Dr\ Adel Albattah

When two or more drugs are given at the same time, they may
exert their effects independently or they may interact.

Interactions said to occur when the effects of one drug are

changed by the presence of another drug, herbal medicine, food
or drink.
The outcome:
a-)Can causes an increase in the toxicity of some drugs
(harmful).
For example:
-MAOIs + tyramine-rich foods( e.g., cheese) hypertensive
crisis.

b-) Can causes reduction in efficacy of some drugs (harmful).

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Drug- food interactions:
Some foods and beverages can interact with drugs.
They can interact in several ways:
i) Food and drink can bind up some drugs in the gut and
decrease absorption.

To avoid this with drugs known to interact with food, don’t eat at
least a 1-2 hours after taking the drug, or vice-versa.

ii)Drug-Food interaction can occurs with certain types of food or

drink after absorption both the drug and food, the food can
change the rate at which the body eliminate the drug.

To avoid this type of interaction, the specific type of food or drink

not be taken.
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Some examples of food or drink that may interact with
drugs:
• Milk: Can bind up some drugs in the gut.
e.g., Tetracycline & Fluoroqinolones.

• Grapefruit juice: Can slow down the rate at which drugs

are
eliminated from the body.
e.g., Nifedipine

• Vitamins and minerals: Different ones can bind drugs in the

gut, can
cancel out drug effects, or can add to drug effects.
e.g., Vitamin K + Warfarin, Vitamin K will promote formation of
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 Types of drug-drug
interactions

a)Pharmaceutical interactions:
Interactions that occur before or prior to administration of drugs.

These interactions are called in vitro interactions or

incompatibility.

For example:
Incompatibility between two or more drugs mixed in an IV fluids.

These interactions may be:

-Physical interactions (with a visible signs) or
-Chemical
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Dr\ Adel(with
Albattah no visible signs).
b)Pharmacokinetics interactions
1-Drug absorption interactions:
I-Decease absorption rate:

a)For drugs that are given long-term, in multiple doses, the rate
of absorption is usually unimportant, provided the total amount of
drug absorbed is not markedly altered.
e.g.,
-Antacids + ketoconazole…… decrease the dissolution and
absorption

-GIT absorption is slowed by drugs that delayed gastric

emptying, such as atropine, propantheline or opiates, or
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accelerated by drugs (e.g. metoclopramide) which hasten gastric
b)For drugs that are given as single doses, intended to be
absorbed rapidly ( hypnotics or analgesics), where a rapidly
achieved high concentration is needed, a reduction in the rate of
absorption may result in failure to achieve an adequate effect.

II-Decease the total amount absorbed:

This type decrease the drug efficacy.

e.g.,

-Antiacid + Ciprofloxacin …………….Reduce absorption

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2-Drug distribution interactions:
Depending on the concentrations and their relative affinities for
the binding sites, one drug may successfully compete with
another and displace it from the sites it is already occupying,
thereby increasing its proportion free to diffuse from plasma to its
site of action.

This only produces a detectable increase in effect if it is an

extensively bound drug (more than 90%) that is not widely
distributed throughout the body.
Examples:

Sulfonamides displace warfarin from binding sites on plasma

proteins
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3- Drug metabolism Interactions:
In all cases the possibility of an interaction must be considered if
toxic
effects occur or if the activity of a drug diminishes.

a-Enzyme induction:
Example:

2-Phenytoin+ theophylline metabolism of

theophylline and decrease its level & reduce its action.

The induction is most commonly in phase-I oxidation

mediated by cytochrome P450 iso-enzymes.
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b-Enzyme inhibition:
Inhibition of the enzyme may be due to the competition on its
binding sites.

Examples:
amiodarone, chloramphenicol, cimetidine, ciprofloxacin ,
erythromycin, Omeprazole ….etc.

Ex: Erythromycin inhibit metabolism of astemazole and

terfenadine

Ex: Omeprazole inhibit metabolism of Diazepam

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4-Drug excretion interactions:
Drugs are eliminated through the kidney both by glomerular
filtration and by active tubular secretion.

Competition occurs between those which share active transport

mechanisms in the proximal tubule.
Ex:
-Probencid + penicillin's Decrease tubular
secretion of penicillin's

-Salicylates + methotrexate Decrease tubular

secretion of
methotrexate
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C-Pharmacodynamics interactions:
These are interactions between drugs which have similar or
antagonistic pharmacological effects or side effects.

They may be due to competition at receptor sites, or occur

between drugs acting on the same physiological system.

They are usually predictable from a knowledge of the

pharmacology of the interacting drugs; in general, those
demonstrated with one drug are likely to occur with related
drugs.

They occur to a greater or lesser extent in most patients who

receive the
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interacting drugs.
Ex:
i-Aspirin + Paracetamol analgesic effect

ii-Benzodiazepines + Antihistamines CNS depression

iii-Morphine + Naloxone toxicity

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The consequence of drug interaction may be:
Major: life threatning
Moderate: deterioration of the patient status
Minor: little effects

The guidelines to reduce and manage drug interactions are:

1-Identify patient risk factors such as : Age, medical
problems(e.g. impaired renal functions), dietary habits and
smoking.
2-Patient history and maintain complete patient record.
3-Knewledge about pharmacological actions of drugs
4-Considered therapeutic alternatives
5-Avoid complex therapeutic regimens if possible
6-Educate the patient to comply with instructions for
administrating medications.
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Relative importance of interactions
Many drug interactions are harmless and many of those which
are potentially harmful only occur in a small proportion of
patients; moreover, the severity of an interaction varies from one
patient to another.

Drugs with a small therapeutic ratio (e.g. phenytoin) and those

which require careful control of dosage (e.g. anticoagulants,
antihypertensives, and antidiabetics) are most often involved.

Patients at increased risk from drug interactions include the

elderly and those with impaired renal or liver function.

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Common drug interactions that could have serious
consequences are identifed within the guidance and include:
• interaction of non-steroidal anti-inflammatory drugs
(NSAIDs), carbamazapine, azole antifungals, metronidazole
and macrolide antibiotics with warfarin.
• incidence of myopathy after prescribing azoles and
clarithromycin in those taking statins.
• asthma symptoms exacerbated following the use of
NSAIDs.
It is important that dentists are aware of potential drug
interactions. Note that antibiotics which do not induce
liver enzymes are no longer thought to reduce the
effcacy of combined oral contraceptives.
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Identifying potential drug interactions that may occur between
drugs prescribed in dental practice and the patient’s current
medication is increasingly important.
Not all drug interactions have serious consequences. However it
is important that dentists are aware of potentially harmful
interactions when prescribing.
The most frequent interactions and side effects observed with
drugs commonly prescribed in dentistry are:
• interactions of non-steroidal anti-inflammatory drugs (NSAIDs),
carbamazapine, azole antifungals and antibiotics with warfarin;
• incidence of myopathy after prescribing azoles and
clarithromycin in those taking statins;
• asthma symptoms exacerbated following the use of NSAIDs.
Drug interactions can be minimised by ensuring that the patient’s
medical history, including information on current medication, is
up to date and by using alternative drugs where indicated.
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The most common potential drug interactions likely to be encountered
when prescribing in dental practice.

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