Drug Interactions of Antihypertensives (Part 8):

Drug Interactions of Thiazide Diuretics:

 

More presentations from Naina Mohamed Pakkir Maideen

©   Thiazide diuretics are useful to treat hypertension and edema.

©    Thiazide diuretics include Hydrochlorothiazide, Chlorthalidone, Indapamide and Metolazone.

©   Thiazide diuretics block Na⁺-Cl⁻ symporter of distal convoluted tubules and inhibit the reabsorption of sodium (Na⁺) and chloride (Cl⁻).

©   Thiazide Diuretics can interact majorly with drugs such as Digoxin, Digitoxin, Flecainide, Dofetilide, Bepridil, Lithium, and Arsenic Trioxide.

©   Moderate interaction of Thiazide Diuretics includes ACE Inhibitors, NSAIDs, Antidiabetics, Licorice, Ginkgo, Gossypol and Calcium.

©   Frequent monitoring of potassium and magnesium is recommended when Thiazide Diuretics and Digitalis glycosides (Digoxin, Digitoxin) are used together.

©   Concomitant use of Thiazide diuretics and Flecainide, Dofetilide, Bepridil or Arsenic Trioxide warrants the monitoring of rhythm.

©    Lithium toxicity (Weakness, Tremor, Excessive thirst, Confusion) can occur due to decreased lithium clearance induced by Thiazide diuretics.

©   Monitor for hypotension, fluid status, and body weight regularly for up to two weeks after the initiation of ACE Inhibitors (Captopril, Lisinopril, Perindopril, etc.) in patients taking Thiazide diuretics.

©   The patients taking both Thiazide diuretics and NSAIDs (Ibuprofen, Diclofenac, Naproxen, etc.) should be monitored for diuretic efficacy and for signs of renal failure.

©   Concomitant use of a diuretic and an Antidiabetic agent warrants the monitoring of glucose levels more frequently.

©   Avoid using Licorice in patients taking Thiazide Diuretics due to increased risk of Hypokalemia.

©   Concomitant use of Ginkgo and thiazide diuretics may increase the blood pressure and requires cautious monitoring.

©   Gossypol use should be discontinued during diuretic treatment due to elevated risk of Hypokalemia.

©   Avoid excessive ingestion of Calcium while receiving thiazide diuretics.

©   The patients with hypertension should bring a list of all of the drugs they are taking including prescription drugs, over-the-counter drugs, and any supplements, herbal or otherwise, during their visit to the doctor or pharmacist.

Clinically Important Drug Interactions of OTC Medicines:

Ø The FDA warns consumers that all Over the Counter (OTC) medicines should be taken carefully to avoid serious problems. 

Ø Many are not aware that OTC medicines can cause potentially serious adverse effects when used in combination with other common medications such as anticoagulants, corticosteroids, or antihypertensive agents.

Ø The common OTC medicines include…

¨   OTC Analgesics (Acetaminophen (Paracetamol), Aspirin, Ibuprofen, Naproxen, etc)

¨   OTC Antihistamines (Chlorpheniramine, Diphenhydramine, Fexofenadine, etc)

¨   OTC Decongestants (Pseudoephedrine, Oxymetazoline,  Xylometazoline)

Ø The risk of hepatotoxicity is elevated by the coadministration of Acetaminophen and CYP inducers (Carbamazepine, Oxcarbazepine, Phenytoin, Fosphenytoin, Deferasirox, Piperaquine, Barbiturates, Isoniazid, Rifampin, and Rifabutin), Smoking or Alcohol.

Ø Concomitant use of Acetaminophen and warfarin may increase the risk of bleeding.

Ø It is contraindicated to use live influenza virus vaccine and Aspirin in children 2 to 17 years of age due to the potential for Reye's syndrome.

