mechanism of all types of interactions which are experienced in routine practice not only in dentistry

3. by definition :
It refers to the modifications to the response to one drug by another when
they are administered in quick session.
• However, interactions may also exist between drugs and foods (drug-
food interactions), as well as drugs and medicinal plants or herbs (
drug-plant interactions).
What is drug interaction?
Factors affection drug interaction:
•Multiple drug treatment
Multiple prescribers
•Genetic make up
•Multiple disease/predisposing illness
•Narrow therapeutic index
•Steep dose-response curve
•Saturable hepatic metabolism
•Multiple pharmacological effect of drug
•Poor patient compliance
•Advancing age of patient
POLYPHARMACY
DRUG DEPENDENT FACTORS

5. Mechanism of drug interaction
There are three mechanisms by which an
interaction can develop:
i. Pharmacokinetic interaction
ii.Pharmacodynamic interaction
iii.Pharmaceutical interaction

6. Pharmacokinetic interaction
(ADME INTERACTION)
• These are the interaction in which ‘ADME’
Properties of the drug altered from the site of
its action.
Absorption or (first pass metabolism)
Distribution
Metabolism (inhibition/induction of
metabolism)
Excreation
the resultant effect is altered plasma concentration of object drug

8. Absorption drug interaction
Absorption of object drug is altered & the net effect is
Faster or slower drug absorption
More,or,less drug absorption
Major mechanism of absorption drug interaction
a) Complexation and adsorption (most common cause)
b) Inhibition of GIT enzymes
c) Malabsorption syndrome
d) Alteration in gut motility (by atropinic drugs)
e) Reduced gut flora (by antibiotics)
f) Alteration in GI ph

9. • These interactions are due to chemical or physical reaction
between drugs or substances result of which is formation of
insoluble complexes or chelates
For example
• This interaction frequently occurs between drugs such as tetracycline or
the fluoroquinolones and dairy products (due to the presence of Ca++
).
• Penicillamine + antacids , food and minerals or supplements containing
Fe Mg Ca etc.
• another possibility is that the drug is retained in the
intestinal lumen forming large complexes that impede its absorption. This
can occur with cholestyramine if it is associated
with sulfamethoxazol, thyroxine, warfarin or digoxin.

10. • Some drugs, such as the prokinetic agents increase
the speed with which a substance passes through the
intestines. If a drug is present in the digestive tract's
absorption zone for less time its blood concentration
will decrease. The opposite will occur with drugs that
decrease intestinal motility.
For example
Prokinetic drugs ( is a type of drug which enhances
gastrointestinal motility )
• Benzamide.
• Cisapride.
• Domperidone.
• Erythromycin.
• Itopride.
• Metoclopramide.
Atopinic drugs
Tricyclic antidepressants
opioids

11. Some drugs can cause local Mucosal damage can decrease absorption of poorly
absorbed drugs e.g. (digoxin, phenytoin)
• Antineoplastic agents inhibit or halt the development of a neoplasm (a tumor)
e.g., cyclophosphamide ,vincristine , procarbazine
Bacterial flora has marked role in metabolization of some drugs
Long term antibiotics may kill normal flora and affect drug absorption
•erythromycin (oral) will increase the level or effect of digoxin (oral) by
suppressing bacteria in the stomach
•Ampicillin, tetracyclin ,cotrimoxazole they reduce the gut flora which normally
deconjugates the ocp steroids secreated in bile as glucorinoids and permits their
enterohepatic circulation
So the decrease in contraceptive level in blood will cause the contraceptive failure

12. Distribution Drug interaction
It is mainly due to the displacement of the drug from its
binding site from plasma protein by another drug
These type of interaction are shown by such
drugs(precipient drug) which are highly bound to plasma
proteins and have a very little amount of volume of
distribution .
The displacing drug should bind to the same site on the plasma protein .
Object drug Percipient drug Influence on object drug
Competitive drug displacement:
ANTICOAGULANTS PHENYLBUTAZONE
CHLORAL HYDRIDE
ed
CLOTTING TIME AND RISK OF
HAEMORRHAGE
TOLBUTAMIDE SULPHONAMIDES ed
HYPOGLYCIMIC EFFECT

14. Metabolism interaction
In these interaction the metabolism of drug (object) is altered.
Mechanism of metabolism interaction
ENZYME INDUCTION: increases the rate of
metabolism and decreases
the bioavailability
ENZYME INHIBITION: decreases the rate of
metabolism of drug and cause
the toxicity of drug.

15. • The liver is the major site of drug metabolism
but other organs can also do e.g.,
WBC,skin,lung, and GIT.
• CYP450 family is the major metabolizing
enzyme in phase I (oxidation process).

