Chapter 26 Basic And Clinical Pharmacology

Front 1

Pain awareness is mediated by nerve ending receptors in ________ tissues and transmitted to the CNS by _______ afferent fibers and relayed by __________ afferent fibers to the brain.

Back 1

Periphery
Primary
Secondary

Front 2

Drugs that effectively and reversibly block impulse conduction along nerve axons and other excitable membranes that use sodium channels as the primary means of action potential generation.

Back 2

Local anesthetics

Front 3

The first local anesthetic introduced into medical practice.

Back 3

Cocaine

Front 4

What are the 3 nociceptors that are recognized?

Back 4

Acid, Heat, and Injury

Front 5

What 2 receptors modulate the transmission process?

Back 5

Alpha2 adrenoceptors and opioid receptors.

Front 6

The axon bears ____ and ____ channels, which are essential for AP propagation.

Back 6

Sodium and Potassium

Front 7

Synaptic transmission involves release of _______ and ______ and activation of their receptors on the secondary neuron.

Back 7

Substance P and glutamate.

Front 8

What is the general physical properties of local anesthetics?

Back 8

Lipophilic group connected by an intermediate chain via an ester or amide to an ionizable group.

Front 9

Which local anesthetic would have a shorter half-life, one with ester or amide linkage?

Back 9

Ester

Front 10

True or False
Local anesthetics are weak acids and at physiolocial pH, are mostly in the charged cationic form (active).

Back 10

False
Weak bases

Front 11

True or False
The uncharged form is important for rapid penetration of biologic membranes and producing a clinical effect, since the local anesthetic receptor is not readily accessible from the internal side of the cell membrane.

Back 11

False
External

Front 12

Why is the cationic form the most active form at the receptor site?

Back 12

Because it cannot readily exit from closed channels.

Front 13

What is the configuration of the m and h gates at a resting membrane potential?

Back 13

M closed
H open

Front 14

What is the configuration of the m and h gates at the activated state?

Back 14

M open
H open

Front 15

What is the configuration of the m and h gates at the inactivated state?

Back 15

M open
H closed

Front 16

What is the primary MOA of local anesthetics?

Back 16

Blockade of voltage-gated sodium channels.

Front 17

What happens to sodium and potassium channels following a depolarization?

Back 17

Sodium closes
Potassium opens and flows out which results in cellular repolarization.

Front 18

How are transmembrane ionic gradients maintained?

Back 18

The sodium pump

Front 19

Why is the cationic form the most active form at the receptor site?

Back 19

Because it cannot readily exit from closed channels.

Front 20

Local anesthetics bind to receptors near the intracellular end of the sodium channel and block the channel in a _______- and _______-dependent manner.

Back 20

Time and voltage

Front 21

What is the primary MOA of local anesthetics?

Back 21

Blockade of voltage-gated sodium channels.

Front 22

What happens to sodium and potassium channels following a depolarization?

Back 22

Sodium closes
Potassium opens and flows out which results in cellular repolarization.

Front 23

For myelinated nerves, what is the critical length of sodium channels required to be blocked in order to abolish the AP?

Back 23

2-3 nodes of Ranvier

Front 24

Channels in the rested state predominate at more _________ membrane potentials have a _______ affinity for local anesthetics.

Back 24

Negative
Lower

Front 25

Elevated extracellular calcium partially ___________ the action of local anesthestics.

Back 25

Antagonizes

Front 26

Elevated extracellular potassium __________ the action of local anesthetics.

Back 26

Enhances

Front 27

At concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via _______, ________, and ____________ receptors in the secondary afferent neurons.

Back 27

Substance P
NMDA
AMPA

Front 28

C.R. requires a long acting, potent local anesthetic for a surgical procedure. What local anesthetics would you recommend?

Back 28

Tetracaine
Bupivacaine
Ropivacaine.

Front 29

True or False
Local anesthetics can block all nerves, cause motor paralysis and residual autonomic block.

Back 29

True

Front 30

True or False
Larger fibers are blocked first relative to smaller fibers.

Back 30

False
smaller fibers are blocked first

Front 31

True or False
Myelinated fibers are blocked before unmyelinated nerves of the same diameter.

Back 31

True

Front 32

True or False
Preganglionic B fibers are blocked before unmyelinated C fibers involved in pain transmission.

