L290 Exercise-Drug Interactions Flashcards

1
Q

Physiological changes with exercise that can influence drug pharmacokinetics - list 7 changes

A
  1. Redistribution of BF (↑ muscle mass)
  2. Altered skin temperature and/or altered hydration
  3. ↑RR and tidal volume
  4. ↓ gastric emptying
  5. ↓ intestinal transit time
  6. Loss of water from plasma into tissues
  7. Altered metabolic enzyme activity
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2
Q

How does sweat affect PK? Which drugs in particular might this affect?

A
  • Sweat increases absorption

- Transdermal drugs

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3
Q

↓ gastric emptying - how does this affect PK?

A

↓ delivery of oral drug to the SI → ↓ abs

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4
Q

↓ intestinal transit time - how does this affect PK?

A

→ speeding up of oral drug movement → ↓ abs

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5
Q

Loss of water from plasma into tissues - how might this affect PK?

A
  • Potentially affects binding proteins, crucial for some drug distribution
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6
Q

Altered metabolic enzyme activity - how might this affect PK? In whom in particular might this occur?

A
  • E.g. in trained individuals - possible consequence for e.g. half-life
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7
Q

↑RR and tidal volume - which drugs might this affect in particular?

A

Inhaled drugs

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8
Q

Re-distribution of blood flow during physical activity: how it might have implications on ADME

A
  • Absorption: depending 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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9
Q

Clinical use of insulin

A

Type 1 diabetes, advanced Type 2 diabetes

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10
Q

Route of admin: insulin

A
  • injection (also inhalation, pump)
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11
Q

Plasma [insulin] with ex vs rest

A

exercise > rest

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12
Q

Mechanisms for increased plasma [insulin] with ex (2)

A

a. ↑BF to skin, muscle → ↑absorption

b. ↑ tissue sensitivity to insulin

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13
Q

Factors determining effect of ex on insulin (5)

A
  1. Type of insulin
    • variable onset and duration
    • dosing schedule and route
  2. Proximity of exercising limbs
    • Close to limb → ↑ abs
  3. Type, duration and intensity of exercise
    • Prolonged ex might need glucose supplements
  4. Amount of muscle mass
  5. Level of fitness
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14
Q

Determinants of blood glucose during ex with insulin (3)

A
  1. Pre-exercise glucose levels
    1. Patency of counter-regulatory mechanisms
    2. Carbohydrate supplementation
      a. simple or complex
      b. rate of absorption
      c. timing of administration
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15
Q

Exercise-induced hypoglycaemia - possible mechanisms (3)

A
  1. Accelerated insulin absorption from sites near exercising muscles
    1. Exercise-mediated enhancement of insulin action
      Lack of decline in insulin secretion during exercise
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16
Q

Exercise-induced hyperglycaemia - mechanisms (3)

A
  1. Excessive carbohydrate supplementation

2. Too large a reduction in insulin dose

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17
Q

GTN: clinical use

A

Angina

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18
Q

Route of admin: GTN

A
  • transdermal for prophylaxis

- (sublingual for acute angina)

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19
Q

Plasma [GTN] with ex vs rest

A
  • sauna > exercise > rest
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20
Q

Mechanisms for increased plasma [GTN] during ex (3)

A
  1. ↑ skin BF
    1. ↑ kinetic energy of drugs with ↑ skin temp
  2. ↑ hydration may improve absorption of drugs
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21
Q

Implications for increased transdermal absorption of GTN (2)

A
  1. May provide benefit for exercising patient to minimise exercise-induced angina
    - Decline in preload ∴ ↓O2 demand of heart
    1. Potential for vasodilation in skin and exercising muscle to cause
      A. Excessive hypotension B. Diversion of coronary BF
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22
Q