17. Object drug Percipient drug Influence on object
drug
Enzyme induction :
CORTICOSTEROIDS, ORAL
CONTRACEPTIVES,
PHENYTOIN
BARBITURATES DECREASED PLASMA
LEVELS; DECREASED
EFFICASY OF OBJECT DRUGS
ORAL CONTRACEPTIVES,
ORAL HYPOGLYCAEMICS
RIFAMICIN DECREASED PLASMA
LEVELS
Enzyme inhibition:
TYRAMINE RICH FOOD MAO INHIBITORS ENHANCED ABSORPTION OF
UN METABOLISED
TYRAMINE.
COUMARINS METRONIDAZOLE
PHENYL BUTAZONE
INCREASED ANTI
COAGULANT ACTIVITY.
ALCOHOL DISULPHIRAM,
METRONIDAZOLE
INCREASED IN PLASMA
ACETALDEHYDE LEVELS
Metabolism interaction

18. Excretion interaction
By definition:- these interaction include the
alteration in excreation pattern of the drug
(object).
Major mechanisms of excretion
interactions are-
• Alteration in renal blood flow
• Alteration of urine PH
• Competition for active secretions
• Forced diuresis

19. Excretion interaction
Object drug Percipient drug Influence on object drug
1.CHANGES IN ACTIVE TUBULAR SECRETION
PENCILLIN,CEPHALOSP
ORINS,NALIDIXIC ACID
PROBENICID ELEVATED PLASMA
LEVELS OF DRUGS
2.CHANGES IN URINE PH
AMPHETAMINE ANTACIDS,THIAZIDESA
CETAZOLAMIDE
INCREASED PASSIVE
REABSORPTION OF
DRUGS.INCRESED RISK Of
TOXICITY
3.CHANGES IN RENAL BLOOD FLOW
LITHIUM
BICARBONATE
NSAIDS DECREASED RENAL
CLEARANCEOF
LITHIUM.RISK OF
TOXICITY

20. Pharmacodynamic interactions:
Such interactions may be direct or indirect.
These are of two types
•1.direct pharmacodynamic interactions.
•2.Indirect pharmacodynamic interactions.

21. DIRECT PHARMACODYNAMIC
INTERACTIONS:
• In which drugs having similar or opposing
pharmacological
• effects are used concurrently.
• The three consequences of direct interactions
are
• 1.Antagonism.
• 2.Addition or summation.
• 3.Synergism or potentiation.

22. Antagonism:
• The interacting drugs have opposing actions
Example: Acetylcholine and noradrenalin have opposing
effects on heart rate.
Addition or summation:
• The interacting drugs have similar actions and the
resultant effect is the sum of individual drug responses
Example : CNS depressants like sedatives and hypnotics,…
etc
Synergism or potentiating:
• It is an enhancement of action of one drug by another
• Example: Ags + beta lactam

23. Indirect pharmacodynamic interaction
• In which both the object and the precipitant
drugs have unrelated effects.but the latter in
Some way alerts the effects of the former
Example: salicylates decrease the ability of the
platelets to aggregate
thus impairing the Homeostasis if warfarin
indused bleeding occurs

24. CONSEQUENCES OF DRUG
INTERACTIONS
• The consequences of drug interactions may
be:
• •Major: Life threatening.
• •Moderate: Detritions of patients status.
• •Minor: Little effect

25. REDUSING THE RISK OF DRUG
INTERACTIONS
• 1.Identify the patients risk factors.
• 2.Take through drug history.
• 3.Be knowledge about the actions of the drugs
being used.
• 4.Consider therapeutic alternatives.
• 5Avoid complex therapeutic regiments when
possible.
• 6.Educate the patient.
• 7.Monitor therapy.

26. INFLUENCE OF SMOKING ON DRUG
INTERACTIONS
• Smoking increases the activity of drug
metabolizing enzymes inducers
• the liver, With the result that certain
therapeutic agents.
• Example: Diazepam, propoxyphene,
theophylline, olanzapine.
• Are metabolized more rapidly,and their effect
is decreased.

27. INFLUENCE OF ALCOHOL ON DRUG
INTERACTION
Chronic use of alcohol beverages may increases the
rate of
•metabolism of drugs such as warfarin and
phenytoin, probably by increasing the activity of
hepatic enzymes.
•Acute use of alcohol by non alcoholic individuals
may cause an inhibition of hepatic enzymes.
•Use of alcoholic beverages with sedatives and
other depressants drugs could result in an excessive
depressant response.

28. INFLUENCE OF FOOD ON DRUG
INTERACTION
Food effects the rate and extent of absorption of drugs from the
• GI tract.
Example: Many anti biotic should be given at least 1hr before or 2hr
• after meals to achieve Optimal absorption.
• The type of food may be important with regard to the absorption of
concurrently administered Drugs.
Example: Dietary items such as milk and other dairy products that
contain calcium may decrease .
• The absorption of tetracycline and flouroquinolone derivatives.
Diet also may influence urinary pH values

29. Reference for more details:
• Stockley’s drug interactions
• Kd tripathi
• Burket’s oral medicines