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Title: Peptic Ulcer Disease
Description: University notes regarding peptic ulcer disease

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Peptic  Ulcer  Disease  
 
An  ulcer  is  diagnosed  when  there  is  a  breach  in  the  continuity  of  the  epithelial  
lining  and  there  is  associated  inflammation
...
   
 
Protective  factors:   -­‐  Mucus  layer  is  hydrophobic
...
 Symptoms  for  PUD  are  similar  to  
those  of  duodenal  ulcer,  gastric  ulcer  and  non  ulcer  dyspepsia
...
 
A  Anaemia  
L  Loss  of  weight  
A  Anorexia  
R  Recent  onset  of  symptoms  
M  Malaena  or  haematemesis  
S  Swallowing  difficulties  
 
Gut  wall  of  the  stomach  
-­‐  The  stomach  is  lines  by  a  single  column  epithelium
...
   
-­‐  depressions  in  the  surface  of  the  gastric  mucosa  are  gastric  pits
...
   
-­‐  Gastric  glands  contain  different  cell  types:  Mucous  neck  cell,  parietal  cell,  chief  
cell  and  enteroendocrine  cell
...
   
-­‐  They  use  a  mechanism  to  secrete  HCl:  
1
...
 
2
...
   
3
...
   
4
...
   
 

The  extrusion  of  H+  ions  into  the  lumen  of  the  gastric  gland  in  exchange  for  K+  
ions
...
   
 
Secretagogues  
-­‐  A  substance  that  allowed  another  substance  to  be  excreted
...
   
 
Gastric  mucosal  injury  
-­‐  Gastric  mucosa  becomes  overwhelmed  by  noxious  substances,  e
...
 hyper  
secretion  of  HCl
...
   
-­‐  Components  of  gastric  juice:  
-­‐  Gastric  acid  is  bactericidal  and  antimicrobial
...
   
-­‐  HCO3-­‐  ions  are  secreted  by  MEC  in  the  corpus  and  antrum:  
• PGE2  stimulates  HCO3-­‐  ions  from  MECs
...
   
• A  pH  of  7  is  maintained  in  the  vicinity  of  the  
apical  membrane
...
 It  acts  as  a  lubricant  
protecting  the  stomach  from  physical  damage  due  to  the  rough  texture  of  food  
being  churned
...
   
 
Restitution  
-­‐  Significant  damage  to  the  mucosa  can  be  repaired  within  minutes  to  hours
...
 
-­‐  Committed  progenitor  cells  differentiate  to  MECs
...
 
 
Proton  pump  inhibitors  mechanism  of  action  
-­‐ Form  disulphide  bonds  with  H+,  K+,  ATPase
...
   
-­‐ Disulfide  bond  is  irreversible
...
 

-­‐
-­‐

Rate  of  reaction  depends  on  the  pKa’s  of  pyridyl  and  benzimidazole  
nitrogen
...
 Electron  releasing  groups  on  pyridinyl  ring  make  it  more  
reactive
...
 
-­‐ Dry  granulation:  typically  mix  powders,  preliminary  compress  using  
rollers  and  large  punches
...
   
 
Tableting  journey  
Mixing  powders  -­‐>  Granulation  -­‐>  Compression  -­‐>  Coating  -­‐>  Packing  
 
Excipients  
-­‐ Other  ingredients  other  than  the  active
...
g
...
g
...
g
...
g
...
g
...
g
...
   
-­‐ Water  uptake  causes  tablet  disintegration,  by  rupturing  the  intraparticles  
cohesive  forces  that  hold  the  tablet  together,  e
...
 starch,  cellulose
...
g
...
 
 
Lubricants  
-­‐ Compression  lubricants  prevent  the  miss  adherence  of  powder  and  
promote  the  smooth  ejection  from  the  die  after  compaction,  e
...
 
magnesium  stearate
...
   
-­‐ Flowability  is  important  during  high  speed  processing
...
g
...
 Helps  with  the  breaking  of  the  tablet
...
   
