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Why is water the starting point for biochemistry?
Life evolved in water, and all biochemical reactions occur in an aqueous medium
What percent of total body weight is water?
About 60%
Is water just a passive solvent?
No, it actively participates in biochemical reactions
What geometry does water have?
Tetrahedral
What is the H-O-H bond angle in water?
About 104.5 degrees
What type of molecule is water (based on its charge distribution)?
Polar (dipole)
What type of bonds form between water molecules?
Hydrogen bonds
Are ionic compounds soluble in water?
Yes, ionic compounds are soluble in water
Are polar compounds soluble in water?
Yes, polar compounds are soluble in water
Are nonpolar compounds soluble in water?
No, nonpolar compounds are not soluble in water
How does water dissociate?
H2O ⇌ H+ + OH- (or H2O ⇌ H3O+ + OH-)
What are [H+] and [OH-] in pure water?
Both equal 10^-7 M
What is the ionic product of water?
[H+][OH-] = 10^-14 M^2
What is pH?
The measurement of [H+] (or [H3O+]) produced when H2O dissociates; pH = -log[H+]
What is the pH of pure water?
7
What is the physiological pH range?
7.35 - 7.45
What is an acid?
A substance that adds H+ or H3O+ ions to H2O
What is the [H+] or [H3O+] of an acid?
Greater than 10^-7 M
What is the pH of an acid?
pH < 7
What is a base (alkali)?
A substance that adds OH- ions to H2O, or removes H+ or H3O+ ions from H2O
What is the [H+] or [H3O+] of a base?
Less than 10^-7 M
What is the pH of a base?
pH > 7
What is the equation for the acid dissociation constant (Ka)?
Ka = [H+][A-] / [HA]
What is the formula for pKa?
pKa = -log(Ka)
What does pKa measure?
How tightly a molecule holds onto its protons, or how easily it donates them
What does pKa equal in terms of acid dissociation?
The pH at which 50% of the acid is dissociated
What does a lower pKa indicate?
A strong acid or weak base
What does a higher pKa indicate?
A weak acid or strong base
What happens to strong acids and strong bases in water?
They dissociate completely
Give examples of a strong acid and a strong base.
Strong acid: HCl. Strong base: NaOH
What happens to weak acids and weak bases in water?
They dissociate partially
Give examples of a weak acid and a weak base.
Weak acid: CH3COOH. Weak base: NH4OH
Which are more common in biological systems, strong or weak acids/bases?
Weak acids and weak bases
Most drugs are what type of compounds?
Weak acids or weak bases
What does the absorption, distribution, and excretion of a drug depend on?
The drug’s pKa and the pH
What is a buffer?
A weak acid and its conjugate base, or a weak base and its conjugate acid
What does a buffer do?
Resists changes in pH
At what pH does a buffer have maximum buffering capacity?
When pH = pKa
What is the effective buffering range of a buffer?
pKa ± 1 pH unit
What is the main bicarbonate buffer system pair?
H2CO3 / NaHCO3
What pH range does the bicarbonate buffer maintain?
7.35 - 7.45 (physiological pH)
What condition is pH < 7.35?
Acidosis
What condition is pH > 7.45?
Alkalosis
What are 4 pharmaceutical benefits of buffers?
Drug stability, drug solubility, patient comfort and safety, and drug action
How do buffers help drug stability?
They prevent degradation of the drug
How do buffers help drug solubility?
They ensure the drug remains dissolved
How do buffers help patient comfort and safety?
They cause less discomfort for patients
In the Henderson-Hasselbalch equation, what is HA?
The protonated (unionized) form of a weak acid
In the Henderson-Hasselbalch equation, what is A-?
The deprotonated (ionized) form of a weak acid
What is the Henderson-Hasselbalch equation?
pH = pKa + log([A-] / [HA])
What relationship does the Henderson-Hasselbalch equation explain?
The relationship between pH, pKa, and the ratio of ionized (A-) to unionized (HA) forms of a weak acid
What are 3 pharmacy applications of the Henderson-Hasselbalch equation?
Predicting drug ionization (absorption, distribution, excretion), designing buffers, and managing drug overdose