Pharmacology in anaesthesia Flashcards
Definition of Volume of Distribution (Vd)
Volume of Distribution (Vd) is the apparent volume into which a drug has mixed or distributed throughout the body.
Factors that affect Volume of Distribution (Vd)
Lipid Solubility: Drugs with higher lipid solubility tend to have a higher Vd because they can easily cross cell membranes.
Protein Binding: Drugs that bind strongly to plasma proteins have a lower Vd, as more of the drug remains in the blood.
Ion Binding: Electrical charge affects drug distribution, with ionized drugs being less likely to cross membranes.
Molecular Weight: Smaller drugs can cross membranes more easily, leading to a higher Vd.
Formula for Volume of Distribution (Vd)
Vd = Total quantity of drug / Plasma concentration at steady state
Definition of Vc (Central Volume)
Vc represents the central volume, which includes plasma and highly perfused organs (organs with a high blood supply).
Definition of Vp (Peripheral Volum
Vp represents the peripheral volume, which includes peripheral tissues and poorly perfused organs (organs with a lower blood supply).
Definition of Bioavailability
Fractional dose of a drug that is actually able to reach the systemic circulation.
Definition of Volume of Distribution
Relationship between the dose of a drug and the resulting serum concentration based on the theoretical volume of fluid
Definition of Phase I Metabolism
Metabolism that results in the loss of pharmacologic activity through cleavage or formation of a new or modified functional group (oxidation, reduction, and/or hydrolysis).
Definition of Phase II Metabolism
Metabolism that involves conjugation of the parent drug or Phase I metabolite with endogenous compounds (glucuronidation, sulfation, or acetylation).
Definition of Hepatic Clearance
Volume of blood or plasma that is completely cleared of a drug by the liver per unit of time (Hepatic blood flow × hepatic extraction ratio).
Definition of Clearance (CL
Clearance (CL) represents the volume of blood or plasma from which the drug is completely eliminated in a unit of time (ml/min).
Formula for Clearance (CL)
CL = CLR + CLH + CLx, where:
CLR = Renal clearance
CLH = Hepatic clearance
CLx = Other routes of clearanc
Rate of Drug Elimination
The rate of drug elimination is the amount of drug eliminated (mg/min) per unit of blood or plasma concentration (mg/ml).
Organs responsible for drug clearance
The liver and kidneys are the primary organs responsible for drug clearance.
Definition of Total Body Clearance
Total body clearance is the sum of different ways of drug elimination from the body.
Definition of the One-Compartment Model
In the one-compartment model, the rate of drug elimination is proportional to the amount of drug in the body (X) at any time (t), following first-order kinetics.
One-Compartment Model: Rate of Drug Elimination
The rate of drug elimination decreases exponentially with time and is represented by the equation:
dX/dt = kX
(where k is the elimination rate constant and X is the amount of drug in the body at time t).
Definition of Agonism
Agonism refers to the stimulation of a receptor, activating it to produce a biological response.
Definition of Antagonism
Antagonism involves the inhibition of a receptor, blocking it from producing a biological response
Definition of Synergism
Synergism refers to an enhanced effect when two or more drugs work together to produce a greater effect than the sum of their individual effects.
Definition of Additivity
Additivity is the combined effect of two drugs, where their total effect is equal to the sum of their individual effects.
Definition of Partial Agonism
Partial agonism refers to the partial stimulation of a receptor, producing a less than maximal biological response.
Definition of Inverse Agonism
Inverse agonism refers to the reversal of receptor activity, producing an effect opposite to that of an agonist.
what is the MOA of thiopental
Thiopental is a barbiturate that enhances the activity of the GABA-A receptor by increasing chloride ion influx, leading to hyperpolarization of neuronal membranes and CNS depression. This results in sedation, hypnosis, and anesthesia.
Why is Thiopental considered ultrashort-acting?
Thiopental is ultrashort-acting primarily due to its rapid redistribution from the brain to other tissues (muscle and fat) after administration. Its high lipid solubility allows it to quickly reach the brain, inducing anesthesia, but it also causes the concentration in the brain to drop quickly as it redistributes, leading to a short duration of action. Metabolism plays a minor role compared to redistribution.
side effects of thiopental
reduced icp
reduced cerrebral flow
hypotention
Mechanism of Action (MOA) of Ketamine
Ketamine primarily acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, inhibiting glutamate, which is a major excitatory neurotransmitter. This action results in dissociative anesthesia, characterized by analgesia, sedation, and amnesia. Ketamine also affects opioid receptors and may have a role in increasing synaptic plasticity and neuroprotection.
side effects of ketamine
increased sympathetic tone
maintains laryngeal tone
increase icp
bronchodilation
which agent is coadministered with ketamine to reduce halluciantions
Benzodiazepines
What is the MOA of propofol
ropofol acts primarily as a positive allosteric modulator of the GABA-A receptor, enhancing the inhibitory effects of gamma-aminobutyric acid (GABA). This leads to increased chloride ion influx, resulting in neuronal hyperpolarization and CNS depression, producing sedation and anesthesia. Propofol also has some effects on sodium channels and may have antioxidant properties.
