Exercise-Drug Interactions

Question 1

How does change in blood flow distribution change pharmacokinetics?

Answer 1

Changes in absorption dependent on route of administration
Distribution - increased muscle and skin blood flow
Metabolism - decreased hepatic blood flow
Excretion - decreased renal blood flow

Question 2

What is the difference between plasma [insulin] in rest and exercise?

Answer 2

[Insulin] increased in exercise

Question 3

List 3 mechanisms of exercise-induced hypoglycaemia

Answer 3

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

Question 4

List 2 mechanisms of exercise-induced hyperglycaemia

Answer 4

Excessive CHO supplementation

Too large a reduction in insulin dose

Question 5

What changes occur to plasma [GTN] with exercise and sauna use?

Question 6

List 3 mechanisms for increased plasma [GTN] with sauna use and exercise

Answer 6

Increased skin blood flow (transdermal administration for prophylaxis)
Increased kinetic energy of drugs with increased skin temperature
Increased hydration may improve absorption

Question 7

What are some of the possible implications of increased GTN absorption in exercise?

Answer 7

May provide benefit (minimise exercise-induced angina)

Potential for vasodilation in skin and exercising muscle to cause excessive hypotension and divert coronary blood flow

Question 8

What are 3 mechanisms underlying the increased plasma [salbutamol] with exercise?

Answer 8

Increased respiratory rate
Increased pulmonary blood flow
Increased epithelial permeability

Question 9

List 2 implications of the increased absorption of salbutamol with exercise

Answer 9

May provide benefit for exercising patient to minimise exercise-induced asthma
Despite higher bioavailbility, bronchodilator effects are less prolonged (need more frequent dosing) due to increased respiratory rate

Question 10

What are the effects of exercise on the gut?

Answer 10

Inhibits gastric emptying (reducing drug delivery to small intestine)
Increases intestinal motility to reduce transit time (less time for absorption of lipophilic drugs)

Question 11

What are some of the risks of warfarin use in sport?

Answer 11

Increased bruising

Question 12

What is the difference between INR in exercise and at rest?

Answer 12

Exercise < rest

Question 13

What is the mechanism of decreased INR in exercise?

Answer 13

Increased binding of warfarin to albumin (due to fluid loss)
Possible increased metabolism with training (decreased free warfarin, decreased INR; shorter clotting time, increased risk of thrombosis)

Question 14

What is the effect of exercise on plasma [digoxin]? What is its effect on muscle [digoxin]?

Answer 14

Plasma [digoxin] reduced in exercise

Muscle [digoxin] increased in exercise

Question 15

What is the mechanism of decreased plasma [digoxin] in exercise?

Answer 15

Redistribution due to increased binding to skeletal muscle

Question 16

What are the implications of decreased plasma [digoxin] in exercise?

Answer 16

Reduced efficacy to increase contractility or control rate

Question 17

What is digoxin used for clinically?

Answer 17

Heart failure

Atrial arrhythmia

Question 18

What is the effect of exercise on plasma [carvedilol] as opposed to propanol and atenolol?

Answer 18

No difference between exercise and rest plasma [carvedilol] (cf propranolol and atenolol where exercise increase plasma concentrations)

Question 19

What is the mechanism of increased plasma levels of most B-blockers in exercise?

Answer 19

Reduced hepatic clearance (propranolol)

Reduced renal clearance (atenolol)

Question 20

What are the implications of increased plasma levels of B-blockers in exercise?

Answer 20

Increased risk of exercise-limiting adverse effects (bronchoconstriction, fatigue)

Question 21

List 2 potential advantages of diuretic use in sport

Answer 21

Loss of fluid reduces weight (to meet weight limits for competition)
Dilution of urine will decrease concentration of other banned drugs

Question 22

List 2 potential disadvantages of diuretic use in sport

Answer 22

Dehydration

Hypokalaemia

Question 23

What is the potential advantage of B1 antagonist use in sport?

Answer 23

Reduce HR and “stress”

Stop tremor in precision sports

Question 24

List 4 potential disadvatages of B1 antagonist use in sport

Answer 24

Lower BP or decreased HR
Reflex vasoconstriction via a1 adrenoceptors
Non-selective block of B2-mediated vasodilation of skeletal/skin blood vessels
Fatigue, decreased performance in endurance events

Question 25

What is the status of B1 antagonists in sport?

Answer 25

Prohibited in particular sports (archery, shooting, skiing, billiards, bridge)

Question 26

What are the potential advantages of systemic administration of B2 agonists in sport?

Answer 26

Increased skeletal muscle blood flow (reduces fatigue)
Exerts anabolic effect to increase muscle mass
Exerts catabolic effect to reduce body fat

Question 27

List 2 potential disadvantages of B2 agonist use in sport

Answer 27

Tachycardia

Muscle tremor

Question 28

What is the status of B2 agonists in sport?

Answer 28

Prohibited for any route other than inhalation

No TUE required for salbutamol (but required for others)

Question 29

What is the potential advantage of GCS in sport?

Answer 29

Anti-inflammatory action can mask pain (athletes can compete despite injury)

Question 30

What are some potential disadvantages of GCS in sport?

Answer 30

Damage to tissues used before full recovery

Chronic use can cause osteoporosis, growth suppression in children, skin fragility and increased infections

Question 31

What is the status of GCS in sport?

Answer 31

Approved without a TUE for topical use and inhalation for asthma (certain preparations only)
Require TUE if administered via intra-articular route (e.g. for an inflamed injury)
Banned for systemic administration

Question 32

What are the potential advantages of androgens in sport?

Answer 32

Increased muscle strength by encouraging new growth

Allow athlete to train harder and longer

Question 33

What are the potential disadvantages of androgens in sport and their adverse effects?

Answer 33

High BP
Decreased HDL, increase LDL
Jaundice and liver damage
Mood swings, depression and aggression
Acne
Baldness, breast development and infertility in males
Hirsutism, deepened voice, menstrual cycle disruption and possible infertility in females

Question 34

What is the status of androgens in sport?

Answer 34

Banned

Question 35

What are the potential advantages of GH use in sport?

Answer 35

Reduced fat mass, increased lean mass

Increased bone density

Question 36

What are the potential disadvantages of GH use in sport?

Answer 36

Joint pain
Increased risk of DM
Acromegaly

Question 37

What is the status of GH in sport?

Answer 37

Banned, alongside GHRP and IGF-1

Question 38

What is AOD-9604? What does it do?

Answer 38

Anti-Obesity Drug 9604 (Lipotropin)
Modified 14 AA fragment of GH
Designed to be catabolic (increase lipolysis) but not anabolic (does not stimulate production of IGF-1)

Question 39

What is the status of substances not addressed in sections of sporting codes and with no current approval for human therapeutic use?

Answer 39

Banned at all times

Question 40

What are the potential advantages of AOD-9604 in sport?

Answer 40

Unproven as anti-obesity drug

Under preclinical trial for repair of cartilage, muscle and joint disorders such as OA

Question 41

What are the potential disadvantages of AOD-9604 in sport?

Answer 41

Some obese people experienced headache, chest tightness, palpitation and euphoric feelings in short-term studies
Long term effects are unknown