Exercise-Drug Interactions

Question 1

Why is the effect of exercise on drugs such as digoxin and warfarin particularly important?

Answer 1

Have narrow therapeutic window

Question 2

What drug pharmacokinetics can altered skin temperature with exercise influence?

Answer 2

Transdermal administration

Question 3

What drug pharmacokinetics can increased respiratory rate and tidal volume with exercise influence?

Answer 3

Inhaled administration

Question 4

What drug pharmacokinetics can altered metabolic enzyme activity with exercise influence?

Answer 4

Drug metabolism

Question 5

How does blood flow distribution to different organs change during exercise?

Answer 5

Muscles: increases
Liver: decreases
Kidney: decreases
Skin: increases

Question 6

What implications does redistribution of blood flow during exercise have on the distribution of a drug?

Answer 6

Increased muscle and skin blood flow > possible decrease in availability of drug at other target organs

Question 7

What implications does redistribution of blood flow during exercise have on the metabolism of a drug?

Answer 7

Decreased hepatic blood flow

Question 8

What implications does redistribution of blood flow during exercise have on the excretion of a drug?

Answer 8

Decreased renal blood flow

Question 9

What is the clinical use of insulin?

Answer 9

Type 1 diabetes

Advanced type 2 diabetes

Question 10

What is the route of administration of insulin?

Answer 10

Injection

Question 11

What effect does exercise have on plasma insulin levels?

Answer 11

Increases them

Question 12

What effect does exercise have on the effect of insulin?

Answer 12

Exercise beneficial in management, but glucose control may be dysregulated due to synergy with insulin

Question 13

What factors influence the effect of glucose on insulin action?

Answer 13

Type of insulin
Proximity of exercising limbs
- Plasma concentration increases more rapidly
Type, duration, and intensity of exercise
Amount of muscle mass
Level of fitness
Pre-exercise glucose levels
Patency of counter-regulatory mechanisms
Carbohydrate supplementation
- Simple/complex
- Rate of absorption
- Timing of administration

Question 14

What are the mechanisms of exercise-induced hypoglycaemia?

Answer 14

Accelerated insulin absorption from sites near exercising muscles
Exercise-mediated enhancement of insulin action
Lack of decline in insulin secretion during exercise

Question 15

How can you ameliorate the effects of accelerated insulin absorption from sites near exercising muscles?

Answer 15

Site of administration away from exercising muscles

Question 16

Why might there be an exercise-mediate enhancement of insulin action?

Answer 16

Probably because of increased adrenergic effects on pancreas

Question 17

What are the mechanisms of exercise-induced hyperglycaemia?

Answer 17

Excessive carbohydrate supplementation

Too large a reduction in insulin dose

Question 18

What is the clinical use of glyceryl trinitrate (GTN)?

Answer 18

Angina

Question 19

What is the route of administration for GTN?

Answer 19

Transdermal for prophylaxis

Sublingual for acute angina

Question 20

What effect does the sauna and exercise have on plasma concentrations of GTN?

Answer 20

Increases them

Question 21

What are the mechanisms for increased plasma levels of GTN during exercise?

Answer 21

Increased skin blood flow
Increased kinetic energy of drugs with increased skin temperature
Increased hydration may improve absorption

Question 22

What are the implications for increased transdermal absorption of GTN during exercise?

Answer 22

May provide benefit for exercising patient to minimise exercise-induced angina
Potential for vasodilation in skin and exercising muscle to cause excessive hypotension and divert coronary blood flow
- Worse in hot enclosed environment

Question 23

What is the clinical use of salbutamol?

Answer 23

Asthma

Question 24

What is the route of administration of salbutamol?

Answer 24

Inhalation

Question 25

What effect does exercise have on plasma levels of salbutamol?

Answer 25

Increases

Question 26

What are the mechanisms for increased plasma levels of salbutamol during exercise?

Answer 26

Increased respiratory rate Increased pulmonary blood flow Increased epithelial permeability in strenuous exercise

Question 27

What are the implications of increased absorption of salbutamol during exercise?

Answer 27

May provide benefit for exercising patient to minimise exercise-induced asthma Despite higher bioavailability, bronchodilator effects less prolonged > need more frequent dosing

Question 28

What are the effects of exercise on the gut?

Answer 28

Inhibits gastric emptying - Reduces drug delivery to small intestine - Adaptation in trained athletes > no inhibition of emptying Increases intestinal motility to reduce transit time - Less time for absorption of lipophilic drugs

Question 29

What is the clinical use of warfarin?

