PHARMACOLOGY

General and Local Anesthetic Agents

Anesthetics
• Drugs that cause COMPLETE or PARTIAL loss of sensation
• Divided into two: General and Local
• General Anesthesia- loss of pain sensation and
consciousness
• Local Anesthesia- loss of pain sensation to a designated
area without systemic effects.
General Anesthesia
• Administration of combination of several different general
anesthetic agents
• To achieve following goals:

Analgesia

Unconsciousness

Amnesia
Risk Factors:
• All body systems are affected because of wide effects,
patients must be evaluated for factors that may
increase their risk:

CNS Factors

Cardiovascular Factors

Respiratory Factors

Renal and Hepatic functions

Balanced Anesthesia
• Therapeutic effects required need to be balanced with the potential
adverse effect.
• Combining of several drugs each with specific effect and amnesia rather
than using one drug.
• Given before the general anesthetic and/or continued during surgery
• E.g. : NMJ blocker
• Commonly involves following agents:
Preoperative medications

Sedative- hypnotics

Antiemetics

Antihistamine

Narcotics
Administration of General Anesthesia:
• Delivered by a physician, nurse or nurse anesthetist along
with intubation, mechanical ventilation, and full life
support.
• Different Stages/ Depth: Different Phases:

Stage 1 // Analgesia Stage INDUCTION

Stage 2 // Excitement Stage MAINTENANCE

Stage 3 // Surgical Anestesia RECOVERY

Stage 4 // Medullary Paralysis

Induction
• Period from the beginning of anesthesia until stage 3, surgical anesthesia.
• Stage 2- danger period due to systemic stimulation
• Rapid acting anesthetic is used in this phase
• NMJ Blockers- facilitate intubation, necessary to support for mechanical
ventilation

Maintenance
• Period from stage 3 until surgical procedure is complete.
• Slower more predictable anesthetic may be used to maintain anesthesia in
stage 3, gas anesthetic

Recovery
• Period from discontinuation of the anesthetic until
regained consciousness, movement and ability to
communicate.
• Requires continues monitoring for adverse effects of
drug and the patient’s vital functions.
General Anesthetic Agents
• Barbiturate, nonbarbiturate anesthetics, gas anesthetics
and volatile liquids.
Barbiturate Anesthetic
• THERAPEUTIC ACTIONS AND INDICATIONS
Thiopental- most widely used IV anesthetics. No analgesic
properties. May need additional analgesics after surgery.
Methohexital- lacks analgesic property. May require
postoperative analgesics.
• PHARMACOKINETICS
Thiopental- very rapid onset usually within 10-30 secs.
Ultrashort recovery period of 5-8 mins.
Methohexital- rapid onset. Recovery period of 3-4 mins.
Lipophilic. Dissolved in water and diffuse to brain rapidly.
Barbiturate Anesthetic
• CONTRAINDICATIONS AND CAUSES
Methohexital cannot come into contact with silicone like rubber
stopper and disposable syringe.
Methohexital and Thiopental should not be used until medical
staffs are ready and equipped for intubation and respiratory
support.
Pregnancy and Lactating. Should not be used unless it clearly
outweighs the potential fetal risk.

• ADVERSE EFFECTS
Related to suppression of CNS with:
-decreased pulse
-hypotension
-suppressed respiration
-Decreased GI activity
-Nausea and vomiting: common after recovery
Barbiturate Anesthetic
• DRUG TO DRUG INTERACTIONS
Cannot be used with any other CNS suppressants.
Barbiturates can cause decreased effectiveness of theophylline, oral
anticoagulants, beta-blockers, corticosteroids, hormonal
contraceptives, phenylbutazones, metronidazole, quinidine,
carbamazepine.

Barbiturate Anesthetics + Narcotics= apnea more commonly than

occurs with other analgesics.
Nonbarbiturate Anesthetic
• THERAPEUTIC ACTIONS AND INDICATIONS
Midazolam- Prototype. Very potent amnesiac. Acts in reticular
activating system and limbic system to potentiate effects of gamma
amino butyric acid. Widely used to produce amnesia or sedation,
induce anesthesia and for continuous sedation for intubated and
mechanically ventilated patients
Doperidol- produces marked sedation and a state of mental
detachment. Has antiemetic effects, reducing the nausea and
vomiting in surgical in diagnostic procedure.
Etomidate- general anesthetic, sometimes used to sedate patients
receiving mechanical ventilation.
Fospropofol- Monitored sedation during therapeutic and
diagnostic procedure. Will be very relaxed and amnesic.
Ketamine- associated with bizarre state of unconsciousness-
awake but unconscious and can’t feel pain. Causes sympathetic
stimulation with increase in bp and heart rate- may be helpful in
situations when cardiac depression is dangerous.
Propofol- Short procedures- very rapid clearance, muchless of a
hangover effect, allows quick recovery, maintain on mechanical
ventilation
Barbiturate Anesthetic
• PHARMACOKINETICS
Midazolam- Rapid onset. Does not reach peak effectiveness to 30-60
mins.
Droperidol- 3 mins. onset. Ultrashort recovery time.
Etomidate- 1 min onset. 3-5 min recovery period.
Fospropofol- Rapid onset. Peaks within -13 mins-half life of nearly an
hour. Slow recovery period.
Ketamine- 30 secs onset. 5mins recovery period.
Propofol- very short acting anesthetic. 30-60 secs onset.

