally fewer receptors available for stimulation, leading to a proportionally less response.
A mixture of 50% nitrous oxide (N2O) and 50% oxygen (O2).
French blue with blue and white striped shoulders.
Nitrogen washout during pre-oxygenation.
If the Meyer-Overton hypothesis is correct, the product of MAC and o:g would be a single constant.
1–2 mg/kg.
Structural changes in the receptor and second messenger-dependent systems.
vD = Dose/c0.
The time it would take for plasma concentration to reach zero if the original rate of change continued; it is the reciprocal of the elimination rate constant.
'e' represents the enzymes involved in drug metabolism, and 's' represents the plasma concentration of the drug.
Dobutamine and adrenaline.
The more soluble an agent, the slower its onset and offset times due to its effects depending on partial pressure in blood and brain.
The concentration effect and the second gas effect.
The ability of a drug to produce the maximal response or effect once bound to its receptor.
Pain on injection, epileptiform movements, complications in patients ≤ 16 years, lipaemia with long-term use, green urine and hair, and increased energy needed for DCCV.
To account for the complexities of drug distribution and elimination that a one-compartment model cannot address.
120 minutes.
A drug that binds to receptors and produces the opposite effect to the endogenous agonist (efficacy = -1).
S-Ketamine is twice as potent and has a higher affinity for NMDA receptors.
A drug that binds to receptors at the same site as the agonist, competing for that site.
The three-compartment model.
The proportion of drug eliminated per minute is constant, e.g., 50% per hour.
Ephedrine.
As a continuous infusion.
csHt varies depending on the duration of the infusion.
The dose of a drug required to produce 50% of its maximal effect.
100.
−7 °C.
Cheap, stable, long shelf life, water soluble, and environmentally safe.
It converts to its liquid phase in a process called lamination.
An exponential decay curve.
A mono-exponential decay curve.
cl = vD × k.
The cylinder should be warmed and inverted several times to ensure mixing before use.
N2O diffuses more rapidly into the blood, reducing alveolar volume and increasing the partial pressure of remaining gases.
Minutes (min).
The reaction velocity (V) approaches V_max, obeying zero-order kinetics due to enzyme saturation.
Increases cerebral blood flow, cerebral metabolic requirement for oxygen, and intracranial pressure.
Megaloblastic anemia and subacute degeneration of the spinal cord, leading to neuropathy.
It allows for quick administration and recovery from anesthesia.
3–7 mg/kg IV.
It increases the duration of opening of GABA Cl– channels in the CNS, causing hyperpolarization and neuronal inhibition.
Depletion of presynaptic noradrenaline stores.
4.5 minutes.
The Poynting effect.
Cl systemic = Cl renal + Cl hepatic + Cl other.
Decreased blood pressure (15%-25%), decreased cardiac output (25%), vasodilatation due to NO production, and bradycardia/asystole.
The body is viewed as a central compartment (C1 - plasma) and a peripheral compartment (C2 - tissues).
A substance that binds to receptors at a different site from the agonist, altering the receptor's conformation and preventing the agonist from eliciting a full response.
At physiological pH, the majority of fentanyl is ionized, leaving only 9% un-ionized.
It provides a hypnotic effect with smooth and rapid induction, decreases cerebral perfusion pressure (CPP), intracranial pressure (ICP), and cerebral metabolic rate of oxygen (CMRO2), and may cause myoclonic movements.
The clearance of alfentanil is slower than that of fentanyl.
They have low partial pressures in blood, requiring more molecules to saturate the liquid phase before increasing partial pressure in the alveoli.
Metabolized in the liver by P450 to norketamine, which is then conjugated to an inactive compound.
105% (only under hyperbaric conditions can N2O produce full anaesthesia).
A drug that binds to receptors but produces a sub-maximal response (efficacy < 1).
They graphically demonstrate the effect of b:g coefficients on onset times for different agents.
A linear graph.
It shows the response of a full agonist compared to the agonist in the presence of a competitive antagonist at low doses.
Nausea and vomiting, especially in conjunction with opioids.
It is inversely related; highly lipid-soluble agents require a lower MAC to achieve CNS effects.
Phencyclidine derivative.
pH 10.8.
Because drug elimination systems are not saturated, indicating first-order kinetics.
Alcohol intoxication, where consuming more than 1 unit/hour leads to enzyme saturation and increased drunkenness.