Why is propofol ideal for LMA
Reduces laryngeal reflexes
Side effects of propofol
Venous irritation can be administered with lidocaine
Properties of Halothane
Halothane is a colorless liquid with a pleasant smell, making it easy to breathe. It decomposes when exposed to light and contains thymol as a preservative.
Cardiac Effects of Halothane
Halothane can cause cardiac dysrhythmias, reduced myocardial contractility, heart rate (HR), cardiac output (CO), and blood pressure (BP).
Halothanes Effects on Cerebral Blood Flow
Halothane increases cerebral blood flow and intracranial pressure (ICP).
Respiratory Effects of Halothane
It reduces tidal volume (VT), increases respiratory rate (RR) and partial pressure of carbon dioxide (PaCO2), and decreases laryngeal reflexes and airway resistance.
What are the Obstetric Considerations with use of Halothane
Halothane causes uterine relaxation, which is a critical consideration in obstetrics.
Properties of Isoflurane
Isoflurane is a halogenated methyl ethyl ether, a colorless volatile liquid with an irritant smell. It is expensive and not widely used in Malawi.
Onset and Recovery of Isoflurane
Isoflurane has a lower blood/gas solubility than halothane, allowing for a rapid onset and recovery from anesthesia.
Toxicity of Isoflurane
Isoflurane has low toxicity to the liver and kidneys.
Cerebral Effects of Isoflurane
Isoflurane increases cerebral blood flow and intracranial pressure (ICP), but to a lesser extent than halothane.
Cardiovascular Effects of Isoflurane
Isoflurane does not cause arrhythmias and does not increase myocardial sensitivity to adrenaline. It causes a dose-dependent decrease in blood pressure due to reduced systemic vascular resistance (SVR) with little effect on myocardial contractility.
Respiratory Effects of Isoflurane
Isoflurane reduces tidal volume (VT) and increases respiratory rate (RR).
Structure of Suxamethonium
Suxamethonium consists of 2 molecules of acetylcholine joined together.
Onset and Duration of Action of Suxamethonium
Suxamethonium has a rapid onset of action (1 minute) and is short-acting (4-6 minutes) after observable muscle fasciculations.
Mechanism of Action of Suxamethonium
Suxamethonium leads to persistent depolarization of the motor endplate, causing muscle paralysis.
Undesirable Effects of Suxamethonium
Can cause mild to severe muscle fasciculations, leading to increased cardiac output (CO), blood pressure (BP), and intracranial pressure (ICP).
Myalgia and Hyperkalemia Risks-suxa
Suxamethonium may cause myalgia and hyperkalemia, particularly in patients with burns, neurological conditions, peripheral nerve injuries, renal failure, or acidosis, which can lead to cardiac arrest.
Other Side Effects of Suxamethonium
Includes dual block, increased intraocular pressure, malignant hyperpyrexia, parasympathetic effects, and prolonged activity due to reduced plasma cholinesterase or genetic variants.
What type of drug is Vecuronium?
Vecuronium is a steroid-based, non-depolarizing neuromuscular blocking agent.
Why is Vecuronium widely used?
Vecuronium is widely used due to its low cost and minimal cardiovascular effects.
Onset and Duration of Action of Vecuronium
Vecuronium has a moderately short onset of action (2 minutes) and a moderate duration of action (20 minutes).
Vecuronium and Histamine Release
Vecuronium rarely causes histamine release, reducing the risk of allergic reactions or hypotension.
What type of drug is Rocuronium?
Rocuronium is a steroid-based, non-depolarizing neuromuscular blocking agent, and a cousin of vecuronium.
Onset and Duration of Rocuronium
Rocuronium has a fast onset of action (60 seconds), similar to suxamethonium, but has a longer duration of action compared to vecuronium.
Potency and Usage of Rocuronium
Rocuronium is less potent than vecuronium but otherwise has similar effects. Due to a reduction in price, it is increasingly being used as a replacement for vecuronium.
What type of drug is Atracurium?
Atracurium is an ester-based, non-depolarizing neuromuscular blocking agent
How is Atracurium metabolized?
Atracurium is metabolized by Hofmann degradation into laudanosine and through ester hydrolysis. This makes it independent of liver and kidney function for metabolism.
Why is Atracurium the drug of choice in renal and hepatic failure?
Atracurium does not rely on the liver or kidneys for metabolism, making it ideal for use in patients with renal or hepatic failure.
Side Effects of Atracurium
Atracurium can cause severe histamine release, which may lead to profound hypotension.
