General Anaesthetics

Question 1

What are the five principles Anaesthesia Represent?

Answer 1

immobility, amnesia, and unconsciousness

Question 2

Immobility?

Answer 2

Immobility- Immobility is the easiest anesthetic end point to measure. Edmond Eger and colleagues
introduced the concept of minimal alveolar concentration (MAC) to quantify the potency of an inhalational and Anesthetic

Question 3

Amnesia?

Answer 3

Amnesia- The ablation of memory arises from several locations in the CNS, including the hippocampus,
amygdala, prefrontal cortex, and regions of the sensory and motor cortices. Memory researchers
differentiate two types of memory: (1) explicit memory, ie, specific awareness or consciousness under
anesthesia, and (2) im

Question 4

Consciousness?

Answer 4

Consciousness- The ability of anesthetic drugs to abolish consciousness requires action at anatomic locations
responsible for the formation of human consciousness. Leading neuroscientists studying consciousness identify
three regions in the brain involved in generating personal awareness: the cerebral cortex, the thalamus, and the reticular activating system. These regions seem to interact as a cortical system via identified pathways,
producing a state in which humans are awake, aware, and perceiving. These neural pathways involved in
the development of consciousness are disrupted by anesthetics.

Question 5

Stages of anaesthesia?

Answer 5

Induction, Maintanace

Question 6

GA MAO?

Answer 6

No specific receptor has been identifieds the locus of GA action
o A variety of molecular mechanism may contribute to the activity of GA
o At [effective], GA increase the sensitivity of - GABAA receptors to the
inhibitory neurotransmitter GABA increase chloride (Cl ion) influx - hyper
polarization of neurons.
o Exception: ( Nitrous oxide and Ketamine; no action on GABAA receptors)
inhibition of the N-methyl-d- aspartate (NMDA) receptors

Question 7

Volatile anesthetics?

Answer 7

halothane
enflurane
isoflurane
desflurane
sevoflurane

Question 8

Gaseous anesthetics

Answer 8

nitrous oxide
xenon

Question 9

GENERAL ANESTHETIC Factors Controlling Uptake?

Answer 9

Solubility - One of the most important factors influencing the transfer of an
anesthetic from the lungs to the arterial blood is its solubility characteristics.

Cardiac output - Changes in pulmonary blood flow have obvious effects on the
uptake of anesthetic gases from the alveolar space.

Anesthetic partial pressure difference between alveolar and mixed venous
blood is dependent - uptake of the anesthetic by the tissues, (incl) non- neural
tissues.

Question 10

GENERAL ANESTHETIC Factors Controlling Uptake?

Answer 10

Solubility - One of the most important factors influencing the transfer of an
anesthetic from the lungs to the arterial blood is its solubility characteristics.

Cardiac output - Changes in pulmonary blood flow have obvious effects on the
uptake of anesthetic gases from the alveolar space.

Anesthetic partial pressure difference between alveolar and mixed venous
blood is dependent - uptake of the anesthetic by the tissues, (incl) non- neural
tissues

Question 11

Nitric Oxide

Answer 11

Laughing gas is non-irrittaing potent analgesic but a weak general anaesthetic commonly combined with other more potent agents

Question 12

Nitric Oxide solubility ?

Answer 12

Poorly soluble in blood and other tissue, allowing it to move very rapidly in and out of body

Question 13

Nitric Oxide pneuomothorax?

Answer 13

It replaces nitrogen in various air spaces faster than nitrogen leaves

Question 14

Nitric Oxide diffusion hypoxia?

Answer 14

Poorly soluble in blood and other tissues. Allowing it to move quickly and out of the body

Question 15

Why induction of anesthesia is slower with more soluble anesthetic gases?

Answer 15

Solubility in blood is represented by the relative size of the blood compartment (the more soluble, the larger the
compartment).
Relative partial pressures (agents) in the compartments - indicated by the degree of filling - each compartment.
Given concentration or partial pressure of the two anesthetic gases (inspired air),
Take longer for the blood partial pressure of the more soluble gas (halothane) to rise - same partial pressure (alveoli).
[Anesthetic agent] in the brain can rise no faster than the the [blood]
Onset of anesthesia will thus be slower with halothane than with nitrous oxide.

Question 16

The time to recovery from inhalation anesthesia depends?

