Exercise drug interactions Flashcards
(28 cards)
How does exercise act as a drug?
What are the physiological changes with exercise that can influence drug pharmacokinetics?
- Redistribution of blood flow (increased muscle mss)
- Altered skin temperature and/or altered hydration
- Increased respiratory rate
- Decreased gastric emptying
- Decreased intestinal transit time
- Loss of water from plasma into tissue
- Altered metabolic enzyme activity (important for protein binding)
What is the blood flow distribution during physical activity?
What are the implications for ADME due to re-distribution of blood flow during pysical activity?
Absorption - Depend on route of administration
Distribution - Increased muscle and skin blood flow
Metabolism - Decreased hepatic blood flow
Excretion - Decreased renal blood flow
What are the properties of Insulin?
Clinical use = T1DM and advanced T2DM
Route of administration = Injection
Plasma insulin = exercise > rest
- Exercise known to be beneficial but glucose control may be dysregulated due to synergy with insulin
What factors need to be considered for insulin administration around exercise?
- Type = Variable onset and duration & dosing schedule and route
- Proximity of exercising limbs
- Type/duration/intensity of exercise
- Amount of muscle mass
- Level of fitness
- Pre-exercise glucose levels
- Patency of counter regulatory mechanisms
- Carb supplementation (simple/complex, rate of absorption, timing)
What adjustments for insulin is recommended for exercse?
No single recommenation
Mechanisms of exercise induced hypoglycaemia
- Accelerated insulin absorption from sites near exercising muscles
- Exercise mediated enchancement of insulin action
- Lack of decline in insulin secretion during exercise
Mechanisms of exercise induced hyperglycaemia
- Excessive carbohydrate supplementation
- Too large reduction in insulin dose
What are the properties of Glyceril Trinitrate (GTN)?
- Clinical use = Angina
- Route = Transdermal for prophylaxis, sublingual for acute angina
- Plasma [GTN] = Sauna > exercise > reset
What is the mechanism for increased plasma levels of GTN during sauna or exercise?
- Increased skin blood flow
- Increased kinetic energy of drugs with increased skin temperature
- Increased hydration may improve absorption of drugs
What are the implications for increased transdermal absorption of GTN in exercise?
- Provide benefit to minimize exercise induced angina
- Potential for vasodialtion in skin and exercising muscle to cause excessive hypotension to divert coronary blood flow (worse in hot enclosed environment)
What are the properties of Salbutamol?
- Clinical use = Asthma
- Administration = Inhalation
- Plasma [Salb] = exercise > rest
What are the mechanisms for increased plasma Salbutamol?
- Increased respiratory rate
- Increased pulmonary blood flow
- Incresed epithelial permeability
What are the implications of increased absorption for Salbutamol?
- May provide benefit to minimise exercise induced asthma
- Despite higher bioavailability, bronchodilator effects are less proloned
What are the effects of exercise on the gut?
-
Inhibits gastric emptying
- Reduces drug delivery to small intestine
- Adaptation occurs in trained athletes
-
Increases intestinal motility to reduce transit time
- Less time for absorption of lipophilic drugs
What are the properties of Warfarin?
- Clinical use = Anticoagulant
- Administration = Oral
- Risk in sport = Increased bruising
- INR = exercise < rest
What are the mechanisms of decreased INR of warfarin during exercise?
- Increased binding of warfarin to albumin
- Increased metabolism with training
- Decreased free warfarin –> decreased INR
- Shorter clotting time, increased risk of thrombosis
What are the properties of Digoxin?
- Clinical use = Heart failure, atrial arrythmia
- Route of administration = Oral
- Plasma [digoxin] = exercise < rest
- Muscle [digoxin] = exercise > rest
Digoxin goes into muscle during exercise
What are the mechanisms and implications for decreased Digoxin plasma levels?
Mechaism fo decreased plasma levels
- Redistribution due to increased binding to skeletal muscle
Implications
- Reduced efficacy to increase contractility and control rate
What are the properties of Beta blockers?
- Clinical use = Hypertension, angina
- Administration = Oral
- Effect of short duration exercise will vary with drug
- Plasma [propanolol] = exercise > rest (Beta non selective)
- Plasma [atenolol] = exercise > rest (B1 selective)
- Plasma [caverdilol] = exercise = rest (non selective has alpha blck]
What are the mechanism and implications of increased plasma levels of beta blockers Propanolol during exercise?
Mechanisms of increased plasma levels
- Reduced hepatic clearance for propanolol
Implications
- Increased risk for exercise-limiting adverse effect
- e.g. bronchoconstriction, fatigue
What are the mechanism and implication for increased plasma level of atnolol?
Mechanism
- Reduced renal clearance for atenolol
Implications
- Increased risk of exercise limiting adverse effects
- e.g. bronchoconstriction, fatigue
What are the effects of Beta blockers in people who exercise?
Usually used to treat hypertension which also requires some form of exercise as treatment
- Reduced heart rate, SV, CO = Reduction in exercise capacity
- Non selective block of B2 mediated vasodilation skeletal muscle
- Patients feels fatigue and ability to exercise is more difficult
Results in = Poor exercise compliance
Why do people use drugs in sports?
- To hide other drugs
- Diuretics
- Improve performance
- Relax (b-block)
- Increased O2 delivery (EPO)
- Mask pain
- Reduce fat
- Anabolic
What are the conditions for prohibiting a substance?
- Potential to enhance or does enchance performance in sport
- Potential risk to athlete’s health
- Violates the spirit of sport