• CONTRAINDICATIONS AND CAUSES

Midazolam- cause nausea and vomiting, used with caution who could
compromised by vomiting. Associated with respiratory depression and
respiratory arrest. Life support should be ready and available.
Droperidol- used with cautions with renal and hepatic failure. Used with
extreme care w/ prolonged QT interval or who’s at risk for it.
Etomidate- Not recommended for children younger than 10 yrs. of age.
Fospropofol- causes marked relaxation and amnesia. Should not be
permitted to drive after use of drug.
Barbiturate Anesthetic
• ADVERSE EFFECTS
Risk for skin breakdown (not be able to move)
Decubitus ulcer formation
Midazolam- Respiratory Depression and CNS suppression.
During recovery…
• Droperidol may cause hypotension, chills, hallucinations and drowsiness, QT
prolongation (puts at risk to cardiac arrythmmias)
• Etomidate- myoclonic and tonic movements, nausea and vomiting
• Ketamine- crosses the blood brain barrier. Hallucinations, dreams and psychotic
episodes.
• Propofol- local burning on injection, bradychardia, hypotension, pulmonary
edema.
• Fospropofol- sensation of perinial burning, stinging, tingling and rash- usually
mild,lasting over a short time, don’t req. intervention but patient should be
alerted that this occur and will pass.
• DRUG TO DRUG INTERACTIONS
Ketamine + Halothane= severe cardiac depression with hypotension and
bradychardia.
X = Droperidol + drugs that prolong QT interval
Ketamine- can potentiate muscular blocking of NMJ blockers, may require
prolonged periods of respiratory support.
Midazolam + Inhaled anesthetics, CNS Depressants, Narcotics, propofol,
thiopental = increased toxicity and length of recovery
Anesthetic Gases
• Inhaled drugs; enters the bronchi and alveoli rapidly passes in capillary
system, to heart pumped to the body.
• Very high affinity to fatty tissues. Lipophilic, includes lipid membrane of
the nerves in CNS.
• Gas passes quickly to the brain causing CNS depression. In stage 3,
regulates amount, ensures it is sufficient to keep unconscious but not
cause severe CNS depression
• Decreasing the concentration of gas that flows into the bronchi, creating a
concentration gradient= results in movement of gas in opp direction.- out
of the tissues and back to expired air.
• Once the best way to achieve anesthesia, but very flammable and
associated with toxic adverse effect. Newer agents with less toxicity has
replaced the drug. Nitrous oxide (blue cylinder) is still used

• THERAPEUTIC ACTIONS AND INDICATIONS

Nitrous oxide- Very potent analgesic- used freq for dental
surgery. Moves quickly in and out-
Doesn’t cause muscle relaxation. Usually combined with other
agents for anesthetic use.
• PHARMACOKINETICS
Nitrous oxide- 1 -2 min onset of action. Rapid recovery
period. Timing of recovery depends on other drug being
used.

• CONTRAINDICATIONS AND CAUSES

Nitrous oxide can block the reuptake of oxygen after surgery
and cause hypoxia. Due to this, its always given in combination
with oxygen.
Pregnancy. Not be used unless benefits clearly outweighs the
potential risk to fetus.
Nursing mothers. Should wait for 4hrs before nursing a baby
when they have been administered nitrous oxide
• ADVERSE EFFECTS
Skin integrity
Acute sinus and middle ear pain, bowel obstruction,
pneumothorax
Inactivates vit b12 (neurological immune and
hematological complications)

• DRUG TO DRUG INTERACTIONS

Caution- combined with other drug that causes CNS
depression.
Halothane and ketamine= severe cardiac arrest with
hypotension and bradychardia.
Volatile Liquids
• Liquids that are unstable at room temp and release gases.
• Acts like gas anesthetics
• Inhaled anesthetics can be volatile liquids

• THERAPEUTIC ACTIONS AND INDICATIONS

Halothane- prototype of volatile liquids. Used as a
maintenance of anesthesia. Effective as an induction agent.
Desflurane- widely used in outpatient surgery (rapid onset and
quick recovery time)
Isoflurane- widely used to maintain anesthesia after induction.
Can cause muscle relaxation.
Sevoflurane- used in outpatient surgery as an induction agent
and is rapidly cleared for quick recovery.
• PHARMACOKINETICS
Halothane- rapid; 1-2 mins onset. 20 min recovery. Metabolized in liver
Desflurane, enflurane and isoflurane- 1-2 min onset. 5-20 min
recovery.
Sevoflurane- newest of volatile liquids. 30 sec onset. 10 min clearance.
These drugs are all cleared through the lungs.

