NITROGLYCERIN

General

Pronunciation:
nye-tro-gli-ser-in

nitroglycerin extended-release capsules


Trade Name(s)

  • Nitro-Time

nitroglycerin intravenous

Trade Name(s)

  • Nitro-Bid IV
  • Nitroject Canadian Tradename
  • Tridil

nitroglycerin sublingual tablets

Trade Name(s)

  • Nitrostat

nitroglycerin transdermal ointment

Trade Name(s)

  • Nitro-Bid

nitroglycerin transdermal patch

Trade Name(s)

  • Nitro-Dur
  • Trinipatch Canadian Tradename

nitroglycerin translingual spray

Trade Name(s)

  • Nitrolingual
  • Nitromist
  • Rho-Nitro Canadian Tradename

Ther. Class.

antianginals

Pharm. Class.

nitrates

Indications

  • Acute (translingual, SL, ointment) and long-term prophylactic (oral, transdermal) management of angina pectoris.
  • PO Adjunct treatment of HF.
  • IV Adjunct treatment of acute MI.
  • Production of controlled hypotension during surgical procedures.
  • Treatment of HF.

Action

  • Increases coronary blood flow by dilating coronary arteries and improving collateral flow to ischemic regions.
  • Produces vasodilation (venous greater than arterial).
  • Decreases left ventricular end-diastolic pressure and left ventricular end-diastolic volume (preload).
  • Reduces myocardial oxygen consumption.

Therapeutic Effect(s):

  • Relief or prevention of anginal attacks.
  • Increased cardiac output.
  • Reduction of BP.

Pharmacokinetics

Absorption: Well absorbed after oral, buccal, and sublingual administration. Also absorbed through skin. Orally administered nitroglycerin is rapidly metabolized, leading to ↓ bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Undergoes rapid and almost complete metabolism by the liver; also metabolized by enzymes in bloodstream.

Half-life: 1–4 min.

TIME/ACTION PROFILE (cardiovascular effects)

ROUTEONSETPEAKDURATION
SL/Translingual1–3 minunknown30–60 min
PO-ER40–60 minunknown8–12 hr
Oint20–60 minunknown4–8 hr
Patch40–60 minunknown8–24 hr
IVimmediateunknownseveral min

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • ↑ intracranial pressure;
  • Severe anemia;
  • Pericardial tamponade;
  • Constrictive pericarditis;
  • Uncorrected hypovolemia;
  • Alcohol intolerance (large IV doses only);
  • Concurrent use of PDE-5 inhibitor (avanafil, sildenafil, tadalafil, vardenafil) or riociguat.

Use Cautiously in:

  • Head trauma or cerebral hemorrhage;
  • Glaucoma;
  • Hypertrophic cardiomyopathy;
  • Severe liver impairment;
  • Malabsorption or hypermotility (PO);
  • Cardioversion (remove transdermal patch before procedure);
  • OB:  May compromise maternal/fetal circulation;
  •  Lactation:  Safety not established in breastfeeding
  • Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: hypotension, tachycardia, syncope

Derm: contact dermatitis (transdermal), flushing

EENT: blurred vision

GI: abdominal pain, nausea, vomiting

Neuro: dizziness, headache, apprehension, restlessness, weakness.

Misc: alcohol intoxication (large IV doses only), tolerance

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Route/Dosage

SL (Adults): Tablets– 0.3–0.6 mg; may repeat every 5 min for 2 additional doses for acute attack; may also be used prophylactically 5–10 min before activities that may precipitate an acute attack.

 Translingual Spray: (Adults): 1–2 sprays; may be repeated every 5 min for 2 additional doses for acute attack; may also be used prophylactically 5–10 min before activities that may precipitate an acute attack.

PO (Adults): 2.5–9 mg every 8–12 hr.

IV (Adults): 5 mcg/min; ↑ by 5 mcg/min every 3–5 min to 20 mcg/min; if no response, ↑ by 10–20 mcg/min every 3–5 min (dosing determined by hemodynamic parameters; max: 200 mcg/min).

