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Comparative Pharmacology for Anaesthetist
Armeen Ahmed, Vipin Dhama, Nitin Garg
1:
Neuromuscular Blocking Agents Neuromuscular Junction (Structure and Function)
SODIUM CHANNELS
SUCCINYLCHOLINE
Chemistry
Pharmacokinetics
ENZYME PSEUDOCHOLINESTERASE
Atypical Pseudocholinesterase
DOSES OF SUCCINYLCHOLINE
Side Effects
FASCICULATIONS (PRESYNAPTIC EVENT)
Mechanism of Action
Phase I Block
Clinical Significance
Phase II Block
Mechanism
Clinical Significance
NON-DEPOLARISING MUSCLE RELAXANT
Classification
On the Basis of Action
On the Basis of Chemical Structure
STRUCTURE-ACTIVITY RELATIONSHIP
PHARMACOKINETICS
Side Effects
Factors Modulating Histamine Release
Autonomic Effect
Clinical Significance
CLINICALLY IMPORTANT DRUG INTERACTIONS OF MUSCLE RELAXANTS
Volatile Anaesthetics
Clinical Significance
Local Anaesthetics
Clinical Significance
Magnesium
Clinical Significance
Antibiotics
Clinical Significance
Other Drugs Potentiating Neuromuscular Blockade
Drugs That Cause Antagonism/faster Recovery from Neuromuscular Blockade
FACTORS AFFECTING NON DEPOLARIZING BLOCKADE
1. RENAL DYSFUNCTION / FAILURE
Clinical Significance
2. HEPATIC DYSFUNCTION/FAILURE
Drugs Largely Dependent on Liver for Metabolism or Excretion or Both
Drugs Partially Dependent on Liver for Metabolism or Excretion or Both
Drugs Independent of Hepatic Metabolism or Excretion
3. AGE
a. INFANTS (< 1 year age)
Clinical Significance
b. ELDERLY
Clinical Significance
4. TEMPERATURE
5. OTHER FACTORS
2:
Opioids
DEFINITION
CLASSIFICATION OF OPIOIDS
OPIOID RECEPTORS
Location
Classification
OP3(µ) Receptor
Action
OP2 (κ) Receptor
Action
OP1(δ) Receptor
σ (SIGMA) Receptors
Concept of Agonist, Partial Agonist and Antagonist
MECHANISM OF ACTION
Analgesia (Pain Control) System of the Body
PHARMACOKINETICS OF OPIOIDS—A COMPARATIVE STUDY
PHARMACOKINETICS OF MORPHINE
Fate of Morphine
PHARMACOKINETICS OF MEPERIDINE
PHARMACOKINETICS OF FENTANYL
PHARMACOKINETICS OF ALFENTANIL
PHARMACOKINETICS OF REMIFENTANIL
ONSET TIME (INTRAVENOUS DRUG)
DURATION OF ACTION
PHARMACODYNAMICS
Analgesia
CARDIOVASCULAR SYSTEM
POINTS OF CLINICAL SIGNIFICANCE
RESPIRATORY SYSTEM
Ventilation
Respiratory Rate and Tidal Volume
Delayed Respiratory Depression
Points of Clinical Relevance
MUSCLE RIGIDITY
CENTRAL NERVOUS SYSTEM
HORMONES AND ENDOCRINE SYSTEM
NEURAXIAL OPIOIDS
LIPOPHILIC VS HYDROPHILIC OPIOIDS
SIDE EFFECTS OF NEURAXIAL OPIOIDS
SIGNIFICANT DRUG INTERACTIONS
1. Sedative – Hypnotics
2. Inhalational Anaesthetics
Note:
3. Muscle Relaxants
4. MAO Inhibitors
5. Calcium-channel Blockers
6. Erythromycin
7. Cimetidine and Ranitidine
COMPLEX ACTION OPIOIDS
Pentazocine (20-60 mg pentazocine = 10 mg morphine)
Chemistry: - Benzomorphan derivative.