Ø The risk of bleeding is increased by Aspirin, Ibuprofen, Ketoprofen or Naproxen in patients taking Warfarin, Heparin, Low Molecular Weight Heparins (LMWHs) (Enoxaparin, Dalteparin, Tinzaparin, etc.), Coumarins and other anticoagulants (Acenocoumarol, Dicumarol, Phenprocoumon, Anisindione, Phenindione), Antiplatelets (Clopidogrel, Prasugrel, Ticagrelor, Ticlopidine, Dipyridamole, Abciximab, Eptifibatide, Tirofiban), Tissue Plasminogen Activators (Alteplase, Reteplase), Direct thrombin inhibitors (Dabigatran, Desirudin, Lepirudin, Bivalirudin, Argatroban), Direct factor Xa inhibitors (Apixaban, Rivaroxaban),Anagrelide, Cilostazol, Selective serotonin reuptake inhibitors (SSRIs) (Escitalopram, Fluvoxamine, Paroxetine, Vortioxetine, Sertraline, Nefazodone, vilazodone) and Selective serotonin and norepinephrine reuptake inhibitors (SNRIs) (Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran, Levomilnacipran, Sibutramine).

Ø Concomitant use of Ibuprofen, Ketoprofen or Naproxen and ACE Inhibitors (Captopril, Enalapril, Imidapril, Temocapril, Delapril, Ramipril, Perindopril, Cilazapril), Angiotensin II receptor blockers (ARBs) (Losartan, Valsartan, Telmisartan), Beta adrenergic blockers, Calcium Channel Blockers, Thiazide Diuretics, Loop Diuretics or Potassium sparing Diuretics could reduce the antihypertensive efficacy.

Ø The risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes) is elevated by the concomitant administration of Brompheniramine or Chlorpheniramine with Antidepressants (SSRIs, SNRIs, TCAs, Trazodone, Vortioxetine, Amoxapine) or serotonergic drugs (Lorcaserin, Almotriptan, Hydroxytryptophan, Fentanyl and Tramadol).

Ø Excessive anticholinergic activity (severe dry mouth, constipation, decreased urination, excessive sedation, blurred vision) may resulted due to combination of Chlorpheniramine or Diphenhydramine and drugs having anticholinergic activity (Belldonna, Clomipramine, Amitriptyline, Triflupromazine, amoxapine and Linezolid).

Ø Coadministration of Diphenhydramine and Opioids (Hydromorphone, Oxycodone, Hydrocodone, Fentanyl, Tapentadol), Other CNS depressants (Zolpidem, Loxapine, Meclizine, Carbinoxamine) or Ethanol increase the risk of CNS depression.

Ø Amiodarone may elevate the risk of “Torsades de pointes” by blocking CYP3A4 induced metabolism of Loratadine or Fexofenadine.

Ø Fruit Juices like Grapefruit juice, Orange juiceand Apple juice decrease the effectiveness of Fexofenadine by inhibiting organic anion transporting polypeptide (OATP).

Ø Concomitant use of Pseudoephedrine and MAO Inhibitors such as Selegiline, Rasagiline, Clorgyline, Pargyline, Toloxatone, Iproniazid, Moclobemide, Nialamide, Procarbazine, Phenelzine , Isocarboxazid, Tranylcypromine, Furazolidone is contraindicated, due to elevated risk of hypertensive crisis characterized by hypertension, hyperpyrexia and headache.

Ø Co-administration of Pseudoephedrine and Dihydroergotamine is contraindicated, due to extreme elevation of blood pressure.

Ø It is contraindicated to use Pseudoephedrine and Linezolid concomitantly, due to increased blood pressure.

Ø Bitter orange contains synephrine which can interact with Pseudoephedrine and increase the risk of hypertensive crisis.

Ø People with heart disease, high blood pressure, diabetes, hyperthyroidism and enlarged prostate should consult a doctor or pharmacist before they take decongestants because side effects can be dangerous.

Ø Patients should thoroughly read the labels of all over-the-counter and prescription medicines.

Ø Patients should talk to their doctor or pharmacist before taking any new prescription or over the counter medication.

Ø Physicians should be aware of potential drug interactions with OTC medicines when prescribing new medications.

