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Lecture# 93: Pharmacology of General and Local Anesthetics
Nervous System Part III
47
Medical
Professional
03/21/2011

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Term
What is MAC-Minimum Alveolar Concentration
Definition
The concentration of anesthetic that prevents movement in response to
stimulation in 50% of patients.

Determines potency of inhaled anesthetics (1.2-1.3 is typicals during surgery)
Term
Describe each stage of anesthesia and the state of the pt in each stage.
Definition
Stage I-Analgesia
Stage II-excitement (seizure potential)
Stage III- surgical anesthesia
Stage IV- medullary paralysis
Term
What are some general principals of inhaled anesthetics
Definition
Mainstay of anesthesia
primarily during maintenance phase
depth of anesthesia can be rapidly changed
Fairly easily eliminated
Term
What determines anesthetic uptake?
Definition
Low solubility is preferred. The lower the blood gas partition coefficient the less soluble the drug, the less of it will stay in blood. This leads to rapid induction and recovery.
Term
What are some Pharmacodynamics of Inhaled Anesthetics
Definition
Decrease cerebrovascular resistance
Bronchodilation
Decrease minute ventilation
Hypoxic pulmonary vasoconstriction.
Term
Which inhaled anesthetic is well tolerated in children, relaxes skeletal and UTERINE muscle but relatively contraindicated in increased ICP and can cause Hepatic necrosis in older patients.
Definition
Halothane
Term
Whyewould you not give succinylcholine plus this inhaled anesthetics in burn victims, Duchenne MD, myotonia, osteogenesis imperfecta ?
Which durg is it?
How would you treat the condition.
Definition
It would cause malignant hyperthermia
The drug is Halothane
Tx with Dantolene
Term
This drug creates a condition that leads to hypotension, bradycardia, arrhyrhmia and potentiates neuromuscular blocking agents. Name the drug and the condition.
Definition
Halothane hepatitis. Caused by the oxidative metabolism of trifluoroethanol and bromide. Leads to hepatic necrosis.
Term
WHich inhaled anesthetic is widely used for maintenance anesthesia and is the preferred agent for neurosurgical procedures and DOES NOT induce arrythmiAS or sesitize heart to catecholamines like Halothane.
Definition
Isoflurane
It is Not tissue toxic
Term
Which inhaled anesthetic is mainly excreted by the kidney and has an adverse effect of CNS excitation and nephrotoxicity
Definition
Enflurane
(not recommended in seizure disorder)
Term
This drug has low volatility and rarely tissue toxic. It can cause increased ICP that can be decreased with hyperventilation It is an airway irritant that can cause laryngospasm, coughing and excess secretions
Definition
Desflurane
Term
Rapid induction and recovery makes this drug a good choice in outpt surgeries. Compound A is it's biochemical breakdown and when mixed with soda lime it causes transient renal injury.
This drug can also cause nephrotoxicity.
Definition
Sevoflurane.
Term
Which drug would you use for induction anesthesia especially with children?
Definition
Sevoflurane
Term
What is used in outpatient dental surgery that is more of a potent analgesic than anesthetic and has no metabolism?
Definition
Nitrous oxide
Term
What happens when 80% of nitrous oxide is used?
Definition
will limit the delivery of oxygen to the blood.
Term
What is the second gas effect and diffusional hypoxia that is caused by nitrous oxide?
Definition

Second gas effect- Need to give a lower MAC of inhaled anesthetic when giving it with nitrous oxide. Nitrous oxide is taken up faster from lungs which increases the partial pressure of the alveoli. Due to the remaining second anesthetic your body thinks you were given a higher dose of the second anesthetic.

Diffusional hypoxia- – Upon discontinuation, N2O can displace O2 in the alveoli thus diluting the lungs. The partial pressure btwn the alveoli and the blood vessel may not be enough to sustain life in this pt. Need to treat with 100% oxygen.

Term
What are some other contraindications with Nitrous Oxide?
Definition
N2O will exchange with N2; N2O enters the potential space faster than N2 exits because of the blood:gas partition coefficients thus causing an increase in volume and/or pressure. Hence contraindicated in pneumothorax, obstructed middle ear embolli, intaocular air bubble, pulmonary bulla, and intracranial air.
Pulmonary hypertension – N2O increases pulmonary vascular resistance
Term
What is the one reason xenon is not used even though it is extremely insoluble and does not have ANY major adverse effects
Definition
Expensive.
Term
Which 2 drugs have metabolites that are eliminated by kidney and may potentially cause nephrotoxicity?
Definition
Enflurane and Sevoflurane
Term
Why are intravenous anesthetics used?
Definition
rapid induction of anesthesia
recovery is accomplished via redistribution
Term
Which IV anesthetic would you use for rapid induction and is used in patients with head injuries or elevated ICP?
Definition
Thiopental and Mehohexital both have rapid induction they are safe in pregnancy

Thiopental decreases cerebral oxygen consumption, cerebral blood flow and intracranial/intraocular pressures, Good for head injury pts and increased ICP
Term
Which IV anesthetic causes CNS excitement phenomena
What are the signs and symptoms?
What drug is contraindicated in acute intermittent porphyria?
Definition
1) Methohexital causes CNS excitement phenomena
2) s/s are severe hypotension hypovolemic shock, respiratory depression, intraarterial injection, inflammation or necrosis.

