Download - Drug Interaction Baru
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Drug interaction Drug interaction can be defined as the
modifications of the effects of one drug by the prior
or concomitant of another drug (poly-pharmacy) 6.5% of adverse drug reactions in USA were
attributed to drug interactions (0.2% of these
patients may have life-treatening interactions) The potential drug interactions has been
observed to be 17% in surgical patients, 22% in
patients in medical wards, 23% in out patients
clinics.
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Outcomes of drug interactions
1) Loss of therapeutic effect
2) Toxicity
3) Unexpected increase in pharmacologicalactivity
4) Beneficial effects e.g additive &
potentiation (intended) or antagonism
(unintended).
5) Chemical or physical interaction e.g I.V
incompatibility in fluid or syringes mixture
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Mechanisms of drug interactions
Pharmacokinetics Pharmacodynamics
Pharmacokiniticsinvolve the effect of a drug on another fromthe point of view that includes absorption ,distribution , metabolism
and excretion.
Pharmacodynamicsare related to the pharmacological activityof the interacting drugs
e.g synergism.antagonism, altered cellular transport, effect
on the receptor site.
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Pharmacokinetic interactions
1) Altered GIT absorption.
Altered pH, Altered bacterial flora, formation of drug
chelates or complexes, drug induced mucosal damage
and altered GIT motility.
a) Altered pH;
The non-ionized form of a drug is more lipid
soluble and more readily absorbed from
GIT than the ionized form does.
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Decreasethe tablet dissolution
ofKetoconazole (acidic)Ex2., H2 antagonists pH
Therefore, these drugs must be separated by at least 2h
in the time of administration of both .
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b)Altered intestinal bacterial flora ;
EX., In 10% 0f patients receive digoxin..40% or more
of the administered dose is metabolized by the intestinal flora
Antibiotics kill a large number of the normal
flora of the intestine
Increase digoxin conc.
and increase its toxicity
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c) Complexation or chelation;
EX1., Tetracycline interacts with iron preparations
or
Milk (Ca
2+
) Unabsorpable complex
Ex2., Antacid (aluminum or magnesium) hydroxide
Decrease absorption of
ciprofloxacin by 85%
due to chelation
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d) Drug-induced mucosal damage.
Antineoplastic agents e.g., cyclophosphamide
vincristineprocarbazine
Inhibit absorption
of several drugs
eg., digoxin
e) Altered motility
Metoclopramide (antiemitic)
Increase absorption of cyclosporine due
to the increase of stomach empting time
Increase the toxicity
of cyclosporine
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f) Displaced protein binding
It depends on the affinity of the drug to plasma protein.
The most likely bound drugs is capable to displace others.
The free drug is increased by displacement by another drug
with higher affinity.
Phenytoin is a highly bound to plasma protein (90%),Tolbutamide (96%), and warfarin (99%)
Drugs that displace these agents are
Aspirin, Sulfonamides, phenylbutazone
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g) Altered metabolism
The effect of one drug on the metabolism of the
other is well documented. The liver is the major site of drugmetabolism but other organs can also do e.g., WBC,skin,lung,
and GIT.
CYP450 family is the major metabolizing enzymein phase I (oxidation process).
Therefore, the effect of drugs on the rate of metabolism
of others can involve the following examples.
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EX1.,Enzyme induction
A drug may induce the enzyme that is responsible
for the metabolism of another drug or even itself e.g.,
Carbamazepine (antiepileptic drug ) increases its own
metabolism
Phenytoin increases hepatic metabolism of theophylline
Leading to decrease its level Reduces its action
N.B enzyme induction involves protein synthesis .Therefore,
it needs time up to 3 weeks to reach a maximal effect
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EX2.,Enzyme inhibition;
It is the decrease of the rate of metabolism of a drug byanother one.This will lead to the increase of the concentration
of the target drug and leading to the increase of its toxicity .
Inhibition of the enzyme may be due to the competition
on its binding sites , so the onset of action is short
may be within 24h.
When an enzyme inducer (e.g.carbamazepine) is administered
with an inhibitor (verapamil)The effect of the
inhibitor will be
predominant
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Ex.,Erythromycin inhibit metabolism ofastemazole and terfenadine
Increase the serum conc.
of the antihistaminic leading to
increasing the life threatening
cardiotoxicity
EX.,OmeprazoleInhibits oxidative
metabolism
of diazepam
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First-pass metabolism:
Oral administration increases the chance for liver
and GIT metabolism of drugs leading to the loss of apart of the drug dose decreasing its action. This is
more clear when such drug is an enzyme inducer
or inhibitor.
Rifampin lowers serum con. ofverapamil level by
increase its first pass . Also, Rifampin induces the
hepatic metabolism ofverapamil
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Renal excretion:
Active tubular secretion;
It occurs in the proximal tubules (a portion of renal tubules).The drug combines with a specific protein to pass through
the proximal tubules.
When a drug has a competitive reactivity to the protein that is
responsible for active transport of another drug .This will reduce
such a drug excretion increasing its con. and hence its toxicity.
Probenecid.. Decreases tubular secretion ofmethotrexate.
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* Passive tubular reabsorption;
Excretion and reabsorption of drugs occur in the tubules
By passive diffusion which is regulated by concentrationand lipid solubility.
Ionized drugs are reabsorbed lower than non-ionized ones
Ex1., Sod.bicarb.Increases lithium clearance
and decreases its action
Ex2., Antacids Increases salicylates clearance and
decreases its action
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Pharmacodynamic interactions;
It means alteration of the dug action without change in its
serum concentration by pharmacokinetic factors.
