Pharm: L14: Anesthetics

Question 1

Routes of Administration

1. Topical: What does that refer to?

Answer 1

1. Skin, Eye, Ear, Nose, Throat, Mucus Membranes

Question 2

Routes of Administration

1. Injection into Peripheral Nerve Endings/Trunks (Blocks)
   a. Inferior Alveolar Nerve Block (IANB)
   b. Retrobulbar Block
   c. Spinal Block
   d. Epidermal Block
   e. Caudal Block
2. Infiltration Anesthesia

Answer 2

1. a. Injection posterior to the Most Distal Mandibular Molar
   b. Injection behind Globe of the Eye
   c. Injection into CSF in Lumbar Region
   d. Injection into Epidural Space
   e. Injection into Epidural Caudal Space
2. Injection into Tissue

Question 3

Chemistry of Local Anesthetics

1. Local Anesthetics are 1 of 2 things?
2. A Hydrophobic (lipophilic) Group connected to a Hydrophilic group by what?
3. Amides and Esters have different Physiological Properties
   a. Esters usually have what duration time?
   b. Esters also have an increased what?
4. Differences in STEREOCHEMISTRY can also have what?
5. Typically Administered as Salts to do what?

Answer 3

1. Esters or Amides
2. by an Amide or Ester Bond
3. a. a Shorter Duration of Action than Amides (Bond Hydrolyzed faster)
   b. Increased Degree of Systemic Toxicity
4. Affect Potency and Clinical Properties
5. Increase Stability and Solubility

Question 4

Transport Across Cellular Membranes and Mechanism of Action

1. Local Anesthetics: Weak or strong Bases?
   a. So in Extracellular space, what type of drug will predominate?
   b. How much is in the other form and where does it go?
   c. Once inside the neuron, what form will dominate?
   d. What form Binds to a Binding site on the Intracellular side of the Na+ Channel?
   e. HYDROPHOBIC PATHWAY

Answer 4

1. WEAK BASES (pKa 8-9)
   a. IONIZED DRUG will be predominant even though both forms are in equilibrium
   b. Quite a bit is in NON-IONIZED and will DIFFUSE thru the Cell membrane into the Cytosol
   c. the iONIZED form dominates and a Majority of Non-ionzied LA becomes IONIZED (Protonated)
   d. the IONIZED LA
   e. Some of the Neutral LA diffuses thru the membrane

Question 5

Transport Across Cellular Membranes and Mechanism of Action

1. INFLAMMATION (from Infection) and Attendent Acidification do what?
   a. EXCEPTION to the RULE?
   b. What ANTAGONIZES the EFFECT?
   c. What POTENTIATES the EFFECT?
   d. Adding what to the drug solution increases the LEVEL of NON-IONIZED LA? This does what?

Answer 5

1. DECREASES the Permeation and thus Decreases the Effect of the Local Anesthetics
   a. BENZOCAINE has a pKa of 3.5. Since pH is higher than pKa, it’s ALWAYS in NON-IONIZED FORM and thus CANT DIFFUSE ACROSS the MEMBRANE. (so it’s a surface only application for this reason)
   b. ELEVATED Ca2+: Increased membrane surface potential: More rested Channels
   c. ELEVATED K+: Depolarized membrane: More Inactivated Channels
   d. BICARBONATE; INCREASES Membrane Transport and Shortens onset of action

Question 6

Mechanism of Action: Sodium Channels and Action Potentials

1. Resting Membrane Potential?
2. VG-Na+ channels open and depolarizes to what?
3. What happens then?

Answer 6

1. -70mV
2. +40mV
3. VG-Na+ inactivate and K+ channels open. Repolarizes membrane, Na+ channels close

Question 7

Mechanism of Action

1. LOCAL ANESTHETICS BLOCK WHAT?
2. They Bind more readily to what?
3. Elevated Ca2+
4. Elevated K+
5. Which LAs have a Faster rate of interaction with the Na+ Channel
6. Long-acting LAs bind more extensively to what?