The serum concentration of a drug required to produce 50% of its maximal effect.
To define potency and compare drugs.
As a carrier gas to reduce the amount of volatile agent used due to its MAC-sparing effect.
0.35 l/kg.
Therapeutic ratio = LD50 / ED50.
The rate of reaction between an enzyme and substrate.
Severe anaphylaxis (1 in 20,000).
96.875%.
50 minutes.
A constant amount of drug is eliminated per unit time, e.g., 10 mg per hour.
Reduces myocardial contractility but increases sympathetic outflow, resulting in minimal change in blood pressure.
N2O diffuses into air-filled cavities more quickly than nitrogen can diffuse out, increasing pressure in those spaces.
It is poorly water soluble, a weak organic acid with a pKa of 11, almost totally un-ionized at pH 7.4, and a free radical scavenger.
Due to the redistribution of the drug from peripheral compartments back to the central compartment.
In first-order kinetics, velocity (V) is directly proportional to substrate concentration [S].
V max is the maximum velocity of the reaction when the enzyme is saturated.
Age, weight, height, and sex.
Plasma and effect site concentration of the drug.
Anaesthesia provided solely by the intravenous route, such as propofol infusion.
The time taken for the plasma concentration to be reduced to half its original concentration.
To predict the drug-handling characteristics of the body, calculate doses, and frequency of drug administration.
The chronic reduction in response to a given dose after repeated administration of the drug.
Remifentanil is rapidly broken down by non-specific plasma and tissue esterases, resulting in a short elimination half-time and a relatively constant CSHT of 3–10 minutes.
2 L/kg.
200, suggesting different sites or mechanisms of action.
Decreased cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR); may cause increased heart rate (HR).
Tissues with high perfusion equilibrate with plasma faster than those with low perfusion.
Causes anaesthesia, decreases cerebral metabolic rate of oxygen (CMRO2), blood flow, and volume, and decreases cerebrospinal fluid (CSF) pressure.
Remifentanil has a relatively constant context-sensitive half-time, often referred to as context-'insensitive' half-time.
Only the D isomer.
α-phase (initial rapid distribution) and β-phase (slower elimination).
A drug that binds to receptors and produces a maximal response (efficacy = 1).
1.5–2.5 mg/kg.
'e', approximately equal to 2.718.
Reduces tidal volume and increases respiratory rate, maintaining minute ventilation.
It oxidizes the cobalt ion in the vitamin B12 complex, impairing its function and leading to bone marrow suppression.
Hypnosis, tremor, involuntary movements, decreased tone, epileptiform activity on EEG in 25%, decreased intracranial pressure (ICP), decreased cerebral perfusion pressure (CPP), and decreased cerebral metabolic rate of oxygen (CMRO2).
Analgesic, no effects on patient’s physiology other than rendering them unconscious, no toxic effects.
The acute reduction in response to a given dose after repeated administration of the drug.
Vd ∝ t½ × Cl; t½ ∝ Vd / Cl; Cl ∝ Vd / t½.
The time taken for drug concentration to reduce by half after stopping an infusion.
A small increase in dosing or plasma drug concentration can result in greatly increased availability of the drug, potentially leading to more pronounced side effects.
The use of nitrous oxide is declining.
A constant proportion of the drug is eliminated per unit time, e.g., 50% per hour.
The ratio of the amount of substance in one phase to the amount in another at a stated temperature when the two phases are in equilibrium.
90%.
It causes depression, decreased laryngeal reflex, increased respiratory rate but decreased tidal volume, and bronchodilation.
Rapid onset and offset, minimal accumulation in body tissues, rapid metabolism, no excitation, and no drug interactions.
First O2, then a mixture of O2 and N2O, and finally only hypoxic N2O.
Painless injection, analgesic, muscle relaxant, antiemetic, no physiological effect, no toxicity, and no hypersensitivity reactions.
The substrate concentration at which the reaction velocity (V) is half of the maximal rate (V_max).
8.1.
A mixture of 50% oxygen and 50% nitrous oxide used for pain relief, especially during labor.
Allosteric modulators affect both affinity and efficacy, while competitive or non-competitive antagonists only alter one of these effects.
Induction and maintenance of anaesthesia, sedation in ICU, analgesia in military field, and neuroaxial blockade.
log(a) + log(b).
Ethanol, phenytoin, aspirin, theophylline, and thiopentone.