EX., Propranolol + verapamilSynergistic or additive
effect
Synergism means =1+1=3
Additive means= 1+1=2
Potentiation means= 1+0=2
Antagonism means 1+1=0 or 0.5
Effect at the receptor site
Antiadrenegicanticholinergic
On the other hand
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* Risk factors:
1) High risk drugs; these are the drugs that show a narrow
therapeutic index e.g., corticosteroids, rifampin,
oral contraceptives, quindine,lidoquine
2) High risk patients; these are the groups of patients
that should be treated with caution due to a specific
heath condition e.g., pregnant women, malignant cases,
diabetic patients, patients with liver or kidney disorders
asthmatic patients and cardiac disorders.
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Onset of drug interaction
It may be seconds up to weeks for example in
case of enzyme induction, it needs weeks for protein synthesis, while enzyme inhibition occurs rapidly.
The onset of action of a drug may be affected by the half lives
of the drugs e.g., cimitidine inhibits metabolism of
theophylline.
Cimitidine has a long half life, while, theophylline has a short
one.
When cimitidine is administered to a patient regimen for
Theophylline, interaction takes place in one day.
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* Prevention of drug interaction
1) Monitoring therapy and making adjustments
2) Monitoring blood level of some drugs with narrow
therapeutic index e.g., digoxin, anticancer agentsetc
3) Monitoring some parameters that may help to
characterize the the early events of interaction
or toxicity e.g., with warffarin administration, it
is recommended to monitor the prothrombin time
to detect any change in the drug activity.
4) Increase the interest ofcase report studies to
report different possibilities of drug interaction
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Prevention foot drug interaction
The main way that food and drugs interact are:
1)Some foods may affect how a drug is absorbed. Thedrug may go into the body faster or slower or more orless of the drug may be absorbed.
2)A food may also alter how a drug works. It may make itlast a longer or shorter time in your body or may make itnot have the desired effect on your medical condition.
3)Similarly, drugs can change how a food or vitamin ormineral is absorbed or metabolized by the body.
4)Finally a drug may make you feel more or less hungrythan usual.
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One beverage is definitely beneficial when
taking medications in pill or capsule form.That is water. Every time you take a pill or
capsule, be sure to drink at least 8 ounces of
water. Water helps to dissolve the medicineand improve its absorption. Diluting and
dissolving some medicines with water also
may make them less likely to irritate or upset
your stomach.
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It is also important to know whether you
should take your medicines with or without
food or milk. Sometimes having something in
your stomach can interfere with drugs
absorption and/or metabolism. Other timeshaving something in your stomach, even just
milk, can protect the stomach from any
irritation from the medicine.
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Definitely do not mix a medicine directly
into a food or beverage unless your
doctor or pharmacist recommends it.Substances in the food can sometimes
bind with the drug and make it either not
work at all or work less well.
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Most importantly, do not take any medication
with an alcohol beverage (wine, beer or
liquor). Drinking alcohol while you are on a
drug can make some drugs more likely to
damage your stomach lining which could lead
to bleeding. Sometimes drinking alcohol canalso increase the chances that a drug will
damage your liver, raise your blood pressure,
make you drowsy or impair your concentrationand coordination.
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A new concern is the effect of grapefruit andgrapefruit juice on drugs. Grapefruit can
inactivate an enzyme that controls the amount of amedicine that is absorbed from the intestines. Formany drugs this increase may result in very highlevels of the medicine in the body that may be
toxic. Also grapefruit can cause some drugs to not work
as well as expected.This is the case for Viagra, theimpotence drug and Allegra, a drug used for
controlling allergies. These negative affects cancontinue for 24 hours after drinking or eating thefruit.
.
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If you regularly take pain relievers like aspirin,
or cortisone for arthritis and other pain
definitely to not take them with alcohol.
Alcohol will just enhance the chances that the
medicine will irritate your stomach and cause
bleeding.
A special concern is with Tylenol or
acetomenophen. There is now a warning on its
label telling people not to drink over threedrinks a day to prevent liver damage.
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Some medicines for high blood pressure cause
to lose or retain more potassium. Too much or
too little potassium in your body can be very
dangerouseven fatal.
Most diuretics or water pills cause a loss of
potassium from the body, but Dyazide and
Maxzide cause you to retain potassium. Too
much potassium could cause heart faillure.
ACE Inhibitors like Capoten and Vasotec alsocan increase potassium levels in the body.
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Alcohol and Other Medicines for the
Heart
Can lower blood
pressure too much with
beta blockers and
nitrate containing drugs Can cause liver damage
with statin drugs
Beta blocker Inderal,
Lopressor
Nitrates Nitro,
Transderm Nitro, Isordil Statins Lipitor,
Mevacor, Zocor,
Prevachol
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Coumadin and Vitamin K
Keep intake of foods containing Vitamin K
constant
Vitamin K is high in spinach, kale, turnip
greens, cauliflower, broccoli, brussel sprouts
and other leafy greens
Also dont take Vitamin K or E supplements
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Some drugs do not work when dairy products
are consumed. These include tetracycline, an
antibiotic and several anti-fungal medicines
like Diflucan and Nizoral. Also ironsupplements can cause tetracycline to not work
well.
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Medicines for Depression and
Anxiety Never mix with
alcohol with any
of these drugs! Also caffeine may
decrease theeffectiveness of
anti-anxietydrugs
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MOA Inhibitors
No beer, red wine orother alcohol
No cheddar,American, bleu, brie,Parmesan ormozzarella cheese
No beef or chicken
liver, cured meats,game meat, caviar ordried fish
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MOA Inhibitors
No avocados,bananas, soysauce, miso soup,
sauerkraut
No ginseng, broador fava beans orfood or beverages
containing caffeinelike coffee,chocolate, coladrinks, tea