Ø Pharmacists can be instrumental in assisting patients with using OTC medications safely and effectively.

Ø Pharmacists should warn consumers of the risks of misusing OTC pain relievers.

   

Drug Interactions of Antihypertensives (Part 7):

Drug Interactions of Loop Diuretics:

More presentations from Naina Mohamed Pakkir Maideen

©   Loop diuretics are useful to treat hypertension and edema associated with congestive heart failure or renal insufficiency. In patients with impaired kidney function, loop diuretics are more effective than thiazide diuretics.

©   Loop diuretics include Furosemide (Frusemide), Bumetanide, Torsemide and Ethacrynic acid.

©   Loop diuretics compete for the Cl⁻ binding site of Na⁺-K⁺-2Cl⁻ symporter (cotransporter) of thick ascending limb of the loop of Henle and inhibit the reabsorption of sodium (Na⁺), chloride (Cl⁻)and potassium (K⁺).   Loop diuretics prevent the generation of a hypertonic renal medulla by disrupting the reabsorption of these ions leading to increased urine production. Loop diuretics induce vasodilation and increased blood supply to the kidney by increasing the production of prostaglandins. 

©   Loop Diuretics can interact majorly with drugs such as Digoxin, Digitoxin, Sotalol, Dofetilide, Droperidol, Metolazone, Foscarnet, Arsenic Trioxide, Ketanserin, Bepridil, Cisplatin, Aminoglycoside Antibiotics and some Antivirals.

©   Moderate interaction of Loop Diuretics includes ACE Inhibitors, NSAIDs, Antidiabetics and Ginseng.

©   Frequent monitoring of potassium and magnesium is recommended when Loop Diuretics and Digitalis glycosides (Digoxin, Digitoxin) are used together.

©   Concomitant use of Loop diuretics and Sotalol, Dofetilide, Droperidol, Arsenic Trioxide, Ketanserin or Bepridil warrants the monitoring of the patients for the signs of Cardiotoxicity (Prolonged QTc interval, faintness, dizziness, and tachycardia).

©    Monitor for additive ototoxicity or nephrotoxicity, if concurrent therapy of Loop Diuretics and Aminoglycoside Antibiotics (Tobramycin, Streptomycin, Gentamicin, Kanamycin, Amikacin, Neomycin, Netilmicin) or Cisplatin is required.

©   The status of fluids and electrolytes should be closely monitored, when Loop diuretics and Metolazone are administered together.

©   Foscarnet elimination is impaired by Loop diuretics and to avoid the Foscarnet toxicity, a Thiazide diuretic is indicated.

©   Antivirals like Ritonavir, Ombitasvir and Dasabuvir may increase the risk of adverse events of Frusemide.

©   Monitor for hypotension, fluid status, and body weight regularly for up to two weeks after the initiation of ACE Inhibitors (Captopril, Lisinopril, Perindopril, etc) in patients taking Loop diuretics.

©   The patients taking both Loop diuretics and NSAIDs (Ibuprofe, Diclofenac, Naproxen, etc) should be monitored for diuretic efficacy and for signs of renal failure.

©    Concomitant use of a diuretic and an Antidiabetic agent warrants the monitoring of glucose levels more frequently.

©   Patients should be advised to discontinue use of Ginseng while taking loop diuretics, to avoid diuretic resistance. 

©   The patients with hypertension should bring a list of all of the drugs they are taking including prescription drugs, over-the-counter drugs, and any supplements, herbal or otherwise, during their visit to the doctor or pharmacist.

Drug Interactions of Antihypertensives (Part 6):

Drug Interactions of Diltiazem (CCB):

More presentations from Naina Mohamed Pakkir Maideen

©   Diltiazem is a Calcium Channel Blocker (CCB) and is used to treat hypertension, to control angina
 and to manage certain arrhythmia.

