Drug Interactions of Antidiabetics

More presentations from Naina Mohamed Pakkir Maideen

Ø Diabetes patients may take a large number of medications to treat various problems along with antidiabetics.

Ø With this amount of medicine use, the probability of drug interaction is very high.

Ø  The antidiabetic drugs are classified as…

·       Injectable Antidiabetics

o  Insulins

o  Incretin Mimetics (Exenatide, Liraglutide)

o  Amylin Analogues (Pramlintide)

·       Oral Antidiabetics

o  Sulfonylureas (Glibenclamide, Gliclazide)

o  Meglitinides (Repaglinide, Nateglinide)

o  Biguanides (Metformin)

o  Thiazolidinediones  (Rosiglitazone, Pioglitazone)

o  Alpha glucosidase Inhibitors (Acarbose, Miglitol)

o  DPP 4 Inhibitors (Sitagliptin, Vildagliptin)

o  Aldose reductase Inhbitors (Epalrestat)

o  Sodium-glucose co-transporter 2 inhibitors (Dapagliflozin, Canagliflozin)

Ø Concurrent therapy with a Beta blocker or Fluoroquinolone and an antidiabetic may increase the risk of hypoglycemia or hyperglycemia due to altered glucose metabolism.

Ø Excessive hypoglycemia, CNS depression, and seizures might be caused by the combination of Antidiabetics and MAO Inhibitors.

Ø The effectiveness of Antidiabetics is reduced by the coadministration of Thyroid hormones, Danazol, Glucosamine or Licorice which results into hyperglycemia.

Ø Concomitant use of Antidiabetics and Alpha lipoic acid, Bitter Melon, Fenugreek, Psyllium, Eucalyptus, Glucomannan, Gymnema, Ginseng or Guar gum may increase the risk of hypoglycemia due to additive blood glucose lowering effects.

Ø The diabetics should review their list with their doctor or pharmacist regularly, particularly when they begin to take a new medicine.

Alcohol - Drug interactions

More presentations from Naina Mohamed Pakkir Maideen

·Alcohol interacts with many drugs by both pharmacokinetic and pharmacodynamics mechanisms.

·Concomitant administration of Cycloserine and Alcohol is contraindicated due to increased risk of seizures.

·Disulfiram and alcohol (found in foods, medications, aftershaves, perfumes, and other products) use is contraindicated because of alcohol intolerance.

·Alcohol ingestion is contraindicated, while the patients are on the medications like Furazolidone and Metronidazole, due to Disulfiram-like reactions (abdominal cramps, nausea, vomiting, headaches and flushing).

·Alcohol use within 6 hours before or after the administration of Topiramate extended-release capsules is contraindicated due to erratic topiramate plasma concentrations.

·Concomitant use of Alcohol and Comfrey is contraindicated due to increased risk of liver damage.

· The risk of hepatotoxicity is increased by the administration of Acetaminophen (Paracetamol) in ingested patients.

·Enhanced CNS depression and impairment of motor skills have been observed in patients taking antidepressants (Amitriptyline, Clomipramine, Imipramine, Desipramine, Trimipramine, Citalopram, Escitalopram, Paroxetine, Venlafaxine, Desvenlafaxine) and alcohol together.

·Co-administration of CNS Depressants (Benzodiazepines(Clonazepam, Midazolam, Alprazolam, Diazepam, Lorazepam),Barbiturates (Amobarbital, Aprobarbital, Mephobarbital, Pentopbarbital, Phenobarbital) and alcohol may result into increased sedation.

·Increased CNS depression is expected with concomitant administration of alcohol and Phenothiazines (Fluphenazine, Prochlorperazine, Thioridazine, Trifluoperazine, Triflupromazine) and Opioids (Morphine, Oxycodone, Oxymorphone, Hydromorphone).

