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Flashcards in Active Transport: The Sodium Pump Deck (30):
1

Why is it called the sodium pump?

Since the extrusion of Na+ takes place against a steep electrochemical gradient (concentration and electrical) the active transport system is called the sodium pump.

2

What are the structures of the sodium pump?

+ Extracellular surface
+ Intracellular surface
+ Cardiac glycoside binding sites
+ ATP binding sites

3

What are features of the sodium pump?

+ α2β2 tetramer, MW 270000 α95000 β 4000

+ ATP must be available intracellulary

+ Cardiac glycosides only inhibit from the extracellular surface

+ Na+ ions bind internally (3 per α)

+ K+ ions bind externally (2 per α)

+ Most cells have around 1 million sodium pump sites

4

What is the sodium pump equation?

[3Na+]i +[2K+]o [3Na+]o +[2K+]i

5

What are some features of the sodium/(Na+ + K+)ATPase pump reaction?

+ ATP is hydrolysed to ADP by the enzyme (Na+ + K+)ATPase

+ Reaction occurs 100 times per second

+ Can be inhibited by removing [K+]o

+ Can be stimulated by increasing [Na+]i

6

What is the effect of a decrease in [K+]o on digoxin inhibition of the sodium pump?

+ An increased affinity between cardiac glycosides and the sodium pump

7

What is the therapeutic index?

+ A ratio: the larger the therapeutic index, the safer the drug

+ Comparison of the amount of a therapeutic agent that causes the therapeutic/clinically desired effect to the amount that causes toxicity
- dose producing toxicity for 50% of the population/Minimum effective dose for 50% of the population

8

What is Remifentanil used for and what it its TI?

+ Patient controlled analgesia during labour (synthetic opiod)

+ 33000:1

9

What is Diazepam used for and what it its TI?

+ Sedative

+ 100:1

10

What is Ethanol used for and what it its TI?

+ Sedative

+ 10:1

11

What is Digoxin used for and what it its TI?

+ Congestive heart failure

+ 2:1

12

What does it mean if a drug has a low TI?

+ May require drug monitoring both to achieve therapeutic levels and to minimize toxicity

13

What is hypokalaemia?

Lower than normal potassium levels in the blood (mEq/L)

+ Less than 3.5

+ Moderate (2.5 - 3.0)

+ Severe (less than 2.5)

14

What is normokalaemia?

Normal potassium levels in the blood (mEq/L)

+ 3.6 - 5.2

15

What is hyperkalaemia?

Higher than normal potassium levels in the blood (mEq/L)

+ More than 5.5

+ Moderate (6.1 - 6.9)

+ Severe (more than 7.0)

16

What is the role of potassium?

+ A nutrient critical to the function of nerve and muscle cells

+ Crucial to heart function

+ Plays key role in skeletal/smooth muscle contraction

+ Important for normal digestive and muscular function.

17

What are the symptoms of hypokalaemia?

+ Abnormal heart rhythms
+ Muscle damage (rhabdomyolysis)
+ Muscle weakness or spasms
+ Paralysis

18

What are the symptoms of hyperkalaemia?

+ Nausea
+ Palpitations
+ Muscle weakness

19

What condition will lead to an increase in digoxin binding?

Hypokalaemia

20

What do diuretics do?

Increase urine output by the kidney (promote diuresis)

21

What can diuretics be used as a treatment for?

+ High blood pressure

+ Excessive fluid retention

22

What are the side effects of loop diuretics such as Furosemide?

Increase urinary excretion of potassium

23

What might happen to patients on digoxin who start diuretics such as furosemide, and why can this contribute to digoxin toxicity?

They may become hypokalaemic

+ Reduction in competition between K+ and digoxin (due to increased urinary excretion of K+) results in increased digoxin binding to sodium pump

+ Due to the narrow therapeutic index, patient develops digoxin toxicity

24

What is the emergency treatment for digoxin toxicity?

+ Administer a digoxin binding antibody such as digibind

+ Rapidly binds to the digoxin

+ Digoxin dissociates from sodium pump reversing toxicity

25

What is primary active transport?

+ Utilises energy in form of ATP to transport molecules across a membrane against their concentration gradient

26

What is secondary active transport?

+Utilises energy stored in the Na+ gradient (generated by the sodium pump) to drive molecular transport against the electrochemical gradient

27

What are the types of glucose transporters?

+ GLUT1: basal uptake in placenta and brain

+ GLUT2: transepithelial transport, β cells

+ GLUT3: basal uptake in brain

+ GLUT4: skeletal muscle (insulin dependent)

+ GLUT5: intestinal absorption of fructose

28

What are glucose transporters and what kind of transport is involved?

+ Wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane

+ Facilitated transport/secondary active co-transport

29

Which glucose transporter is insulin dependent?

GLUT4

30

What kind of transport is involved with the sodium calcium exchanger?

Secondary active counter transport