Download adrenoceptor agonist sympathomimetics

General Anesthetics
Drugs used to induce a state of
unconsciousness with the overall aim of
ensuring hypnosis, amnesia, analgesia,
immobility, skeletal muscle relaxation, and loss
of control of reflexes of the autonomic nervous
system.
Features of ideal anesthetic
1. Rapid and smooth induction and recovery.
2. Wide safety margin.
3. Minimal side effects.
Balanced anesthesia
Use of more than one agent to obtain ideal
anesthesia.
Adjuncts to general anesthetics
I. Muscle relaxants
II. Pre-anesthetic medications.
Muscle relaxants
Facilitate intubation.
Suppress muscle tone.
Atracurium, Vecuronium, Succinylcholine.
Pre-anesthetic medication
Anticholinergics: prevent secretion of fluids
into the respiratory tract .
Benzodiazepines: relieve anxiety.
Thiopental-Propofol: rapid induction of
anesthesia .
Antiemetic : post surgical N&V.
Antihistaminics: allergic reactions.
H2-receptor blockers: reduce gastric acidity
Opiates: induce analgesia.
Depth of anesthesia
( Four stages).
Stage I
- Analgesia.
- Loss of pain sensation.
- The patient is conscious and conversational.
Stage II
- Excitement.
- Increased, irregular blood pressure.
- Increased respiratory rate.
- Patient may experience delirium & violent behavior.
- Dilated & reactive eye.
Stage III
- Surgical anesthesia.
- Regular respiration & relaxation of sk. muscles.
- Eye reflexes decrease until the pupil is fixed.
Stage IV
- Medullary paralysis.
- Severe depression of vasomotor and respiratory
centers.
- Death may occur.
Classification
1. Inhalation Anesthetics
 Gases: nitrous oxide
 Volatile Liquids:
 Ether
 Halogenated compounds
2. Intravenous Anesthetics
Mechanism of action

Interaction with membrane ion channels.
Enhancing the action of inhibitory
neurotransmitters, GABA and glycine thus
decrease neuronal excitability.

Inhibition of excitatory neurotransmitters e.g.
ketamine is NMDA receptor antagonist

Inhalation Anesthetics
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Methoxyflurane
Halothane
Enflurane
Isoflurane
Desflurane
Sevoflurane
Nitrous oxide .
Pharmacokinetics of general anesthetics
 Induction of anesthesia
 Maintenance of anesthesia
 Depth of anesthesia.
 Recovery of anesthesia
 MAC value
Induction, Maintenance and Recovery
Induction
Time elapsed between onset of administration of
anesthetic and development of effective surgical
anesthesia.
Maintenance
Time during which the patient is surgically
anesthetized.
Recovery
The time from discontinuation of anesthetic drug
until consciousness is regained.
Factors controlling induction & recovery

The anesthetic concentration in the inspired air
(Direct).

Blood solubility: Blood: gas partition coefficient
(Inverse relation).

Pulmonary blood flow (Inverse).

