[5] Biotrans 2.5 - 4 Flashcards
PECULIARITY ON METABOLIZING DRUGS
Maybe metabolized by gastric fluid
Must be given 2 hours before meals if given
through the oral route
PENICILLIN
Lower bioavailability
Must be given 2 hours before
meals so that the gastric acids
cannot degrade it
PECULIARITY ON METABOLIZING DRUGS
Cannot be given in the
oral route as it will be
degraded down as amino
acids
Should be given
subcutaneously
Insulin
Short half life; you need to
give it 30 minutes prior to
the intake to mimic the
natural secretion of
insulin
PECULIARITY ON METABOLIZING DRUGS
Intestinal wall enzymes:
Especially for those who have cardiac arrests to stimulate pumping of the heart
Given intravascular/
intravenously
Epinephrine
Most important organ for drug metabolism
Smooth endoplasmic reticulum (SER) contains high
concentration of PHASE I enzymes
LIVER
PHASE I enzymes: Activity of these enzymes require…
NADPH (reducing agent)
- REdox reactions
Molecular form of oxygen
- Final electron acceptor
That’s why the liver is bombarded
with many reactive oxygen species
and will try to
regenerate/neutralize them
DETERMINANTS OF BIOTRANSFORMATION RATE
(3) GENETIC FACTORS:
- HYDROLYSIS OF ESTERS
- ACETYLATION OF AMINES - SLOW ACETYLATORS
- OXIDATION
DETERMINANTS OF BIOTRANSFORMATION RATE
GENETIC FACTORS: In most individuals, the process occurs rapidly. Some individuals cannot hydrolyze esters properly
HYDROLYSIS OF ESTERS
Duration of action is 5 minutes
DETERMINANTS OF BIOTRANSFORMATION RATE
GENETIC FACTORS: Succinylcholine. Ester that is metabolized by plasma cholinesterase
Plasma cholinesterase has high metabolizing activity Trivia: plasma cholinesterase = same nzyme that degrades acetylcholine
HYDROLYSIS OF ESTERS
ACETYLATION OF AMINES - SLOW ACETYLATORS
T/F: If you are a slow acetylator, you are prone to hepatotoxicity when given such drug
True
Not a problem in Filipinos because we are
fast acetylators compared to other
individuals
DETERMINANTS OF BIOTRANSFORMATION RATE
GENETIC FACTORS: Isoniazid (INH) - (Anti TB drug) .Amines such as hydralazine, and procaina
Individuals deficient in acetylating capacity
ACETYLATION OF AMINES - SLOW ACETYLATORS
○ If you have high levels of this drug in your system, it can produce toxic effects
○ Quite hepatotoxic
DETERMINANTS OF BIOTRANSFORMATION RATE
GENETIC FACTORS: Dextromethorphan, metoprolol and some tricyclic
antidepressants
Some are dependent on enzyme activity present in
the body
OXIDATION
Oxidation by P450 isoenzymes are genetically
predetermined
DETERMINANTS OF BIOTRANSFORMATION RATE
(2) INDIVIDUAL DIFFERENCES
Diet and environmental factors
Age and sex
DETERMINANTS OF BIOTRANSFORMATION RATE
INDIVIDUAL DIFFERENCES: Grapefruit juice increases the amount of
drug in the body
Some food supplements include
grapefruit juice which would
increase the amount of drug in the
body
Diet and environmental factors
DETERMINANTS OF BIOTRANSFORMATION RATE
INDIVIDUAL DIFFERENCES: Charcoal inhibits the effect of the drug
- Activated charcoal used to neutralize poisoning
- Inhibition would require a higher
dose to achieve its effect
Diet and environmental factors
DETERMINANTS OF BIOTRANSFORMATION RATE
INDIVIDUAL DIFFERENCES: Drug metabolites differ in young and old
In the extreme of ages, the very young and very old, metabolize the drug slower than that of a normal
adult
● Age and sex
It is susceptible for children and
elderly to have adverse effects
because these drugs are tested on
normal adults.
DISEASE AFFECTING DRUG MECHANISM
hormone increases the metabolism
which increases the drug metabolism.
● Hyperthyroidism
Thyroid hormone
When a drug is tagged as an enzyme inducer, it
means that it will increase the rate of synthesis of the metabolizing enzyme that degrades the drug.
