Exercise and Drug Interactions Flashcards
What physiological changes accompanying exercise can influence pharmacokinetics?
- redistribution of blood flow ( + increased muscle mass with training)
- **altered skin temperature and/or hydration **
- **increased respiratory rate and tidal volume **
- **decreased gastric emptying **
- **decreased intestinal transit time **
- **loss of water from plasma into tissues **
- altered metabolic enzyme activity
Discuss the interactions between exercise and insulin
There is no single recommended adjustment of insulin treatments for exercise - each individual must adjust themselves
Plasma [insulin] = exercise > rest
Mechanism of exercise induced hypoglycaemia:
- accelerated insulin absorption from sites near exercising muscle
- exercise-mediated enhancement of insulin action
- lack of decline of insulin secretion during exercise
Mechanism of exercise-induced hyperglycaemia
- excessive CHO supplementation
- too larger reduction of insulin in preparation for exercise
Discuss the interaction between exercise and glyceryl trinitrate (GTN)
GTN is clinically used in the treatment of angina and is applied transdermally (prophylaxis) or sublingual (acute angina)
Plasma [GTN] = sauna > exercise >rest
- vasodilation increases the surface blood area for transdermal absorption
- increased kinetic energy of drugs with increased skin temperature
- increased hydration may improve absorption
Implications of increased transdermal absorption of GTN:
- Benefit = minimises exercise induced angina
- Danger = excessive vasodilation of skin + muscle leading to hypotension and diversion of coronary blood flow
Discuss the interactions between exercise and Salbutamol
Salbutamol is a short-acting B2 adrenoceptor agonist that is inhaled in the treatment of asthma
Plasma [salbutamol] = exercise > rest
- increased respiratory rate
- increased pulmonary blood flow
- increased epithelial permeability of airways in exercise to help gaseous exchange
Implications of increased absorption:
- Benefit: minimises exercise induced asthma
- Danger: despite higher bioavailibility, the bronchodilator effects are less prolonged which requires more frequent dosing
Discuss the interactions between exercise and gut function
Exercise has widely variable effects on gut function; primarily:
- Inhibits gastric emptying
- reduces gut delivery to small intestine
- adaptation occurs in trained athletes
-
Increases intestinal motility to reduce transit time
* less time to absorb lipophilic/fat soluble drugs
Actually effects will depend on the drug, exercise duration and intensity
Discuss the interactions between exercise and warfarin
**Warfarin **is an **oral anticoagulant **
**Prothrombin INR = **exercise < rest
Mechanism of reduced INR:
- increased binding of warfarin to albumin as a result of lost plasma water/fluid content and training adaptations
- increased warfarin metabolism from training
Implications of reduced INR:
- Shorter clotting time leading to increased risk of thrombosis
Discuss the interaction between exercise and digoxin
**Digoxin **is used clinically to treat **heart failure and atrial arrhythmias **and is administered orally
Plasma [digoxin] = exercise < rest
Muscle [digoxin] = exercise > rest
- exercise leads to a redistribution of digoxin to bind skeletal muscle rather than remain free in plasma
Implications of reduced digoxin:
- reduced efficacy to increase heart contractility or control heart rate
Discuss the interactions between exercise and beta-blockers
Beta-blockers are orally administered B1 adrenoceptor antagonists which are used in the treatment of hypertension and angina
Plasma [propanol] = exercise > rest
- reduced hepatic clearance of propanolol as metabolism is highly dependent on hepatic blood flow
**Plasma [atenolol] = exercise > rest **
- reduced renal clearance of atenolol due to renal blood flow dependent metabolism
Plasma [carvedilol] = exercise = rest
Implications of increased plasma levels:
- increased risk of exercise-limiting adverse effects including bronchoconstriction, fatigue and other on/off target effects of beta-blockers
What constitutes a banned substance/method according to WADA?
- Potential to enhance, or does enhance, performance in sport
- Potential risk to athlete’s health
- WADA has determined that the substance or method violates the spirit of sport
Why are diuretics considered performance enhancing drugs?
Potential advantage in sport:
- loss of fluid reduces weight in order to meet competition weight limits
- dilution of urine will decrease concentration of other banned drugs
Dangers of diuretic use in sport:
- dehydration
- hypokalaemia (?)
What beneficial effects do adrenoceptor activation have in exercise/sport
β1
- cardiac pacemaker tissue - increase heart rate
- cardiac muscle – increase stroke volume
- adipose tissue – lipolysis
β2
- airway smooth muscle - bronchodilation
- blood vessels in skeletal muscle and skin - increase blood flow
- skeletal muscle – growth, speed of contraction, tremor
- liver – glycogenolysis
Why are ß1 antagonists considered banned performance enhancing drugs?
ß1 antagonists are used clinically in the treatment of hypertension
Potential advantages in sport:
- reduce heart-rate and stress
- stop hands and bodies shaking in accuracy/precision sports
Potential disadvantages:
- lowered BP or HR
- reflex vasoconstriction via a1adrenoceptors
- non-selective block of B2- mediated vasodilation of skeletal/skin blood vessels
- fatigue + decreased performance in endurance events
Note: **Only prohibited in certain sports: archery, shooting, skiing, billiards and bridge
Why are B2antagonists considered performance enhancing?
B2 antagonists are used clinically in the treatment of asthma. It is prohibited if administed by any route other than inhalation.
Potential advantage of systemic administration:
- increased skeletal muscle blood flow -> increased O2 delivery and lactic acid removal reduces fatigue
- anabolic effect to increase muscle mass for strength
- catabolic effect to reduce body fat -> meet weight categories
Potential dangers:
- Tachycardia -> non-selective effect on B1adrenoceptors
- Muscle tremor -> activation of skeletal muscle B2 adrenoceptors
Status in sport:
- prohibited for any route other than inhalation
- no TUE required for salbutamol (max dose 1600 ug/day, urine concentration < 1 ug/ml) or salmeterol
- TUE required for other β2 agonists e.g. formoterol, terbutaline
Why are glucocorticoids considered performance enhancing drugs?
Glucocorticoids include dexamethasone and cortisone which are used in hormone replacement therapies, asthma preventer therapeutics and as anti-inflammatory agents clinically
Potential advantage in sport:
- anti-inflammatory action can mask pain
- athlete can compete despite injury
Potential disadvantage in sport and adverse effects
- damage to tissues used before full recovery
- chronic use can cause
- osteoporosis
- growth suppression (children)
- skin fragility
- increased infections
Status in sport:
- Banned for systemic administration
- No TUE required for topical applications
*
Why are androgens considered performance enhancing drugs?
Androgens are anabolic steroids (includes testosterone) that build muscle and bone mass by upregulating protein production
Clinically used in hypogonadism and delayed puberty syndromes
Potential advantage in sport:
- increase muscle strength by encouraging new growth
- allow the athlete to train harder and longer
_Potential disadvantages in sport _
- high blood pressure
- decreased “good” cholesterol, increased “bad” cholesterol
- jaundice and liver damage
- mood swings, depression and aggression
- acne
- males - baldness, breast development, infertility
- females - hair growth on face and body, deepened voice, menstrual cycle disruption, possible infertility