Thiopental and Methohexital is contraindicated in acute intermittent porphyria
Term
What is the most common used IV anesthetic in the US and has antiemetic effect? It is the agent of choice in outpt surgery. Also can be used in head injuries and increased ICP.
Definition
Proprofol
Term
When would you use etomidate (IV anesthetic) what are some adverse effects?
Definition
Used for induction in pts with high risk hypotension
Adverse effects are nausea and vomiting, inhibits adrenal cortisol and aldosterone biosynthesis
Term
Which IV anesthetic is used in pts at high risk for hypotension and bronchospasm
It is CONTRAINDICATED in elevated ICP and causes CNS emergenece phenomena, indirect sympathomimetic activity.
Definition
Ketamine
Term
Why are benzos used as an adjunct and how would you treat its toxicity.
Definition
For sedation prior to induction or procedures.
Use Flumazenil to treat toxicity
Term
What is an anesthetic adjunct that is highly selective agonist of alpha2 AR
receptor

Used short term in intubated and mechanically ventilated ICU pts
Definition
Dexmedetomidine
Term
Which 2 inhaled anesthetics cause increased intracranial pressure that can be reduced by hyperventilation?
Definition
Desflurane and Sevoflurane
Term
What are the therapeutic uses of local anesthetics?
Definition
Surgery-skin, subcut. ears, eyes joint, or pelvis.
Labor and Delivery
Diagnostic procedure
management of pain
Term
What are some physiochemical characteristics of local anesthetics?
Definition
Weak bases (pKa 8-9)
At physiologic pH, cationic form predominate
Small molecular size → more rapid dissociation from receptor site (shorter duration of action)
Ester links more prone to hydrolysis than amide links
Esters usually have shorter duration of action than amides (t1/2 < 1 minute)
Specific steriochemical configurations associated with different potencies
Term
What kind of receptors do local anesthetics bind to?
Definition
They bind intracellular sodium channels. Drug acts on Na channels in an open (inactivated) state to prolong inactivation so conduction of action potential is blocked.

Lengthens refractory period
Term
What kind of periphernal nerves are blocked more easily?
Definition
small diameter, unmyelinated C, lightly myelinated pain fibers, autonomic and sensory fibers are blocked more easily
Term
How would you increase the action of a local anesthetic
Definition
add epinepherine to block peripheral alpha-AR
Term
Why is it important to not inject local anesthetic into the vein?
Definition
local anesthetic can cause systemic toxicity leading to seizures if injected into veins. Can only do this with a turnicate and must remove within short period of time.
Term
Why are hypersensitivity reactions, asthma, dermatitis more common in esters?
Definition
B/c they are hyrolyzed to PABA
Term
What is the concern with using amides in patients with cardiovascular or pulmonary problems?
Definition
Amides are metabolized by the liver to methemoglobinemia which tightly binds oxygen leading to a hypoxic state in these pts.
Amides are highly protein bound. (Drug interactions)
Term
Which local anesthetics are esters?
Definition
Cocaine, Procaine, Tetracaine, Benzocaine
Term
Which local anesthetics are amides?
Definition
Lidocaine, Mepivacaine, Bupivacaine, Prilocaine, Ropivacaine
Term
Which local anesthetic has an intrinsic vasocontrictor activity? How does this work?
Definition
Cocaine
blocks NE reuptake. High abuse potential.
H
Term
Which local anesthetic is not effective when applied topically so must be injected. Is metabolized to PABA has low potency. May produce loss of consciousness.
Definition
Procaine aka novacaine
Term
Which local anesthetic is used for its long duration of action for spinal anesthesia?
Definition
Tetracaine-but may increase systemic toxicity due to slow metabolism
Term
Which local anesthetic can be applied topically and can be bought without a prescription?
Definition
Benzocaine
Term
Why do ppl like Lidocaine?
Definition
Faster, more intense, longer suration of action and extensive anesthesia. Found parenteral, Tpical, transdermal.

Can cause loss of consioudness
Term
WHat is special about prilocaine?
Definition
Does not cause vasodilation. But converted to methemoglobinemia.
Term
Which amide is long acting and used for prolonged analgesia in labor and delivery but can cause Cardiotoxicity
Definition
Bupivacaine.
low concentration is enough and does not cause cardiotoxicity
Term
What is an intermediate acting amide with similar effects as lidocaine but more toxic to neonates?
Definition
Mepivacaine
Term
Which amide is long acting similar to bupivacaine and used for epidural or regional anesthesia?
Definition
Ropivacaine
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