Functional groups, ph, acid/base, absorption Flashcards
MTC wk 2
For acidic drugs to pass through the membrane, what form must they be in?
neutral, unionised pronated form as HA
For basic drugs to pass through the membrane, what form must they be in?
neutral, un-ionised deprotonated form as B
If the pH is 1 unit away from pKa….
10% left
If the pH is 2 units away from pKa….
1% left
For ACIDIC functional groups, if the pH is LESS than pKa.
stays protonated as HA
For ACIDIC functional groups, if the pH is GREATER than pKa….
gets deprotonated (ionised) to A-
For BASIC functional groups, if the pH is LESS than pKa….
gets protonated (ionised) to BH+
For BASIC functional groups, if the pH is GREATER than pKa….
stays deprotonated as B
why will some molecules have more than one pKa?
If they have more than one charged/acidic/basic functional group
why is pH important in biological systems?
Vitally important as biochemical reactions and pathways can only occur/operate in optimal ranges of pH.
what is a buffer?
A solution that resits the change in pH
What buffers are used to regulate the pH of blood?
Bicarbonate, phospate and protien buffers
what is the equation for a bicarbonate buffer?
CO2 + H20 <->H2CO3 + H+
what is the equation for a Phosphate buffer?
H2PO4 + OH –> HPO4 + H2O
What happens if the pH of the surrounding medium is lower/higher than pKa
the functional group will become protonated or deprotonated
How do protein pump inhibitors manipulate pH of biological systems?
shut down stomach acid production and can have an affect on other drugs.
How does acidosis manipulate the pH of biological systems?
lowers blood pH via metabolic and respiratory acidosis.
what is Metabolic acidosis?
increased production of metabolic acids.
what is Respiratory Acidosis?
increase in blood CO2 (hypoventilation)
How does alkalosis manipulate the pH of biological systems?
increases blood pH via metabolic and respiratory alkalosis.
what is Respiratory Alkalosis?
loss of stomach acid from repeated vomiting.
What is Metabolic Alkalosis?
decreased blood CO2 (hyperventilation)
what are examples of drugs that can change the pH of the body and what do they do?
Asprin- lowers pH, and Antacids, increase pH of the stomach.
what is the pH of a full stomach?
2-4
What is the pH of an empty stomach?
1-1.5
What is the pH of the intestine?
8-9
what can happen if take medications with soft drinks?
may have a different effect on body as the pH of the soft drink interacts with the pH of the drug.
What is the pH of plasma?
7.4
Why can the ionisation of functional groups be misleading?
1st hydrophobic group compensates for 1st ionised function group, le chatlliers principle and ion channels,
what functional group usually has the biggest impact on ionisation?
Carboxyl groups.
what happens when ions disfavour absorption?
ions can’t cross non-polar phospholipd bilayer
what happens when ions favour distribution?
ions dissolve easily in blood
what is the impact of the acidic/basic/neutral nature of functional groups on absorption?
Determines where in the body it will be absorbed and how will interact with other drugs (cause potential side effects or make it ineffective)
what is pKa (in terms of biochem)
strength of an acid/base according to the functional group
For ACIDS, a smaller pKa
= stronger Acid
For bases, larger pKa
= stronger base
What are Prodrugs?
inactive compound that is converted into an active drug
what may prodrugs do which is potentially bad?
mask problematic functional groups and cause toxic or ineffective drugs.
What are the applications of prodrugs?
improve absorption, reduce toxicity (if processed correctly), remove bad taste and increase the duration of action.
what is an example of a prodrug?
Salicylic acid- good painkiller but can cause gastric bleeding
what are the two types of competitive inhibitors?
Reversible and irreversible
what is an irreversible inhibitor and an example?
PERMENANT blocking of enzyme forming covalent bonds and changing the lock/key relationship. E.g. treatment for skin cancer that acts as a suicide for uracil and blocks the rapid reproduction of cancer cells.
what is a reversible inhibitor?
TEMPORARY binding of drug through NON-COVALENT bonding.
what is the role of enzyme inhibitors?
block enzymes as the drug interacts with target via functional groups.
What are the acidic side chains?
aspartic acid, glutamic acid, cytesine and trysine
what are the basic side chains?
arginine, hisidine and lysine
if the pH is 3 units away from the pKa what happens?
100% of the molecule is changed
if the pH is less than the pKa in an acidic solution what stays (when says 10% and 1%)
molecule stays protonated as HA
if the pH is GREATER than the pKa in an acidic solution what stays (when says 10% and 1%)
stays deprotonated to A-
if the pH is LESS than the pKa in an BASIC solution what stays (when says 10% and 1%)
protoanted to A-
if the pH is GREATER than the pKa in an BASIC solution what stays (when says 10% and 1%)
stays deprotonated at B
are acids proton donors or acceptors?
donors
what is the impact that of functional groups on drug absorption?
Determines the charge state which impacts the absorption.
When do acidic solutions become ionoised?
When the pH is greater then the pKA so becomes deprotonated