Answer 16

The time to recovery from inhalation anesthesia depends on the rate of
elimination of the anesthetic from the brain.

Question 17

Important factors governing rate of recovery?

Answer 17

The blood:gas
partition coefficient of the anesthetic agent.

Question 18

Other factors controlling rate of recovery?

Answer 18

Other factors controlling rate of recovery include pulmonary blood flow,
magnitude of ventilation, and tissue solubility of the anesthetic.
Two features differentiate the recovery phase from the induction phase.

Question 19

How can transfer of anaesthetic from lungs to blood be transferred and what for the reverse?

Answer 19

First, transfer of an anesthetic from the lungs to blood can be enhanced
by increasing its concentration in inspired air, but the reverse transfer process cannot be enhanced because the concentration in the lungs cannot be reduced
below zero.

Question 20

Two parameters that can be manipulated by the anesthesiologist
are useful in controlling the speed of induction of and recovery
from inhaled anesthesia?

Answer 20

(1) Concentration of anesthetic in the inspired gas and
(2) Alveolar ventilation.

Question 21

Metabolism of anesthetics?

Answer 21

Modern inhaled anesthetics are eliminated mainly by ventilation and are only metabolized to a
very small extent; thus, metabolism of these drugs does not play a significant role in the
termination of their effect.

Question 22

What role does metabolism play?

Answer 22

However, metabolism may have important implications for their toxicity (see Toxicity of
Anesthetic Agents).

Question 23

Hepatic metabolism contribution?

Answer 23

Hepatic metabolism may also contribute to the elimination of and recovery from some older
volatile anesthetics.

Question 24

Nitrous oxide and human tissues?

Answer 24

Nitrous oxide is not metabolized by human tissues. However, bacteria in the gastrointestinal
tract may be able to break down the nitrous oxide molecule.

Question 25

Nitrous oxide effect on brain?

Answer 25

Nitrous oxide can increase cerebral blood flow and cause increased intracranial pressure.

Question 26

Solution of nitrous oxide admin.?

Answer 26

Therefore, nitrous oxide may be combined with other agents (intravenous anesthetics) or techniques (hyperventilation) that reduce cerebral blood flow in patients with increased intracranial pressure. o Potent inhaled anesthetics produce a basic pattern of change to brain electrical activity as recorded by standard electroencephalography (EEG).

Question 27

When is adminstration of high concentrations of volatile anesthetics undesirbale?

Answer 27

Therefore, administration of high concentrations of volatile anesthetics is undesirable in patients with increased intracranial pressure

Question 28

Drugs that depress normal cardiac contractility

Answer 28

Halothane, enflurane, isoflurane, desflurane, and sevoflurane

Question 29

Inhalation anaesthetics drugs?

Answer 29

SHINED Sevoflurane Halothane Isoflurane Nitrous Oxide Enflurane Desflurane

Question 30

Halothan: -Arrythmias -Sensitivity to DA, NE -Cardiac Output -Blood Presssure -respiratory reflex -hepatix toxicity -renal toxicty

Answer 30

-Arrythmias: Increased -Sensitivity to DA, NE: Increased -Cardiac Output: Decreased -Blood Presssure: Dose-dependent -respiratory reflex: inibited -hepatix toxicity: high risk -renal toxicty: Low risk

Question 31

Isoflurane: -Arrythmias -Sensitivity to DA, NE -Cardiac Output -Blood Presssure -respiratory reflex -hepatix toxicity -renal toxicty

Answer 31

-Arrythmias: No-effect -Sensitivity to DA, NE: No-effect -Cardiac Output: Minimum Effect -Blood Presssure: Dose-dependent hypotension -respiratory reflex: +++ irrittation -hepatix toxicity: low risk -renal toxicty: low risk

Question 32

Desflurane? -Arrythmias -Sensitivity to DA, NE -Cardiac Output -Blood Presssure -respiratory reflex -hepatix toxicity -renal toxicty

Answer 32

-Arrythmias: No-effect -Sensitivity to DA, NE: No-effect -Cardiac Output: Minimum Effect -Blood Presssure: Dose-dependent hypotension -respiratory reflex: stimulation -hepatix toxicity: low risk -renal toxicty: low risk

Question 33

Sevoflurane? -Arrythmias -Sensitivity to DA, NE -Cardiac Output -Blood Presssure -respiratory reflex -hepatix toxicity -renal toxicty

Answer 33

-Arrythmias: No-effect -Sensitivity to DA, NE: No-effect -Cardiac Output: Minimum Effect -Blood Presssure: Dose-dependent hypotension -respiratory reflex: inhibited -hepatix toxicity: low risk -renal toxicty: high risk

Question 34

Haloothane therapeutic uses?

