Exercise-Drug Interactions Flashcards
Vasoconstriction is mediated by
alpha 1 receptors
Vasodilation is mediated by
beta 2 receptors
The effects of redistributed blood flow in exercise affect absorption
based on route of administration
The effects of redistributed blood flow in exercise affect distribution by
increased muscle and skin blood flow
The effects of redistributed blood flow in exercise affect metabolism by
decreased hepatic blood flow
The effects of redistributed blood flow in exercise affect excretion by
Decreased renal blood flow
What is the risk of exercise in insulin-dependent diabetes?
plasma insulin can rise during exercise and tf glucose control may be dysregulated
What are 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 (ie secrete insulin during exercise)
What are mechanisms of exercise-induced hyperglycaemia?
Excessive CHO supplementation; too large a reduction in insulin dose pre-exercise
What is the risk in using transdermal glyceryl trinitrate in exercise (or hot environments)?
plasma levels of GTN can be increased by the associated: inc skin blood flow, inc kinetic energy of drugs with inc skin temperature, inc hydration which improves absorption of drugs with diffusion rate-limited absorption
What are the implications of increased transdermal absorption of GTN in exercise?
may be beneficial by further minimizing risk of exercise-induced angina; potential for vasodilation in skin and exercising muscle to cause excessive hypotension and divert coronary blood flow esp in hot environments - can get precipitous hypotension (severely low BP)
Salbutamol
works on B2 receptors in airways to cause bronchodilation
What are the consequences of taking salbutamol prior to or during exercise?
plasma levels can become increased due to the increased respiratory rate, increased pulmonary blood flow, and increased epithelial permeability
What are the implications of increased absorption of salbutamol in exercise?
May provide benefit by minimizing exercise-induced asthma; despite higher bioavailability though, bronchodilator effects are less prolonged - it wears off quicker so dosing needs to be more frequent
How does exercise impact the gut?
inhibits gastric emptying; increases intestinal motility to reduce transit time; decreases splanchnic blood flow
How does inhibition of gastric emptying in exercise affect drugs in the gut?
reduces drug delivery to the SI tf decreasing absorption; adaptation occurs in trained athletes
How does increased intestinal motility in exercise affect drugs in the gut?
reduced transit time means less time for absorption of lipophilic drugs
How does decreased splanchnic blood flow in exercise affect drugs in the gut?
more time for absorption of drugs where diffusion is the rate limiting step
What are the risks of warfarin in exercise?
Increased bruising and decreased INR (clotting time)
How is INR purportedly shortened by exercise?
Warfarin is more bound to plasma albumin because of fluid loss; may be an increase in metabolism of the drug with training; in both, get decreased free warfarin = more clotting/decreased INR
What is the implication of decreased INR with exercise?
Increased clotting and risk of thrombosis
How does exercise affect levels of digoxin in the body?
Digoxin has a high volume distribution tf goes into muscle, not much in plasma; in exercise, there is reduced plasma digoxin but increased distribution and binding to skeletal muscle
What is the mechanism of decreased plasma levels of digoxin in exercise?
Redistribution due to increased binding to skeletal muscle tf not much is left in plasma
What are the implications of decreased plasma digoxin in exercise?
Digoxin is used to maintain contractility or control HR - can dysregulate this, lead to arrythmias
How does exercise affect propranalol (non-selective b-blocker)?
increased in plasma due to reduced hepatic clearance (metabolism)
How does exercise affect atenolol (selective B1 b-blocker)?
increased in plasma due to reduced renal clearance (excretion)
How does exercise affect carvedilol (mixed B-blocker and A-antagonist)?
unchanged
What are the implications of increased plasma levels of beta-blockers with exercise?
Increased risk of exercise-limiting adverse effects eg not being able to increase HR, off-target (not on heart) B2-mediated bronchoconstriction can block B2-mediated bronchodilation, reduced blood flow to skeletal muscle through B2 vasodilation, fatigue
What advantage do diuretics confer in sport?
dilution of urine to mask banned drugs; fluid loss leading to weight loss to meet a lower weight class
Clinically, diuretics are used for
oedema, hypertension, cardiac failure
What are the disadvantages and adverse effects of diuretics in sport?
dehydration; hypokalaemia due to inhibition of Na+ reabsorption
What is the role of B1 receptors in exercise?
SNS activation increases NA & A –> cardiac pacemaker tissue to +HR; cardiac muscle to +SV; adipose tissue to +lipolysis
What is the role of B2 receptors in exercise?
SNS activation increases NA & A –> airway smooth muscle to bronchodilate; blood vessels in skeletal muscle and skin to increase blood flow; skeletal muscle to increase growth, speed of contraction, tremor; liver to promote glycolysis
Clinically, B1 antagonists are used for
hypertension; reducing HR, SV, CO, BP by blocking cardiac B1 receptors
B1 antagonists
propranolol, atenolol
What is the advantage of B1 antagonist use in sport?
reduction of HR and stress; reduce tremor in hands and bodies in precision accuracy sports
What are the disadvantage of B! antagonists in sport?
lowered BP and decreased HR so can’t increase to meet demand; reflex vasoC via A1rs; nonselective block of B2r vasoD of skeletal/skin blood vessels; fatigue, decreased performance in endurance events
What is the advantage of B2 agonist use in sport?
systemic administration or high dose inhalation: increased skeletal muscle blood flow to +O2 supply and remove lactic acid , reducing fatigue; anabolic effects of increasing muscle mass and strength; catabolic effects to reduce body fat to meet weight category
What are the adverse effects of B2 agonists in sport?
tachycardia via nonselective activation of cardiac B1aRs; muscle tremor via activation of skeletal muscle B2aRs
What is the advantage of glucocorticosteroids in sport?
Anti-inflammatory use can mask pain
What are the disadvantages of glucocorticosteroid use in sport?
damage to tissues before full recovery; chronic use can precipitiate cushings-like syndorme - osteoporosis, growth suppression in children, skin fragility, increased infections
What is the status of glucocorticosteroid use in sport?
topical and inhalation are approved; abbreviated TUE for intra-articular; banned systemically
What is the advantage of anabolic steroid use in sport?
increased muscle strength by encouraging new growth; allows for longer, harder training
What are the disadvantages of anabolic steroid use in sport?
high BP; decreased good/increased bad cholesterol; jaundice & liver damage; mood swings, depression, aggression; acne; male baldness, breast development, infertility; female hair growth on face and body, deepened voice, menstrual disruption, possible infertility
What is the advantage of growth hormone use in sport?
Reduced fat mass, increased lean mass, increased bone density
What are the adverse effects of GH use in sport?
joint pain, increased diabetes risk, acromegaly
AOD9604
(unproven) Anti-obesity drug 9604 aka Lipotropin - designed to be catabolic to break down fat but not anabolic (doesn’t stimulate IGF-1)
What is the advantage of AOD9604 use in sport?
unproven as anti-obesity; under preclinical trials for repair of cartilage, muscle, and joint disorders eg OA
What are the potential adverse effects of AOD9604 use in sport?
headache, chest tightness, palpitations, euphoria; long-term effects are not known