- ENZYME INDUCTION
- ENZYME INHIBITION
- ENZYME INDUCTION
Increase rate of synthesis of the enzyme
- ENZYME INDUCTION
- ENZYME INHIBITION
ENZYME INDUCTION
Reduce the rate of degradation of the enzyme
- ENZYME INDUCTION
- ENZYME INHIBITION
○ May also induce self metabolism of the drug
○ May also induce metabolism of other drugs and reduce its effect
- ENZYME INDUCTION
○ Phenobarbital
○ Carbamazepine + drug = decreased effects
○ Phenytoin
○ Rifampicin
- ENZYME INDUCTION
- ENZYME INHIBITION
- ENZYME INDUCTION
Inhibit CP450
- ENZYME INDUCTION
- ENZYME INHIBITION
- ENZYME INHIBITION
Metabolism of the drug is diminished
- ENZYME INDUCTION
- ENZYME INHIBITION
ENZYME INHIBITION
Increase effect of the drug
- ENZYME INDUCTION
- ENZYME INHIBITION
- ENZYME INHIBITION
Enzyme inhibitors of ENZYME INHIBITION
ACKRF
○ Amiodarone
○ Cimetidine
○ Ketoconazole + drug = increased effect
○ Ritonavir
○ Furanocoumarin
4 TYPES OF DRUG INTERACTION MECHANISM
Altered absorption
Altered metabolism
Altered plasma binding protein
Altered excretion
TYPES OF DRUG INTERACTION MECHANISM
Cholestyramine inhibits the effect digoxin
when combined with it
- Altered absorption
- Altered metabolism
- Altered plasma binding protein
- Altered excretion
Since they are intestinal binders,
they will decrease the absorption
of the digoxin
Altered absorption
TYPES OF DRUG INTERACTION MECHANISM
Affects drug action
- Altered absorption
- Altered metabolism
- Altered plasma binding protein
- Altered excretion
Either through enzyme induction or enzyme inhibition
Altered metabolism
TYPES OF DRUG INTERACTION MECHANISM
Plasma proteins combined with drugs with
high plasma protein binding, the plasma
proteins can actually diminish the amount
of drug that reaches the receptors.
- Altered absorption
- Altered metabolism
- Altered plasma binding protein
- Altered excretion
They will compete.
Whichever has the highest protein binding
will be the one to stick, thus it will increase
the concentration of the other drug
Plasma proteins combined with drugs with
TYPES OF DRUG INTERACTION MECHANISM
Probenecid inhibits the secretion of weak
acids
- Altered absorption
- Altered metabolism
- Altered plasma binding protein
- Altered excretion
Altered excretion
TYPES OF DRUG INTERACTION MECHANISM
Penicillin inhibits the excretion of
probenecid
- Altered absorption
- Altered metabolism
- Altered plasma binding protein
- Altered excretion
Altered excretion
(4) DRUG INTERACTION
ADDITIVE (=)
SYNERGISTIC (>)
POTENTIATION (enhances)
ANTAGONISM (inhibits)
DRUG INTERACTION
1 + 1 = 2
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
In an arcade, this would be a double hit
ADDITIVE (=)
DRUG INTERACTION
Response elicited by combined drugs is equal to the combined response of the individual drugs
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
ADDITIVE (=)
DRUG INTERACTION
Combining drugs with similar effects would have the combined effect of the two drugs
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
ADDITIVE (=)
Sedative + alcohol
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
For example, drinking a sedative like
phenylpropanolamine with alcohol would
increase the sleepiness effect (you’ll fall
asleep faster)
ADDITIVE (=)
DRUG INTERACTION
1 + 1 = 3
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
Like a combo hit of a power-up
SYNERGISTIC (>)
DRUG INTERACTION
Response elicited by combined drugs is greater than the combined responses of each individual
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
Combining the two drugs would make it more effective
SYNERGISTIC (>)
It is not just an added effect, but synergistic
DRUG INTERACTION
Penicillin G removes the cell wall
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
Gentamicin inhibits production of protein
Individually, each drug could kill the
bacteria, but it would take longer
SYNERGISTIC (>)
0 + 1 = 2
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
- POTENTIATION (enhances)
Drug which has no effect enhances the effect of the second drug
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
POTENTIATION (enhances)
Cimetidine + anticoagulant (enhances the
anticoagulation)
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
Cimetidine has no anticoagulant
properties, but when combined with an
anticoagulant, the enzyme inhibiting
mechanism of cimetidine will inhibit the
metabolizing enzyme for the anticoagulant,
thus increasing the anticoagulant effect
POTENTIATION (enhances)
1 + 1 = 0
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
Combining the two cancels the effect of
one another
- ANTAGONISM (inhibits)
Drug inhibits the effect of another drug
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
ANTAGONISM (inhibits)
Heparin + protamine
- ADDITIVE (=)
- SYNERGISTIC (>)
- POTENTIATION (enhances)
- ANTAGONISM (inhibits)
○ Heparin is an anticoagulant,
○ Protamine is a procoagulant
ANTAGONISM (inhibits)
process of creating new medicines that can treat
or prevent diseases
DRUG DEVELOPMENT