·Due to the inhibition of aldehyde dehydrogenase enzyme by drugs like Cephalosporins (Cefamandole, Cefmenoxime, Cefoperazone, Cefotetan and Moxalactam), Sulfonylureas Gliclazide, Glipizide, Glyburide, Tolazamide and Tolbutamide), Griseofulvin, ketoconazole, Isoniazid, Isotretinoin, Procarbazine, Tinidazole, Tolazoline and Trimethoprim, disulfiram-like reactions  (Facial flushing, Tachycardia, Increased blood pressure, and a feeling of severe intoxication) are expected with alcohol ingestion.

·The duration of Teratogenic risk of Acitretin is increased by alcohol consumption.

·The hypoglycemic effect of sulfonylureas (Gliclazide, Glipizide, Glyburide, Tolazamide and Tolbutamide), is prolonged by alcohol ingestion.

·Alcohol potentiates the bleeding time prolongation and gastrointestinal irritation caused by Aspirin.

·In summary, Adverse drug interactions of Alcohol causes mainly

v Disulfiram like reactions (Occur with Furazolidone, Metronidazole, Cephalosporins, Sulfonylureas, Griseofulvin, ketoconazole, Isoniazid, Isotretinoin, Procarbazine, Tinidazole, Tolazoline and Trimethoprim)

v Enhanced CNS depression (Barbiturates, Benzodiazepines, Phenothiazines and Opioids)

v Increased risk of Hepatotoxicity(Acetaminophen, Methotrexate, Milnacipran, Trabectedin, Comfrey, Chaparral, Germander and Pennyroyal)

v Increased risk of seizures (Cycloserine and Bupropion)

·As the alcohol consumption is involved in many adverse drug interactions, patients should be advised to avoid alcohol.

Top 10 Dangerous Drug Interactions

·       According to American Medical Directors Association (AMDA) and American Society of Consultant Pharmacists (ASCP) the following are summerised as top 10 dangerous drug combinations…

      1. Warfarin and NSAIDs

      2. Warfarin and Sulpha drugs

      3. Warfarin and Macrolides

      4. Warfarin and Quinolones

      5. Warfarin and Phenytoin

      6. ACE inhibitors and Potassium supplements

      7. ACE inhibitors and Spiranolactone

      8. Digoxin and Amiodarone

      9. Dogoxin and Verapamil

    10. Theophylline and Quinolones

·       Warfarin increases the GI bleeding risk when it is coadministered with NSAIDs.

·       Concomitant administration of Warfarin and sulpha drugs may elevate the risk of bleeding.

·       The risk of bleeding is increased by the interaction of warfarin with macrolide antibiotics such as Erythromycin, clarithromycin and telithromycin.

·       Bleeding risk is raised by the coadministration of warfarin and Quinolones too.

·       The risk of bleeding is varied with individuals due to the action of phenytoin on the metabolism of warfarin and its diaplacement from protein binding.

·       Coadministration of ACE inhibitors and Potassium supplements may increase the risk of hyperkalemia.

·       Hyperkalemia risk is also increased by the concomitant administration of ACE inhibitors and Spiranolactone.

·       Digoxin toxicity is induced when digoxin and amiodarone are administered together.

·       Digoxin toxicity is also induced by the concomitant administration of digoxin and verapamil.

·       Concomitant administration of Theophylline and Quinolones, increases the risk of Theophylline toxicity.

P –Glycoprotein (P-gp) – Drug Interactions:

v P-glycoprotein is one of the transporter protein and it helps the drugs and endogenous substances to cross biological membranes, by carrier-mediated processes.

v P-gp Substrates:

Digoxin, Loperamide, Quinidine, Vinblastine, Talinolol.

v P-gp Inducers:

Carbamazepine, Phenytoin, Rifampin, St John’s wort.

v P-gp Inhibitors:

Amiodarone, Azithromycin, Captopril, Cyclosporine, Quinidine, Quinine, Reserpine, Ritonavir, Tacrolimus, Valspodar, Verapamil.

v P-glycoprotein is an efflux pump found in the membranes of certain cells, which can push metabolites and drugs out of the cells and affect drugs’

ü Absorption (in the intestine)

ü Distribution (to the brain, testis, or placenta)

ü Elimination (in the urine and bile) of drugs

v Many drugs which are substrates for CYP3A4 are also substrates for P-glycoprotein.

v There is an overlap between CYP3A4 and P-glycoprotein inhibitors, inducers and substrates.

