caffeine and you
TRANSCRIPT
![Page 1: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/1.jpg)
CAFFEINE & YOU
![Page 2: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/2.jpg)
CAFFEINE & YOU
david ardiansyah & koh jia lei
![Page 3: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/3.jpg)
Caffeine noun caf·feine \ka-ˈfēn, ˈka-ˌ\German Kaffein, from Kaffee coffee, from French café
![Page 4: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/4.jpg)
Caffeine noun caf·feine \ka-ˈfēn, ˈka-ˌ\German Kaffein, from Kaffee coffee, from French café
the world consumes 2 billion cups of coffee daily!
![Page 5: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/5.jpg)
a sharpened focus
extra boost of energy
warding off drowsiness
sleep disorders
anxiety
addiction and withdrawal syndrome
PROLONGEDconsumptions
STIMULANTS
![Page 6: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/6.jpg)
STRUCTURE
![Page 7: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/7.jpg)
odourless
tastes bitter
white powder
CAFFEINE
![Page 8: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/8.jpg)
purine ring
two ketone
purine xanthine
1,3,7-trimethylxanthine
CAFFEINE
![Page 9: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/9.jpg)
causes drowsiness
dilation of blood vessels (vasodilation)
slowing down cerebral cell activity
ADENOSINE
![Page 10: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/10.jpg)
purine ring
ribose ring
(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
ADENOSINE
caffeine
amine
![Page 11: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/11.jpg)
adenosine tri-phospate (ATP)
adeninebuilding blocks of DNA (‘A’ ’T’ ‘C’ ‘G’)
energy storage for biochemical process
adenosine
induces sleep
![Page 12: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/12.jpg)
Adenosine docking at Adenosine A2a receptor
π bond interaction
![Page 13: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/13.jpg)
RESONANCE
Glu169A
Asn253A
His278A
resonance effect strengthens the hydrogen bonds
glutamic acid
asparagine
histidine
![Page 14: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/14.jpg)
MECHANISM OF ACTION
![Page 15: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/15.jpg)
CROSSING BLOOD-BRAIN BARRIER
highly lipophilic
![Page 16: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/16.jpg)
Caffeine has a value of approx. -0.25 to -0.55
Partition-coefficient (P)
To cross the blood-brain barrier, the log P value is < 3
Passive diffusion of caffeine
Ride on Adenosine transport mechanism
![Page 17: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/17.jpg)
Caffeine docking at Adenosine A2a receptor
π bond interaction
![Page 18: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/18.jpg)
CaffeineAdenosine
π bond interaction π bond interaction
![Page 19: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/19.jpg)
METABOLISM OF CAFFEINE
Caffeine
Paraxanthine 84%
Theobromine 12%
Theophylline 4%
![Page 20: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/20.jpg)
increases the rate of lipolysis process
Paraxanthine
dilation in the blood vessels
increases urine production
Theobromine
induces bronchodilation
Theophylline
increased heart rate and contractility
![Page 21: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/21.jpg)
caffeine crash
caffeine resistance
caffeine withdrawal symptoms
up regulation of receptors increased number of receptor active sites
more adenosine can bind into extra receptor actives site higher sensitivity of adenosine in the brain
caffeine unbinding once being metabolised adenosine readily binds to active side
AFTER EFFECT
![Page 22: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/22.jpg)
ADENOSINE RECEPTORS
![Page 23: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/23.jpg)
four different subtypes: A1, A2a, A2b and A3
purinergic receptors
ADENOSINE RECEPTORS
decrease the amount of cAMP (cyclic Adenosine Mono-Phosphate)
inhibiting enzyme Adenylate Cyclase
A1 and A2a play a complementary role
![Page 24: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/24.jpg)
ADENOSINE A2a RECEPTOR AGONISTS
ligand that binds into a receptor and begins to activate the receptor
strict requirements
esp. structure and stereochemistry of the ribose group
1
2
3 tolerated modifications are shown at (1), (2) and (3).
![Page 25: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/25.jpg)
adenosine A2a receptor agonists
5’-hydroxyl group of the ribose ring, 2- and N-6 position of the purine group
![Page 26: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/26.jpg)
Ki value for Adenosine A2a Agonists
![Page 27: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/27.jpg)
NECA and Adenosine docking at Adenosine A2a Agonists
![Page 28: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/28.jpg)
ADENOSINE A2a RECEPTOR ANTAGONISTS
ligand that binds to a receptors and causes the blocking of the agonist-mediated response
a planar configuration, aromatic or π electron rich and nitrogen containing heterocycle
lack of ribose group
N1, N3, N7 and C8
![Page 29: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/29.jpg)
xanthine antagonists at adenosine A2a receptor
modification at N1, N3, N7 and C8
![Page 30: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/30.jpg)
non-xanthine antagonists at adenosine A2a receptor
![Page 31: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/31.jpg)
Ki value for Adenosine A2a Antagonists
Ki value for Caffeine is 4,5000, 18,000 and 13,000 at A1, A2a and A3 respectively
![Page 32: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/32.jpg)
Caffeine and XAC docking at Adenosine A2a Agonists
![Page 33: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/33.jpg)
ADENOSINE A2a RECEPTOR PARTIAL AGONISTS
less than half the intrinsic activity
a combination of an antagonistic substituent of purine ring and the unchanged agonistic ribose group
modifications on the purine group
Theophylline-7-riboside 1,3-dibutylxanthine-7-riboside
![Page 34: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/34.jpg)
FURTHER APPLICATION
![Page 35: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/35.jpg)
ANALGESICS
synergistic effect with paracetamol
caffeine on its own has no analgesic effects
adenosine often detected in migraine attacks
competitive inhibition of the adenosine receptors
![Page 36: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/36.jpg)
PARKINSONS
caffeine may have beneficial effect in treatment of Parkinson
up-regulation of adenosine receptors changes adenosine-dopamine proportions
dopamine pathway would be stimulated
theophylline may also achieve similar effect
dopamine pathway has similar mechanism of action to that of Anti-Parkinsonian drugs induces
![Page 37: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/37.jpg)
PARKINSONS
adenosine A2a receptor is found co-localised with the Dopamine D2 receptor
dopamine receptors are known to be obligatory synergistic
adenosine-receptor binding decreases the affinity of the D2 receptors agonists
![Page 38: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/38.jpg)
MÉRCI
![Page 39: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/39.jpg)
KOPITALK
![Page 40: Caffeine and You](https://reader031.vdocuments.us/reader031/viewer/2022021813/58aa7cda1a28abbc1e8b6f6d/html5/thumbnails/40.jpg)