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MD1 Exercise > Exercise-Drug Interactions > Flashcards

Exercise-Drug Interactions Flashcards

1
Q

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

A

Have narrow therapeutic window

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2
Q

What drug pharmacokinetics can altered skin temperature with exercise influence?

A

Transdermal administration

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3
Q

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

A

Inhaled administration

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4
Q

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

A

Drug metabolism

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5
Q

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

A

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

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6
Q

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

A

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

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7
Q

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

A

Decreased hepatic blood flow

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8
Q

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

A

Decreased renal blood flow

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9
Q

What is the clinical use of insulin?

A

Type 1 diabetes

Advanced type 2 diabetes

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10
Q

What is the route of administration of insulin?

A

Injection

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11
Q

What effect does exercise have on plasma insulin levels?

A

Increases them

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12
Q

What effect does exercise have on the effect of insulin?

A

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

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13
Q

What factors influence the effect of glucose on insulin action?

A 
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
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14
Q

What are the mechanisms of exercise-induced hypoglycaemia?

A

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

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15
Q

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

A

Site of administration away from exercising muscles

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16
Q

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

A

Probably because of increased adrenergic effects on pancreas

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17
Q

What are the mechanisms of exercise-induced hyperglycaemia?

A

Excessive carbohydrate supplementation

Too large a reduction in insulin dose

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18
Q

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

A

Angina

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19
Q

What is the route of administration for GTN?

A

Transdermal for prophylaxis

Sublingual for acute angina

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20
Q

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

A

Increases them

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21
Q

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

A

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

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22
Q

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

A

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

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23
Q

What is the clinical use of salbutamol?

A

Asthma

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24
Q

What is the route of administration of salbutamol?

A

Inhalation

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25
Q

What effect does exercise have on plasma levels of salbutamol?

A

Increases

26
Q

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

A

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

27
Q

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

A

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

28
Q

What are the effects of exercise on the gut?

A

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

29
Q

What is the clinical use of warfarin?

A

Anticoagulant

30
Q

What is the route of administration of warfarin?

A

Oral

31
Q

What is the risk of using warfarin in sport?

A

Increased bruising

32
Q

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

A

Decreased clotting time

33
Q

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

A

Increased binding to albumin

Possible increased metabolism with training

34
Q

What is the clinical use of digoxin?

A

Heart failure

Atrial arrhythmia

35
Q

What is the route of administration of digoxin?

A

Oral

36
Q

What is the effect of exercise on digoxin plasma levels?

A

Decreased

37
Q

What is the effect of exercise on digoxin muscle levels?

A

Increased

38
Q

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

A

Redistribution due to increased binding to skeletal muscle

39
Q

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

A

Skeletal

Cardiac

40
Q

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

A

Reduced efficacy to increase contractility and control rate

41
Q

What is the clinical use of beta-blockers?

A

Hypertension

Angina

42
Q

What is the route of administration of beta-blockers?

A

Oral

43
Q

What is the selectivity of propranolol?

A

Non-selective

44
Q

What is the selectivity of atenolol?

A

Beta-selective

45
Q

What is the selectivity of carvedilol?

A

Beta- and alpha1-selective

46
Q

What is the effect of exercise on plasma propranolol levels?

A

Increased

47
Q

What is the effect of exercise on plasma atenolol levels?

A

Increased

48
Q

What is the effect of exercise on plasma carvedilol levels?

A

Unchanged from rest

49
Q

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

A

Reduced hepatic clearance - metabolism highly dependent on hepatic blood flow

50
Q

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

A

Reduced renal clearance - excretion highly dependent on renal blood flow

51
Q

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

A

Increased risk of exercise-limiting adverse effects

  • Bronchoconstriction
  • Fatigue
52
Q

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

A

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

53
Q

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

A

Yes

54
Q

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

A 
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
55
Q

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

A

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

56
Q

What is the status of beta2-agonists in sport?

A

Prohibited for any route other than inhalation

57
Q

What is the clinical use of glucocorticoids?

A

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

58
Q

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

A

Anti-inflammatory action can mask pain

Can compete despite injury

59
Q

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

A 
Damage to tissue before full recovery
Chronic use can cause
- osteoporosis
- Growth suppression
- Skin fragility
- Increased infections
60
Q

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

A

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

MD1 Exercise (10 decks)

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