-­‐ Class  1  –  High  solubility  and  High  permeability  
-­‐ Class  2  –  Low  solubility  and  High  permeability  
-­‐ Class  3  –  High  solubility  and  Low  permeability  
-­‐ Class  4  –  Low  solubility  and  Low  permeability  
 
Implications  for  drug  bioavailability  
-­‐ Class  1  –  dissolve  and  readily  cross  the  mucosa  
-­‐ Class  2  –  Poor  dissolution,  good  absorption  
-­‐ Class  3  –  Dissolve  rapidly,  poor  absorption  
-­‐ Class  4  –  Poor  dissolution,  poorly  permeable  
 
Limitations  of  BCS  
-­‐ Does  not  consider  stability,  formation  and  first  pass  metabolism  
-­‐ Take  arbitrary  limits  
 
Three  pathways  of  gastric  acid  stimulation  
1) The  neurocrine  pathway  which  delivers  transmitters  such  as  
acetylcholine  
2) The  endocrine  pathway  which  released  hormones  such  as  gastrin  

3) The  paracrine  pathway  which  releases  hormones  
 
Gastric  defensive  factors  
-­‐ Mucus  production  
-­‐ Bicarbonate  production  
-­‐ Mucosal  blood  flow  
-­‐ High  epithelial  cell  turnover  
 
Gastric  aggressive  factors  
-­‐ H
...
pylori  tests  
-­‐ Endoscopy  
 
H
...
 
-­‐ Mode  of  acquisition  unidentified
...
   
-­‐ The  organism  is  able  to  burrow  through  the  gastric  mucous  layer
...
 
-­‐ Treatment:  Amoxicillin,  metronidazole,  clarithromycin
...
 
 
H2  receptor  agonists  
-­‐ Mechanism  of  action:  block  the  action  of  histamine  on  the  parietal  cells  of  
the  stomach,  decreasing  the  production  of  gastric  acid
...
 
-­‐ Adverse  effects:  headache,  confusing,  diarrhea,  and  gynaecomastia
...
 
-­‐ Therapeutic  use:  dyspepsia,  PUD,  GORD,  barrretts  oesphagus
...
   
 
Prostaglandin  analogue  
-­‐ Mechanism  of  action:  Inhibits  the  secretion  of  gastric  acid  by  acting  at  the  
parietial  cells
...
 
Increases  mucosal  blood  flow
...
 

 
Treatment  of  NSAID  induced  ulceration  
-­‐ Once  ulcer  developed  discontinue  the  NSAID  and  treat
...
   
-­‐ High  dose  h2  receptor  agonists  may  be  used
...
 Under  highly  
standard  conditions,  298k  and  1  atmosphere  of  pressure
...
   
 
Amperometry  
-­‐ Measurement  based  on  the  detection  of  ions  using  electric  current  
(amperes)  or  change  in  current
...
 
 
Voltammetry  
-­‐ Measurement  based  on  the  securing  information  about  an  analyte  by  
measuring  the  current  as  the  potential  (voltage)
...
 
-­‐ Sample  is  swept  through  the  stationary  phase  (is  eluted)  by  the  mobile  
phase  (eluent)
...
 
-­‐ The  analyte  can  only  move  when  in  the  mobile  phase,  therefore  the  more  
time  in  the  mobile  phase  the  faster  it  moves  through  the  stationary  phase
...
 
 
Glas  liquid  chromatography  
-­‐ Used  for  fairly  volatile  materials
...
   

-­‐
-­‐
-­‐
-­‐
-­‐

The  sample  is  injected  and  vaporized  by  heat,  passes  along  a  column,  
partitioning  continually  by  dissolving  in  the  stationary  phase,  and  
evaporating  into  the  mobile  phase
...
   
The  injection  temperature  should  be  more  than  the  boiling  point  of  
analytes
...
   
Column  temperature:  Column  thermostatted  in  the  oven  is  important  in  
analysis  and  set  to  the  average  boiling  point  of  the  mixture
...
 Ions  carry  current  between  2  electrodes
...
   
-­‐ Electron  capture  detector:  Mobile  phase  is  ionized  and  carried  current  
between  2  electrodes
...
 
