# data[].attributes.body
1. Compare and contrast “drug dependence” and “drug addiction.” Based on this comparison, justify under which category you would place caffeine consumption.
drug dependence
- drug dependence is a state of being physically dependent on a certain substance. Dependence occurs when your body as a whole becomes used to the effects of a drug and goes into withdrawal if you stop using that substance. The symptoms of withdrawal vary by drug.
- Drug dependence means physical or physiological dependence, as indicated by tolerance and withdrawal symptoms. It is a state of neuroadaptation that can occur after repeated substance use, whereby continued substance use is needed to prevent withdrawal symptoms.
https://www.arcare.net/addiction-vs-dependence-understanding-the-differences/

https://blogs.scientificamerican.com/observations/is-there-really-a-difference-between-drug-addiction-and-drug-dependence/
- Do not  keep taking drug to satisfy craving and get pleasurable effect.

- Do not keep taking the drug to the point where they do not care about the harmful effect to themselves.

drug addiction
- Drug addiction, also called substance use disorder, is a disease that affects a person's brain and behavior and leads to an inability to control the use of a legal or illegal drug or medication. Substances such as heroine, marijuana and nicotine also are considered drugs. When you're addicted, you may continue using the drug despite the harm it causes.
- Addiction is a health condition in which you have strong cravings for a certain substance. These cravings occur due to physical changes in your brain after repeated exposure to a drug. These cravings can lead to uncontrolled drug use, which takes a toll on your health, relationships, career, finances, and other aspects of your life. Being addicted to drugs can cause you to engage in self-destructive behavior or make decisions that hurt other people, such as taking dangerous risks or acting in an aggressive manner toward others.

https://www.mayoclinic.org/diseases-conditions/drug-addiction/symptoms-causes/syc-20365112
- Keep taking drug to satisfy craving and get pleasurable effect.

- Keep taking the drug to the point where they do not care about the harmful effect to themselves.

Therefore, caffeine consumption is classified as drug dependence. It is because when a person who always consume caffeine and  stop taking it, that person will develop withdrawal symptoms such as headache. Other than that, caffeine consumption is more about the physical dependence because most of people take caffeine to feel energetic and more alert to do work whenever they feel tired or sleepy. So, this shows that people consume caffeine not to  satisfy craving and get pleasurable effect like drug addiction. Furthermore, caffeine consumption is not a drug addiction because it is not considered as substance use disorder like other drug such as cocaine and people do not take caffeine until to the point they could do harm things to the themselves or others.

2. Explain the mechanism by which adenosine contributes to caffeine dependence or

addiction.
- As we know, adenosine binds to its receptors which is located at neural membrane will cause neural activity slows down, and you feel sleepy. Mostly, people who want to stay up late doing work or want to fell fresh early in the morning are taking caffeine. This is because caffeine can make us feel energetic and increase our alertness and these are why people will keep on depending to caffeine. This can happens due to the fact that caffeine, a methylxanthine, is a nonselective adenosine receptor antagonist that can bind to adenosine receptors and block adenosine from binding to its receptor.  Whenever people who always take caffeine start to stop taking caffeine, they will get affected by the withdrawal symptoms such as headache, dizziness or nausea. One of the withdrawal symptoms is fatigue. This can happen because adenosine can bind back to its receptors because of no presence of caffeine. Therefore, people will keep taking caffeine to prevent the caffeine withdrawal symptoms which are worse and last longer at least 2 to 9 days. This leads to the caffeine dependence and it is not a substance use disorder like drug addiction that involving cocaine.

https://www.healthline.com/health/how-long-does-caffeine-withdrawal-last

3. Explain how dopamine can contribute to caffeine dependence or addiction.

-Dopamine is a neurotransmitter and is released when your brain is expecting a reward. That is why, it contributes to a pleasure feeling. Other than that, it can also increase an alertness, focus, motivation.

https://www.healthline.com/health/dopamine-effects#definition
- Dopamine works more effectively when the adenosine receptors are blocked. A previous study reported that caffeine can induce marked changes in certain behaviors, including high level of alertness and poor sleep, in humans. This effect was associated with an increase in the availability of dopamine receptors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132598/
- Caffeine causes an increase of dopamine within the brain, but it is not a large enough  to cause unbalance the reward system in the brain , such as amphetamines and cocaine that stimulate the area of the brain linked to reward and motivation to a higher extent than caffeine does.

https://www.addictioncenter.com/stimulants/caffeine/

- That is why caffeine addiction that happen to people who always consume caffeine is not classified as substance use disorder as the dopamine effect caused by caffeine is weaker than other stimulants such as cocaine.

