Download General and Local Anesthetics

General and Local Anesthetics
‫قاسم صالح النعيمي‬. ‫د‬.‫م‬.‫أ‬
General anesthetics
General anesthesia is a reversible state of central nervous system
(CNS) depression, resulting in loss of perception and response to
external stimuli.
General anesthesia is essential to surgical practice, because it renders
patients analgesic, amnesic, and unconscious, and provides muscle
relaxation and suppression of undesirable reflexes. Because no single
agent provides all desirable properties, several categories of drugs are
used in combination to produce optimal anesthesia.
Adjuncts to inhalation anesthesia
Adjuncts to anesthesia are drugs employed to complement the
beneficial effects of inhalation anesthetics and to counteract their adverse
effects. Some adjunctive agents are administered before surgery, some
during surgery, and some after surgery.
Preanesthetic medications
PA medications are administered for 3 main purposes:
• Reduction of anxiety.
• Production of perioperative amnesia.
• Relief of preoperative and postoperative pain.
Preanesthetic medications includes:
1.Benzodiazepines, like diazepam, to reduce anxiety and promote
amnesia.
2.Opioids (e.g. morphine), to relieve preoperative and postoperative pain.
3.Anticholinergic drugs. E. g. atropine, may be given to decrease the risk
of bradycardia during surgery, prevent excessive bronchial secretions
associated with anesthesia.
4.Neuromuscular blocking agents. Performance of most surgical
procedures requires that skeletal muscles be relaxed; neuromuscular
blocking agents (e.g. succinylcholine, pancuronium) are given to induce
relaxation. By using neuromuscular blockers, we can reduce the dose of
general anesthetic.
Preanesthetic medications
Postanesthetic medications:
1.Analgesic. Analgesics are needed to control postoperative pain. If pain
is severe, opioid are indicated. For mild pain, aspirin-like drugs may
suffice.
2.Antiemetics. Patients recovering from anesthesia often experience
nausea and vomiting. This can be suppressed with antiemetics. Examples:
ondansetron, and promethazine.
3.Muscarinic agonists. Abdominal distention (from atony of the bowel)
and urinary retention are potential postoperative complications. Both
conditions can be relieved through stimulation of muscarinic receptors.
The muscarinic agonist employed most frequently is bethanechol.
General anesthetics
Classification
• Inhalation anesthetics.
• Intravenous anesthetics.
Inhalation Anesthetics:
Inhaled gases are a mainstay of anesthesia and are used primarily for the
maintenance of anesthesia after administration of an IV agent.
1.Volatile liquids: halothane, enflurane, isoflurane, sevoflurane.
2. Gases: nitrous oxide.
Mechanism of action :
The general anesthetics increase the sensitivity of the γ
aminobutyric acid (GABAA) receptors to the neurotransmitter, GABA .
This causes a prolongation of the inhibitory chloride ion current after a
pulse of GABA release resulting in diminished of postsynaptic neuronal
excitability .
Other receptors are also affected by volatile anesthetics. For
example, the activity of the inhibitor glycine receptors in the spinal motor
neurons is increased. In addition, the inhalation anesthetics block the
excitatory postsynaptic current of the nicotinic receptors.
The mechanism by which the anesthetics perform these modulatory
roles is not understood.
Halothane
-Halothane is the prototype of the volatile inhalation anesthetics.
- Halothane is a high-potency anesthetic.
-Induction of anesthesia is smooth and relatively rapid.
- Halothane is only weakly analgesic. Consequently, when this agent is
used for surgical anesthesia, coadministration of a strong analgesic is
usually required. The analgesic most commonly employed are opioid
(e.g. morphine) and nitrous oxide.
- Muscle relaxation. Although halothane has muscle relaxant actions, the
degree of relaxation produced is generally inadequate for surgery.
Accordingly, concurrent use of a neuromuscular blocking agent (e.g.
pancuronium) is usually required.
- Halothane is not hepatotoxic in pediatric patients (unlike its potential
effect on adults).
Adverse effects
1-CVS:
1. Hypotension. Halothane causes hypotension by 2 mechanisms:
a-The drug has a direct depressant effect on the myocardium; the
resultant decrease in contractility can reduce cardiac output by 20% to
50%.
b. Halothane increases vagal tone, thereby slowing heart rate and
reducing cardiac output even further.
2.Sensitization of the heart to catecholamines. Some anesthetics, most
notably halothane, can increase the sensitivity of the heart to stimulation
by catecholamines. While in this sensitized state the heart may develop
dysrhythmias in response to catecholamines.
2-Respiratory depression.
3. Malignant hyperthermia. MH is a rare but potentially fatal reaction
that can be triggered by all inhalation anesthetics. MH is characterized by
muscle rigidity and a profound elevation of temperature.
