Case 3: Caffeine Flashcards
(27 cards)
What is caffeine ?
A naturally occurring alkaloid and a stimulant
Found in kola nut, cocoa bean etc.
What is the safe limit of caffeine in the UK ?
Single doses of upto 200mg
Daily intakes of 400mg
It is under the food standards agency advice as it is a supplement
Is caffeine an agonist or antagonist ?
It is an adenosine receptor antagonist
It has affinity for the receptor but no intrinsic activity
What are the adenosine receptors ?
They are GPCRs
1. Adenosine 1 receptor= Gi
2. Adenosine A2A receptor= Gs
Explain the mechanisms underlying caffeine’s ability to improve sports performance
- By binding to and blocking adenosine receptors, Cafteine increases altertness and decreases percieved exertion in exercise. It makes your body think that you aren’t exhausted.
- Caffeine preserves muscle glycogen and increases the uptake of fatty acids from the blood-stream. This is caused by an increase in lipolysis. This mean there is more energy availabie for muscles to use.
- Caffeine increases the release ot calcium ions by a neuro - muscular stimulus , enhancing contraction power in muscles.
What is the effect size ?
The magnitude of difference between the 2 groups
What are the historical and current guidelines regarding the use of caffeine in sport ?
- Caffeine was considered a performance enhancing dug, so added to the list of banned substances by the international Olympic commitee (IOC) in 1984 and the world anti-doping Agency (WADA) in 2000.
- In 2004, IOC and WADA removed caffeine from the list of banned substances. It was moved to a ‘Monitoring program’. This means that it is monitored to detect patterns of misuse in sport.
• Effective dose: 3-6 mg / kg body mass
• Higher dose: 9mg/kg associated with side effects + no improvement in performance
How is caffeine metabolised ?
Caffeine is metabolised by CYP1A2 into 3 main metabolites:
• Theobromine
• Paraxanthine
• Theophylline
- Paraxanthine is then further metabolised.
- CYP1A2 polymorphism alters speed of metabolism.
How is caffeine excreted ?
- Excreted via the kidneys in urine .
- Mean plasma elimination half-life is about 5 hours (3-7 hours)
- Less than 5 % of caffeine Is excreted unchanged in the urine
How is caffeine absorbed?
- Primarily absorbed in small intestine
- Oral availability upto 99%
- No first pass metabolism
- Peak plasma conc within 20-60mins
How is caffeine distributed ?
- It is hydrophilic, so distributes freely into intracellular tissue water
- Lipophillic so passes through biological membranes and the BBB
What are the symptoms of caffeine overdose?
Metabolic :
- Hypokalaemia - low potassium
- Hypergiycaemia - high glucose
• GIT:
- Nausea
- vomiting
• CNS :
- Agitation
- seizure
• CV:
- Palpitations
- Tachycardia - fast HR
What are the symptoms of a seizure?
- Loss of consciousness
- Body goes stiff
- Jerking of limbs
- Loss of bladder control
How does activated charcoal treat symptoms of caffeine overdose ?
- Highly adsorbent powder of carbon with a large SA, covered in functional groups that bind to chemicals upon contact.
- Dose: 50g orally
- Activated charcoal binds to caffeine while still in the GI tract, which prevents absorption into the blood stream and distribution to the organs, resulting in reduced toxicity.
- It must be used within 2 hours of caffeine ingestion.
What is a seizure ?
Abornmal synchronous electrical discharge in the brain that leads to involuntary movement
How does caffeine overdose cause seizures ?
Caffeine blocks the adenosine receptors, leading to an increase in Glutamate and a decrease in GABA.
This causes increased neuronal excitability, causing a seizure
What is glutamate ?
The key excitatory NT
What is GABA ?
The key inhibitory NT
How do we treat a seizure ?
- Benzodiazepines eg. Diazepam which is a positive allosteric modulator at GABAa receptors, which enhances the receptors.
- Diazepam binds to GABA receptors, enhancing the effect Of GABA. When GABA binds to its receptor, the ligand gated ion channel opens, allowing Cl- ions to enter the neuron.
This causes hyperpolarisation, causing reduced neuronal excitability and decreasing seizure activity.
How does caffeine cause palpitations and tachycardia ?
- Caffeine stimulates the CNS and binds to and blocks adenosine receptors on the adrenal medulla.
This causes an increase in adrenaline release, which then binds to and activates B-adrenoreceptors.
This causes an increase in HR, contractile heart force and glucose in the bloodstream in order to increase delivery of glucose and oxygen to key tissues.
However, caffeine overdose causes hyperglycaemia, palpitations and tachycardia due to over stimulation.
How do we treat palpitations and tachycardia?
- Beta-blockers eg. Propranolol
- They are B-adrenoreceptor antagonists that bind to the receptor and prevent adrenaline binding, so reduces HR, contractile heart force and glucose increase in blood
Define withdrawal
Physiological changes caused by the removal of a substance the body has become dependent on
How does caffeine withdrawal lead to increased drowsiness?
• When caffeine is present, the brain increases the no. Of adenosine receptors by up-regulation to try to restore normal signalling.
• As caffeine is withdrawn, there Is no caffeine to bind to receptors, so adenosine binds to the upregulated receptors.
This causes adenosine activity to be stronger, causing even more drowsiness and decreased wakefulness.
This also results in increased CNs inhibition.
Define substance use disorder
According to the DSM-V:
A maladaptive pattern of substance use leading to clinically significant impairment or distress
