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MD1 - Exercise Block > Exercise drug interactions > Flashcards

Exercise drug interactions Flashcards

1
Q

How does exercise act as a drug?

A
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2
Q

What are the physiological changes with exercise that can influence drug pharmacokinetics?

A
  • 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)
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3
Q

What is the blood flow distribution during physical activity?

A
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4
Q

What are the implications for ADME due to re-distribution of blood flow during pysical activity?

A

Absorption - Depend on route of administration

Distribution - Increased muscle and skin blood flow

Metabolism - Decreased hepatic blood flow

Excretion - Decreased renal blood flow

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5
Q

What are the properties of Insulin?

A

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
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6
Q

What factors need to be considered for insulin administration around exercise?

A
  • 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)
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7
Q

What adjustments for insulin is recommended for exercse?

A

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
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8
Q

What are the properties of Glyceril Trinitrate (GTN)?

A
  • Clinical use = Angina
  • Route = Transdermal for prophylaxis, sublingual for acute angina
  • Plasma [GTN] = Sauna > exercise > reset
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9
Q

What is the mechanism for increased plasma levels of GTN during sauna or exercise?

A
  • Increased skin blood flow
  • Increased kinetic energy of drugs with increased skin temperature
  • Increased hydration may improve absorption of drugs
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10
Q

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

A
  • 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)
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11
Q

What are the properties of Salbutamol?

A
  • Clinical use = Asthma
  • Administration = Inhalation
  • Plasma [Salb] = exercise > rest
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12
Q

What are the mechanisms for increased plasma Salbutamol?

A
  • Increased respiratory rate
  • Increased pulmonary blood flow
  • Incresed epithelial permeability
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13
Q

What are the implications of increased absorption for Salbutamol?

A
  • May provide benefit to minimise exercise induced asthma
  • Despite higher bioavailability, bronchodilator effects are less proloned
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14
Q

What are the effects of exercise on the gut?

A
  • 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
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15
Q

What are the properties of Warfarin?

A
  • Clinical use = Anticoagulant
  • Administration = Oral
  • Risk in sport = Increased bruising
  • INR = exercise < rest
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16
Q

What are the mechanisms of decreased INR of warfarin during exercise?

A
  • Increased binding of warfarin to albumin
  • Increased metabolism with training
  • Decreased free warfarin –> decreased INR
  • Shorter clotting time, increased risk of thrombosis
17
Q

What are the properties of Digoxin?

A
  • Clinical use = Heart failure, atrial arrythmia
  • Route of administration = Oral
  • Plasma [digoxin] = exercise < rest
  • Muscle [digoxin] = exercise > rest

Digoxin goes into muscle during exercise

18
Q

What are the mechanisms and implications for decreased Digoxin plasma levels?

A

Mechaism fo decreased plasma levels

  • Redistribution due to increased binding to skeletal muscle

Implications

  • Reduced efficacy to increase contractility and control rate
19
Q

What are the properties of Beta blockers?

A
  • 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]
20
Q

What are the mechanism and implications of increased plasma levels of beta blockers Propanolol during exercise?

A

Mechanisms of increased plasma levels

  • Reduced hepatic clearance for propanolol

Implications

  • Increased risk for exercise-limiting adverse effect
  • e.g. bronchoconstriction, fatigue
21
Q

What are the mechanism and implication for increased plasma level of atnolol?

A

Mechanism

  • Reduced renal clearance for atenolol

Implications

  • Increased risk of exercise limiting adverse effects
  • e.g. bronchoconstriction, fatigue
22
Q

What are the effects of Beta blockers in people who exercise?

A

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

23
Q

Why do people use drugs in sports?

A
  • To hide other drugs
    • Diuretics
  • Improve performance
    • Relax (b-block)
    • Increased O2 delivery (EPO)
    • Mask pain
    • Reduce fat
    • Anabolic
24
Q

What are the conditions for prohibiting a substance?

A
  1. Potential to enhance or does enchance performance in sport
  2. Potential risk to athlete’s health
  3. Violates the spirit of sport
25
Q

What is the Therapeutic Use Exemptons (TUE)?

A
  • Available in athletes with chronic medical condition
  • can use prohibited substances for legitimate medical purpose but level of enhancement must noe exceed level of performance before condition
  • Must receive approval
  • must be declared
26
Q

What are the potential advantage of B2 agonists in sport?

A

Used to treat asthma

  • Salbutamol (short), salmeterol (long, incombination with GCS)

Potential advantages

  1. Increases skeletal muscle blood flow (more O2, less lactic acid) = less fatigue
  2. Anabolic effect on muscle
  3. Catabolic effect on fat
27
Q

What are the potential adverse effects of B2 agonists? and what are its status in sport?

A

Side effects

  1. Tachycardia - Non selective activation of cardiac b1
  2. Muscle tremor - activtation of skeletal muscle b2 adrenoreceptors

Status in sport

  1. Prohibited for ay route other than inhalation
  2. No TUE required for salbutamol, salmeterol or formeterol
  3. TUE required for other b2 agonists
28
Q

What is the TUE status on GCS? What drugs are allowed and what are its potential advantages and disadvantages?

A

GCS

  • Cortisol
  • Dexamethasone, cortisone

Advantage

  • Anti-inflammatory action can mask pain
  • Athlete can compete despite injury

Disadvantage

  • Damage to tissue before full recovery
  • Chronic use can cause
    • Osteoporosis
    • Growth supression
    • Skin fragility
    • Increased infetion

Status in sport

  1. Approved without TUE
    1. Topical use, eye drop, topical mouth, nasal spray, ear drops
    2. Inhalation for asthma
  2. Require TUE if intra-articular
  3. Prohibit for systemic (oral, IV, rectal)

MD1 - Exercise Block (3 decks)

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