# data[].attributes.body
1. Discuss whether drinking coffee might be beneficial or harmful for asthmatic
patients.
-beneficial
- caffeine structure is chemically same as theophylline ( used in therapy for respiratory diseases, bronchodilator tranquilizer)
-caffeine also can enhance lung function/help with breathing
-can reduce respiratory muscle fatigue, ease symptom of asthma e.g. wheezing/whacking/shortness of breath

2. Explain why many headache contains caffeine
- FDA has approved caffeine for use in pain relievers to treat migraine headache
- during headache, blood vessel swell -> increase in blood flow  -> increase in blood flow pressure that surround nerves -> send pain message to brain -.the cause of headache
- caffeine has vasoconstrictive properties (narrow blood vessels to restrict blood flow) -> helps alleviating the pain
~ used as analgesic adjuvant, enhance analgesic effect. e.g. when caffeine is combined with acetaminophen and aspirin, the pain relieving effect is increased by 40%
# Caffeine; migraine treatment vs migraine trigger https://www.mdpi.com/2072-6643/12/8/2259/htm
# Caffeine in headache:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655397/

3. Discuss any other medications that can have interactions with caffeine. (ADME /
pharmacodynamics)
#list of medication that interact with caffeine :
~https://www.drugs.com/drug-interactions/caffeine-index.html
~https://www.webmd.com/vitamins/ai/ingredientmono-979/caffeine
~https://www.caffeineinformer.com/caffeine-drug-interactions
CAFFEINE WITH
e.g. 3. Discuss any other medications that can have interactions with caffeine. (ADME /
pharmacodynamics)
e.g. antidepressant drug/ antibacterial drug/asthma drug
=slow caffeine metabolism, increase caffeine effect
e.g. stimulant drugs
= Increased heart rate and high blood pressure

# data[].attributes.body
1. HOW WOULD CAFFEINE BINDING TO AN ADENOSINE RECEPTOR AFFECT THE ACTIVITY INSIDE THE NEURON?

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053814

-      Adenosine acts in the basal forebrain as sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness especially during prolonged wakefulness and and lead to increased sleep and subsequent rebound sleep.

-      Adenosine in basal forebrain acts via adenosine A1 receptors that inhibit the cholinergic neurons and provide input to the cerebral cortex.

-      A2a receptor also implicated in sleep as A1 receptor involve normal sleep pattern and exhibit rebound sleep which affected by caffeine

-      Highly amount of adenosine in brain by breakdown of ATP to produce energy, then adenosine can bind to the adenosine receptor and make us sleep.

https://chem.ku.edu/sites/chem.ku.edu/files/docs/CHEM190/caffeine.pdf

a. caffeine acts as an adenosine receptor antagonist.
b. it binds to adenosine receptors on the surfaces w/o activates them ( the molecule is a competitive inhibitor for adenosine)
c. when molecules bind with adenosine receptor , adenosine is blocked from attaching to them and cannot cause response of sleepiness.
d. caffeine binding to adenosine receptor causes the opposite effect which nerve cell activity speeds up, and brain blood vessels constrict. it prevents us from tiredness.
e. when caffeine binds to adenosine receptor, the pituitary gland of brain will regulates the release of hormones and increase the activity of signal to produce adrenaline or epinephrine.
f. caffeine blocking adenosine receptors is an increase in the neurotransmitter dopamine.
g. dopamine function is improves focus and attention, regulate the movements.

2. WHAT EFFECTS WOULD CAFFEINE HAVE? when adenosine levels rise and adenosine acts on its receptor to inhibit other neurons
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769007/pdf/CN-7-238.pdf
https://thebrain.mcgill.ca/flash/a/a_11/a_11_m/a_11_m_cyc/a_11_m_cyc.html
-when adenosine levels rise up
in basal forebrain, extracellular adenosine level start to rise up due to prolonged activity during wakeful period., thus associated with depletion of ATP that reserves as glycogen in the brain
-lead of decrease neuronal activity which cause blood dilate to give good oxygenation during sleep.
-it inhibit cholinergic and noncholinergic neurons which decrease acetylcholine when adenosine receptor level is rise

The accumulation of adenosine in the body is related to the quantity of caffeine consumed during the day. By drinking beverages with high levels of caffeine, the body builds up an excessive amount of adenosine. Often this excess is not fully flushed from the body during sleep. This surplus of adenosine, therefore, contributes to the grogginess many suffer each morning. This feeling encourages people to load up on more caffeine. And on and on it goes! It’s a vicious cycle that results in poorer sleep and feeling tired all day.
https://www.sleepscore.com/blog/learn-about-adenosine/

https://pubmed.ncbi.nlm.nih.gov/1356551/
mechanism of action of caffeine on the CNS system
1. mobilization of intracellular calcium
- caffeine prolongs during the active period muscle contracting by promoting translocation of calcium through plasma membrane.
- caffeine in high concentration will interfere with the uptake and storage of calcium and increase the translocation of Ca2+ ion through plasma membrane.