Answer 29

Anticoagulant

Question 30

What is the route of administration of warfarin?

Answer 30

Oral

Question 31

What is the risk of using warfarin in sport?

Answer 31

Increased bruising

Question 32

What is the effect of exercise whilst using warfarin on clotting time?

Answer 32

Decreased clotting time

Question 33

What are the mechanisms of decreased clotting time whilst using warfarin during exercise?

Answer 33

Increased binding to albumin | Possible increased metabolism with training

Question 34

What is the clinical use of digoxin?

Answer 34

Heart failure | Atrial arrhythmia

Question 35

What is the route of administration of digoxin?

Answer 35

Oral

Question 36

What is the effect of exercise on digoxin plasma levels?

Answer 36

Decreased

Question 37

What is the effect of exercise on digoxin muscle levels?

Answer 37

Increased

Question 38

What are the mechanisms of decreased digoxin plasma levels with exercise?

Answer 38

Redistribution due to increased binding to skeletal muscle

Question 39

What type of muscle does digoxin have a high affinity for?

Answer 39

Skeletal | Cardiac

Question 40

What are the implications of decreased digoxin plasma levels during exercise?

Answer 40

Reduced efficacy to increase contractility and control rate

Question 41

What is the clinical use of beta-blockers?

Answer 41

Hypertension | Angina

Question 42

What is the route of administration of beta-blockers?

Answer 42

Oral

Question 43

What is the selectivity of propranolol?

Answer 43

Non-selective

Question 44

What is the selectivity of atenolol?

Answer 44

Beta-selective

Question 45

What is the selectivity of carvedilol?

Answer 45

Beta- and alpha1-selective

Question 46

What is the effect of exercise on plasma propranolol levels?

Answer 46

Increased

Question 47

What is the effect of exercise on plasma atenolol levels?

Answer 47

Increased

Question 48

What is the effect of exercise on plasma carvedilol levels?

Answer 48

Unchanged from rest

Question 49

What are the mechanisms of increased plasma propranolol levels with exercise?

Answer 49

Reduced hepatic clearance - metabolism highly dependent on hepatic blood flow

Question 50

What are the mechanisms of increased plasma atenolol levels with exercise?

Answer 50

Reduced renal clearance - excretion highly dependent on renal blood flow

Question 51

What are the implications of increased plasma levels of beta-blockers during exercise?

Answer 51

Increased risk of exercise-limiting adverse effects - Bronchoconstriction - Fatigue

Question 52

Why is there poor exercise compliance with the use of beta-blockers?

Answer 52

Decreased - Heart rate - Stroke volume - Cardiac output Non-selective block of beta2-mediated vasodilation in skeletal muscle Patient feels fatigued and ability to exercise more difficult

Question 53

Does fatigue improve with a few weeks of compliance to exercise whilst using beta-blockers?

Answer 53

Yes

Question 54

What are the potential advantages in sport of using beta2-agonists with systemic administration?

Answer 54

``` Increases skeletal muscle blood flow - Increased O2 supply - Increased lactic acid removal Anabolic effect to increase muscle mass and may increase strength Catabolic effect to reduce body fat ```

Question 55

What are the potential adverse effects of beta2-agonists in sports?

Answer 55

Tachycardia - non-selective activation of cardiac beta1-adrenoceptiors Muscle tremor - activation of skeletal muscle beta2-adrenoceptors

Question 56

What is the status of beta2-agonists in sport?

Answer 56

Prohibited for any route other than inhalation

Question 57

What is the clinical use of glucocorticoids?

Answer 57

Replacement hormone for adrenal insufficiency Inhaled asthma preventer/oral for exacerbations Anti-inflammatory - local/systemic administration

Question 58

What are the potentiatial advantages in sport with the use of glucocorticoids?

Answer 58

Anti-inflammatory action can mask pain | Can compete despite injury

Question 59

What are the potential disadvantages in sport with the use of glucocorticoids?

Answer 59

``` Damage to tissue before full recovery Chronic use can cause - osteoporosis - Growth suppression - Skin fragility - Increased infections ```

Question 60

What is the status in sport for the use of glucocorticoids?

Answer 60

Without TUE - Topical use - Inhalation for asthma Abbreviated TUE if administerd via intra-articular route Prohibited TUE if systemic administration