Other drugs

Drug interaction

1. Muscarinic receptor antagonist: Atropine

2. Opiates: Morphine

3. Positive inotropic agents: Levosimendan, Milrinone

4. Potassium binders: Patirome

5. Potassium-sparing diuretics: Amiloride, Triamterene

6. Vasodilators:

• a-adrenergic receptor antagosnists: Doxazosine, Prazosin
• Centrally Acting Sympatholytics: Methyldopa
• Direct acting vasodilators: Hydralazine
• Imidazoline receptor subtype 1 recepto agonist: Moxonidine
• Nitrovasodilator: Sodium nitroprusside
• Nonselective phosphodiesterase inhibitors: Pentoxifylline
• Potassium channel activator: Diazoxide

Atropine

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Drugs with anticholinergic activity:
- Antiparkinsonian MAOIs: Rasagiline, Selegiline
- Antispasmodics drugs
- Disopyramide
- Histamine H1-receptor antagonists : Diphenhydramine, Mequitazide
- Neuroleptics
- Phenothiazines
- Quinidine
- Tricyclic antidepressants
They increase the adverse effects of atropine (urinary retention, constipation, dry mouthWith caution. Avoid the combination if possible

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Diazoxide

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Antihypertensive
Vasodilators
Diazoxide can potentiate their effects.
Risk of hypotension
Monitor BP
InsulinDecrease the glycemic effects
Loop diuretic thiazidesPotentiate the hyperglycemic and hyperuricemic effects of diazoxideWith caution
PhenytoinLoss of seizure control Diazoxide increases the metabolism of phenytoin
WarfarinIncrease the risk of bleedingIt displaces warfarin from plasma proteins and increases its plasma levelsMonitor the INR

Diazoxide should not be administered within 6 h of hydralazine, reserpine, alphaprodine, methyldopa, b-blockers, prazosin, minoxidil, nitrites and other papaverine-like compounds.

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Doxazosin

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Antihypertensives
Diuretics
Risks of hypotension and rarely syncopeMonitor BP
PDE-5 inhibitorsRisks of hypotension and rarely syncopeMonitor BP

Doxazosin does not present drug interactions with thiazide diuretics, furosemide, b-blockers, NSAIDs, antibiotics, oral hypoglycaemic drugs, uricosuric agents, or anticoagulants.

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Hydralazine

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Alcohol
Anesthetics
Antihypertensives
Nitrates
Tricyclic antidepressants
Vasodilators
Potentiate the vasodilator effectMonitor BP
AdrenalineThis combination increases heart rateAvoid adrenaline to correct hydralazine-related hypotension in surgery
EstrogensAntagonize the hypotensive effect of hydralazine
MAO inhibitorsThey may potentiate the decrease in BPThey should be used with caution in patients receiving hydralazine
NSAIDsAntagonize the hypotensive effect of hydralazine
Nitrate toleranceHidralazine inhibits free radical formationHidralazine decreases nitrate tolerance
PropranololEnhances the effect of propranololHydralazine increases the bioavailability of propanolol and other β-blockers which are subject to significant first-pass metabolismIt may be necessary to reduce the dose of propranolol

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Levosimendan

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
NitratesOrthostatic hypotensionMonitor BP

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Methyldopa

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
AntihypertensivesIncrease the vasodilator and hypotensive effects of methyldopaMonitor BP
Anesthetic agentsIncrease the vasodilator and hypotensive effects of methyldopaPatients taking methyldopa may require lower doses of anaesthetic agents
MAOIs
- Phenothiazines
- Sympathomimetics
- Tricyclic antidepressants
Decrease the antihypertensive effect of methyldopa Monitor BP
Iron salts (Ferrous sulphate or gluconate)Decrease the antihypertensive effect of methyldopaDecrease the oral bioavailability of methyldopaMonitor BP response
LithiumMonitor for symptoms of lithium toxicity.
Vasodilators Increase the vasodilator and hypotensive effects of methyldopaMonitor BP

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Milrinone

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Loop diuretics:
- Bumetanide
- Furosemide
Risk of hypokalemiaThere is an immediate chemical interaction with the formation of a precipitate when furosemide is injected into an IV line of an infusion of milrinoneHypokalemia should be corrected in advance of, or during, the use of milrinone

There are no interactions between milrinone and digitalics, lidocaine, quinidine; nitrates, hydralazine, prazosin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin and potassium supplements.