Rate and depth of ventilation (Direct).
DRUGS
Solubility
Induction & Recovery
(Blood : gas partition coefficient )
Methoxyflurane
12
Slow
Halothane
2.3
Slow
Enflurane
1.8
Medium
Isoflurane
1.4
Medium
Sevoflurane
0.69
Rapid
Desflurane
0.42
poor & Rapid
Nitrous Oxide
0.47
Rapid
Minimum Alveolar Concentration (MAC)
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It is the concentration of inhalation anesthetic that
produce immobility in 50 % patients in response
to surgical incision.
Depends on potency of anesthetic agents.
The lower the MAC value the more potent the
drug.
MAC is increased by CNS stimulants.
MAC is decreased by CNS depressants & in old
people.
POTENCY
MAC
Methoxyflurane
0.16
Halothane
0.75
Isoflurane
1.4
Enflurane
1.7
Sevoflurane
2
Desflurane
6-7
Nitrous oxide
>100
Pharmacological Actions
CNS
-  metabolic rate.
-  ICP (due to cerebral vasodilatation) # in
head injuries.
- Dose - dependent EEG changes (Enflurane).
CVS
-
Hypotension
-
Bradycardia except ( Isoflurane, Desflurane)
-
Myocardial depression (Halothane , Enflurane)
- Sensitize heart to catecholamines (Halothane)
Respiratory system
- All respiratory depressants.
- Bronchodilators (Halothane – Sevoflurane).
-  mucociliary movement.
- Airway irritation (Desflurane- Enflurane).
Liver
- Decrease hepatic flow.
- Hepatotoxicity (Only halothane ).
Uterus
- Uterine relaxation
- Nitrous oxide: has minimal relaxant effect
(labor).
Skeletal muscles
- All are skeletal muscle relaxants to varying
degree.
Methoxyflurane
– The most potent (high lipid solubility).
–50 % is metabolized to fluoride
(nephrotoxic).
– Slow induction (20 minutes).
– For veterinary use only.
Halothane (Fluothane)
 Non
irritant (pleasant odor)
 Potent anesthetic.
 Weak analgesic.
 Weak skeletal muscle relaxant.
 Slow induction and recovery (blood solubility).
 Metabolized to hepatotoxic metabolite,
trifluroethanol.
 CVS
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depression
– Hypotension
– Bradycardia (vagomimetic action)
–  Myocardial contractility.
–  Cardiac output
Respiratory depression.
Uterine relaxant.
The agent of choice in children (Pleasant).
Adverse Effects
1. Hepatotoxicity (repeated use).
2. Malignant hyperthermia.
3. Decrease the cardiac output.
4. Sensitizes heart to action of
catecholamines  cardiac arrhythmias.
Enflurane (Ethrane)
More rapid induction and recovery than
halothane.
 Less potent than halothane.
 Better muscle relaxation.
 Better analgesic properties.
 is metabolized to fluoride (8%).
 Excreted in the kidney

CVS depression
- Hypotension
-  Cardiac output
- No sensitization of the heart to catecholamines
Disadvantages
 Pungent (less induction -not for pediatrics).
 CNS stimulation (Epilepsy-like seizureabnormal EEG).

Contraindications
 patients with seizure disorders.
 renal failures.
Isoflurane (Forane)
 Less potent than halothane
 Better analgesic action.
 More rapid induction & recovery than
halothane
 Stable compound (2%).
 Low biotransformation (less fluoride).
 No hepatotoxicity.
 No sensitization of the heart.
 No cardiac arrhythmias.
 CVS depression
- Hypotension ( VR)
- Potent coronary vasodilator.
-  HR
Disadvantages
Pungent (not for pediatrics).
Desflurane (Suprane)
 Pungent odor (irritation - cough)
 Rapid induction & fast recovery (low blood
solubility).
 Less potent than halothane.
 Less metabolized (0.05 %).
 CVS
- Hypotension
-  VR
- HR
Sevoflurane
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Less potent than halothane
Rapid induction and recovery.
Less metabolized (3- 5% fluoride)
Better smell
No airway irritation (children)
CVS
- Hypotension
-  VR
- Little effect on HR
Nitrous Oxide (N2O)
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The most potent analgesic.
Weak anesthetic (low potency, combined).
The most rapid induction & recovery
due to low blood solubility.
No muscle relaxation.
No respiratory depression.
Not hepatotoxic.
Minimal CVS adverse effects.
Adverse Effects
1.
2.
3.
4.
Diffusion hypoxia: (respiratory diseases).
Nausea and vomiting.
Inactivation of B 12  megaloblastic
anemia.
Chronic use:
Bone marrow depression- leukopenia
Abortion - Congenital anomalies
Therapeutic Uses
1.
2.
3.
4.
Outpatient anesthesia (dental procedures).
As a component of balanced anesthesia.
Neuroleptanalgesia.
Delivery
Contraindications
1. Pregnancy.
2. Pernicious anemia.
3. Immunosuppression.
Intravenous Anesthetics
1. Ultra short acting barbiturates.
2. Benzodiazepines.
3. Opioids.
4. Ketamine.
5. Propofol
6. Etomidate.
7. Neuroleptics
Intravenous Anesthetics
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Rapid induction & recovery except BZs
Should be injected slowly.
Recovery is due to redistribution from CNS.
Can be used alone in short operation.
Outpatients anesthesia.
NO need for special equipments.
Analgesic activity (Opioids & ketamine ).
Amnesic action (BZs & ketamine).
Ultra Short acting Barbiturates
Thiopental (Pentothal)
Methohexital (Brevital)
Thiamylal (Surital)
Thiopentone
Rapid onset of action 1 min (high lipid solubility)
Ultra short duration of action 15 - 20 min
Metabolized slowly by the liver.
Pharmacodynamics
 Potent
anesthetic.
 No
analgesic activity
 No
skeletal muscle relaxation.
 CNS:
 ICP (Used in head injuries).
 CVS:
Hypotension & Dysrhythmia.
 Respiratory
depression (dose-dependent).
Uses
1. As anesthetic alone in minor surgery.
2. Induction of anesthesia in major surgery.
Adverse Effects
1.
Respiratory depression
2.
CVS collapse.
2.
Extravasations.
3.
Precipitation of porphyria attack.
4.
Hypersensitivity reaction.
Contraindication
1. Chronic obstructive lung disease.
2. Porphyria.
3. Hypersensitive patients.
4. Severe hypotension (hypovolemic & shock
patient).
Benzodiazepines
Midazolam (Versed)
Diazepam (Valium)
Lorazepam (Ativan)
 The
best one is Midazolam
 Amnesic action.
 Reduce anxiety.
 No analgesic activity
Uses
1. Induction of general anesthesia.
2. Alone in minor procedure (endoscopy).
3. Balanced anesthesia (midazolam).
4. Pre-anesthetic medication (diazepam)
Side Effects
1. Slow induction & recovery.
2. Respiratory depression.
Etomidate (Amidate)
- Ultra-short acting hypnotic (non barbiturates).
- No analgesic activity.
- Rapid onset of action
- Short duration of action.
- Decreases  ICP.
- Minimal CVS and respiratory depressant
effects.
Uses
Induction of Anesthesia
Side Effects
1. Involuntary movements during induction
(diazepam).
2. Postoperative nausea -vomiting.
3. Adrenal suppression (inhibition of
steroidogenesis)
4. Pain at sit of injection.
5. Teratogenic.
Propofol
- Hypnotic (non barbiturates).
- No analgesia.
- Rapid onset – Faster recovery than thiopental.
- Short duration of action.
- Decreases  ICP.
- Antiemetic action.
Uses
1. Induction of anesthesia
2. Maintenance of anesthesia (balanced
anesthesia).
Side Effects
1. Hypotension (PVR).
2. Excitation (involuntary movements).
3. Pain at site of injection.
4. Expensive.
5. Clinical infections due to bacterial
contamination.
Ketamine