It shows the response of a full agonist compared to the agonist in the presence of a non-competitive antagonist or a partial agonist.
It approaches, but never touches, the x-axis, reaching a steady state known as an asymptote.
To enhance patient comfort during the induction process.
The graph plateaus, producing a rectangular hyperbola curve.
To produce a sigmoid-shaped plot that is easier and more accurate for extrapolating estimated responses.
Fentanyl is significantly more lipid soluble than alfentanil.
t½ = 0.693/τ or t½ = 0.693/k.
The drug disperses instantaneously and uniformly throughout a single central compartment.
The differences in their pKa values and the percentage of un-ionized forms at physiological pH.
The kinetics of the body’s enzymes and the rate of reaction between an enzyme and substrate to form a product.
The process via endocytosis that leads to receptor down-regulation and loss of active receptors.
It measures the solubility of a substance in blood and influences anaesthetic onset and offset times.
k12 (drug distribution from plasma to tissues) and k10 (drug elimination from the central compartment).
Increases respiratory rate and maintains airway reflexes with profound bronchodilation.
A bi-phasic exponential decay curve.
41 minutes.
They achieve higher partial pressures in alveoli, blood, and brain quickly, leading to a faster onset of anaesthesia.
Rapidly by hepatic and plasma esterases.
A tri-phasic exponential decay curve.
Benzodiazepines, which increase the opening of the chloride channel at the GABA_A receptor.
Picrotoxin at the GABA_A receptor.
No, teratogenic effects have only been observed in rats.
Lipid solubility, percentage plasma protein binding, percentage tissue protein binding, and blood flow to various tissues.
Remifentanil, propofol, and alfentanil.
10/50/100 mg/mL.
Logging the concentration produces a straight line, making it mathematically easier to work with.
Usually, the more lipid soluble a drug, the greater its potency.
k01.
It varies and is directly proportional to the concentration of the drug in the body.
k10.
Higher lipid solubility corresponds to lower MAC values.
In cylinders coloured ‘French blue’ as a liquid below its critical temperature (36.5 °C).
Because the body contains more enzymes than needed to metabolize the clinically effective dose.
Dissociative anaesthesia, increased cerebral blood flow, intracranial pressure, and amnesia.
36.5 °C.
360 minutes.
The ratio of fractional alveolar to fractional inspired concentrations, indicating how quickly different agents reach equilibrium.
It remains constant regardless of the quantity of drug available for metabolism.
75%.
Induction of anaesthesia and treatment of Cushing’s syndrome before surgery.
By heating ammonium nitrate to 250 °C, causing it to decompose.
1.3 minutes.
NH3, N2, NO, NO2, and HNO3.
The volume of plasma completely cleared of a drug per unit time.
It allows for a combination of 0.5 MAC N2O and 0.5 MAC sevoflurane to equal 1 MAC.
The extent to which a drug activates or stimulates a receptor once bound.
A straight line.
Alfentanil has a smaller Vd, which ensures a shorter half-life (t½).
A substance that binds to a receptor at a site separate from the endogenous agonist, altering the shape of the molecule and affecting the agonist's affinity and efficacy.
20%.
90%.
They can act as stores for the drug, maintaining the central compartment's fullness even after drug administration has ceased.
It is a greenhouse gas, although anesthetic emissions are a small proportion of total emissions.
Porphyria and hypersensitivity reactions.
Tissues have a higher concentration of the drug compared to plasma.
The dose of a drug required to produce a lethal effect in 50% of the sample population.
How avidly a drug binds to its receptor, irrespective of the response.
By extrapolating back onto the y-axis from the log concentration-time graph.
Their effects are not overcome by increasing the agonist concentration.
-88 °C.
Ketamine acting at the NMDA receptor.
The reaction velocity (V) is proportional to substrate concentration ([S]), obeying first-order kinetics.
10.
Post-operative nausea and vomiting (PONV).
Fast (α) and slow (β) distribution phases followed by an elimination phase.
A drug that binds to receptors but exerts no effect of its own (efficacy = 0), inhibiting the action of agonists.
Induction and maintenance of anaesthesia, sedation, refractory nausea and vomiting, and treatment of status epilepticus.
It is the most stable induction agent with slight decrease in systemic vascular resistance (SVR), but does not affect myocardial oxygen consumption, contractility, or blood pressure.
It inhibits steroid synthesis by inhibiting 11 β and 17 α-hydroxylase for 24 hours after only one dose.