Back 32

True

Front 33

Why are type A delta and C fibers blocked earlier and with lower concentrations of local anesthetics?

Back 33

They are small and high-frequency pain transmission fibers.

Front 34

True or False
During infiltration block of a large nerve, sensory analgesia first develops distally and then spreads proximally as the drug penetrates deeper into the core of the nerve.

Back 34

False
Proximally then distally

Front 35

How can we reduce systemic absorption of local anesthetics from the injection site?

Back 35

Give epinephrine to reduce blood flow to these areas.

Front 36

What alpha 2 agonist is used to prolong the local anesthetic affect by inhibition of the release of substance P and reduction of neuronal firing?

Back 36

Dexmedetomidine

Front 37

With local anesthetics, acidification of urine leads to ____ _____________.

Back 37

Rapid elimination.

Front 38

How are ester linkages hydrolyzed?

Back 38

Butyrylcholinesterase

Front 39

How are amide linkages hydrolyzed?

Back 39

Liver microsomal CYP450 isozymes.

Front 40

Toxicity from amide-type local anesthetics is more likely to occur in patients with ________ disease.

Back 40

Hepatic

Front 41

Which local anesthetic has a fast onset and an intermediate duration of action that makes it suitable for use in dental procedures?

Back 41

Articaine

Front 42

How can you accelerate the onset of a local anesthetic?

Back 42

Sodium bicarb

Front 43

True or False
Topical anesthetics are commonly used for ENT procedures and in chronic pain.

Back 43

True

Front 44

How can repeated injections of local anesthetics result in loss of effectiveness?

Back 44

Extracellular acidosis due to depletion of the buffering capacity of the local tissues. This increases extracellular cationic forms which results in tachyphylaxis.

Front 45

What are early signs of CNS toxicity?

Back 45

Tongue numbness, metallic taste

Front 46

How does pregnancy affect the susceptibility of local anesthetics?

Back 46

Increases it.

Front 47

When large doses of a local anesthetic are required, how can you protect against local anesthetic-induced CNS toxicity by raising the seizure threshold?

Back 47

Premedication with a parenteral benzodiazepine (diazepam or midazolam)

Front 48

True or False
Topical anesthetics are commonly used for ENT procedures and in chronic pain.

Back 48

True

Front 49

True or False
You can treat seizures by hyperventilating.

Back 49

True.

Front 50

What are early signs of CNS toxicity?

Back 50

Tongue numbness, metallic taste

Front 51

What are the most neurotoxic local anesthetics?

Back 51

Chloroprocaine and lidocaine

Front 52

What effects do local anesthetics have on the cardiac pacemaker activity, excitability, and conduction?

Back 52

Depression

Front 53

When large doses of a local anesthetic are required, how can you protect against local anesthetic-induced CNS toxicity by raising the seizure threshold?

Back 53

Premedication with a parenteral benzodiazepine (diazepam or midazolam)

Front 54

True or False
You can treat seizures by hyperventilating.

Back 54

True.

Front 55

What effects do local anesthetics have on the cardiac pacemaker activity, excitability, and conduction?

Back 55

Depression

Front 56

True or False
Except for cocaine, local anesthetic toxicity causes systemic hypertension.

Back 56

False
Depress myocardial contractility
Induces arteriolar dilation
Systemic hypotension.

Front 57

Which long-acting local anesthetic is more cardiotoxic than any other?

Back 57

Bupivacaine

Front 58

What happens in bupivacaine cardiotoxicity?

Back 58

Idioventricular rhythm, broad QRS, and electromechanical dissociation.

Front 59

How do you resuscitate from bupivacaine cardiovascular toxicity?

Back 59

Propafol

Front 60

Which bupivacaine isomer is safer?

Back 60

S

Front 61

Large doses of prilocaine can lead to accumulation of what metabolite capable of converting hemoglobin to methemoglobin.

Back 61

O-toluidine

Front 62

C.R. is released from surgery. Nurses document "chocolate-colored blood". What local anesthetic has the patient been given? How can you treat her toxicity?

Back 62

Prilocaine.
Methylene blue or ascorbic acid.

Front 63

Which group of local anesthetics are metabolized to p-aminobenzoic acid derivatives, which cause allergic reactions?

Back 63

Ester-type local anesthetics