©   Diltiazem is a potent vasodilator of coronary and peripheral vessels and it reduces peripheral resistance and afterload. Diltiazem decreases heart muscle contractility (Negative Inotropy), the heart rate (Negative Chronotropy) by slowing sinoatrial node and conductivity through A-V node (Negative Dromotropy) which all result in reduction of oxygen consumption by the heart, reducing angina symptoms. The blood pressure is also be reduced by these effects causing less blood to be pumped out.

©   Diltiazem can interact significantly with drugs such as Cisapride, Colchicine, Lomitapide, Erythromycin, Amiodarone, Clopidogrel, Beta blockers, Droperidol, Dantrolene, Lacosamide, Clonidine, Fingolimod, CYP3A4 Inhibitors, CYP3A4 Inducers, CYP3A4 substrates and P-gp Substrates.

©   Concomitant use of Diltiazem and Cisapride is contraindicated due to elevated risk of cardiotoxicity (QT prolongation, Torsades de pointes, cardiac arrest).

©   It is contraindicated to use Diltiazem along with colchicine in patients with renal or hepatic impairment, due to increased risk of colchicine toxicity (Neuromuscular toxicity, etc).

©   Use of Diltiazem in patients taking Lomitapide is contraindicated due to the inhibition of CYP3A4-mediated metabolism of Lomitapide.

©    Monitor QT interval, if Diltiazem and Erythromycin used concurrently.

©   Coadministration of Diltiazem and Amiodarone should be avoided in patients with sick sinus syndrome or partial AV block, due to elevated risk of Bradycardia, Atrioventricular block and/or Sinus arrest.

©   The patients should be monitored for loss of Clopidogrel efficacy, when it is coadministered with Diltiazem.

©   Use of Diltiazem in patients taking Beta blockers, warrants careful monitoring of cardiac function and blood pressure.

©    Droperidol should be administered with extreme caution in patients taking Diltiazem.

©   Monitor blood pressure and serum potassium, if Diltiazem is used concurrently with Dantrolene.

©   Obtain ECG prior to treatment and following dose titration, if concurrent therapy of Diltiazem and Lacosamide is required.

©   Heart rate should be monitored, when Clonidine and diltiazem are administered concurrently.

©   Continuous overnight ECG monitoring is recommended after the first dose of Fingolimod, if concomitant use with Diltiazem is required.

©   The drug levels and adverse effects of Diltiazem should be monitored closely, when it is coadministered with CYP3A4 inhibitors such as Clarithromycin, Ceritinib, Atazanavir, etc.

©   Monitor patients for loss of efficacy, if Diltiazem is used concurrently with CYP3A4 inducers such as Carbamazepine, St.John’s wort, etc.

©   Closely monitor for CYP3A4 substrates associated adverse events, if Diltiazem and CYP3A4 substrates such as Simvastatin, Atorvastatin, Lovastatin, Apixaban, Domperidone, Donepezil, Dronedarone, Clozapine, Fentanyl, Hydrocodone, Piperaquine, Erlotinib, Nilotinib, Crizotinib, Bosutinib, Ibratinib, Doxorubicin, Simeprevir, Lurasidone, Ranolazine, Eplerenone, Everolimus, Aripiprazole, Eliglustat, Cilostazol, Tolvaptan, Ivabradine, etc. are coadministered.

©   Diltiazem inhibits the efflux transport of P-gp substrates such as Dabigatran, Apixaban, Everolimus, Vincristine, Nilotinib, Afatinib, Bosutinib, Trabectedin, Ombitasvir, Simeprevir, Dasabuvir, Paritaprevir, Topotecan, etc. 

©   Use caution and monitor the patient for signs and symptoms of increased exposure of P-gp substrates, when Diltiazem and P-gp substrates such as Dabigatran, Apixaban, Everolimus, Vincristine, Nilotinib, Afatinib, Bosutinib, Trabectedin, Ombitasvir, Simeprevir, Dasabuvir, Paritaprevir, Topotecan, etc. are administered concurrently.

Drug Interactions of Antihypertensives (Part 5):

Drug Interactions of Verapamil (Calcium Channel Blocker):

More presentations from Naina Mohamed Pakkir Maideen

©   Verapamil is used to treat hypertension, to control angina
 and to manage certain arrhythmia.