Answer 34

Usually co-administrated with nitrous oxide, opiods or local anaesthetics?

Question 35

Halothane P/K?

Answer 35

Metabolised in the body to tissue

Question 36

How to avoid a halothane toxic reaction?

Answer 36

Halothan must not be administered at intervals of less than 2-3 weeks

Question 37

Halothan hepatoxicity in children?

Answer 37

Not hepatoxic in children and combined with its pleasant odour, its suitable in paediatrics for inhlations induction

Question 38

Halothane adverse cardiac effects?

Answer 38

Bradycardia Cardiac arrhythmias Concentration-dependent hypotension

Question 39

Halothane and malignant hyperthermia?

Answer 39

in very small percentage of susceptible patients expouser to halogenated hydrocarbon anaesthetics or the NM, Succiny;choline may induce malignant hyperthermia Uncontrolled in skeletal muscle oxidative metabolism, overwhelming the bodys capcity to supply oxygen, remove carbon dioxide and regulate temperature and causes circulatory collapse and death if not treated immediately

Question 40

Malignant hyperthermia susceptible patients?

Answer 40

Burn victims and individuals

Question 41

Halothane Rx?

Answer 41

Dantrolene(blocks release of Ca2+) from the sarcoplasmic reticulum of muscle cells, reducing. heat production and relaxing muscle tone

Question 42

Isoflurane metabolism?

Answer 42

Undergoes little metabolism and is therefore not toxic to the liver or kidney also, it does not induce cardiac arrhymias

Question 43

Isoflurane and hyotension?

Answer 43

Produce dose-dependent

Question 44

Isoflurane odour and respiratory effects?

Answer 44

Pungeny odur and stimulates respiratory effects(irritation, salivation, coughing, laryngospasm) therefore not used for inhalation induction in high risk patients

Question 45

Desflurane onset recoevry?

Answer 45

Provides very rapid onset and recovery due to low blood solubulity

Question 46

Desflurane use in outpatients?

Answer 46

Popular anaesthetics for outpatient procedures

Question 47

Desflurane volatility?

Answer 47

Low volatility , requiring admin. via special heated vaporizer

Question 48

Sevoflurane ability to allow rapid induction?

Answer 48

Has low pungency allowing rapid induction without irritating the airways

Question 49

What is sevoflurane suitable for?

Answer 49

Paediatric patients

Question 50

Sevoflurane onset?

Answer 50

Rapid onset and recovery due to low blood solubility?

Question 51

Sevoflurane metabolsim?

Answer 51

Metabolsied by the liver-metabolited can be nephrotic

Question 52

Propofol-1 replaced which drugs?

Answer 52

Propofol is the most frequently administered drug for induction of anesthesia and has largely replaced barbiturates for this indication.

Question 53

What is the propofol-1 P/k profile?

Answer 53

pharmacokinetic profile allows for continuous infusions

Question 54

Propofol-1uses during anesthesia?

Answer 54

propofol is also used during maintenance of anesthesia and is a common choice for sedation in the setting of monitored anesthesia care. o propofol is also used for sedation in the ICU as well as conscious sedation and short-duration general anesthesia in locations outside the operating room

Question 55

Propofol-1 MOA?

Answer 55

The presumed mechanism of action of propofol is through potentiation of the chloride current mediated through the GABA A receptor complex.

Question 56

Propofol-1 metabolism?

Answer 56

Propofol is rapidly metabolized in the liver; the resulting watersoluble compounds are presumed to be inactive and are excreted through the kidneys.

Question 57

Propodol-1 clearance?

Answer 57

Plasma clearance is high and exceeds hepatic blood flow, indicating the importance of extrahepatic metabolism, which is thought to occur to a significant extent in the lungs and may account for the elimination of up to 30% of a bolus dose of the drug

Question 58

clinical uses of propofol?

Answer 58

The most common use of propofol is to facilitate induction of general anesthesia by bolus injection

Question 59

Propofol pharmacological effects?