Cytochrome P450 enzymes - Drug Interactions

}  Cytochrome P450 (CYP) is a family of isoenzymes responsible for the oxidation of organic substances.

}  Most of the oxidative reactions of drugs are performed by six main enzymes:

v CYP 1A2

v CYP 2C9

v CYP 2C19

v CYP 2D6

v CYP 2E1

v CYP 3A4

}  Enzyme induction:

v The main drugs responsible for induction of the most clinically important cytochrome P450 isoenzymes are Griseofulvin, Phenytoin, Rifampicin, St. John’s wort, Carbamazepine, Phenobarbitone and Cigerette Smoke.

                     GPRS Cell Phone

v CYP 1A2 is induced by tobacco smoke (Smoking)

v CYP2E1 is induced by alcohol consumption.

}  Enzyme inhibition:

v The main drugs responsible for inhibition of the most clinically important cytochrome P450 isoenzymes are Sulphonamides, Antifungals ( Itraconazole, Ketoconazole, Fluconazole), Macrolide Antibiotics (Clarithromycin, Azithromycin, Erythromycin), Ciprofloxacin, Sertraline, Cimetidine, Omeprazole, Metronidazole, Antivirals (Ritonavir, Indinavir, Nelfinavir, Amprenavir), Antiarrhythmics (Amiodarone, Quinidine), Antidepressants (Fluoxetine, Paroxetine), Isoniazid and Alcohol.

                SICK FACES.COM

}  Understanding the mechanism underlying drug interactions helps to prevent drug toxicity or adverse effects.

}  Prediction of drug interactions in advance may reduce the number of expensive clinical studies.

Pharmacodynamic Drug Interactions

·       Alteration (Increase or Decrease) of effect of one drug, by the administration of another drug, is termed as “Pharmacodynamic Drug Interaction”.

·       Pharmacodynamic interactions either…

v Receptor mediated or

v Non receptor mediated

·       Pharmacodynamic interactions further classified in to…

v Additive (Summation) interactions

v Synergistic interactions

v Potentiation interactions

v Antagonism interactions

ü Functional antagonism

ü Chemical antagonism

ü Dispositional antagonism

ü Receptor antagonism

·       When the sum of individual effects of two drugs is equal to the combined effect of them, is known as “Additive interaction”.   

                   i.e. 1 + 1 = 2

       Ex: Aspirin + Ibuprofen

·       “Synergistic interaction” implies the combined effect of two drugs is greater than the sum of their individual effects at the same doses.

                  i.e. 1 + 1 > 2

      Ex: Aminoglycoside + Penicillin = Increased antibacterial activity

·       The creation of a toxic effect from one drug due to the presence of another drug, describes “Potentiation interaction”.

                   i.e. 1 + 0 = 2

          Ex: Fluoroquinolones + Macrolides = Excessive QT prolongation (Torsades de pointes)

           

·       “Antagonistic interaction” means the sum of individual effects of two drugs is less than the effect of the drugs taken independently of each other.

                  i.e. 1 - 1 = 0 or 0.5.

·       Functional or physiological antagonism occurs when one drug counteract the effects of another substance without binding to the same receptor.

       Ex: Adrenaline for hypersensitivity reaction (Histamine)

·       A drug counters the effect of another by simple chemical reaction or neutralization, in Chemical antagonism or Inactivation.

       Ex: Protamine sulphate is antidote for  Heparin overdosage

·       The alteration of the disposition of a substance (absorption, biotransformation, distribution, or excretion), known as Dispositional antagonism.

        Ex: Cholestyramine reduces the absorption of bile acids

·       Receptor antagonism involves the blockade of the effect of a drug (Agonist) by another drug (Antagonist) that competes at the receptor site.

·       Types of Receptor antagonists include…

v Competitive antagonists

v Reversible competitive antagonists

v Irreversible competitive antagonists

v Non competitive antagonists

v Uncompetitive antagonists

v Partial agonists

v Inverse agonists