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Morphine

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
AnticholinergicsThe combination increases constipation and urinary retentionMonitor patients for signs of urinary retention or reduced gastric motility
Antidiarrheal and antiperistaltic agentsThey may increase the risk of severe constipation
Histamine H2-receptor antagonists:
- Cimetidine
- Ranitidine
Cimetidine can potentiate morphine-induced respiratory depressionInhibit the metabolism of morphine and can potentiate morphine-induced respiratory depressionWith caution. Monitor patients for respiratory depression
CNS depressants:
- Alcohol
- General anesthetics
- Hypnotics
- Neuroleptics
- Muscle relaxants
- Phenthiazines
- Sedatives
- Tricyclic antidepressants
Increase the depressant and hypotensive effects of morphineAlcohol can increase morphine plasma leading to a potentially fatal overdose of morphineWith caution. Monitor patients receiving CNS depressants and morphine. The dose of one or both agents should be reduced
DiureticsMorphine may reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Morphine may produce acute retention of urine by causing spasm of the sphincter of the bladderWith caution in prostatic patients
Domperidone
MAO inhibitorsThe effects of morphine may be potentiated by MAOIs. CNS excitation or depression with hyper- or hypotensive crisesThis combination is contraindicated. Morphine sulfate extended-release tablets should not be used in patients taking MAOIs or within 14 days of stopping such treatment
Metoclopramide Enhances the sedative effect of morphine
Mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) They may reduce the analgesic effect of morphine sulfate extended-release tablets or precipitate withdrawal symptomsAvoid the use of agonist/antagonist and partial agonist analgesics in patients receiving morphine
QuinidineInhibit P-gp and increase the absorption and exposure of morphineMonitor patients for signs of respiratory and CNS depression
RitonavirReduce the analgesic effects of morphineRitonavir increases the metabolism of morphine
Skeletal muscle relaxantsMorphine may enhance their effects and increase the degree of respiratory depressionWith caution and under monitoring of the patient

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Moxonidine

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
AntihypertensivesAdditive effectMonitor BP
Vasodilators
- Alcohol
- Antidepressants
- Benzodiazepines
- Hypnotics
Moxonidine can potentiate their vasodilator and sedative effects Monitor BP
Tricyclic antidepressantsReduce the effectiveness of moxonidineMonitor BP

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Patiromer

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Ciprofloxacin
Levothyroxine
Metformin
Decreases exposure to these drugsNo interaction when patiromer and these drugs were taken 3 h apart

It does not affect the bioavailability of amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil and warfarin.

In vitro studies have shown no potential interaction with: allopurinol, amoxicillin, apixaban, acetylsalicylic acid, atorvastatin, cephalexin, digoxin, glipizide, lisinopril, phenytoin, riboflavin, rivaroxaban, spironolactone and valsartan.

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Pentoxyfylline

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
AntiaggregantsExert an additive effect with platelet aggregationMonitor the clinical response
AnticoagulantsBleeding and/or prolonged PTMonitor for signs of bleeding, including hematocrit and haemoglobin
AntihypertensivesIncrease the effects on BPMonitor BP and possibly drug reduction
Antidiabetic drugs:
- Insulin
- Oral hypoglycemiant
Increase the hypoglycemic action of insulin and oral hypoglycemic agentsMonitor the diabetic patients and a moderate adjustment in the dose of hypoglycemic agents may be required
CimetidineEnhances the adverse effects of cimetidineIncreases the steady-state plasma concentration of pentoxifyllineMonitor the clinical response
SSRIs:
- Paroxetine
- Sertraline
- Venlafaxine
Increase the risk of bleedingSSRIs increase the plasma levels of pentoxifylline by reducing hepatic CYP1A2 metabolismCaution
TheophyllineEnhances the adverse effects of theophyllinePentoxifylline increases theophylline plasma levelsMonitor the clinical response to theophylline
Vitamin K antagonistsPentoxyfylline increases anti-coagulant activity of VKAsMonitor the INR

