Transcript File - Riske Science

Lesson 6 pH Regulation in the
Stomach
Tuesday, March 15, 2016
Understandings
• Non-specific reactions, such as the use of
antacids, are those that work to reduce the
excess stomach acid.
• Active metabolites are the active forms of a
drug after it has been processed by the body.
Applications
• Explanation of how excess acidity in the stomach can be
reduced by the use of different bases.
• Construction and balancing of equations for neutralization
reactions and the stoichiometric application of these
equations.
• Solving buffer problems using the Henderson–Hasselbalch
equation.
• Explanation of how compounds such as ranitidine (Zantac)
can be used to inhibit stomach acid production.
• Explanation of how compounds like omeprazole (Prilosec)
and esomeprazole (Nexium) can be used to suppress acid
secretion in the stomach.
Your Gut
• The gastro-intestinal tract, or gut, generates
and maintains different pH environments
along its length, which play an important role
in controlling the activity of digestive
enzymes.
Why so acidic?
• Normally the pH in the stomach is between 1 and 2,
owing to the production of hydrochloric acid by the
millions of parietal cells that line the stomach. The
stomach is maintained at such a low pH for two main
reasons:
– the acidic environment is not tolerated by the majority of
microorganisms (e.g. bacteria) that may enter the digestive
system with food – the low pH plays a role in the body’s
natural defense against disease-causing microorganisms
– the digestive enzymes in the stomach (e.g. pepsin, which
breaks down proteins) require a low pH for optimum
catalytic activity.
When It Goes Wrong
• However, some factors, such as excess alcohol, smoking,
caffeine, stress, and some anti-inflammatory drugs, can
cause excess production of this acidic secretion, known as
gastric juice. This can lead to the following problems:
– acid indigestion – feeling of discomfort from too much acid in
the stomach
– heartburn – acid from the stomach rising into the esophagus
(often called acid reflux)
– ulceration – damage to the lining of the gut wall, resulting in
loss of tissue and inflammation.
• The term dyspepsia is used to refer to feelings of pain and
discomfort in the upper abdomen, which include
indigestion and heartburn.
Removing The Cause
• In some cases, the first line of defense is to try
to remove the cause; eating less, avoiding
spicy foods, avoiding alcohol, reducing stress
and reducing BMI
• In some cases (for example, when you are
teaching or taking IB Chemistry HL) you
cannot remove all the stressors that cause
indigestion and acid reflux. What to do?
Antacids
• Antacids are used to treat these conditions. They are
weakly basic compounds that neutralize acids, relieving the
pain, discomfort or burning sensation and allowing repair
of the mucous layer. In the case of peptic ulcers,
neutralization of the acid prevents further erosion of the
gut lining allowing ulcers to heal.
• The most commonly used antacids are metal hydroxides,
carbonates and hydrogencarbonates (bicarbonates):
1.
2.
3.
4.
magnesium hydroxide
aluminium hydroxide
calcium carbonate
sodium hydrogencarbonate (also called sodium bicarbonate).
Mix Of Salts
• Some antacid preparations contain mixtures of
two different antacids, such as magnesium
compounds and aluminum compounds (usually
magnesium and aluminum hydroxides).The
rationale for using these two different antacids is
that magnesium salts are faster acting and so
work quickly to neutralize the acid, but aluminum
salts have a slower and more prolonged effect, so
the time interval between doses is increased.
Also, magnesium salts in repeated doses can
cause a laxative effect, but this is o set by
aluminum salts which can induce constipation.
Equations
• calcium hydroxide,
– Ca(OH)2(aq) + 2HCl(aq) → CaCl2(aq) + 2H2O(l)
• magnesium hydroxide
– Mg(OH)2(aq) + 2HCl(aq) → MgCl2(aq) + 2H2O(l)
• aluminum hydroxide
– Al(OH)3(aq) + 3HCl(aq) → AlCl3(aq) + 3H2O(l)
• sodium hydrogencarbonate
– NaHCO3(aq) + HCl(aq) → NaCl(aq) + H2O(l) + CO2(g)
• sodium carbonate
– Na2CO3(aq) + 2HCl(aq) → 2NaCl(aq) + H2O(l) + CO2(g)
Gas can cause flatulence!!
Side Effects
• The gas released can cause bloating of the stomach
and flatulence. To reduce this side-effect, antifoaming
agents are often added to the formulation
(dimethicone).
• Some antacids also contain alginates which oat to the
top of the stomach, forming a ‘raft’ which acts as a
barrier preventing reflux into the esophagus.
• Note that because antacids change the pH of the
stomach, they can alter other chemical reactions,
including the absorption of other drugs. Although they
are over-the-counter drugs, they should not be taken
for an extended period without medical supervision.
Why not strong bases like NaOH?
• You’d cause harm to your stomach!
H2 Receptor Antagonists
• The body is equipped with complex
mechanisms to protect it from the self-harm
that could result from uncontrolled release of
stomach acid. Together these mechanisms
ensure that gastric juice is released only when
required – stimulated by the presence of food
and distension (stretching) of the stomach
walls. Several transmitters and chemical
messengers called hormones are involved, and
of these histamine is of specific interest.
Histamine
Histamine
• Histamine has different functions in the body and several
different receptor sites. In the stomach it stimulates
secretion of stomach acid by interacting at receptors known
as H2 (not to be confused with hydrogen gas!) in the
parietal cells in the gastric glands.
• This histamine interaction initiates a sequence of events,
leading to the release of acid into the stomach lumen. This
suggests that a possible target for a drug which will reduce
stomach acid secretion would be to block the histamine–H2
interaction. Drugs which do this and which compete with
histamine for binding at the H2 receptors are known as H2receptor antagonists.