Answer 7

1. Na+ Channels and INHIBIT Neuronal Firing and the Propagation of APs
2. to the Activated or Inactivated Channel than the Resting channel
3. Increase membrane potential. More channels in Resting State; Block is Diminished
4. Depolarizes membrane; More channels in Inactivated State; BLOCK is ENHANCED
5. Smaller and More Lipophilic LAs
6. to Proteins

Question 8

Dynamics of Channel Blockade

1. The BLOCKADE of SODIUM CHANNELS by most Local ANESTHETICS is both what?
2. Local Anesthetics have a HIGH AFFINITY for CHANNELS in what states?
3. COMPLETE BLOCK: How does it happen?

Answer 8

1. BOTH VOLTAGE and TIME DEPENDENT
2. in ACTIVATED and INACTIVATED STATE
3. due to drug binding more and more Na+ channels following repeated administration

Question 9

Pharmacokinetics

1. Local anesthetics are intended to exert their effect and remain at the site of application, and although systemic absorption and distribution may not be as important as they are for systemic therapeutics, THEY ARE IMPORTANT for what?

Answer 9

1. for ELIMINATION and POTENTIAL for ADVERSE EFFECTS (Specifically, CNS and Cardiac Toxicity)

Question 10

Pharmacokinetics: Distribution

1. Duration of Action DEPENDS on what?
2. Toxic EFFECTS depend on what?
3. VASOCONTRICTORS (Epinephrine) do what?
4. POTENCY is CORRELATED to what?

Answer 10

1. on TIME at SITE OF ACTION
2. on HALF-LIFE
3. Reduce the Diffusion of the Drug.; DO NOT use in fingers, toes, nose cuz it can lead to NECROSIS!
4. It’s POSITIVELY CORRELATED with LIPID SOLUBILITY and DURATION of ACTION

Question 11

Duration of Action

1. SHORT ACTING? (1)
2. INTERMEDIATE? (3)
3. LONG ACTING? (3)

Answer 11

1. Procaine
2. Lidocain, Mepivacaine, Prilocaine
3. Bupivacaine, Ropivacaine, Tetracaine

Question 12

Pharmacokinetics

1. Systemic ABSORPTION is AFFECTED by what 5 things?

Answer 12

1. Dosage
2. Drug-tissue binding
3. Physiochemical properties of the drug
4. Site of Injection
5. Vasoconstricting Agents (Epinephrine)

Question 13

Pharmacokinetics

1. Metabolism: Since Local Anesthetics in the NON-IONIZED form diffuse readily thru what?
2. Amides
   a. Metabolized by WHAT?
   b. Fastest to Slowest Metabolism?
   c. Toxicity more likely in patients with what?
3. Esters
   a. ESTER Drugs are RAPIDLY what?
   b. Mutations can affect what?

Answer 13

1. thru Lipid Membranes, and Little or No Urinary Excretion of the Neutral Form Occurs
2. a. by CYP450s
   b. Lidocaine > Mepivacaine > Ropivacaine about the same as Bupivacaine

c. Hepatic Disease or Reuced Hepatic BF.
3. a. metabolized by BUTYRLCHOLINESTERASE in PLASMA
b. can affect metabolism of ester LAs.

Question 14

Factors that Affect Anesthetic Action

1. DIFFERENTIAL BLOCK
   a. 2 types of Administration?
   b. Can lead to what 2 things?
   c. Hypotension due to what?
   d. ANATOMIC ARRANGEMENT: Effect hits what fibers then does what?
   e. INTRINSIC SUSCEPTIBILITY of NERVE FIBERS to BLOCKS: In general, the larger and more myelinated fibers are what?

Answer 14

1. a. Spinal and Epidural administration
   b. Motor Paralysis and Respiratory Impairment
   c. Due to Autonomic Blockage
   d. Proximal Fibers then proceeds to more Distal fibers w/in a Nerve Bundle
   e. are Less Sensitive.

Question 15

General Side Effects & Toxicities

1. CNS: Depression of what?
2. PNS: Prolonged what after HIGH DOSES?
3. Cardiovascular: Inhibition of what can lead to what?
   a. Negative Ionotropic Action can cause what?
   b. Bupivacaine: does what?
   c. Administration of LIPIDS does what?
   d. Cocaine: Does what?
4. Blood: PRILOCAINE Metabolite may Produce what?
5. Allergic Reactions: Mostly with what?
6. Localized Toxicity
   a. Neural Injury: How common?
   b. Transient Neurological Symptoms: What is it?

