low efficacy stimulants - caffeine

Question 1

what class of alkaloids does caffeine belong to?

Answer 1

methylxanthines

Question 2

in what plants do we find methylxanthines?

Answer 2

• caffeine
• theophylline (tea)
• theobromine (cocoa)

Question 3

what is the most popular stimulant in the world?

Answer 3

caffeine

Question 4

what is the route of administration for caffeine? how much caffeine do we usually see taken?

Answer 4

route: ALWAY ORAL (drinks, food, pill)

10-200 mg

Question 5

1. where does caffeine absorption occur?
2. how much is absorbed within 45 minutes of ingestion?
3. when do blood concentrations peak after ingestion?

Answer 5

1. absorbed by stomach and small intestines
2. 99% is absorbed
3. 20-30 minutes after ingestion even though effects are felt sooner

Question 6

1. how fast does caffeine distribute throughout the body?
2. what barriers can it cross?
3. does it have plasma protein binding?

Answer 6

1. very fast
2. BBB and placental
3. no, it is very low levels

Question 7

1. where is caffeine broken down in?
2. what metabolites are formed?
3. what enzymes form the metabolites?

Answer 7

1. liver
2. active (paraxanthine, theobromine, theophylline)
3. CYP450

Question 8

what are the 3 active metabolites that are formed after caffeine metabolism and what is their function?

Answer 8

• 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

Question 9

when and what populations do we see a slower caffeine metabolism?

Answer 9

• men
• pregnant woman
• newborns
• if you use birth control pills
• if you have liver damage
• asian population

Question 10

when and what populations do we see a faster caffeine metabolism?

Answer 10

• if used with cigs
• in women and children
• Caucasian population

Question 11

if caffeine is taken while smoking tobacco what occurs?

Answer 11

1. increases caffeine clearance by 50%
2. enzyme induction occurs - caffeine is leaving system faster
3. increases caffeine tolerance and coffee consumption for regular smokers

Question 12

if caffeine is taken while using a nasal congestion (ephedrine), what occurs?

Answer 12

increase risk of of hypertension, heart attack, stroke, seizures

Question 13

if caffeine is taken while using a SSRI, what occurs?

Answer 13

anxiety, confusion, restlessness, sleep disturbances

Question 14

1. what order kinetics are seen with caffeine?
2. what is the form of excretion?
3. how much is excreted as metabolites?

Answer 14

1. first order
2. urine
3. 95%

Question 15

1. what is the half life of caffeine?
2. what is the half life of pregnant women in the 3rd trimester?

Answer 15

1. about 5 hours
2. increases to 18 hours

Question 16

1. when is plasma clearance increased?
2. when is plasma clearance decreased?
3. what withdrawal symptoms do we see in heavy coffee drinkers?

Answer 16

1. when smoking nicotine
2. when smoking ends
3. cigarette withdrawal symptoms

Question 17

when are sleep disturbances often reported with caffeine?

Answer 17

if greater than 50mg is still in your system

Question 18

1. what is the neuromodulator found in caffeine use?
2. where is it produced?
3. in what activity do we see this modulator?

Answer 18

1. adenosine
2. throughout nervous system
3. in sleep

Question 19

what are the 2 ways adenosine are formed?

Answer 19

1. as an energy byproduct from brain cells that are breaking down ATP molecules (ex. neurons and astrocytes)
2. produced in astrocytes as a byproduct of making glucose from stored glycogen

Question 20

what are the 2 receptors that adenosine binds to? (it binds to 4 but we only need to know 2)

Answer 20

• 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

Question 21

what does caffeine act as at A1 and A2A receptors?

Answer 21

antagonists

Question 22

where do we see A1 and A2 receptors?

Answer 22

A1: reticular activating system
A2: basal ganglia and nucleus accumbens (in our mesolimbic and nigrostriatal DA system)

Question 23

what happens when A1 and A2A receptors are blocked?

Answer 23

it increases dopamine and norepinephrine signaling in the brain leading to mild arousal and psychomotor activation

Question 24

what are acute physiological actions of caffeine?

Answer 24

• increased alertness, mood, physical energy
• activates sympathetic nervous system to increase respiration rate
• Causes release of stress hormones from adrenal medulla : increases arousal/ vigilance

Question 25

what effects occur at Adenosine receptors found in the heart & kidneys?

Answer 25

increased BP, vasoconstriction, diuretic

Question 26

what is the daily healthy consumption of caffeine?

Answer 26

400 mg but at 250mg itself u can see the effects of it

Question 27

what does caffeine do?

Answer 27

- improved mental performance (increased alletness) - improved physical performance (increased endurance) - improved migraine symptoms (constricts blood vessels)

Question 28

are lethal doses common with caffeine?

Answer 28

no; but 100 reported cases of caffeine overdose fatalities

Question 29

when do we see lethal doses of caffeine?

Answer 29

when ingested as a powder or pill ; more than 3 grams

Question 30

1. what happens if you take more than 400mg? 2. what happens if you take more than 1,200 mg?

Answer 30

1. severe anxiety, panic attacks, insomnia, irritability, increased heart rate & blood pressure, palpitations, tremor, paresthesia 2. seizures, metabolic acidosis, kidney dysfunction

Question 31

since the half life is 5 hours, what does it tell about toxicity?

Answer 31

toxic levels can be reached quickly and last for prolonged periods of time

Question 32

1. what receptors does high doses of caffeine block? 2. what does it cause the release of? 3. what is the result of this?

Answer 32

1. GABA 2. Ca+ release intracellularly 3. prevents inhibitory signals which lead to heightened risk of seizures

Question 33

1. what does chronic caffeine use result in? 2. where do we see mild dependence?

Answer 33

1. physical and psychological dependence and upregulation of adenosine receptors 2. in people who use more than 100mg a day and withdrawal symptoms appear up on cessation

Question 34

if you take high doses of caffeine, what may occur?

Answer 34

produce complete tolerance in some individuals - caffeine no longer produces physiological arousal!

Question 35

what are the withdrawal symptoms of caffeine?

Answer 35

- 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

Question 36

1. when do withdrawal symptoms start? 2. when do the peak? 3. how long do they last for?

Answer 36

1. 12-24 hr after last use 2. 24-48 hrs post use 3. 2-9 days