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Prazosin

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Antihypertensives
PDE-5 inhibitors
Vasodilators
Increase the risk of hypotensionMonitor BP

May produce false positives in some tests of noradrenaline metabolites (vanillylmandelic acid, VMA; and methoxyhydroxyphenyl glycol, MHPG).

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Sodium nitroprusside

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
Antihypertensives
Some anesthetic drugs
PDE-5 inhibitors
Vasodilators
Increase the vasodilator and hypotensive effects of sodium nitroprusside Close monitoring of BP

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Potassium-sparing diuretics (Amiloride, Triamterene)

DrugPharmacodynamic interactionsPharmacodynamic interactionsCautions
ACE inhibitors Potentiate the antihypertensive response and the hyperkalemia produced by each drug Monitor serum potassium levels.
Greater risk if renal insufficiency present
Amantadine Potentiate the effect of amantadineIn patients treated with hydrochlorothiazide + triamterene, it decreases renal excretion and increases the Cp of amantadineAtaxia, agitation and hallucinations Readjust the dose of amantadine
Amphotericin B Produces hypokalemia and nephrotoxic effectsRisk of nephrotoxicity and hypokalemia. Reduce the dose of furosemide
Angiotensin receptor blockersPotentiate the antihypertensive response and the hyperkalemia produces by each drug Monitor serum potassium levels.
Greater risk if renal insufficiency present
CarbenoxoloneAmiloride antagonises the ulcer-healing effect of carbenoxoloneUse triamterene
Drugs that increase the risk of hypotension:
- Alcohol
- Aldesleukin
- Alprostadil
- Antihypertensives
- General anesthetics
- Nitrates
- Tricyclic antidepressants
Potentiate the antihypertensive response
Drugs producing hyperkalemia:
- Aliskiren
- β2-adrenergic agonists
- Ciclosporin
- NSAIDs
- Potassium supplements
- RAAS inhibitors
- Tacrolimus
- Trilostane
- Trimetoprim-Sulfametoxazol
Increase the risk of hyperkalemia
Increase the risk of nephrotoxicity with ciclosporin and amiloride
Monitor serum potassium levels
Hypoglycemic agentsDose adjustments of hypoglycemic agents may be necessary
LithiumAmiloride increases the risk of lithium toxicityAmiloride may reduce the renal clearance of lithium Monitor serum lithium levels and adjust the lithium dosage as necessary
MethotrexateTriamterene may exert anti-folate activity. Pancytopenia.Avoid the combination
NSAIDsReduce the diuretic effect and increase the risk of nephrotoxicityMonitor the diuresis, BP and serum creatinine
Ranitidine Decrease (50%) the absorption of triamtereneReadjust the dose of triamterene
Thiazide or loop diureticsAdditive diuretic effects. Decrease the urinary excretion of K and MgMonitor diuresis and electrolyte disturbances
Vasodilators:
- Alcohol
- Alprostadil
- Antihypertensives
- eneral anaesthetics
- Hydralazine
- Nitrates
- Phenothiazines
- Tricyclic aantidepressants
Potentiate their effects and increase the risk of hypotensionMonitor BP
Vitamin K antagonists Increase the anticoagulant effectMonitor the prothrombin time

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Abbreviations

BP: blood pressure
CNS: central nervous system
DM: diabetes mellitus
IV: Intravenous
NSAIDs: nonsteroidal anti-inflammatory drugs
PT: prothrombin time
VKAs: vitamin K antagonists.