Midazolam Hydrochloride and Quinapril Hydrochloride

• Generic Name: midazolam
• Dosage Forms: n.a.
• Other Brand Names: Versed, Nayzilam

Used preoperatively to produce sedation, anxiolysis, and anterograde amnesia.

Particularly useful when relief of anxiety and diminished recall of events associated with the surgical procedure are desired.

Some clinicians consider midazolam the benzodiazepine of choice for preoperative use for short surgical procedures because of its relatively rapid onset and short duration of effect and improved local tolerance at the site of injection compared with other currently available parenteral benzodiazepines.

Use only in monitored settings. (See Boxed Warning.)

Used alone or in combination with other CNS depressants for procedural sedation, anxiolysis, and amnesia. Has been administered prior to dental or other minor surgical procedures; diagnostic, therapeutic, or endoscopic procedures such as upper GI endoscopy, bronchoscopy, or cystoscopy; cardiac catheterization; coronary angiography; oncology procedures; radiologic procedures (e.g., computerized tomography); and suture of lacerations.

Particularly useful when relief of anxiety and diminished recall of events associated with the procedure are desired.

Produces amnestic and sedative effects, but no analgesia; therefore, usually administered in conjunction with an analgesic agent.

Some clinicians consider midazolam the benzodiazepine of choice for moderate sedation (formerly known as conscious sedation) prior to short procedures because of its relatively rapid onset, short duration of action, pronounced amnesic effect, and improved local tolerance at the site of injection compared with other currently available IV benzodiazepines.

Use only in monitored settings. (See Boxed Warning.)

Used IV for induction of general anesthesia prior to administration of other anesthetic agents.

Induction with midazolam provides anxiolysis, anterograde amnesia, and dose-related hypnotic effects (progressing from sedation to loss of consciousness), but not analgesia.

Also may be used for maintenance of anesthesia during short surgical procedures, usually in conjunction with inhalation anesthetic agents, balanced anesthesia (e.g., nitrous oxide and oxygen), and/or opiate agonists (e.g., fentanyl). Should not be used alone for maintenance of anesthesia.

Used as a continuous IV infusion for sedation of intubated and mechanically ventilated patients in critical care settings (e.g., ICU).

Nonbenzodiazepine sedatives (dexmedetomidine or propofol) are generally preferred to benzodiazepines in mechanically ventilated critically ill adults because of some modest clinical benefits that have been demonstrated (e.g., reduced duration of mechanical ventilation, shorter time to extubation, reduced risk of delirium).

When selecting an appropriate sedative agent, consider patient's individual sedation goals in addition to specific drug-related (e.g., pharmacology, pharmacokinetics, adverse effects, availability, cost) and patient-related (e.g., comorbid conditions such as anxiety, seizures, or alcohol withdrawal) factors.

Used IM for treatment of status epilepticus.

Benzodiazepines are considered initial drugs of choice for management of status epilepticus because of their rapid onset of action, demonstrated efficacy, safety, and tolerability. Evidence supports use of IV lorazepam, IV diazepam, or IM midazolam. Individualize choice of therapy based on local availability, route of administration, pharmacokinetics, cost, and other factors (e.g., treatment setting).

IM midazolam may be useful when IV administration of a benzodiazepine is not possible (e.g., in a prehospital setting).

Used intranasally for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from the patient's usual seizure pattern.

Has been used for management of acute agitation.

• Generic Name: quinapril
• Dosage Forms: n.a.
• Other Brand Names: Accupril

Management of hypertension (alone or in combination with other classes of antihypertensive agents).

ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors. However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.

Heart Failure

Management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).

Some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.