Drug interaction and chemical delivery system

1. DRUG
INTERACTIONS

2. Definition
• Drug interaction is defined as the pharmacological
activity of one drug is altered by the concominant
use of another drug or by the presence of some
other substance.
• The drug whose activity is effected by such an
interaction is called a "object drug".

3. • Drug interactions are
thus:
Types of drug interactions:
①Drug-drug
interactions.
②Drug-food
interactions.
③Chemical-drug
interactions.
④ Drug-laboratory test
interactions.
⑤ Drug-disease
interactions

4. • Mechanisms of drug
interactions:
Factors contributing to drug interactions:
Multiple drug therapy.
Multiple prescribers.
Multiple pharmacological
effects of drug.
 Multiple disease.
poor patient compliance.
 Advancing age of patient.
Drug-related factors.
a. Pharmaceutical
interactions.
b. Pharmacokinetic
interactions.
c. Pharmacodynamic
interactions.

5. Pharmaceutical Interactions
• It is a physicochemical interaction that occurs when
drugs are mixed.infusions causing precipitation or
inactivation of active substance.
• Example :Ampicilin,chlorpromazine& barbituates
interact with dextran in solutions and are broken
down or form chemical compounds.

6. These are classified as:
1. Absorption
interactions
2. Distribution
interactions
3. Metabolism
interactions
4. Excretion interactions.
Pharmacokinetic Interactions:
"These interactions are
those in which ADME
properties of the object
drug is altered by the
precipitant such
interactions are called
pharmacokinetics or ADME
interactions."
 The resultant effect is
altered plasma
conecntration of the
object drug.

7. Major mechanism of
absroption interactions:
① Complexation and
adsorption.
② Alteration in GI pH.
③ Alteration in gut motility.
④ Inhibition of GI enzymes.
⑤ Alteration of GI micro
flora.
⑥ Malabsorption
syndrome.
Absorption interactions
• Are those where the
absorption of the object
drug is altered.
• The net effect for such
interaction is:
a. Faster or slower drug
absorption.
b. More or less complete
drug absorption.

8. Distribution Interactions
• Are those where the
distribution pattern of
the object drug is
altered.
• The major mechanism
for distribution
interaction is alteration
in protein-drug binding.

9. Metabolism Interactions:
Are those where the metabolism of the object drug is
altered.
Mechanisms of Metabolism interactions include:
1. Enzyme Induction:
increase rate of metabolism.
2. Enzyme inhibition:
decreased rate of metabolism. It is the
significant interaction in comparison to other
interactions and can be fatal.

10. Excretion Interactions:
• Are these where the excretion pattern of the object
drug is altered.
• Major mechanisms of excretion interactions are:
 Alteration in renal blood flow.
 Alteration of urine pH.
Competition for active secretions.
forced diuresis.

11. Pharmacodynamic interactions:
• Are those in which the activity of the object drug in
its site of action is altered by the precipitant.
• There are 2 types of pharmacodynamic
interactions:
1. Direct pharmacodynamic interactions.
2. Indirect pharmacodynamiv interactions.

12. • Atagonism:The interacting
drugs have opposite actions.
eg.noradrenaline have
opposing effect on heart
rate.
• Addition:Drugs have similar
effect. eg.:CNS depressants
like sedatives, hypnotics etc.
• synergism:It is an
enhancement of action of
one drug by another.eg.
alchol enhances analgesic
activity of aspirin.
Direct pharmacodynamic
Interactions:
• In which drugs having
similar or opposing
pharmacological effects
are used.
• The 3 consequences of
direct interactions are:
1. Antagonism.
2. Addition.
3. synergism.

13. • Reducing The Risk of
drug of drug
interaction:
1. Identify the patients risk
factor.
2. Take through drug
history.
3. Be knowledge about the
actions of the drug being
used.
4. Educate the patient.
5. Monitor therapy.
Indirect pharmacodynamic interactions: Both the object
and the precipitant drugs have unrelated effects. eg.salicylate
decrease the ability of the platelate to aggregate.
• Consequence of drug
interactions:
• Major:life threatening.
• Moderate:deteriotion
of patient status.
• Minor:little effect.