4. Aspiration of gastric contents. During the state of anesthesia, reflexes
that normally prevent aspiration of gastric contents into the lung are
abolished.Aspiration of gastric fluids can cause bronchospasm and
pneumonia.
5.Hepatotoxicity. Rarely, patients receiving inhalation anesthesia
develop serious liver dysfunction. Rarely halothane produces hepatitis,
sometimes progressing
to massive hepatic necrosis and death.
Hepatotoxicity is thought to result from an autoimmune process triggered
by reactive metabolites of halothane that have formed complexes with
liver proteins.
Nitrous oxide:
-
NO is a gas anesthetic
Has very low anesthetic potency.
Has very high analgesic potency.
Because of its low anesthetic potency, It is never employed as a
primary anesthetic agent (cannot produce surgical anesthesia
alone).
- Because of its high analgesic potency, nitrous oxide is employed
with great regularity as an adjuvant to other inhalation agents to
provide supplemental analgesia.
- In certain settings, nitrous oxide can be used alone. When
administered alone, nitrous oxide is employed for analgesia-not
anesthesia. Nitrous oxide alone is used for analgesia in dentistry
and during delivery.
The most important toxic effect of nitrous oxide is postoperative nausea
and vomiting.
Intravenous anesthetics:
IV anesthetics cause the rapid induction of anesthesia. This is often
described as occurring within one "arm-brain circulation time,” or the
time it takes the drug to travel from the site of injection (usually the arm)
to the brain, where it has its effect. IV anesthetics may be used as the sole
agents for short procedures or administered as infusions to help maintain
anesthesia during longer procedures.
Three drug families are employed as anesthetics:
1- Barbiturates (Thiopental).
2- Benzodiazepines (Diazepam, lorazepam and midazolam.)
3- Opioids. (Fentanyl).
Thiopental:
-
Thiopental is a short acting barbiturate.
Employed for induction of anesthesia.
Analgesic and muscle relaxant effects are weak.
Has rapid onset of action and short duration of action.
Act rapidly to produce unconsciousness.
Unconsciousness occurs 10 to 20 seconds after IV injection. If
thiopental is not followed by inhalation anesthesia, the patient will
wake up in about 10 minutes.
Thiopental is highly lipid soluble and therefore enters the brain rapidly to
begin its effects. Anesthesia is terminated as thiopental undergoes
redistribution from the brain and blood to other tissues.
Pharmacological effects:
Thiopental has minor effects on the cardiovascular system, but it may
contribute to severe hypotension in patients with hypovolemia or shock.
All barbiturates can cause apnea, coughing, chest wall spasm,
laryngospasm, and bronchospasm. [Note: The latter is of particular
concern for asthmatic patients.
Benzodiazepines
The benzodiazepines are used in conjunction with anesthetics to
sedate the patient. The most commonly used is midazolam [mi-DAZ-olam]. Diazepam [dye-AZ-uh-pam] and lorazepam [lore-AZ-uh-pam] are
alternatives. All three facilitate amnesia while causing sedation,
enhancing the inhibitory effects of various neurotransmitters, particularly
GABA. Minimal cardiovascular depressant effects are seen, but all are
potential respiratory depressants (especially when administered
intravenously).
Opioid ( Fentanyl).
Fentanyl is an opioid drug. It is administered in combination with a
neuroleptic drug known as droperidol ( Neuroleptic opioid
combination). Neuroleptic analgesia is a state that is produced by the
administration of this combination. It is characterized by quiescence,
indifference to surroundings and insensitivity to pain; the patient appears
to be sleep but is not (i.e. complete loss of consciousness does not occur).
Neuroleptic analgesia is employed for diagnostic and minor surgical
procedures( e.g. bronchoscopy, repeated changing of burns dressings).
For some procedures, the combination of fentanyl plus droperidol is
supplemented with nitrous oxide. The state produced by this three-drug
regimen is called neuroleptic anesthesia. Neuroleptic anesthesia produces
more analgesia and a greater reduction of consciousness occurs with
neuroleptic analgesia. Neuroleptic anesthesia can be used for major
surgical procedures.
Local anesthetics
Classification:
• Esters: contains an ester linkage in their structure. Examples:
procaine (novocaine), benzocaine, cocaine, tetracaine.
• Amides: contains an amide linkage. Examples: lidocaine
(xylocine), dibucaine.
Mechanism of action:
Local anesthetics stop axonal conduction by blocking sodium channels
in the axonal membrane. By blocking sodium channels, local anesthetics
prevent sodium entry into axon, thereby preventing the propagation of
action potential, and bring conduction to a halt.