-­‐ Mass  spectrometer:  Eluent  enters  mass  spectrometer
...
   
-­‐ Katharometer:  Measures  thermal  conductance
...
 Only  volatiles  are  injected
...
   
-­‐ Thermal  desorption:  Volatiles  collected  in  absorption  tubes
...
   
 
Problems  
-­‐ Acidic  or  basic  compounds  may  show  peaks  with  extensive  tailing
...
   
-­‐ Make  chemical  derivatives  which  are  less  polar  and  more  volatile
...
   
-­‐ Stationary  phase  is  small  particles  packing  into  a  column
...
   
-­‐ Solvent  reservoir  -­‐>  Pump  -­‐>  Injector  -­‐>  Column  -­‐>  Detector  
-­‐ Pump:  Delivers  a  constant  reproducible  pulse  free  flow  against  back  
pressure
...
 Loop  injection  is  usually  used  to  inject  a  sample  with  the  
excess  passing  to  waste
...
   
-­‐ Fixed  wavelength  –  254nm,  as  most  
drugs  have  an  absorption  here
...
   

-­‐
-­‐

-­‐
-­‐

Fluorescence  detectors:  Selective  and  sensitive
...
 
-­‐ Conductance  detectors:  May  be  used  for  ionic  materials
...
 Very  sensitive
...
 
Generally  the  more  polar  the  analyte,  the  longer  the  retention  time
...
   

 
Chromatography  efficiency  
-­‐ Peak  corresponding  to  Gaussian  curve
...
   
-­‐ Resolution:  Figure  that  indicates  how  well  peaks  are  separated
...
 The  resolution  of  peaks  is  defined  in  terms  of  retention  time  
differences  and  peak  widths
...
   
 
Tablets  for  PUD  
-­‐ H2  antagonist  –  Ranitidine  
-­‐ PPI  –  Omeprazole  
 
Particle  size  reduction  
-­‐ Increases  specific  surface  area,  therefore  higher  dissolution  rate  and  
perceived  higher  bioavailability
...
   
-­‐ Methods  of  comminution:  cutter,  runner,  hammer,  vibration,  roller,  ball,  
fluid  energy  and  pin
...
 
-­‐ Energy  applied  during  comminution  concentrates  at  
tip  of  the  crack
...
   
-­‐ Bond  rupture  cascasdes  along  regions  with  the  most  
flaws
...
   
 
Material  properties  
-­‐ Touchness:  Ability  to  absorb  energy  without  fracturing
...
   

-­‐

Surface  hardness:  Ability  to  resist  hardness
...
   

 
Granulation  
-­‐ Granules:  Aggregates  of  powder  particles
...
   
-­‐ Why  granulate?    Particles  aggregate  in  correct  proportion
...
 Improve  
compaction  characteristics
...
 
Usually  volatile  solvent  and  binder
...
   
-­‐ Low  shear  method:  Shear  granulators  
-­‐ High  shear  method:  High  speed  mixer  
-­‐ Fluidised  bed  method:  Lfuidised  bed  
granulator
...
 Liquid  
bridges  form  and  turn  to  solid  bridges  upon  cooling
...
   
-­‐ Intra  granular  bonding:  Adhesion  and  cohesion  in  immobile  films
...
 Attractive  forces  between  solid  particles
...
   
 
Power  granule  compression  
-­‐ Mechanism:    
-­‐ Repositioning  
-­‐ Deformation  
-­‐ Fragmentation  
-­‐ Densification  
-­‐ Attrition  
-­‐ Deformation  of  primary  particles  
 
Tablet  coating  
-­‐ A  process  by  which  an  essential  dry,  outer  layer  of  coating  material  is  
applied  to  the  surface  of  a  dosage  form
...
 Thin  film  of  a  polymer  based  formulation
...
 Confectionary
...
 Thin  sugar  layer  
around  tablet
...
 
Modified  tablet  release
...
   


Title: Peptic Ulcer Disease
Description: University notes regarding peptic ulcer disease