2. inhibition of phosphadiesterases
- caffeine increase intracellular concentrations of cyclic adenosine monophosphate (cAMP) by inhibit phosphodiesterase enzymes in skeletal muscle and adipose tissue.
- it promotes the lipolysis via the activation of hormone sensitive lipases with release the free fatty acid and glycerol
- accumulation of cAMP stimulates the action of catecholamines
-cAMP is a second messenger that used for intracellular signal transduction (transferring into cells the effects of hormone like glucagon and adrenaline)

3. antagonism at the level of adenosine receptor
- caffeine inhibit adenosine receptor and release of norepinephrine,dopamine,acetylcholine,serotonin ,glutamate and gamma-aminobutyric acid(GABA) and perhaps neuropeptides
- main classes of adenosine receptor : a1 and A2 which caffeine acts as nonselective antagonists
- when caffeine bind to adenosine receptor, it increases the neuronal activity which causes blood vessel constrict --> prevent sleepiness.
-when neuronal activity increase, adrenaline increase, increase heartbeat,excitation and energy
- DOPAMINE- release and increase the focus, attention, regulating movement--> increase fell pleasure and stimulate us to do pleasurable thing --> dependency on caffeine

4. interaction with benzodiazepine binding
- caffeine more potent antagonism of adenosine receptor than benzodiazepine sites
-affinity of caffeine is weak ;- due to competition of two substances at the benzodiazepine receptors.
-toxic effects of high doses of caffeine can occur due to interaction with benzodiazepine receptor.

https://www.ncbi.nlm.nih.gov/books/NBK223808/

additional information
d. other effect of caffeine
- decrease in plasma potassium concentration
- increase coronary blood flow  via phosphodiesterase inhibition
-smooth muscle relaxation and bronchial dilation
- increase the blood flow, diuresis on kidney

3. HOW DOES CAFFEINE GET INTO THE THE BRAIN?

a. caffeine is both water and fat soluble which allows it pass through all membranes easily.
b. it attaches to a transporter that associated with adenosine.
c. due to the similarity structural of adenosine , adenosine acts inhibitory neurotransmitter or CNS depressant. it binds to neurotransmitter in the brain and binding which create a pathway that slows the activity of nerve cells and cause the brain blood vessel to dilate, and lead to drowsiness.
d. when adenosine enter the brain, it will bind with the specific receptors. however, caffeine is so close in structure with adenosine which can bind to the receptor which specific to adenosine.
e. but the affinity of caffeine higher than adenosine receptor which makes strong antagonist.
f. similar adenosine and caffeine ;- built up from 2 ring system (purines) (pyrimidine & imidazole ring)
caffeine has  alkene, amide, amine, carbonyl ( soluble in water)
fat soluble from 3 methyl group on the surface of caffeine,  trimethylxanthine
adenosine has amine, ether, imine, hydroxyl
(caffeine being competitive antagonist of adenosine)

https://www.acs.org/content/acs/en/education/resources/highschool/chemmatters/past-issues/archive-2013-2014/caffeine.html

https://examine.com/nutrition/how-caffeine-works-in-your-brain/

https://chem.ku.edu/sites/chem.ku.edu/files/docs/CHEM190/caffeine.pdf

# data[].attributes.body
1. What are G-protein coupled receptors? Where are these receptors located in the cell? How do they work? Draw a diagram.

What are G-protein coupled receptors? ? Also called Seven-transmembrane receptor or heptahelical receptor
-       protein located in the cell membrane that binds extracellular substances and transmits signals from these substances to an intracellular molecule called a G protein (guanine nucleotide-binding protein)

-       A GPCR is made up of a long protein that has three basic regions: an extracellular portion (the N-terminus), an intracellular portion (the C-terminus), and a middle segment containing seven transmembrane domains.
-       Mediate most of the physiological responses of hormones, neurotransmitters and environmental stimulants
-       Can regulate immune system, growth, sense of smell, taste, visual, behavior, mood
-       The adenosine receptor (A2A) is a G-protein coupled receptor, which is a transmembrane protein that consists of secondary structures, such as seven alpha helical domains. When caffeine binds to this receptor, it inhibits adenosine from binding to the extracellular binding domain of the A2A receptor.