Selectivity of anesthetic effects: Local anesthetics are
nonselective modifiers of neuronal function. That is, these drugs will
block action potential in all neurons to which they have access. The only
way that we can achieve selectivity is through delivery of the anesthetic
to a limited area.
Onset of action of local anesthetics:
Before anesthesia can occur, the anesthetic must diffuse from its site
of administration to its sites of action inside the axon membrane;
anesthesia is delayed until this movement has occurred
Onset and duration of action of local anesthetics are influenced by
several factors. These include :
- tissue pH,
- molecular size of the drug,
- nerve morphology,
- concentration, and
- lipid solubility of the drug.
Of these, the most important are pH of the tissue and molecular size of
the drug. At physiologic pH, these compounds are charged. The ionized
form interacts with the protein receptor of the sodium channel to inhibit
its function and, thereby, achieve local anesthesia.
The pH may drop in sites of infection, which causes onset to be
delayed or even prevented.
Higher concentration and greater lipid solubility improve onset to some
degree.
Anesthetics of small size, high lipid solubility, and low ionization
cross the axon membrane rapidly. In contrast, anesthetics of large size,
low lipid solubility, and high ionization cross slowly.
Use of anesthetics with vasoconstrictors:
Local anesthetics cause vasodilation, which leads to rapid diffusion
away from the site of action and results in a short duration of action
when these drugs are administered alone. By adding the vasoconstrictor
epinephrine to the local anesthetic, the rate of local anesthetic diffusion
and absorption is decreased. This both minimizes systemic toxicity
and increases the duration of action.
Adverse effects:
1-CNS: When absorbed in sufficient amounts, local anesthetics cause
CNS excitation followed by depression.
2-CVS: When absorbed in sufficient amounts, local anesthetics can affect
the heart and blood vessels. In the heart, local anesthetics suppress
excitability in the myocardium and conducting system, and thereby can
cause bradycardia, heart block, reduced contractile force, and even
cardiac arrest. In blood vessels, anesthetics relax vascular smooth muscle;
the resultant vasodilation can cause hypotension.
3-Allergic reactions: Allergic reactions are much more likely with the
ester type anesthetics than with the amides. Examples: allergic dermatitis
and anaphylaxis.
Clinical uses of local anesthetics:
Local anesthetics may be administered in 2 ways:
• Topically, for surface anesthesia.
• By injection, for 1) infiltration anesthesia, 2)nerve block
anesthesia, 3)intravenous regional anesthesia, 4)epidural
anesthesia, and5) spinal anesthesia.
1)Surface anesthesia:
Surface anesthesia is accomplished by applying a local anesthetic to
the skin or a mucous membrane. The agents employed most commonly
are lidocaine, tetracaine, and cocaine.
Local anesthetics are applied to the skin to relieve pain, itching, and
soreness of various causes, including infection, thermal burns, sunburn,
wounds, abrasions, and insect bites. Application may be made to mucous
membranes of the nose, mouth, pharynx, trachea, bronchi and vagina. In
addition, local anesthetics may be used to relieve discomfort associated
with hemorrhoids, anal fissures, and pruritus ani.
2)Infiltration anesthesia:
Infiltration anesthesia is achieved by injecting a local anesthetic
directly into the immediate area of surgery or manipulation.
3)Nerve block anesthesia: Nerve block anesthesia is achieved by
injecting a local anesthetic into or near the nerves that supply the surgical
field, but at a site distant from the field itself. An advantage of this
technique is that anesthesia can be produced using doses that are smaller
than those needed for infiltration anesthesia.
4)Intravenous regional anesthesia: IRA is employed to anesthetize the
extremities (hands, feet, arms, lower leg, but not the entire leg-because
too much anesthesia would be needed). Anesthesia is produced by
injection into a distal vein of an arm or leg. Lidocaine, without
epinephrine is the preferred agent for intravenous regional anesthesia.
5)Epidural anesthesia: EA is achieved by injecting a local anesthetic
into the epidural space. A catheter placed in the epidural space allows
administration by bolus or continuous infusion. Following administration,
diffusion of anesthetic across the dura into the subarachnoid space blocks
conduction in nerve roots and the spinal cord itself. Diffusion through
intervertebral foramina blocks nerves located in the paravertebral region.
With epidural administration, anesthetic can reach the systemic
circulation in significant amounts. Lidocaine and bupivacaine are popular
drugs for epidural anesthesia.
6)Spinal (subarachnoid) anesthesia:
Spinal anesthesia is produced by injecting local anesthetic into the
subarachnoid space. Injection is made in the lumbar region below the
termination of the cord. Spread of anesthetic within the subarachnoid
space determines the level of anesthesia achieved. Anesthetics employed
most commonly are bupivacaine, lidocaine, and tetracaine.