Answer 59

Depressese the CNS accompanied by excitatory phenomenal Transient pain at the injection site is common It decreases blood pressure without depressing the myocardium, also decreases intracranial pressure It does not provide analgesia, has some antiemetic effects Propopol is commonly infused in lower doses to provide sedation

Question 60

S/E of Propofol?

Answer 60

Tremorme Urine Retension Green urine flushing Infusion syndrome

Question 61

Clinical doses of fospropofol?

Answer 61

Fospropofol is approved for sedation during monitored anesthesia care. o Supplemental oxygen must be administered to all patients receiving the drug. o Hence, it is recommended that fospropofol be administered only by personnel trained in airway management. o The dose should be reduced by 25% in patients older than 65 years and in those with an American Society of Anesthesiologists o Injection pain during administration of propofol is often perceived as severe, and the lipid emulsion has several disadvantages.

Question 62

Fosproprol?

Answer 62

o Fospropofol is a water-soluble prodrug of propofol

Question 63

Fospropofo organ system effects?

Answer 63

Because the active compound is propofol and fospropofol is a prodrug that requires metabolism to form propofol, the pharmacokinetics are more complex than for propofol itself. o Multicompartment models with two compartments for fospropofol and three for propofol have been used to describe the kinetics. o The effect profile is similar to that of propofol, but onset and recovery are prolonged compared with propofol because the prodrug must first be converted into an active form. o Although patients receiving fospropofol do not appear to experience the injection pain typical of propofol, a common adverse effect is the experience of paresthesia, often in the perianal region, which occurs in up to 74% of patients. The mechanism for this effect is unknown.

Question 64

Thiopental?

Answer 64

An ultra-short acting barbiturate with high lipid solubility

Question 65

Thiopental anaesthetic and analgesic?

Answer 65

A potent anaesthetic but a weak analgesic

Question 66

Thiopental S/E?

Answer 66

Apnoea, coughing, chest well spasm, laryyngospasm and bronchospasm

Question 67

Clinical uses of barbiturates?

Answer 67

The principal clinical uses of thiopental or methohexital is for induction of anesthesia (unconsciousness) which usually occurs in less than 30 seconds. o Patients may experience a garlic or onion taste after administration. o Barbiturates such as methohexital o (20–30 mg/kg) may be administered per rectum; o Facilitate induction of anesthesia in mentally challenged and uncooperative pediatric patients.

Question 68

Barbiturates?

Answer 68

Barbiturate hypnotics have been largely replaced as induction agents by propofol. o The anesthetic effect of barbiturates presumably involves a combination of enhancement of inhibitory and inhibition of excitatory neurotransmission. o Although the effects on inhibitory transmission probably result from activation of the GABA A receptor complex, the effects on excitatory transmission are less well understood. 63 o Barbiturates should not be administered to patients with acute intermittent porphyria because they increase the production of porphyrins through stimulation of amino levulinic acid synthetase.

Question 69

Diazepam conjuction for sedation?

Answer 69

BDZs are used in conjunction with anaesthetics for sedation

Question 70

Diazepam metabolised?

Answer 70

Metabolised by liver, and erthromycin may prolong their effects

Question 71

BDz and amenesia?

Answer 71

BDZ can induce anterograde amnesia in which the patient retains memory of past events but new information is not transferred into long-term memory

Question 72

BDZ clinical uses and dosage?

Answer 72

Used-preoperative medication, intravenous sedation – suppression - seizure activity -(desired effects anxiolysis/anterograde amnesia o Midazolam and Diazepam (Less frequently) - also be used to induce general anesthesia. o Lorazepam- slow onset /prolonged duration of action – limit (usefulness); for preoperative medication or induction of anesthesia; o Rapid and sustained awakening at the end of surgery (desirable) o Flumazenil (antagonist) (8–15 mcg/kg IV) useful for treating patients experiencing delayed awakening; o Duration of action is brief (about 20 minutes) and re-sedation may occur. o Benzodiazepines -Delayed awakening (potential disadvantage); o Limiting (usefulness) - induction of general anesthesia despite their advantage of less pronounced circulatory effects. o Benzodiazepines - unique among the group of intravenous anesthetics; o Action can readily be terminated by administration of their (selective antagonist)-Flumazenil. o Benzodiazepines (highly lipid-soluble) - rapidly enter the CNS; o Accounts - rapid onset of action,- redistribution to inactive tissue sites and subsequent termination of the drug effect

Question 73

Etomidate?