Where are these receptors located in the cell?
Located in cell membrane of a wide range of organisms, including mammals, plants, microorganisms, and invertebrates
https://www.britannica.com/science/G-protein-coupled-receptor

How do they work? Draw a diagram. (summarization)

- GPCR has seven transmembrane alpha helices (unique characteristic)

- G Proteins is a specialized protein that can bind to GDP and GTP

- G Proteins associated with GCPR are heterotrimeric meaning that they have three different subunits (alpha, beta, gamma subunits)

Steps of signal transducing pathway:

1.    Ligand binds to GCPR

2.    GPCR undergoes conformational change

3.    Alpha subunit exchanges GDP for GTP

4.    Alpha subunit dissociates and regulates target proteins, beta dimer subunit also regulate another protein

5.    Target protein relay a signal

6.    GTP is hydrolyzed to GDP, GTP loses a phosphate in hydrolysis and become GDP, turns to normal, ligand leave

2. What is an antagonist for a receptor? What would an antagonist do? Draw a diagram to explain this.

3. Discuss potency and efficacy. Use caffeine vs adenosine in your discussion
Potency caffeine vs adenosine
depends on the affinity of the receptors to bind the drug and how effectively the drug-receptor interaction leads to clinical response.
- Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas
- Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases
- Caffeine acts most potently at A2A receptors, followed closely by A1 receptors, then A2B receptors, and as a weak antagonist at human A3  receptors.
- Adenosine A and A2A receptors are characterized by high affinity for adenosine, while A2B and A₃ receptors show significantly lower affinity for adenosine.
- Adenosine initiates its biological effects via four receptor subtypes, namely the A1, A2A, A2B and A3. The A1 and A2A possess high affinity for adenosine while the A2B and A3 show relatively lower affinity for adenosine receptors. These receptors belong to the superfamily of G protein-coupled receptors (GPCR).
- A1 receptor and A2A play roles in the heart that regulate mycordial oxygen consumption and coronary blood flow. A2A receptor also has broader anti-inflammatory effects in the body.

# data[].attributes.body
PART 3
1. how long will caffeine intake affected the body? relate with the distribution pattern of caffeine

a. caffeine rapidly absorbed following oral consumption peak blood level usually within 30 minutes.
b. maximum caffeine concentration in blood are reached within 1 to 1.5 hour after ingestion.
c. how long it takes to leave caffeine from body:-
adult- 3 to 5 hours
pregnant women - 7 to 8 hrs
smoker 2 to 3 hrs.

https://www.researchgate.net/publication/279923885_Effects_of_caffeine_on_health_and_nutrition_A_Review
distribution pattern of caffeine:-
i. absorbed caffeine is readily distributed  throughout the entire body.
ii. it passes across the blood-brain barrier  because caffeine is lipophilic so it can pass through the biological membrane easily.
iii. caffeine can distribute through placenta and amniotic fluid ,fetus and breast milk
iv. caffeine can be detected in semen.
https://www.researchgate.net/publication/10957470_Effect_of_caffeine_on_human_health
Pharmacology of Caffeine - Caffeine for the Sustainment of Mental Task Performance - NCBI Bookshelf (nih.gov)

2. is it discourage to take coffee is someone pregenant? how can caffeine consumed by the mother affecting the babies.

-Caffeine is a stimulant and a diuretic. Because caffeine is a stimulant, it increases your blood pressure and heart rate, both of which are not recommended during pregnancy.
-Caffeine also increases the frequency of urination that causes a reduction in your body fluid levels and can lead to dehydration.
-Caffeine crosses the placenta to your baby by passive diffussion.  Although you may be able to handle the amounts of caffeine you feed your body, your baby cannot. Your baby’s metabolism is still maturing and cannot fully metabolize the caffeine. Any amount of caffeine can also cause changes in your baby’s sleep pattern or normal movement pattern in the later stages of pregnancy. Remember, caffeine is a stimulant and can keep both you and your baby awake. Heavy caffeine consumers can affect the premature infants with high level of caffeine.
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption | Pharmacological Reviews (aspetjournals.org)

https://americanpregnancy.org/healthy-pregnancy/pregnancy-health-wellness/caffeine-intake-during-pregnancy-946/

limit the caffeine intake for pregnancy women < 200mg daily

effects of pregnancy women to baby :--
1. miscarriage
2. IUGR ;- intrauterine growth retardation

baby outcomes:
1. low birth weight
2. small head circumference
3. execess infant growth
4. childhood overweight
5. cognitive impairments

https://www.researchgate.net/publication/337811825_Impacts_of_Caffeine_during_Pregnancy

3.list common symptoms of caffeine withdrawal
# fatigue or drowsiness
# low alertness
# mood disturbances
# low sociability/ motivation to work
# headache

4. timeframe for onset of caffeine withdrawal symptoms? how low can they last?

caffeine withdrawal symptoms emerge after 12-24 hour of caffeine ,peak in the first day and two. last from 2 to  9 days.

https://www.academia.edu/2079779/Development_of_the_Caffeine_Withdrawal_Symptom_Questionnaire_Caffeine_withdrawal_symptoms_cluster_into_7_factors
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PART 6
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SITI AISYAH BINTI 'ASRI
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PART 6
1. HOW WOULD CAFFEINE BINDING TO AN ADENOSINE RECEPTOR AFFECT THE ACTIVITY INSIDE THE NEURON?

