Neurology 342 -- Caffeine

methylxanthines

What class of naturally occurring alkaloids does caffeine belong to?

- caffeine

- theophylline(tea)

- theobromine(cocoa)

What are different types of methylxanthines found in plants?

oral administration

What is the main route of administration of caffeine?

20-30 min

When does the blood concentration peak after ingestion of caffeine?

metabolized in the liver by CYP450 enzyme

What causes the metabolism of caffeine?

- paraxanthine

- theobromine

- theophylline

Caffeine is broken down into what 3 active metabolite?

lipolysis

What does paraxanthine do?

dilates blood vessels and increases urine production

What does theobromine do?

relaxes smooth muscle of bronchi

- can cause nausea or irregular heartbeat

What does theophylline do?

- men

- pregnant women

- newborns

When is caffeine metabolism slower?

- women

- used w/ cigs.

- caucasian people

When is caffeine metabolism faster?

body produces more enzymes to breakdown substances

enzyme induction is what?

increases caffeine clearance

- enzyme induction

When caffeine is combined with tobacco what does that do?

increase risk of hypertension, heart attack, or stroke

When caffeine is combined with ephedrine(nasal decongestant) what does that do?

cause serotonin syndrome

- anxiety, confusion, sleep disturbances

When caffeine is combined with SSRIs(nasal decongestant) what does that do?

~ 5 hours

What is the half life of caffeine?

> 50 mg

sleep disturbances are reported when caffeine in the system is greater than what?

increases to 18 hours

What happens to the Half life of caffeine in pregnant women?

adenosine

What neuromodulator implicated in sleep?

- energy byproduct from brain cells using and breakdown of ATP molecules

- produced in astrocytes from a byproduct of making glucose

How is adenosine formed?

- inhibitory A1 receptors

- excitatory A2A receptors

What are two types of adenosine receptors adenosine binds to?

adenosine A1 and A2A receptors

What is caffeine an antagonist to?

reticular activating(arousal) system

Where are A1 receptors located?

basal ganglia and nucleus accumbens

Where are A2A receptors located?

enhance DA and NE signaling

What does blocking of A1 and A2A receptors lead to?

increased alertness, mood, and physical energy

What are the acute actions of caffeine?

- increased BP, vasoconstriction, and diuretic

Name physiological effects of caffeine?

sympathetic nervous system

What nervous system is activated due to caffeine?

400mg

What is the daily caffeine consumption that poses little to no risk?

mental performance: increased alertness, attention

physical performance: increased endurance and delayed fatigue

What performances are heightened due to caffeine?

greater than 400mg in a day

What is caffeinism?

3+ grams of caffeine

Lethal dose of caffeine is associated when?

anxiety, panic attacks, insomnia

- increased HR and BP, palpitations

name some symptoms of caffeinism?

- seizures, metabolic acidosis, or kidney dysfunction

Greater than 1200mg of caffeine does what?

block GABA receptors

- increase intracellular Ca2+ release

High does of caffeine can block what receptors, what does this cause?

blocking of inhibitory signals in the brain

How are seizures a risk as a result from too much caffeine?

- headaches/migraine

- fatigue

- difficulty concentrating

Name some withdrawal symptoms of caffeine?

physical and psychological dependence

What can chronic caffeine use result in?

withdrawal symptoms

What can appear after cessation of caffeine?

up regulation of adenosine receptors

chronic use of caffeine leads to tolerance, what does this do to adenosine receptors?

700-1000mg per day

- caffeine doesn't produce a physiological response

When does the body produce a complete tolerance to caffeine?

12-24 hours

When do withdrawal symptoms generally begin after last caffeine use?

2-9 days

How long do these withdrawal symptoms from caffeine use last?