Local Anaesthetics and Anti-Dysrhythmics

Question 1

What is the key action of LAs?

Answer 1

Reversible regional loss of sensation/pain - without loss of consciousness

Question 2

What are the 3 components of the general structure of an LA?

Answer 2

Aromatic group
Intermediate chain - ester/amide bond
Tertiary/secondary amino group

Question 3

Describe the pH of most LAs

Answer 3

Weak bases

Question 4

What are LAs administered as?

Answer 4

Water-soluble hydrochlorides (B.HCl)

Question 5

What happens to B.HCl upon entering the tissue fluid and what is the corresponding equation?

Answer 5

Alkaline pH of tissue fluid liberates tertiary amine base (B)
B.HCl + HCO3- B + H2CO3 + Cl-

Question 6

Describe the hydrophilic pathway of LA action

Answer 6

B moves through nerve sheath, perineurium, and neuron membrane - into axoplasm
Becomes ionised - BH+
Moves into open Na+ channel - blocks
Use-dependent - faster and greater block with higher AP frequency - more frequent Na+ channel opening

Question 7

Describe the hydrophobic pathway of LA action

Answer 7

B moves into neuron membrane
Moves through pore portal into Na+ channel
Ionised to BH+ - blocks

Question 8

In which state does an Na+ channel have a higher affinity for an LA?

Answer 8

Inactivated

Question 9

What determines LA potency?

Answer 9

Lipid solubility - ease of moving through neuronal membrane (positive correlation)

Question 10

What determines block duration?

Answer 10

Capacity to bind to plasma and tissue proteins (positive correlation)

Question 11

What is pKa?

Answer 11

pH where 50% of agent ionic - 50% non-ionic

Question 12

Which fibre characteristics increase ease of block?

Answer 12

Small diameter

Myelination

Question 13

Name an amino ester LA and describe its metabolism

Answer 13

Procaine

Rapidly hydrolysed in body - by plasma ChE

Question 14

Name an amino amide LA and describe its metabolism

Answer 14

Lidocaine

Slowly metabolised - by hepatic amidases - in liver

Question 15

What are the CNS side effects of LAs?

Answer 15

Low conc - tinnitus, blurred vision, drowsiness

High conc - Agitation, convulsions, CNS and respiratory depression

Question 16

What are the cardiovascular side effects of LAs?

Answer 16

Vasodilation, myocardium depression, cardiac slowing (cardiac block) - hypotension

Question 17

Which LA can cause an allergic reaction and why?

Answer 17

Ester LAs - breakdown product is PABA - allergen

Question 18

Name and describe the methods of LA administration

Answer 18

Surface - topical application
Infiltration - inject into tissue to affect nerve endings
Nerve block - inject near nerve trunk to affect area innervated
Spinal - inject into subarachnoid space
Epidural - Inject into epidural space - diffuses across dura mater
Intravenous regional - intravenous injection distal to cuff on limb

Question 19

What are the phases of an electrocardiogram?

Answer 19

P - Atrial contraction
QRS - Ventricular contraction (and atrial relaxation)
T - Ventricular relaxation

Question 20

Describe the stages of a ventricular AP

Answer 20

Rest - large K+ permeability - leak K+ channels and some voltage-gated K+ channels open
Rising phase - voltage-gated Na+ channels open
Initial repolarisation - voltage-gated Na+ channels inactivate
Plateau - delayed voltage-gated K+ channels and voltage-gated Ca2+ channels open - cancel out
Repolarisation - voltage-gated Ca2+ channels inactivate - potential moves towards EK - some voltage-gated K+ channels close - voltage-gated Na+ channels close

Question 21

What is depolarisation in SA and AV nodes due to?

Answer 21

Ca2+ influx

Question 22

How does sympathetic stimulation of the SA and AV nodes affect pacemaker APs?

Answer 22

NA acts on B1-adrenoceptors - activates Na+ and Ca2+ currents - depolarisation - shorter time between APs

Question 23

How does parasympathetic stimulation of the SA and AV nodes affect pacemaker APs?

Answer 23

ACh acts on M2 receptors - increases K+ conductance - slows depolarisation - longer time between APs

Question 24

How does delayed hyperpolarisation cause a dysrhythmia?

Answer 24

Ca2+ increases above normal
Stimulates Na+/Ca2+ exchanger - 3Na+ in/Ca2+ out - net +2 charge entry - transient inward current
Depolarisation - ectopic (early) beat

Question 25

How does re-entry cause a dysrhythmia?

Answer 25

Damaged atrial muscle - unidirectional block Activation wavefront of anterograde signal interacts with repolarisation of preceding wave Re-excites tissue (if not refractory) Circulates indefinitely

Question 26

How does abnormal pacemaker activity cause a dysrhythmia?

Answer 26

Damage makes ectopic foci - in atria/ventricles | Beats out of synchrony with normal rhythm

Question 27

How does heart block cause a dysrhythmia?

Answer 27

Failure of impulse generation in SA node/failure of propagation through AV node Ventricular contraction maintained by abnormal pacemaker - slow

Question 28

What type of drugs are in class I of Vaughan-William's classification, and what is their effect?

Answer 28

Na+ channel blockers Slow depolarisation of SA node and slow conduction of propagating AP to extinguish before re-excitation in re-entry dysrhythmia Class Ia also increase refractory period - cells not re-excited by re-entrant AP

Question 29

What type of drugs are in class II of Vaughan-William's classification, and what is their effect?

Answer 29

B-adrenoceptor antagonists | Inhibit plateau phase

Question 30

What type of drugs are in class III of Vaughan-William's classification, and what is their effect?

Answer 30

K+ channel blockers | Slow repolarisation

Question 31

What type of drugs are in class IV of Vaughan-William's classification, and what is their effect?

Answer 31

Ca2+ channel blockers | Inhibit plateau phase and block conduction through AV node

Question 32

Name a class I anti-dysrhythmic drug

Answer 32

Quinine - quinidine isomer more effective

Question 33

Name a class II anti-dysrhythmic drug

Answer 33

Propranolol

Question 34

Name a class III anti-dysrhythmic drug

Answer 34

Amiodarone

Question 35

Name a class IV anti-dysrhythmic drug

Answer 35

Verapamil

Question 36

Name a cardiac glycoside and describe its action

Answer 36

Digoxin Inhibit Na+/K+-ATPase - intracellular Na+ increases - inhibits Na+/Ca2+ exchanger - intracellular Ca2+ increases - increases contraction force Lengthens refractory period of AV node - decreases contraction rate

Question 37

What is the action of adenosine?

Answer 37

Activates A1 receptors - opens linked K+ channels - AV node conduction block

Question 38

What is the QT interval, which drugs prolong it, and how?

Answer 38

Ventricular depolarisation Class I and III antidysrhythmics, erythromycin, lithium, tricyclics, salbutamol Occupy binding pocket in voltage-gated K+ channel - block - reduces IKr - prevents repolarisation - prolongs QT