• CONTRAINDICATIONS AND CAUSES

Halothane- avoidance with hepatic impairment. Associated with
bradycardia and hypotension.
Desflurane- avoidance with respiratory problems and with increased
sensitivity. Not recommended in induction with pediatric patients
Enflurane- avoidance with known cardiac or respiratory disease or
renal dysfunction
Isoflurane and Sevoflurane-be used with caution with respiratory
depression
All of the drugs has potential to trigger malignant hyperthermia and
never used with high risk developing it. Dantrolene should be
available.
Pregnancy and lactating. Should be avoided unless the benefit clearly
outweighs the risk of fetus.
• ADVERSE EFFECTS
Halothane- recovery syndrome characterized by fever,
anorexia, nausea, vomiting , hepatitis which can lead to fatal
hepatic necrosis-rare. Should not be used freq more than 3
weeks.
Desflurane- collection of respiratory reactions (cough,
increased secretion, larnygospasm)
Isoflurane- hypotension, hypercapnia, muscle soreness, and a
bad taste in mouth.
Enflurane- renal impairment
Sevoflurane- adverse effects are thought to be minimal

• DRUG TO DRUG INTERACTIONS

Caution when any other drug is combined with other CNS
suppressants
Local Anesthesia
• Loss of sensation to limited areas of body.
• Achieved by following methods:
Topical Administration

Infiltration

Field Block

Nerve Block

Intravenous Regional Anesthesia

Topical Administration
• Includes application of lotion, cream, ointment or drop of
local anesthetic to traumatized skin to relieve pain.
• Involve application to the mucous membranes.

Infiltration
• Involves injecting the anesthetic directly to the
tissues to be treated
Field Block
• Injecting the anesthetic all around the area that
will be affected by the procedure or surgery.
• More intense than infiltration anesthesia
• Often used for tooth extraction
Nerve Block
• Involves injecting anesthetic at some point along the nerve or
nerves that run to and from the region in which the loss of pain
sensation or muscle paralysis is desired.
• More potential for adverse effects
• Several types of nerve blocks:

Peripheral Nerve Block

Central Nerve Block

Epidural Anesthesia

Caudal Block

Spinal Anesthesia
 Intravenous Regional
Local Anesthesia
• Carefully draining all of the blood from patient’s
arm or leg
• Securing a tourniquet to prevent anesthetic from
entering the general circulation, injecting
anesthetic into the vein of the arm or leg.
• This technique is used for very specific surgical
procedures
 Local Anesthetic Agents
• Used to prevent from feeling pain for varying periods of time.

• Works by causing a temporary interruption in production and conduction of

nerve impulses.
• In increasing concentrations, local anesthetic can also cause loss of: (1)
temperature, (2) touch, (3) proprioception, (4) skeletal muscle tone.
• Powerful nerve blockers, effects be limited to particular body area
• Should not be absorbed systemically
• Classifies as esters or amides.

• THERAPEUTIC ACTIONS AND INDICATIONS

Helps increase effectiveness by delivering it directly to the affected area.
Indicated for infiltration anesthesia, peripheral nerve block, spinal anesthetic, and the
relief of local pain
Local Anesthetic Agents
• PHARMACOKINETICS
Ester Local Anesthetics broken down immediately in the
plasma by enzymes. (plasma esterases)
Amide Local Anesthetics metabolized more slowly in the
liver. Can possible lead to toxicity

• CONTRAINDICATIONS AND CAUSES

History of allergies
Heartblock
Shock
Decreased plasma esterases
Pregnancy and lactating. Can be used only if the benefit
outweighs potential risk to fetus.
• ADVERSE EFFECTS
Local blocking of sensation, loss of skin integrity,
CNS EFFECTS: headache, restlessness, anxiety, dizziness,
tremors, blurred vision, backaches
GI EFFECTS: nausea, vomiting,
CARDIOVASCULAR EFFECTS: peripheral vasodilation,
myocardial depression, arrhythmias
BP changes
can lead to fatal cardiac arrest and respiratory arrest

• DRUG TO DRUG INTERACTIONS

Local anesthetics + Succinylcholine = increased and
prolonged neuro muscular blockage.
Local anesthetics + Epinephrine = less risk of systemic
absorption, increased local effects
THANK YOU!
General and Local Anesthetic Agents