Clinical use: salbutamol

A

Asthma

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23
Q

Route of admin: salbutamol

A

Inhalation

24
Q

Plasma [salbutamol] with ex vs rest

A

exercise > rest

25
Mechanisms for ↑ plasma [salbutamol] during ex (3)
1. ↑ RR 2. ↑ pulmonary blood flow 3. ↑ epithelial permeability
26
Implications of ↑ plasma [salbutamol] (2)
1. may provide benefit for exercising patient to minimise exercise-induced asthma 2. *despite higher BA, because of ↑BF and RR, bronchodilator effects are less prolonged - need more frequent dosing!
27
Effects of exercise in the gut are...
variable
28
List to possible effects of exercise on gut
A. Inhibits gastric emptying | B. ↑ intestinal motility
29
Which cohort is not affected by decreased gastric emptying with ex?
Trained athletes - adaptation occurs
30
Clinical use: warfarin
Anticoagulant
31
Route of admin: warfarin
Oral
32
INR (no PK data) with warfarin in ex vs rest
exercise
33
Mechanisms of decreased INR (unconfirmed) with ex (using warfarin) (2)
1. ↑ binding of warfarin to albumin | 2. ↑ metabolism with training
34
Implications of decreased [warfarin] with ex
↓ free warfarin, ↓ INR (i.e. shorter clotting time) → ↑ risk of thrombosis with ex
35
Clinical use: digoxin
heart failure, atrial arrhythmia
36
Route of admin: digoxin
Oral
37
plasma/muscle [digoxin] with ex vs rest
- Plasma [digoxin]: exercise less than rest | - Muscle [digoxin]: ex > rest
38
Mechanisms of ↓ plasma [digoxin] with ex
redistribution due to increased binding to skeletal muscle
39
Implications for ↓ plasma [digoxin] with ex
• reduced efficacy to increase contractility and control rate
40
TI and Vd of digoxin
- narrow TI | - high Vd - high binding affinity to skeletal muscle normally
41
Clinical use of b-blockers
hypertension, angina
42
Route of admin of b-blockers
oral
43
[b-blocker] with ex vs rest
Effect of short duration exercise will vary with drug: • Plasma [propranolol]: exercise > rest - Propranolol NS β blocker • Plasma [atenolol]: exercise > rest - Atenolol S β blocker • Plasma [carvedilol]: exercise = rest - Carvedilol NS β and α blocker
44
Mechanisms of ↑ plasma [beta-blockers] with ex (2)
1. ↓ hepatic clearance for propranolol (→ ↓ metabolism) | ↓ renal clearance for atenolol (→ ↓ excretion)
45
Implications of ↑ plasma [beta-blockers] with ex
* ↑ risk of exercise-limiting adverse effects e.g. bronchoconstriction, fatigue (from NS block of b2-mediated skeletal muscle VD) * → patient's ability to exercise is more difficult → poor exercise compliance: important to encourage compliance because this effect tapers off
46
Why use drugs in sport? (2 reasons)
1. Hide the use of other drugs - Diuretics (→ ↓ [banned substance] in urine) 2. Improve performance
47
For a substance to be prohibited in sport, what conditions must it meet?
Must meet two of the following three conditions: 1. Potential to enhance, or does enhance performance in sport 2. Potential risk to the athlete’s health 3. World Anti-Doping Agency has determined that the substance or method violates the spirit of sport
48
Therapeutic Use Exemptions (TUE): what are they?
* Available if an athlete suffers an acute or chronic medical condition that a doctor can only treat with a prohibited substance * Athletes must receive approval before using substance
49
Clinical use: b2-agonists
Asthma
50
Route of admin: b2-agonists
Inhalation
51
Potential advantages in sport with b2-agonists (3)
With systemic administration: • ↑skeletal muscle BF → ↑ O2 supply and lactic acid removal reduces fatigue • Anabolic effect: ↑ muscle mass ( → strength) • Catabolic effect: ↓ body fat
52
Potential adverse effects with b2-agonists (2)
1. Tachycardia: NS activation of cardiac b1-adrenoceptors | 2. Muscle tremor: activation of skeletal muscle b2-adrenoceptors
53
Status in Sport: b2-agonists
* Prohibited for any route other than inhalation | * No TUE required for salbutamol (maximum dose 1600 mg/day, urine concentration
54
Potential advantage in sport: GCS (1)
• Anti-inflammatory action can mask pain so athlete can compete despite injury
55
Potential disadvantage in sport and adverse effects: GCS (5)
1. Damage to tissue before full recovery (bc can't heed body's warning signs) 2. Chronic use can cause: A. Osteoporosis B. Growth suppression (children) C. Skin fragility Increased infections
56
Status in Sport: GCS
• Approved without a TUE - Topical use with skin creams, eye drops, topical mouth applications, nasal sprays and ear drops - Inhalation for asthma (certain preparations only) • Require abbreviated TUE if administered via intra-articular route • Prohibited TUE required for systemic administration (oral, intravenous, rectal)