Answer 15

1. Depression of Cortical Inhibitory Pathways (Sleepy, Visual/Auditory disturbances, circumoral and tonge numbness, nystagmus, muscular twitching, convulsions, death)
2. Prolonged Sensory and Motor Deficit following High Doses
3. Inhibition of Na+ and Ca2+ channels can lead to CARDIAC ARRHYTHMIAS
   a. VASODILATION
   b. More toxic than others due to INCREASED BINDING TO RESTING CHANNELS
   c. will REVERSE TOXICITY of LIPID SOLUBLE DRUGS
   d. Special Toxicity due to INCREASED SYMPATHETIC TONE (Vasoconstriction, hypertension, local ischemia, cardiac arrhythmia)
4. METHEMOGLOBINEMIA
5. MOSTLY ESTERS; May cause HYPERSENSITIVITY. RARE with AMIDES
6. a. RARE; adverse affects produced by direct contacts w/neural elements
   b. Syndrome of Transient Pain; Dysesthesia; Linked to Use of Lidocaine for Spinal Anesthesia

Question 16

Local Anesthetics

1. What 4 are the ESTER drugs? (PTBC)
2. Amides: What 6? (LB RAMP)

Answer 16

1. Procaine; Tetracaine, Benzocaine, and Cocaine

2. Lidocaine, Bupivacaine, Ropivacaine, Articaine, Mepivacaine, Prilocaine

Question 17

Procaine

1. Type of drug?
   a. RAPIDLY Metabolized by what?
   b. Duration of Action (long or short)?
   c. What is a METABOLIC PRODUCT of PROCAINE? What does it INHIBIT?
   d. WHAT DOES IT LACK?
   e. Toxicity?
   f. Potency of other local anesthetics is measured as being relative to what?
2. USE?
3. PREPARATIONS available with what?

Answer 17

1. Ester Type Drug
   a. PSEUDOCHOLINESTERASE
   b. SHORT
   c. PABA; Inhibits action of SULFONAMIDES
   d. TOPICAL ACTIVITY
   e. Minimal systemic and No local irritation
   f. to Procaine (Potency = 1)
2. used for INFILTRATION ANESTHESIA and diagnostic nerve blocks
3. with and w/o Epinephrine

Question 18

Tetracaine (Potency: 16)

1. Type of drug?
2. Onset?
3. Duration of Action?
4. Potency and Toxicity compared to PROCAINE?
5. PREFERRED for what 2 things?

Answer 18

1. Ester type
2. Slow (more than 10 minutes)
3. Long. 2-3 hours
4. 10 TIMES MORE POTENT AND MORE TOXIC
5. Preferred for OPHTHALMOLOGICAL USE, and SPINAL ANESTHESIA (combined w/10% dextrose to increase the specific gravity; solution is Heavier than CSF)

Question 19

Benzocaine

1. Type of Drug?
2. pKa?
   a. What does this mean?
3. USED TOPICALLY to treat what?
4. Risk of what occurring?

Answer 19

1. ESTER
2. Very LIPOPHILIC; 3.5
   a. it’s ALWAYS in a NON-IONIZED form at Physiological pH (7.4)
3. ONLY to TREAT SUNBURN, Minor Burns and Pruritus in OTC Preparations
4. METHEMOGLOBINEMIA

Question 20

Cocaine (Potency: 2)

1. Type of Drug?
2. How long does it act?
3. Topical Anesthesia of what? Typically used around what organ?
4. What can it do to bleeding?
5. What does it INHIBIT?

Answer 20

1. ESTER Type
2. Short acting
3. of Mucous Membranes typically around the UPPER RESPIRATORY TRACT
4. Can reduce it
5. Na+ Channels

Question 21

Adverse Effects of Cocaine

1. CNS Effects
   a. Initially produces what?
   b. Followed by what 2 things?
2. Cardiovascular Effects
   a. Blocks uptake of what?
   b. Causes what 3 things?
3. 3 Major issues that can occur?
4. Should be cautiously used for patients with what 3 things?