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053814

-      Adenosine act in the basal forebrain as sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness especially during prolonged wakefulness and and lead to increased sleep and subsequent rebound sleep.
-      Adenosine in basal forebrain acts via adenosine A1 receptors that inhibit the cholinergic neurons and provide input to the cerebral cortex.
-      A2a receptor also implicated in sleep as A1 receptor involve normal sleep pattern and exhibit rebound sleep which affected by caffeine
-      Highly amount of adenosine in brain by breakdown of ATP to produce energy, then adenosine can bind to the adenosine receptor and make us sleep.

https://chem.ku.edu/sites/chem.ku.edu/files/docs/CHEM190/caffeine.pdf

a. caffeine acts as an adenosine receptor antagonist.
b. it binds to adenosine receptors on the surfaces w/o activates them ( the molecule is a competitive inhibitor for adenosine)
c. when molecules bind with adenosine receptor , adenosine is blocked from attaching to them and cannot cause response of sleepiness.
d. caffeine binding to adenosine receptor causes the opposite effect which nerve cell activity speeds up, and brain blood vessels constrict. it prevents us from tiredness.
e. when caffeine binds to adenosine receptor, the pituitary gland of brain will regulates the release of hormones and increase the activity of signal to produce adrenaline or epinephrine.
f. caffeine blocking adenosine receptors is an increase in the neurotransmitter dopamine.
g. dopamine function is improves focus and attention, regulate the movements.

2. WHAT EFFECTS WOULD CAFFEINE HAVE? when adenosine levels rise and adenosine acts on its receptor to inhibit other neurons
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769007/pdf/CN-7-238.pdf
https://thebrain.mcgill.ca/flash/a/a_11/a_11_m/a_11_m_cyc/a_11_m_cyc.html
-when adenosine levels rise up
in basal forebrain, extracellular adenosine level start to rise up due to prolonged activity during wakeful period., thus associated with depletion of ATP that reserves as glycogen in the brain
-lead of decrease neuronal activity which cause blood dilate to give good oxygenation during sleep.
-it inhibit cholinergic and noncholinergic neurons which decrease acetylcholine when adenosine receptor level is rise

https://pubmed.ncbi.nlm.nih.gov/1356551/
mechanism of action of caffeine on the CNS system
1. mobilization of intracellular calcium
- caffeine prolongs during the active period muscle contracting by promoting translocation of calcium through plasma membrane.
2. inhibition of phosphadiesterases
- roles of cAMP in the process
- caffeine prevents enzymatic breakdown of cAMP in inhibiting cyclic nucleotide phosphodiesterase
- accumulation of cAMP stimulates the action of catecholamines
3. antagonism at the level of adenosine receptor
- caffeine reduces the accumulation of cAMP in cerebral slides
-A1- high affinity of adenosine while A2 have low affinity
4. interaction with benzodiazepine binding
- caffeine more potent antagonism of adenosine receptor than benzodiazepine sites
-toxic effects of high doses of caffeine can occur due to interaction with benzodiazepine receptor.

https://www.ncbi.nlm.nih.gov/books/NBK223808/
a. caffeine and adenosine receptors
- caffeine inhibit adenosine receptor and release of norepinephrine,dopamine,acetylcholine,serotonin ,glutamate and gamma-aminobutyric acid(GABA) and perhaps neuropeptides
- main classes of adenosine receptor : a1 and A2 which caffeine acts as nonselective antagonists
- when caffeine bind to adenosine receptor, it increases the neuronal activity which causes blood vessel constrict --> prevent sleepiness.
-when neuronal activity increase, adrenaline increase, increase heartbeat,excitation and energy
- DOPAMINE- release and increase the focus, attention, regulating movement--> increase fell pleasure and stimulate us to do pleasurable thing --> dependency on caffeine

b. caffeine and phosphodiesterase
- caffeine increase intracellular concentrations of cyclic adenosine monophosphate (cAMP) by inhibit phosphodiesterase enzymes in skeletal muscle and adipose tissue.
- it promotes the lipolysis via the activation of hormone sensitive lipases with release the free fatty acid and glycerol

c. caffeine and calcium mobilization
- caffeine in high concentration will interfere with the uptake and storage of calcium in the sarcoplasmic reticulum and increase the translocation of Ca2+ through plasma membrane.