Answer 73

Used-preoperative medication, intravenous sedation – suppression - seizure activity -(desired effects anxiolysis/anterograde amnesia o Midazolam and Diazepam (Less frequently) - also be used to induce general anesthesia. o Lorazepam- slow onset /prolonged duration of action – limit (usefulness); for preoperative medication or induction of anesthesia; o Rapid and sustained awakening at the end of surgery (desirable) o Flumazenil (antagonist) (8–15 mcg/kg IV) useful for treating patients experiencing delayed awakening; o Duration of action is brief (about 20 minutes) and re-sedation may occur. o Benzodiazepines -Delayed awakening (potential disadvantage); o Limiting (usefulness) - induction of general anesthesia despite their advantage of less pronounced circulatory effects. o Benzodiazepines - unique among the group of intravenous anesthetics; o Action can readily be terminated by administration of their (selective antagonist)-Flumazenil. o Benzodiazepines (highly lipid-soluble) - rapidly enter the CNS; o Accounts - rapid onset of action,- redistribution to inactive tissue sites and subsequent termination of the drug effect

Question 74

Clinical Uses and dosage of etomidate?

Answer 74

o Alternative to propofol and barbiturates for the rapid (IV) induction of anesthesia- (patients with compromised myocardial contractility). o After a standard induction dose (0.2–0.3 mg/kg IV); o Onset – unconsciousness- comparable - achieved by thiopental and propofol. o Injection (intravenous)- high incidence –pain - followed by venous irritation-(Similar to propofol) o Involuntary myoclonic movements are also common but may be masked by the concomitant administration of neuromuscular blocking drugs. o Awakening rapid -single (IV) dose - little evidence- residual depressant effects. o No analgesia effect. o Postoperative nausea and vomiting- more common- thiopental or propofol

Question 75

Ketamine?

Answer 75

Partially water-soluble/ highly lipid soluble (phencyclidine derivative) differing - most other (IV) anesthetics- produces significant analgesia. o The characteristic state observed after an induction dose of ketamine is known as “dissociative anesthesia,” wherein the patient’s eyes remain open with a slow nystagmic gaze (cataleptic state). o Of the two stereoisomers the S (+) form is more potent than the R (–) isomer, but only the racemic mixture of ketamine is available in the USA. o Mechanism of action (complex) ; Major effect- produced -inhibition - N-Methyl-D-aspartate receptor (NMDA) complex.

Question 76

P/K Ketamine?

Answer 76

High lipid solubility - ensures a rapid onset of its effect. o Effect of a single bolus injection- terminated by redistribution to inactive tissue sites. As with other (IV) induction drugs, o Metabolism- primarily (liver) – (N –demethylation) cytochrome P450 system. o Nor-ketamine- primary active metabolite, less potent (one third to one fifth the potency) ketamine; o Subsequently hydroxylated and conjugated into water-soluble inactive metabolites that are excreted in urine. o Only (IV) anesthetic that has low protein binding (12%)

Question 77

Clinical Uses & Dosage-Ketamine?

Answer 77

o Unique properties- (incl) profound analgesia, stimulation of the sympathetic nervous system, bronchodilation- minimal respiratory depression, o Important alternative to the other (IV) anesthetics - desirable adjunct in - despite the unpleasant psychotomimetic effects. o Administered -multiple routes (intravenous, intramuscular, oral, rectal, epidural) - useful option for premedication in mentally challenged and uncooperative pediatric patients. o Popular as an adjunct administered at sub- analgesic doses to limit or reverse opioid tolerance.

Question 78

Dexmedetomidine?

Answer 78

o Highly selective α 2 -adrenergic agonist. o Effects can be antagonized- α 2 -antagonist drugs. o Active S –enantiomer - medetomidine o Water soluble- available as a parenteral formulation. o Rapid hepatic metabolism involving conjugation, N - methylation, and hydroxylation, followed by conjugation. o Metabolites are excreted in the urine and bile. o Clearance is high - elimination half-time is short. 78 Clinical Uses & Dosage - DEXMEDETOMIDINE o Principally used -short-term sedation- intubated /ventilated patients ICU setting. o Operating room - used as an adjunct