Exercise-Drug Interactions Flashcards
Why is the effect of exercise on drugs such as digoxin and warfarin particularly important?
Have narrow therapeutic window
What drug pharmacokinetics can altered skin temperature with exercise influence?
Transdermal administration
What drug pharmacokinetics can increased respiratory rate and tidal volume with exercise influence?
Inhaled administration
What drug pharmacokinetics can altered metabolic enzyme activity with exercise influence?
Drug metabolism
How does blood flow distribution to different organs change during exercise?
Muscles: increases
Liver: decreases
Kidney: decreases
Skin: increases
What implications does redistribution of blood flow during exercise have on the distribution of a drug?
Increased muscle and skin blood flow > possible decrease in availability of drug at other target organs
What implications does redistribution of blood flow during exercise have on the metabolism of a drug?
Decreased hepatic blood flow
What implications does redistribution of blood flow during exercise have on the excretion of a drug?
Decreased renal blood flow
What is the clinical use of insulin?
Type 1 diabetes
Advanced type 2 diabetes
What is the route of administration of insulin?
Injection
What effect does exercise have on plasma insulin levels?
Increases them
What effect does exercise have on the effect of insulin?
Exercise beneficial in management, but glucose control may be dysregulated due to synergy with insulin
What factors influence the effect of glucose on insulin action?
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
What are the mechanisms of exercise-induced hypoglycaemia?
Accelerated insulin absorption from sites near exercising muscles
Exercise-mediated enhancement of insulin action
Lack of decline in insulin secretion during exercise
How can you ameliorate the effects of accelerated insulin absorption from sites near exercising muscles?
Site of administration away from exercising muscles
Why might there be an exercise-mediate enhancement of insulin action?
Probably because of increased adrenergic effects on pancreas
What are the mechanisms of exercise-induced hyperglycaemia?
Excessive carbohydrate supplementation
Too large a reduction in insulin dose
What is the clinical use of glyceryl trinitrate (GTN)?
Angina
What is the route of administration for GTN?
Transdermal for prophylaxis
Sublingual for acute angina
What effect does the sauna and exercise have on plasma concentrations of GTN?
Increases them
What are the mechanisms for increased plasma levels of GTN during exercise?
Increased skin blood flow
Increased kinetic energy of drugs with increased skin temperature
Increased hydration may improve absorption
What are the implications for increased transdermal absorption of GTN during exercise?
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
What is the clinical use of salbutamol?
Asthma
What is the route of administration of salbutamol?
Inhalation
What effect does exercise have on plasma levels of salbutamol?
Increases
What are the mechanisms for increased plasma levels of salbutamol during exercise?
Increased respiratory rate
Increased pulmonary blood flow
Increased epithelial permeability in strenuous exercise
What are the implications of increased absorption of salbutamol during exercise?
May provide benefit for exercising patient to minimise exercise-induced asthma
Despite higher bioavailability, bronchodilator effects less prolonged > need more frequent dosing
What are the effects of exercise on the gut?
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
What is the clinical use of warfarin?
Anticoagulant
What is the route of administration of warfarin?
Oral
What is the risk of using warfarin in sport?
Increased bruising
What is the effect of exercise whilst using warfarin on clotting time?
Decreased clotting time
What are the mechanisms of decreased clotting time whilst using warfarin during exercise?
Increased binding to albumin
Possible increased metabolism with training
What is the clinical use of digoxin?
Heart failure
Atrial arrhythmia
What is the route of administration of digoxin?
Oral
What is the effect of exercise on digoxin plasma levels?
Decreased
What is the effect of exercise on digoxin muscle levels?
Increased
What are the mechanisms of decreased digoxin plasma levels with exercise?
Redistribution due to increased binding to skeletal muscle
What type of muscle does digoxin have a high affinity for?
Skeletal
Cardiac
What are the implications of decreased digoxin plasma levels during exercise?
Reduced efficacy to increase contractility and control rate
What is the clinical use of beta-blockers?
Hypertension
Angina
What is the route of administration of beta-blockers?
Oral
What is the selectivity of propranolol?
Non-selective
What is the selectivity of atenolol?
Beta-selective
What is the selectivity of carvedilol?
Beta- and alpha1-selective
What is the effect of exercise on plasma propranolol levels?
Increased
What is the effect of exercise on plasma atenolol levels?
Increased
What is the effect of exercise on plasma carvedilol levels?
Unchanged from rest
What are the mechanisms of increased plasma propranolol levels with exercise?
Reduced hepatic clearance - metabolism highly dependent on hepatic blood flow
What are the mechanisms of increased plasma atenolol levels with exercise?
Reduced renal clearance - excretion highly dependent on renal blood flow
What are the implications of increased plasma levels of beta-blockers during exercise?
Increased risk of exercise-limiting adverse effects
- Bronchoconstriction
- Fatigue
Why is there poor exercise compliance with the use of beta-blockers?
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
Does fatigue improve with a few weeks of compliance to exercise whilst using beta-blockers?
Yes
What are the potential advantages in sport of using beta2-agonists with systemic administration?
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
What are the potential adverse effects of beta2-agonists in sports?
Tachycardia - non-selective activation of cardiac beta1-adrenoceptiors
Muscle tremor - activation of skeletal muscle beta2-adrenoceptors
What is the status of beta2-agonists in sport?
Prohibited for any route other than inhalation
What is the clinical use of glucocorticoids?
Replacement hormone for adrenal insufficiency
Inhaled asthma preventer/oral for exacerbations
Anti-inflammatory - local/systemic administration
What are the potentiatial advantages in sport with the use of glucocorticoids?
Anti-inflammatory action can mask pain
Can compete despite injury
What are the potential disadvantages in sport with the use of glucocorticoids?
Damage to tissue before full recovery Chronic use can cause - osteoporosis - Growth suppression - Skin fragility - Increased infections
What is the status in sport for the use of glucocorticoids?
Without TUE
- Topical use
- Inhalation for asthma
Abbreviated TUE if administerd via intra-articular route
Prohibited TUE if systemic administration