Answer 21

1. a. Euphoria
   b. Dysphoria and Poststimulatory Depression
2. a. of Catecholamines at Adrenergic Nerve Terminals
   b. Tachycardia, Vasoconstriction and Hypertension
3. Tolerance, Abuse, and Overdose Toxicity
4. HYPERTENSION, CARDIOVASCULAR DISEASE, or THHYROTOXICOSIS

Question 22

Lidocaine (Potency: 4)

1. Type of Drug?
2. Used for what 2 things?
3. Pharmacokinetics?
   a. Metabolized by what?
4. Pharmacologic Effects include what 4 things?
5. NOT PREFERRED for what?
6. Preparations?

Answer 22

1. AMIDE Drug
2. INFILTRATION BLOCKS and EPIDURAL ANESTHESIA
3. same as those for Amides
   a. by Liver CYP450s
4. Rapid onset of Anesthesia; Minimal Local irritation; Moderate topical Activity; Greater potency and longer duration of action than procaine
5. for SPINAL BLOCKS (risk of TNS)
6. with or w/o Epi

Question 23

Prilocaine

1. Type of Drug?
2. Has the HIGHEST what of the AMIDES?
3. CONTRAINDICATED in Patients with what 2 diseases?
4. MEthemoglobinemia can be REVERSED by administration of what?
5. Mainly USED in what setting?

Answer 23

1. Amide
2. RATE of CLEARANCE
3. CARDIAC or RESPIRATORY DISEASES (also in patients w/methemoglobinemia)
4. METHYLENE BLUE
5. DENTISTRY

Question 24

Bupivacaine (Potency = 16)

1. Type of drug?
2. Duration of ACTION?
3. ANALGESIA for what 4 situations?
4. GREATER what than other amide local anesthetics?
5. Preferred as EPIDURAL during what 2 situations?

Answer 24

1. Amide
2. LONG
3. POST-OPERATIVE PAIN CONTROL, SPINAL ANESTHESIA, INFILTRATION and EPIDURAL BLOCKS
4. Greater CARDIOTOXICITY than other amides (binds to more resting cardiac Na+ Channels and Dissociates slower than other LAs)
5. PREGNANCY and LABOR

Question 25

Mepivacaine (Potency = 2) 1. Type of DRUG? 2. DURATION of ACTION? 3. Similar to what other drug? 4. PREFERRED for what type of BLOCK? 5. What 2 situations is it NOT USED FOR?

Answer 25

1. AMIDE 2. INTERMEDIATE 3. LIDOCAINE 4. PERIPHERAL NERVE BLOCKS 5. Not used Topically nor in LABOR ANESTHESIA!

Question 26

Ropivacaine (Potency = 16) 1. Type of Drug? 2. How long does it ACT for? 3. What is it of BUPIVACAINE? 4. Less what than BUPIVACAINE? 5. Used for what 2 types of Blocks? 6. What happens at CLINICAL DOSES?

Answer 26

1. AMIDE 2. LONG-ACTING 3. S-ENANTIOMER 4. Less Lipid Soluble and cleared more rapidly; Also LESS CARDIAC TOXICITY (adverse effects less likely and produces pain relief similar to Bupivacaine) 5. PERIPHERAL and EPIDURAL BLOCKS 6. VASOCONSTRICTING EFFECTS

Question 27

Articaine 1. Type of Drug? 2. Is also has an ADDITIONAL what? a. Makes it subject to Metabolism by what? b. This Decreases what? 3. WIDESPREAD USE in what profession? a. Why? 4. Allows for injection of More Drug later in what? 5. ADVERSE EFFECTS?

Answer 27

1. AMIDE 2. ESTER Group a. by Plasma Esterases b. Decreases Half-life and Potential for systemic Toxicity 3. in DENTAL MEDICINE a. LARGER Therapeutic window and Low Potential for Systemic Toxicity 4. later in the procedure 5. Rare. But could develop PERSISTENT PARESTHESIAS (3 x's more likely with this drug)