©   Verapamil blocks voltage-dependent calcium channels of smooth muscle of blood vessels leading to vasodilation and reduction of vascular resistance useful to treat hypertension. Vasodilation induced by Verapamil is also useful to control Angina by increasing the supply of blood and oxygen to the heart. Verapamil blocks voltage-dependent calcium channels of Sinoatrial (SA node) and Atrioventricular (AV node) nodes to decrease impulse conduction through the AV node and protects the ventricles from atrial tachyarrhythmias.

©   Verapamil can interact significantly with drugs such as Dofetilide, Lomitapide, Colchicine, Digoxin, Amiodarone, Adenosine, Beta blockers, Clonidine, Clopidogrel, Droperidol, Fingolimod, Lacosamide, Bupivacaine or Mepivacaine, Dantrolene, Cyclobenzaprine, CYP3A4 Inhibitors, CYP3A4 Inducers, CYP3A4 substrates and P-gp Substrates.

©   Use of Verapamil in patients taking Dofetilide is contraindicated due to the elevated risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest).

©   Concomitant use of Verapamil and Lomitapide is contraindicated due to increased risk of Lomitapide toxicity.

©   It is contraindicated to use Verapamil and Colchicine in patients with renal or hepatic impairment, due to increased risk of colchicine toxicity (Neuromuscular toxicity, etc.)

©   The risk of digitalis toxicity is increased by the coadministration of Verapamil with Digoxin.

©   Bradycardia, Atrioventricular block and/or Sinus arrest may occur due to the interaction Verapamil with Amiodarone.

©   Concomitant use of Verapamil with Adenosine may elevate the risk of ventricular fibrillation.

©   When Verapamil is used along with Beta blockers, Hypotension and Bradycardia might be resulted due to additive cardiac effects.

©    Use of Verapamil and Clonidine together may lead to increased incidence of sinus bradycardia.

©   The risk of thrombotic events is increased by the concomitant use of Verapamil and Clopidogrel.

©   Coaministration of Verapamil with Droperidol may elevate the risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest).

©   Severe bradycardia or heart block may occur as a result of combination of Verapamil and Fingolimod.

©   The risk of PR interval prolongation, atrioventricular block, or bradycardia increased by the concomitant use of Verapamil with Lacosamide.

©   Administration of Verapamil in patients taking Bupivacaine or Mepivacaine, may increase the risk of heart block.

©   Severe hyperkalemia with cardiovascular collapse may result due to the administration of Verapamil along with Dantrolene.

©   Concomitant use of Verapamil and Cyclobenzaprine may increase the risk of serotonin syndrome.

©   Verapamil is a CYP3A4 substrate and the risk of it’s toxicity may be elevated by CYP3A4 inhibitors including Amiodarone, Clarithromycin, Erythromycin, Ketoconazole, Cobicistat, Ceritinib, Atazanavir, etc.

©   The therapeutic efficacy of Verapamil might be lost due to the addition of CYP3A4 inducers such as Carbamazepine, Eslicarbazepine, Primidone, Mitotane, Dabrafenib, etc.

©   Verapamil is also a weak CYP3A4 inhibitor and it can increase the plasma concentrations of CYP3A4 substrates such as Simvastatin, Atorvastatin, Lovastatin, Apixaban, Domperidone, Donepezil, Dronedarone, Clozapine, Fentanyl, Hydrocodone, Piperaquine, Erlotinib, Nilotinib, Crizotinib, Bosutinib, Ibratinib, Doxorubicin, Simeprevir, Lurasidone, Ranolazine, Eplerenone, Everolimus, Aripiprazole, Eliglustat, Cilostazol, Tolvaptan, etc.

©   Verapamil is a P-gp inhibitor and it can increase the plasma concentrations of P-gp substrates such as Dabigatran, Apixaban, Everolimus, Vincristine, Nilotinib, Afatinib, Trabectedin,