•
Zantac
(Ranitidine)
Ranitidine (Zantac) is an example of an H2receptor antagonist drug. It was developed from
analogues of histamine using knowledge of the
H2-receptor structure, and refined from earlier
drugs to increase its potency. In many countries it
is now available as an over-the-counter drug, but
higher dosages need prescription.
Video
• https://www.youtube.com/watch?v=jstP3IZGL
sc&feature=youtu.be
Proton Pump Inhibitors (PPIs)
• In the last step of gastric acid secretion, the parietal
cells in the gastric glands pump protons (H+) across
their membranes and into the lumen of the stomach.
• For each H+ ion pumped into the lumen, one K+ ion is
pumped in the opposite direction so there is no charge
build-up.
• Movement of the ions occurs against their
concentration gradients and so requires energy. This is
provided by the hydrolysis of an energy carrier known
as ATP, using the enzyme ATPase which is embedded in
the cell membrane. The enzyme is therefore known as
the H+/K+ ATPase or simply as a gastric proton pump.
Video
• https://www.youtube.com/watch?v=Y2xCZkS9
l_c&feature=youtu.be
Omeprazole
• Got me through my first two years of
teaching!
• The first proton pump inhibitor was
omeprazole, marketed as Prilosec, which was
followed by the release of esomeprazole or
Nexium when the patent for Prilosec expired
in 2001.
Prilosec
Nexium
Summary
Let’s Practice
• Compare the volume of stomach acid
(hydrochloric acid) of pH 1.50 that is
neutralised by taking one indigestion tablet
containing 1.00 g of calcium carbonate with
one containing 1.00 g of sodium
hydrogencarbonate.
Let’s Practice
• Work out the volume of hydrochloric acid of
pH 2.00 that reacts with:
a 1.00g of aluminum hydroxide
b 1.00g of magnesium hydroxide
Active Metabolites
• Active metabolites are the active forms of drugs after they
have been processed in the body.
• We have already seen examples of drugs that are converted
into a different form in the body – the form that causes the
desired action of the drug.
– codeine is converted into morphine in the body and it is the
morphine that binds much more strongly to the opioid
receptors than codeine, producing an analgesic e ect
– omeprazole/esomeprazole are converted into di erent forms
that are able to bind to proton pumps
– aspirin is converted into the active form – salicylic acid. Salicylic
acid cannot be taken orally because it causes severe irritation of
the stomach lining, resulting in vomiting and gastric bleeding.
Therefore it is taken in ester form; this causes much less gastric
irritation but is converted back into the active analgesic in the
body.
Reasons
• There are many reasons for making a drug in a
different form to that of the active metabolite and
these include:
1. to avoid side effects – e.g. aspirin
2. to allow the drug to pass through cell membranes – the
active form of omeprazole is charged and would not pass
through the cell membrane into the parietal cells;
diamorphine is another drug that fits into this category
3. to allow the drug to dissolve in water more easily – e.g.
fosphenytoin
4. to target drugs to a particular area – for example,
omeprazole again, where the active drug is formed only
in the highly acidic conditions of the cells in the stomach
lining.
Lesson 7: Buffers Revisited
Wednesday, March 16, 2016
Buffers
• A buffer solution is one that resists changes in
pH when small amounts of acid or alkali are
added.
• Biological systems are very sensitive to
changes in pH. This is why complex buffering
systems exist in cells that help to prevent
major fluctuations in the pH.
• REFER BACK TO ACID/BASE if you do not
remember buffers!
Buffer Calculations
• On Paper 2, you must write out an equilibrium
equation to solve for buffers
• On Paper 3, you can make the following
assumptions:
– The dissociation of the weak acid is so small that it
can be considered to be negligible.
– The salt is considered to be fully dissociated into
its ions.
• From this we can derive the HendersonHasselbalch equation to make these problems
Henderson-Hasselbalch
• These equations, known as the Henderson–
Hasselbalch equations, are given in section 1
of the IB data booklet. The beauty of these
expressions is that they enable us to know the
pH of a buffer solution directly from the
following:
– the Ka or Kb values of its component acid or base
and
– the ratio of initial concentrations of acid and salt
used to prepare the buffer.
Let’s Practice
• Calculate the pH of a buffer solution at 298 K,
prepared by mixing 25 cm3 of
0.10 mol dm–3 ethanoic acid (CH3COOH) with
25 cm3 of 0.10 cm3 sodium ethanoate
(Na+CH3COO–). Ka of CH3COOH = 1.8 × 10–5 at
298 K.
Let’s Practice
• How would you prepare a buffer solution of
pH 3.75 starting with methanoic acid (HCOOH)
and NaOH?
Let’s Practice
• How much 0.10 mol dm–3 butanoic acid
solution and solid potassium butanoate
should be used to make 1.00 dm3 of pH 5.00
buffer solution? State the assumptions made
in the calculation.
More Problems
• A student wants to make up a bu er solution
of pH 7.7 using 0.100 mol dm−3 solutions of
HEPES (pKa = 7.5) and its sodium salt.
Calculate how much of each solution must be
used to make 500 cm3 of a buffer of pH 7.7
• Therefore the volume of the HEPES solution
required is 194 cm3 and that of the solution of
its sodium salt
is 306 cm3.
More Problems
• What mass of solid sodium ethanoate must be
added to 100.0 cm3 of 0.200 mol dm−3
ethanoic acid to produce a bu er solution of
pH 4.00? Assume there is no change in
volume when the sodium ethanoate is
added.The pKa for ethanoic acid is 4.76.
• 0.285 g of sodium ethanoate must be
dissolved in the ethanoic acid to produce a bu
er solution of pH = 4.00.
13 H2-receptor antagonists: block the binding
of histamine, which prevents the reactions
leading to stomach acid secretion. Proton-pump
inhibitors: directly prevent the release of acid
into the stomach lumen.