d. other effect of caffeine
- decrease in plasma potassium concentration
- increase coronary blood flow  via phosphodiesterase inhibition
-smooth muscle relaxation and bronchial dilation
- increase the blood flow, diuresis on kidney

3. HOW DOES CAFFEINE GET INTO THE THE BRAIN?
-how it is metabolize?
a. caffeine is both water and fat soluble which allows it pass through all membranes easily.
b. it attaches to a transporter that associated with adenosine.
c. due to the similarity structural of adenosine , adenosine acts inhibitory neurotransmitter or CNS depressant. it binds to neurotransmitter in the brain and binding which create a pathway that slows the activity of nerve cells and cause the brain blood vessel to dilate, and lead to drowsiness.
d. when adenosine enter the brain, it will bind with the specific receptors. however, caffeine is so close in structure with adenosine which can bind to the receptor which specific to adenosine.
e. but the affinity of caffeine higher than adenosine receptor which makes strong antagonist.
f. similar adenosine and caffeine ;- built up from 2 ring system (purines) (pyrimidine & imidazole ring)
caffeine has  alkene, amide, amine, carbonyl ( soluble in water)
fat soluble from 3 methyl group on the surface of caffeine,  trimethylxanthine
adenosine has amine, ether, imine, hydroxyl
(caffeine being competitive antagonist of adenosine)

https://www.acs.org/content/acs/en/education/resources/highschool/chemmatters/past-issues/archive-2013-2014/caffeine.html

https://examine.com/nutrition/how-caffeine-works-in-your-brain/

https://chem.ku.edu/sites/chem.ku.edu/files/docs/CHEM190/caffeine.pdf

# data[].attributes.body
1. how long will caffeine intake affected the body? relate with the distribution pattern of caffeine

a. caffeine rapidly absorbed following oral consumption peak blood level usually within 30 minutes.
b. maximum caffeine concentration in blood are reached within 1 to 1.5 hour after ingestion.
c. how long it takes to leave caffeine from body:-
adult- 3 to 5 hours
pregnant women - 7 to 8 hrs
smoker 2 to 3 hrs.

https://www.researchgate.net/publication/279923885_Effects_of_caffeine_on_health_and_nutrition_A_Review
distribution pattern of caffeine:-
i. absorbed caffeine is readily distributed  throughout the entire body.
ii. it passes across the blood-brain barrier  because caffeine is lipophilic so it can pass through the biological membrane easily.
iii. caffeine can distribute through placenta and amniotic fluid ,fetus and breast milk
iv. caffeine can be detected in semen.
https://www.researchgate.net/publication/10957470_Effect_of_caffeine_on_human_health
Pharmacology of Caffeine - Caffeine for the Sustainment of Mental Task Performance - NCBI Bookshelf (nih.gov)

2. is it discourage to take coffee is someone pregenant? how can caffeine consumed by the mother affecting the babies.

-Caffeine is a stimulant and a diuretic. Because caffeine is a stimulant, it increases your blood pressure and heart rate, both of which are not recommended during pregnancy.
-Caffeine also increases the frequency of urination that causes a reduction in your body fluid levels and can lead to dehydration.
-Caffeine crosses the placenta to your baby by passive diffussion.  Although you may be able to handle the amounts of caffeine you feed your body, your baby cannot. Your baby’s metabolism is still maturing and cannot fully metabolize the caffeine. Any amount of caffeine can also cause changes in your baby’s sleep pattern or normal movement pattern in the later stages of pregnancy. Remember, caffeine is a stimulant and can keep both you and your baby awake. Heavy caffeine consumers can affect the premature infants with high level of caffeine.
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption | Pharmacological Reviews (aspetjournals.org)

https://americanpregnancy.org/healthy-pregnancy/pregnancy-health-wellness/caffeine-intake-during-pregnancy-946/

limit the caffeine intake for pregnancy women < 200mg daily

effects of pregnancy women to baby :--
1. miscarriage
2. IUGR ;- intrauterine growth retardation

baby outcomes:
1. low birth weight
2. small head circumference
3. execess infant growth
4. childhood overweight
5. cognitive impairments

https://www.researchgate.net/publication/337811825_Impacts_of_Caffeine_during_Pregnancy

3.list common symptoms of caffeine withdrawal
# fatigue or drowsiness
# low alertness
# mood disturbances
# low sociability/ motivation to work
# headache

4. timeframe for onset of caffeine withdrawal symptoms? how low can they last?

caffeine withdrawal symptoms emerge after 12-24 hour of caffeine ,peak in the first day and two. last from 2 to  9 days.

https://www.academia.edu/2079779/Development_of_the_Caffeine_Withdrawal_Symptom_Questionnaire_Caffeine_withdrawal_symptoms_cluster_into_7_factors

# data[].attributes.body
overview of metabolism of caffeine
https://pharmrev.aspetjournals.org/content/70/2/384#:~:text=Caffeine%20is%20primarily%20metabolized%20in,metabolism%20(Arnaud%2C%202011).

