Drug Interaction Baru

7/29/2019 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

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Drug Interaction Baru