Inhibiting Cell Transport

Question 1

How do calcium channel blockers work?

Answer 1

Block calcium entering cells by binding to calcium channels on smooth muscles

Question 2

What is effect of calcium channel blockers?

Answer 2

Smooth muscle relaxation and decreased heart rate

Question 3

What are the 3 classes of calcium channel blockers?

Answer 3

1. Dihydropyridines
2. Phenylalkylamine
3. Benzothiazepine

Question 4

What is function of dihydropyridine?

Answer 4

Most common, most smooth muscle selective

Question 5

What is function of phenylalkylamine?

Answer 5

Selective to myocardium and less effective as a vasodilator

Question 6

What is function of benzothiazepine?

Answer 6

Has both cardiac depressant and vasodilator actions

Question 7

What structure do local anaesthetics have?

Answer 7

Lipophilic hydrophobic aromatic group and a charged, hydrophilic amine group

Bond between these groups determines class of drug –> amide or ester

Question 8

Are LAs acids or bases?

Answer 8

Tend to be weak bases - more unionised so can cross cell membrane

Question 9

Difference between amide and ester LAs?

Answer 9

Esters:

• Rapidly hydrolysed
• Breakdown product PABA is associated with allergic and hypersensitive reactions

Amides:

• Relatively stable and hypersensitivity reactions are rare
• Bond stronger and more stable than ester

Question 10

Why can amides be stored for longer than esters?

Answer 10

Ester linkage more easily broken so ester drugs are less stable in solution

Question 11

What is mechanism of LAs?

Answer 11

Disrupt ion channel function within neurone cell membrane –> prevents transmission of neuronal action potential

1. Specific binding of LA molecules in ionised form to sodium channels
2. Holds them in inactive state
3. No further depolarisation can occur
4. Stops action of Na+ moving into post-synaptic cleft (Na+ channel blocked)
5. Stops pain sensation feedback to brain

Question 12

What is result of LAs?

Answer 12

Transient and reversible loss of sensation in restricted area of body without loss of consciousness

Causes depression of excitation in nerve endings or inhibition of the conduction process in peripheral nerves (reversible)

Question 13

What are side effects of LA?

Answer 13

1. Block NA channels in conduction system of the heart - myocardial depression and vasodilation
2. Can affect CNS - stimulation causes restlessness and convulsions at high doses
3. Addition of adrenaline causes constriction of peripheral blood vessels - lessening distribution, prolonging action, producing relatively bloodless field

Question 14

Absorption of LA

Answer 14

Administered to areas around nerves to be blocked

Question 15

Distribution of LA

Answer 15

Influenced by degree of tissue and plasma protein binding of drug
- More protein bound = longer duration of action as free drug is made more slowly available for metabolism

Question 16

Metabolism & Excretion of LA

Answer 16

Ester and amide LAs differ

• Esters broken down by plasma esterase’s to inactive compounds and have short half life (broken down quicker)
• Amides are metabolised hepatically by amides (half life is longer and they can accumulate if given in repeated doses or by infusion)