# data[].attributes.body
Overview of caffeine pharmacokinetics
https://innovareacademics.in/journals/index.php/ijpps/article/view/9857/4997

# data[].attributes.body
1)List of common foods and drinks

# data[].attributes.body
1. Compare and contrast caffein and adenosine structure.
-similar structure causes competition  to bind to same receptor
-built up from 2 ring system (purines) (pyrimidine & imidazole ring)
caffeine has alkene, amide, amine, carbonyl
adenosine has amine, ether, imine, hydroxyl

2. What is the pKa of caffeine? Explain the absorption of caffeine in the intestinal tract (mouth, stomach, small intestine)
pka : 10.4 (weak base)
- absorption at mouth: pH 6 (lecture note) less ionization, more absorption of weak base //unionized form- higher absorption
-absorption at stomach: -pH stomach(lecture note):1.4
low pH 1.4 , more ionization of weak base, ion trapped//
-absorption at small intestine: pH 5-8(lecture note)
less ionization of weak base, more absorption of weak base//unionized form-high absorption
#additional info
Food or food components, such as fibers, in the gut can delay how quickly caffeine in the blood peaks. Therefore, drinking your morning coffee on an empty stomach might give you a quicker effect than if you drank it while eating breakfast.

3. . Explain how caffeine is excreted out from our body.
Major excretion- Renal 70% of 7.5 mg/kg
-readily reabsorbed by the renal tubules (98%) once filtered by glomeruli , low urine excretion
- caffeine metabolism transfer caffeine to dimethylxanthines, dimethyl and monomethyl uric acids, trimethyl and dimethylallantoin, and uracil derivatives, are filtered by the kidneys and exit the body in the urine
-only 1.5% caffeine found in urine

4. Caffein is transported via OAT1, if coffee is consumed, can this increase or
decrease bioavailability of certain drugs?
--when caffeine is consumed in coffee, absorb rapidly
-caffeine metabolite 1-methylxanthine inhibits OAT1 (organic anion transporter 1)
-may alter pharmacokinetics of  drugs
-decrease bioavailability of drug

# data[].attributes.body
SYMPTOMS OF COFFEE WITHDRAWAL
coffee withdrawal affected for those always consumed caffeine

https://www.verywellmind.com/what-to-expect-from-caffeine-withdrawal-21844

# data[].attributes.body
caffeine is weak base

# data[].attributes.body
Caffeine metabolism occurs primarily in the liver, catalyzed by hepatic microsomal enzyme systems. It is metabolized in the liver to dimethylxanthines ((Paraxanthine (forms 84%), which breaks down fats and increases blood levels of glycerol and fats. Theobromine (forms 12%), which dilates blood vessels and also has a diuretic effect, increasing urination. Theophylline (forms 4%), which dilates the airways and is used in the treatment of asthma))

, uric acids, di- and trimethylallantoin, and uracil derivatives. In humans 3-ethyl demethylation to paraxanthine is the primary route of metabolism. This first metabolic step accounts for approximately 75–80 percent of caffeine metabolism and involves cytochrome P450. The enzyme responsible for metabolism of caffeine is coded for by the gene CYP1A2 in liver.

CYP1A2 catalyzes the 1-, 3-, and 7- demethylations of caffeine, the 7-demethylation of paraxanthine, and the 1- and 3-demethylations of theophylline. CYP1A2 is virtually responsible for most of the biochemical reactions concerning caffeine and its metabolites. Caffeine biotransformation by CYP1A2 accounts for a mean value of 84% for paraxanthine, 12% for theophylline, and 4% for theobromine. On the other hand, CYP2E1 is predominantly responsible for the formation of theophylline and theobromine. CYP2D6-Met also catalyzes caffeine demethylation and 8-hydroxylation, whereas CYP2E1 plays a more minor role in these pathways. CYP3A4 predominantly mediates 8-hydroxylation and may be involved in the in vivo synthesis of 1,3,7-TMU (trimethylurea). Thus, at least four CYP isoforms contribute to caffeine metabolism at a 3 μmol/ml caffeine concentration

These metabolites are then further broken down and excreted in the urine.
https://scihub.se/10.1124/pr.117.014407

2. Discuss on how Alex is not as affected by caffeine than Jenna. Could it be because he metabolizes caffeine differently than Jenna?
Yes. Someone who produces a very active version of the CYP1A2-enzyme will metabolise caffeine quickly, and it will have a shorter-lasting and mild effect throughout the body. Smokers often have increased CYP1A2 activity.(Alex).