14. • Influence of Alcohol on
Interaction:
• chronic use of alcohol may
increase the rate of
metabolism of drug.
• Acute use of Alcohol by non
alcoholic individuals may
cause an inhibition of
hepatic enzyme.
• Influence of food on drug
Interaction :
• Food effect the rate and extent of
the drugs from the GI tract.
eg.Many antibiotics should be given
before 1h or after 2hrs to achieve the
optimal absorption.
• The type of food may be important.
eg.Dietary items such as milk contain
Ca may decrese absorption.
Influence of smoking on drug interaction:
smoking increases the activity of drug metabolizing enzyme in the
liver.eg. Diazepam are metabolized more rapidly and their effect is
decreased.

15. CHEMICAL DELIVERY SYSTEM

16. • Definition:
pharmacologically inactive molcules that require
several steps of chemical and enzymatic conversion
to the active drug and enhance drug delivery to
particular organs or sites.
eg.Brain-specific chemical delivery system.
Chemical delivery systems are utilized for sustained
drug delivery as well as site specific target delivery.
Types: Two main classes are represented by:
1.The enzymatic physicochemical-based CDSs
2.The site specific enzyme-activated CDSs

17. • It also involves incorportion of some groups in the
structure of the active molecule so as to deactivate
or detoxify tthe drug subsequent to exerting its
biological factors.
• It allows targeting of molecules to specific target
sites or organs based on predictable enzymatic
activation "
• chemical approach represents a novel, systematic
method to design safe localized delivery of drug
compounds.

19. • Limitations:
• Hard to justify the
pharmacokinetics to the
intermediate along with
the active and inactive
metabolites.
• Ezymatic modification may
effect the pharmacological
action.
• Reduction in dose due to effective
targeting.
• longer duration of time (sustain
release.)
• Improved therapeutic Index.
• prodrug readily transported to the
site of action.
• prodrug is rapidly absorped at the
site.
• selective and rapid conversation to
the active drug.
Advantage:

20. Applications:
• CDS on brain:
Dihydropridine pyridiniam type redox system was
developed for brain specific sustain delivery of drug.The
drug containing amine group is made lipophilic by coupling
to dihydropyridine promoiety that facilitate the penetration
of pro drrug through the BBB.In CNS dihydropridine group
oxidize to polar pyridinium salt and becomes poorly
permeates to BBB and causes retention at the site and
cleavage provides sustain release for action.
• CDS on lung:
In case of beta -2 stimulant, esterification of catechol
function to improve lung uptake of Improve lipophilic drug
that undergoes cleavage by lung esterage to release active
parent molecule.

21. • Treatment of
glaucoma:propanolol is
converted into prodrug
propranolol oxime.On
application to the eye it
undergoes hydrolysis to
give propranol one
followed by reduction to
give propranolol.
• CDS on colon:
sulphasalazine is a
example of colon
specific CDS.It is
synthesized by coupling
diazotized 2-
sulphanilamide pyridine
and 5-amino salicylic
acid,after reaching the
colon, the pro drug is
cleaved into active 5-
amino salicylic acid by
azo reductase associated
with colonic
microflora.This enables
the selective delivery of
5-amino salicylic acid to
colon.

22. • CDS on kidney:
kidney possess high
concentration of L-glutamyl
transpeptidase and L-
amino acid decarboxydase
enzymes These enzymes
are used to provide
selective delivery of
dopamine to kidney in the
form of its prodrug L-
glutamyl dopa.The prodrug
is first cleaved by L-
glutamyl transpeptidase
producing L-dopa, which is
converted to dopamine by
L-amino acid carboxylase.
This leads to selective
delivery of drug to kidney
resulting in renal
vasodilation avoiding
systemic hypotension.
• Recent therapy:
new therapies have been
proposed which attempt
the localization of prodrug
activation enzyme specific
cancer cells prior to
prodrug administration.
These new approaches are:
1.Antibody directed
enzyme prodrug therapy.
2.Gene directed enzyme
pro drug therapy.

23. Thank you.