Enalapril drug interactions

A possible drug interaction with enalapril has been reported a patient with diabetes receiving teicoplanin for osteomyelitis developed renal insufficiency requiring dialysis after the addition of enalapril (54). 

Diclofenac is a non-steroidal anti-inflammatory drug. NSAIDs interact with both angiotensin-converting enzyme inhibitors, such as enalapril, and beta-adrenoceptor blockers, such as atenolol, resulting in antagonism to the hypotensive reaction, leading to a hypertensive reaction. NSAIDs interact with... 

Drug/Food interactions Food significantly reduces the bioavailability of captopril by 30% to 40%. Administer captopril 1 hour before meals. The rate and extent of quinapril absorption are diminished moderately (25% to 30%) when administered during a high-fat meal. The rate, but not extent, of ramipril and fosinopril absorption is reduced by food. Food does not reduce the Gl absorption of benazepril, enalapril, and lisinopril. 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

There appear to be significant differences between the pioneer drug, captopril, and the enalapril analogues. Differences in these characteristics influence mainly the onset and duration of action. Captopril has a short onset time (1 h) and a relatively short duration of action, and therefore is administered three times daily. Captopril has potential drug-food interactions, and is the only agent that should be spaced from meals. Therefore, captopril is no longer used as a first-choice ACE-inhibitor in clinical practice, except for hypertensive emergencies, acute myocardial ischemia, and acute CHF. 

ACE inhibitor drugs were developed by modelling interaction with the active site of the enzyme of a snake-venom-derived bradykinin-potentiating peptide, and from this the necessary structure of non-peptide inhibitors was inferred. The first such ACE inhibitor used medicinally was caplopril. Later examples in clinical use include cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril. Several ACE inhibitors are now administered clinically as prodrugs - which have good bioavailability, but are inactive in their own right. They are then converted to the active molecule in vivo, usually by esterases (e.g. enalapril to enalaprilat. and ramipril to ramiprilat). 

M. L. Cotton, D. W. Wu, and E. B. Vadas, Drug-excipient interaction study of enalapril maleate using thermal analysis and scanning electron microscopy, Int. J. Pharm. 40, 129-142(1987). 

Epoetin may cause hypertension and thereby reduce the effects of antihypertensive drugs. An additive hyperkalaemic effect is theoretically possible with ACE inhibitors or angiotensin II receptor antagonists and epoetin. It is not entirely clear whether captopril, enalapril, fosinopril or other ACE inhibitors affect the efficacy of epoetin or not, but any interaction may take many months to develop. 

Cimetidine did not appear to alter the pharmacokinetics or pharmacological effects of captopril or enalapril, or the pharmacokinetics of fosinopril or quinapril in studies in healthy subjects. The manufacturers of cilazapril say that no clinically significant interaction occurred with H2-receptor antagonists (not specifically named) and the manufacturers of moexipril, " ramipril, and trandolapril say that no important pharmacokinetic interaction occurred with cimetidine. The manufacturers of spirapril briefly note in a review that cimetidine did not alter the plasma concentrations of spirapril or its active metabolite spiraprilat. None of these pairs of drugs appears to interact to a clinically relevant extent, and no special precautions appear to be necessary. 

A 74-year-old patient stabilised on acenocoumarol, enalapril, piretanide, and digoxin had the piretanide and enalapril switched to furosemide and fosinopril. Eleven days later, he presented with dark faeces (melaena) and had a low haemoglobin. Fosinopril and acenocoumarol were stopped, and then enalapril and acenocoumarol were restarted. On gastrointestinal endoscopy, no explanation for the melaena was found, and his haemoglobin level had returned to normal 15 days later. This case was attributed to possible potentiation of the effect of acenocoumarol by fosinopril, but as the drugs were not taken alone, the interaction is not proven. 

Severe hypoglycaemia (1.6 mmol/L) and coma occurred in a patient with renal impairment taking gliclazide and allopurinol. Hypoglycaemia has been seen in another patient taking both drugs, but an interaction is less clear, as enalapril and ranitidine, which may also (rarely) interact were also involved. ... 

There are isolated cases of apparent hypotensive interactions between clozapine, and enalapril, lisinopril or propranolol. Additive hypotensive effects are possible with clozapine and any antihypertensive drug. 

The importance of proline as the C-terminal amino acid in ACE inhibitors is best seen, if this building block is removed from enalaprUate that leads to a complete loss of activity. If the terminal carboxylic acid function is converted into the corresponding amide, or if proline is replaced by phenylalanine, this results in relatively poor affinity as well. However, good activity is found with bicyclic proline derivatives, which are optimised for their interactions in the S2-pocket (Fig. 5.15). [14,15] Many of the active compounds following on from enalapril possess this structural motif, e.g. ramiprilate (Hoechst) and tran-dolaprUate (Roussel) (Fig. 5.16). Like the majority of ACE inhibitors approved up to 2003, these compounds are administered as pro-drugs (ethyl esters). 

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