In contrast, a person with a less active version of the CYP1A2-enzyme will inactivate caffeine more slowly and retain it in the body for longer, and therefore experience longer-lasting and more pronounced effects(Jenna)

Adenosine A2 receptors are key to the stimulating effect of caffeine . Human studies have shown that polymorphisms of these receptors may have an effect on the body. Research suggests that the probability of having the ADORA2A genotype decreases as habitual caffeine consumption increases, meaning that individuals with this genotype may be less sensitive to the effects of caffeine and therefore be more likely to choose caffeinated beverages
https://www.coffeeandhealth.org/topic-overview/caffeine-and-metabolism/

3. What other factors affecting caffein metabolism?

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1. List FIVE (5) common foods/drinks that are sources of caffeine. How much caffeine is found in each?
The upper intake limit (%UL) of caffeine intake is 400mg for adults (4 cups), and less than 85mg for kids. But usually not recommended for the kids to consume caffeine.
1. filtered coffee (85 mg)
2. espresso (60mg)
3. tea (32mg)
4. energy drink (80mg)
5. dark chocolate (60mg)

Per 8oz cup, Coffee contains 95mg of caffeine. Energy drinks 91mg, espresso 63mg, sodas 49mg and dark chocolate 24mg

From the case study, Alex has can of Redbull which contains 30mg of caffeine

https://www.coffeeandhealth.org/topic-overview/sources-of-caffeine/

2. what is the chemical structure of caffeine? what class of chemical molecules does caffeine belong to?
-methylxanthines class. it is a group of pharmaceuticals that antagonize adenosine receptors in the central nervous system and peripheral tissues
-Caffeine belongs to alkaloid group called methylxanthine class
·         The IUPAC name for caffeine is 1,3,7-trimethylpurine-2,6-dione

·         Molecular Formula (C8H10N402)

·         Caffeine and adenosine have similar structures, which allows it to bind to adenosine receptor

https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-20790-2_30-1

3. How is caffeine formed and used in nature?
How caffeine is formed?

·         Caffeine is a stimulant drug that result from millions of years of plant evolution.

·         A natural alkaloid that can be found in about sixty plant species, the most common are coffee bean, tea leaf, kola nut, and the cocoa bean

·         A single mutation occurred, which was then replicated.

Mutations occurred for many times until caffeine was produced as a byproduct.

How caffeine is used in nature?

As pesticide

·         To repel insect from damaging plants

·         Inhibits enzymes in herbivorous insects’ nervous system, triggering paralysis and even death

·         But it also can harm other animals who ingest the plant or contaminate water supplies

4. What are common physiological effects of caffeine consumption?

- Physiological effects are those that result from some imbalance to the overall human system, or some specific part of it.

- Activities which affect organs and systemic functions without regard to a particular disease

-Caffeine is central nervous stimulant

1)    CENTRAL NERVOUS SYTEM

·         Can cause alertness (feel more awake, focus, less tired)

·         Manage drowsiness, headache and migraine

·         However if caffeine tolerance suddenly stop consuming it, caffeine withdrawal can occur

The symptom of caffeine withdrawal includes:

§  Anxiety

§  Irritability

§  Drowsiness

§  Achy muscle

·         It is best to reduce consumption slowly rather than immediately

·         Thy symptom of caffeine overdose includes

§  Confusion

§  Hallucination

§  Vomiting

§  Irregular heartbeat and breathing trouble

2)    DIGESTIVE AND EXCRETORY SYSTEM

·         Increase the amount of acid in the stomach (cause hearburn or upset stomach)

·         Increase in urination

3)    CIRCULATORY AND RESPIRATORY SYTEM

·         Can increase blood pressure for a short time

·         For people that have irregular heart rhythms, caffeine may increase workload for the heart

4)    SKELETEL AND MUSCULAR SYSTEM

·         Can cause bone thinning (osteoporosis) as caffeine in excess amount interfere with absorption and metabolism of calcium

5)    REPRODUCTIVE SYSTEM

·         Cause baby’s heart rate and metabolism to increase

·         Cause slow fetal growth if too much consume

·         Cause miscarriage if too much consume

·         Can interfere with estrogen production and metabolism needed to conceive

·         limit caffeine consumption between 200 and 300 milligrams per day if you’re trying to get pregnant.