low efficacy stimulants - caffeine Flashcards
what class of alkaloids does caffeine belong to?
methylxanthines
in what plants do we find methylxanthines?
- caffeine
- theophylline (tea)
- theobromine (cocoa)
what is the most popular stimulant in the world?
caffeine
what is the route of administration for caffeine? how much caffeine do we usually see taken?
route: ALWAY ORAL (drinks, food, pill)
10-200 mg
- where does caffeine absorption occur?
- how much is absorbed within 45 minutes of ingestion?
- when do blood concentrations peak after ingestion?
- absorbed by stomach and small intestines
- 99% is absorbed
- 20-30 minutes after ingestion even though effects are felt sooner
- how fast does caffeine distribute throughout the body?
- what barriers can it cross?
- does it have plasma protein binding?
- very fast
- BBB and placental
- no, it is very low levels
- where is caffeine broken down in?
- what metabolites are formed?
- what enzymes form the metabolites?
- liver
- active (paraxanthine, theobromine, theophylline)
- CYP450
what are the 3 active metabolites that are formed after caffeine metabolism and what is their function?
- paraxanthine: undergo lipolysis which mobilizes stored energy in fat during fasting and exercise
- theobromine: dilates blood vessels, increases urine
- theophylline: relaxes smooth muscles of bronchi ( used to treat asthma), can cause nausea, irregular heartbeat
when and what populations do we see a slower caffeine metabolism?
- men
- pregnant woman
- newborns
- if you use birth control pills
- if you have liver damage
- asian population
when and what populations do we see a faster caffeine metabolism?
- if used with cigs
- in women and children
- Caucasian population
if caffeine is taken while smoking tobacco what occurs?
- increases caffeine clearance by 50%
- enzyme induction occurs - caffeine is leaving system faster
- increases caffeine tolerance and coffee consumption for regular smokers
if caffeine is taken while using a nasal congestion (ephedrine), what occurs?
increase risk of of hypertension, heart attack, stroke, seizures
if caffeine is taken while using a SSRI, what occurs?
anxiety, confusion, restlessness, sleep disturbances
- what order kinetics are seen with caffeine?
- what is the form of excretion?
- how much is excreted as metabolites?
- first order
- urine
- 95%
- what is the half life of caffeine?
- what is the half life of pregnant women in the 3rd trimester?
- about 5 hours
- increases to 18 hours
- when is plasma clearance increased?
- when is plasma clearance decreased?
- what withdrawal symptoms do we see in heavy coffee drinkers?
- when smoking nicotine
- when smoking ends
- cigarette withdrawal symptoms
when are sleep disturbances often reported with caffeine?
if greater than 50mg is still in your system
- what is the neuromodulator found in caffeine use?
- where is it produced?
- in what activity do we see this modulator?
- adenosine
- throughout nervous system
- in sleep
what are the 2 ways adenosine are formed?
- as an energy byproduct from brain cells that are breaking down ATP molecules (ex. neurons and astrocytes)
- produced in astrocytes as a byproduct of making glucose from stored glycogen
what are the 2 receptors that adenosine binds to? (it binds to 4 but we only need to know 2)
- A1 INHIBITORY receptors found on arousal neurons - promotes sleep! (IPSP, hyperpolar)
- A2A EXCITATORY receptors found on sleep active neurons - promotes sleep (EPSP, depolar)
Adenosine binding promotes one by suppressing the other
what does caffeine act as at A1 and A2A receptors?
antagonists
where do we see A1 and A2 receptors?
A1: reticular activating system
A2: basal ganglia and nucleus accumbens (in our mesolimbic and nigrostriatal DA system)
what happens when A1 and A2A receptors are blocked?
it increases dopamine and norepinephrine signaling in the brain leading to mild arousal and psychomotor activation
what are acute physiological actions of caffeine?
- increased alertness, mood, physical energy
- activates sympathetic nervous system to increase respiration rate
- Causes release of stress hormones from adrenal medulla : increases arousal/ vigilance
what effects occur at Adenosine receptors found in the heart & kidneys?
increased BP, vasoconstriction, diuretic
what is the daily healthy consumption of caffeine?
400 mg but at 250mg itself u can see the effects of it
what does caffeine do?
- improved mental performance (increased alletness)
- improved physical performance (increased endurance)
- improved migraine symptoms (constricts blood vessels)
are lethal doses common with caffeine?
no; but 100 reported cases of caffeine overdose fatalities
when do we see lethal doses of caffeine?
when ingested as a powder or pill ; more than 3 grams
- what happens if you take more than 400mg?
- what happens if you take more than 1,200 mg?
- severe anxiety, panic attacks, insomnia, irritability, increased heart rate & blood pressure, palpitations, tremor, paresthesia
- seizures, metabolic acidosis, kidney dysfunction
since the half life is 5 hours, what does it tell about toxicity?
toxic levels can be reached quickly and last for prolonged periods of time
- what receptors does high doses of caffeine block?
- what does it cause the release of?
- what is the result of this?
- GABA
- Ca+ release intracellularly
- prevents inhibitory signals which lead to heightened risk of seizures
- what does chronic caffeine use result in?
- where do we see mild dependence?
- physical and psychological dependence and upregulation of adenosine receptors
- in people who use more than 100mg a day and withdrawal symptoms appear up on cessation
if you take high doses of caffeine, what may occur?
produce complete tolerance in some individuals - caffeine no longer produces physiological arousal!
what are the withdrawal symptoms of caffeine?
- headache/migraine: : relaxation of blood vessels leading to sudden increase in blood circulation
- fatigue, difficulty concentrating, irritability, mild depression or anxiety, flu-like symptoms, impaired motor abilities, vigilance, & cognitive performance
- when do withdrawal symptoms start?
- when do the peak?
- how long do they last for?
- 12-24 hr after last use
- 24-48 hrs post use
- 2-9 days