Non barbiturate

Dissociative anesthesia
– Analgesia.
– Amnesia.
– Immobility.
– Complete separation from the surrounding
environment.
Pharmacokinetics
- Rapid onset of action (slower than thiopental)
- Short duration of action.
- Metabolized in the liver to active metabolite
(Norketamine).
Pharmacodynamics
1. BP & cardiac output (central sympathetic
activity)
2.  Increases plasma catecholamine levels.
3.  ICP
4. Potent bronchodilator (asthmatics).
Advantages

Can be given IV, IM (Children).
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No bronchospasm.
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Hypovolemic or shock patients.
Side Effects

Post operative hallucination, vivid dreams
& disorientation & illusions (Diazepam).

Risk of hypertension & cerebral
hemorrhage.

 ICP
Contraindications
1. CVS diseases (hypertension-stroke).
2. Head injuries.
Uses
1. Minor operations (children, elderly, shock
patients .
2. Short duration diagnostic procedures
Opiate Drugs
Fentanyl (Sublimaze)
Alfentanil (Alfenta)
Sufentanil (Sufenta)
Fentanyl
-Rapid onset
- Short duration of action.
- Potent analgesia.
- No muscle relaxation
Uses
1. Cardiac surgery ( + nitrous oxide).
2. Neuroleptanalgesia (fentanyl + droperidol ).
3. Neuroleptanesthesia (Fentanyl + droperidol+
nitrous oxide).
Side Effects
1. Respiratory depression, bronchospasm
(wooden rigidity).
2. Hypotension.
3. Nausea & vomiting.
4.
5.
6.
Increase in ICP.
Prolongation of labor & fetal distress.
Urinary retention.
Contraindication
1. Head injuries.
2. Pregnancy.
3. Bronchial asthma.
4. Chronic obstructive lung diseases.
5. Hypovolemic shock (Large dose only).
Neuroleptanalgesia
 A state of analgesia, sedation, muscle
relaxation BUT no loss of consciousness.
 Innovar (Fentanyl + Droperidol ).
 Contraindicated in parkinsonism.
 Diagnostic procedures that require
co-operation of the patient.
Neuroleptanesthesia : a combination of
(Fentanyl + Droperidol + nitrous oxide).
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