Pharmacokinetics:-
Buprenorphine (Thebaine Derivative)
Introduction
Key Points
Routes of Administration
Dose
BUTORPHANOL
Introduction
Key Points
NALBUPHINE
Introduction
Key Points
OPIOID ANTAGONISTS
Opioids not Reversed by Naloxone
Other Drugs Reversed by Naloxone
NALTREXONE
NALMEFENE
Conducting the Case of an Opioid Addict
Points of clinical Significance
Pethidine
Key Points
TRAMADOL
DOSES OF COMMON OPIOIDS
3:
Volatile Anaesthetics
PHARMACOKINETICS
FATE OF INHALED ANAESTHETIC
A. Factors Affecting Inspiratory Concentration
B. Factors Affecting Alveolar Concentration
Partial Pressure
Equilibrium
Partition Coefficient
SOLUBILITY
CARDIAC OUTPUT
PARTIAL PRESSURE DIFFERENCE BETWEEN ALVEOLAR GAS AND VENOUS BLOOD
VENTILATION
CONCENTRATION EFFECT
A. Concentrating Effect
B. Augmentation of Tracheal Inflow
SECOND GAS EFFECT
C. Factors Affecting Arterial Concentration
Effects of Shunts
Effect of Dead Space
FACTORS AFFECTING RECOVERY FROM INHALATIONAL ANAESTHESIA
A. Solubility and Duration of Anaesthesia
B. Metabolism
PHARMACODYNAMICS
Mechanism of Action of Inhalational Agents
Exception to this theory
Minimum Alveolar Concentration (MAC)
Advantages of MAC Concept
Factors Affecting MAC in Humans
MAC Values
PHARMACODYNAMICS
METABOLISM
PHYSICAL PROPERTIES
NITROUS OXIDE
Manufacture
Storage/Commercial Preparation
Properties
Mechanism of Action
Pharmacodynamics
Metabolism, Toxicity
NITROUS OXIDE AND CLOSED GAS SPACES
Clinical Significance
DIFFUSION HYPOXIA
Clinical Significance
4:
Intravenous Induction Agents
COMMERCIAL PREPARATION
STRUCTURE – ACTIVITY RELATIONSHIP
MECHANISM OF ACTION
PHARMACOKINETICS
PHARMACODYNAMICS
Neurotransmitters in the Brain
GABA (γ-AMINOBUTYRIC ACID)
CENTRAL NERVOUS SYSTEM
CARDIOVASCULAR EFFECTS
CARDIOVASCULAR EFFECTS
EFFECT ON RESPIRATORY SYSTEM
RESPIRATORY SYSTEM
SIDE EFFECTS AND COMPLICATIONS
Intra-arterial Injection of Thiopentone
Signs and Symptoms
Pathophysiology
Treatment: LEAVE IV CANNULA IN ARTERY
CONTRAINDICATIONS
ONSET OF ACTION
DURATION OF HYPNOSIS
CLINICAL USES
DOSES
5:
Inotropes
INOTROPE/VASOPRESSOR
Therapy
When Your Inotrope/Vasopressor Doesn't Work?
RECENT ADVANCES
Renal Dose Dopamine –Is it useful?
6:
Anticholinergic Drugs
7:
Anticholinesterases
REVERSAL OF NEUROMUSCULAR BLOCKADE
WHICH ONE TO GIVE?
FACTORS AFFECTING REVERSAL OF NEUROMUSCULAR BLOCKADE
HOW MUCH TO GIVE?
MINIMIZING THE SIDE-EFFECTS
COMPARATIVE STUDY OF ANTICHOLINESTERASES
Pharmacodynamics
PHYSOSTIGMINE
8:
Local Anaesthetics
COMMERCIAL PREPARATION
STRUCTURE – ACTIVITY RELATIONSHIP
CLASSIFICATION
MECHANISM OF ACTION
Characteristics of Blockade
THREE STATES OF NA+ CHANNEL
PROPERTIES OF LOCAL ANAESTHETICS
1. Lipid Solubility:- Determines – Potency
2. Dissociation Constant (Pka)
Determines – Onset of Action
3. Protein Binding
Determines – Duration of Action
4. Frequency Dependent Blockade
Determines – Sensory Motor Dissociation
In Vivo Properties (Properties studied in human subjects)
1. Vasodilation
2. Tissue Penetrance
3. Differential Conduction Blockade
Order of Sensitivity to Blockade Clinically
4. Mantle Effect
5. Concentration Effect
PHARMACOKINETICS
FATE OF LOCAL ANAESTHETIC
FACTORS AFFECTING PHARMACOKINETICS
ADJUVANTS
Vasoconstrictors
Adrenaline
Advantages
Disadvantages
ALKALINIZATION
CARBONATION
SYSTEMIC TOXICITY OF LOCAL ANESTHETICS
CARDIOVASCULAR TOXICITY
Cardiotoxicity of LA
Why Bupivacaine is more cardiotoxic than lidocaine ?
FACTORS AFFECTING CARDIOTOXICITY OF LOCAL ANAESTHETICS
CC/CNS RATIO
CENTRAL NERVOUS SYSTEM TOXICITY
Mechanism
Symptoms
FACTORS AFFECTING CNS TOXICITY
MANAGEMENT OF CNS TOXICITY
LOCAL TISSUE TOXICITY OF LOCAL ANESTHETICS TRANSIENT RADICULAR IRRITATION CLINICAL FEATURES
Pathophysiology
Factors Affecting Neurotoxicity
CAUDA-EQUINA SYNDROME
Clinical Features
Mechanism of Injury
ALLERGIES DUE TO LOCAL ANAESTHETIC
COMPARATIVE STUDY OF LIGNOCAINE AND BUPIVACAINE
ROPIVACAINE
Chemistry
Salient Features
PRILOCAINE
Chemistry
Salient Features
EMLA
Chemistry
Salient Features
Uses
BENZOCAINE AND BUTYLAMINOBENZOATE
OXETHAZAINE
DIBUCAINE (CINCHOCAINE)
9:
Miscellaneous Drugs
FUROSEMIDE
Site of Action
Other Actions of Furosemide
Pharmacokinetics
SIDE EFFECTS OF DIURETIC THERAPY
DRUG INTERACTIONS
METOCLOPRAMIDE
Action
Side Effects
Used for
ONDANSETRON
PHARMACOKINETICS
Common points about both the drugs
CORTICOSTEROIDS
ROLE OF STEROIDS IN ANESTHETIC PRACTICE
OTHER USES
INDEX
TOC
Index
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