I/- DRUGS INTERACTIONS :
Drug interactions are modifications of the pharmacodynamic and / or clinically significant pharmacokinetic
observed in vivo, expected effects of a drug when co-administered with another drug, food, alcohol or tobacco. These interactions can be beneficial or harmful.
clinically significant, if intesité and / or duration of pharmacological variations it causes :
- Are sufficient to alter the benefit / risk to the patient.
- Require dosage adjustment.
SOUGHT THE INTERACTIONS :
- Increase the benefit / risk (combination of two drugs with my same therapeutic indication and the various side effects.
- Antagonize a toxic effect : antidote.
- Decrease the cost of treatment.
- Decrease taking frequency.
TYPE D’INTERACTIONS MEDICAMENTEUSES :
1/- pharmaceutical interaction : Physicochemical interaction between two active ingredients or between an AP and an excipient, observed on the solutions mix in the same syringe.
2/- pharmacokinetic interaction : A drug will affect the pharmacokinetics of another drug resulting in a variation of the drug blood levels.
3/- Interaction pharmacodynamique : A drug will alter the pharmacodynamics of another drug without changing the plasma concentration of the first drug.
CONSEQUENCES OF DRUG INTERACTION :
Synergy : the sum of the effects of both drugs is equal to the effects of both drugs taken alone.
potentiation : the sum of the effects of the two drugs is greater than the simple addition.
L & rsquo; antagonism : l & rsquo; & rsquo effect; a drug is reduced or eliminated during the & rsquo; administration of the second drug.
II/- DRUG INTERACTIONS Pharmacokinetic PHASE :
1/- DEFINITON :
Changing the pharmacological response caused by a change in the plasma of one of the two drug concentrations.
Occur at all stages of the fate of the drug in the body :
2/- INTERACTIONS DURING THE STAGE OF ENTRY :
Are observed during the use of oral. They can result in a variation in the absorption rate and or the amount absorbed from which altered bioavailability
2.1/- Mechanisms for modifying the absorption of a drug by another :
2.1.1/- Change in diffusible form of the drug : The mechanisms are especially likely physicochemical.
220.127.116.11/- Variation of the ionization of a drug by altering the ph gastro intestinal :
A medicament which causes a rise in gastric pH may reduce the absorption of weak acidic drugs.
↑??→ ↓??????????→ ↓???????????????é→ ↓????→??is????????is ??is??????????
Exp : antiulcer (omeprazole), antisecretaoire acid (ranitidine).
18.104.22.168/- Creating a physical barrier gastrointestinal :
Digestive dressings represent an actual physical barrier lining the gastric lumen and part of the duodenum, preventing the absorption of the associated drug. Exp : (aluminum hydroxide).
↓??????????→ ↓???????????????é→??is????????is ??is??????????
Note : Observe a period of two hours between the intake of a gastric dressing and another oral form.
22.214.171.124/- Solubilizing a diffusible compound in a non-absorbable liquid :
Association of fat-soluble drugs (vit Adek) with mineral oil used as a laxative decreases absorption
126.96.36.199/- complexing not resolved :
- Tetracyclines and calcium salts or iron form non-resorbed insoluble compounds.
- Fluoroquinolones and calcium Sels.
- calcium and iron salts.
Note : Always respect a period of two hours.
2.1.2/- Changing the gastrointestinal transit – intestinal :
188.8.131.52/- gastric emptying :
A drug that accelerates gastric emptying as the antiemetic metoclopramide such increase drug contact time with the intestinal mucosa increased absorption associated drugs.
↑??????????→ ↑???????????????é→ ?????? ?? ???????is
184.108.40.206/-intestinal peristalsis :
- A drug slows the intestinal transit as diarrheal antis like loperamide increases the drug's contact time with intestinal mucosa increasing the absorption associated drugs.
- Drugs that accelerate intestinal transit as laxatives reduce the absorption of the other particular drug has those enteric slows.
3/- INTERACTIONS DURING THE STAGE DISTRIBUTION :
↑ ????? ????? → ↑ ???????is
↓ ????? ????? → ↓ ???????is
|oral anticoagulants + aspirin||haemorrhage|
|oral anticoagulants + miconazole||haemorrhage|
|weak acids :
|weak bases :
B blockers Antidepressants
|α-1 Glycoprot ac
4/- INTERACTIONS DURING THE STAGE OF METABOLISM :
- Drug detoxification :
- Principale source d’interaction.
- high variability.
- Induced and / or inhibited !
|Induction||effect decreased||effect increased|
|Inhibition||effect increased||effect decreased|
Cytochrome P540 :
- Superfamille d’isoenzymes.
- Located in the liver +++, but also in other tissues (rein, brain, lymphocytes… ).
- oxidative metabolism (pharmaceuticals, xenobiotics, endogenous products (Fatty acids, prostaglandins, steroids)).
- CYP1A2, 2C9, 2C19, 2D6, 3A4.
+ Inhibition = competition at the enzyme,
+ Induction = stimulates the synthesis of the enzyme.
4.1/- enzyme inhibition :
|Antiinfective||Fungal : ketoconazole, fluconazole ;
antiretrovirals : delavirdine ; protease inhibitors : ritonavir, nelfinavir ;
Quinolones 2 generation ; chloramphenicol ;
Macrolides (except spiramycin).
|anti depressants||fluoxetine, fluvoxamine, paroxetine.|
|Divers||cimétidine, calcium channel blockers
(diltiazem, verapamil, nicardipine).
4.2/- enzyme induction :
Key enzyme inducers :
|Antiinfective||Rifampicine, rifabutine ; antivirals ; Antiprotéases ; Fungal : griséafulvine.|
|anticonvulsants||carbamazepine, phenobarbital, phenytoin.|
|Divers||corticosteroids, Modafinil, Bupropion|
5/- INTERACTIONS DURING THE STAGE OF ELIMINATION :
L & rsquo; hepatic excretion may be slowed by decreased blood flow in the portal circulation-cellar (Beta-blockers ; anti-H2, omeprazole).
Mechanism : Elimination :
1/- glomerular filtration :
Modification of protein binding
Moving the free balance bound
Increased toxic active fraction
Increased renal clearance
2/- tubular reabsorption :
Course of Dr A. Ayadi – Faculty of Constantine