Transdermal (Adults): Ointment– 1–2 in. every 6–8 hr.  Transdermal patch– 0.2–0.4 mg/hr initially; may titrate up to 0.4–0.8 mg/hr. Patch should be worn 12–14 hr/day and then taken off for 10–12 hr/day.

Availability (generic available)

Extended-release capsules: 2.5 mg, 6.5 mg, 9 mg

Sublingual tablets: 0.3 mg, 0.4 mg, 0.6 mg

Translingual spray: 400 mcg/spray in 4.9–g bottle (60 doses) or 14.6-g bottle (200 doses) (Nitrolingual), 400 mcg/spray in 8.5–g bottle (230 doses) (Nitromist)

Transdermal patch: 0.1 mg/hr, 0.2 mg/hr, 0.3 mg/hr, 0.4 mg/hr, 0.6 mg/hr, 0.8 mg/hr

Transdermal ointment: 2%

Solution for injection: 5 mg/mL

Premixed solution (in D5W): 25 mg/250 mL, 50 mg/250 mL, 100 mg/250 mL

Assessment

  • Assess location, duration, intensity, and precipitating factors of patient's anginal pain.
  • Monitor BP and pulse before and after administration. Patients receiving IV nitroglycerin require continuous ECG and BP monitoring. Additional hemodynamic parameters may be monitored.

Lab Test Considerations:

May cause ↑ urine catecholamine and urine vanillylmandelic acid concentrations.

  • Excessive doses may cause ↑ methemoglobin concentrations.
  • May cause falsely ↑ serum cholesterol levels.

Implementation

  • PO Administer dose 1 hr before or 2 hr after meals with a full glass of water for faster absorption.  DNC: Sustained-release preparations should be swallowed whole; do not break, crush, or chew. 
  • SL Tablet should be held under tongue until dissolved. Avoid eating, drinking, or smoking until tablet is dissolved.
  • Translingual spray: Spray  Nitrolingual  under tongue. Spray  Nitromist  on or under tongue.
  • Topical 

    Rotate sites of topical application to prevent skin irritation. Remove patch or ointment from previous site before application.

    • Doses may be increased to the highest dose that does not cause symptomatic hypotension.
    • Apply ointment by using dose-measuring application papers supplied with ointment. Squeeze ointment onto measuring scale printed on paper. Use paper to spread ointment onto nonhairy area of skin (chest, abdomen, thighs; avoid distal extremities) in a thin, even layer, covering a 2–3-in. area. Do not allow ointment to come in contact with hands. Do not massage or rub in ointment; this will increase absorption and interfere with sustained action. Apply occlusive dressing if ordered.
    • Transdermal patches may be applied to any hairless site (avoid distal extremities or areas with cuts or calluses). Apply firm pressure over patch to ensure contact with skin, especially around edges. Apply a new dose unit if the first one becomes loose or falls off. Units are waterproof and not affected by showering or bathing. Do not cut or trim system to adjust dosage. Do not alternate between brands of transdermal products; dose may not be equivalent. Remove patches before MRI, cardioversion or defibrillation to prevent patient burns. Patch may be worn for 12–14 hr and removed for 10–12 hr at night to prevent development of tolerance.

IV Administration

  • IV Doses must be diluted and administered as an infusion. Standard infusion sets made of polyvinyl chloride (PVC) plastic may absorb up to 80% of the nitroglycerin in solution. Use glass bottles only and special tubing provided by manufacturer.
  • Continuous Infusion:   Dilution:  Vials must be diluted in D5W or 0.9% NaCl. Premixed infusions already diluted in D5W and are ready to be administered (no further dilution needed). Admixed solutions stable for 48 hr at room temperature or 7 days if refrigerated. Stability of premixed solutions based on manufacturer's expiration date. Concentration: Should not exceed 400 mcg/mL.
  • Rate: See Route/Dosage section. Administer via infusion pump to ensure accurate rate. Titrate rate according to patient response.
  • Y-Site Compatibility:
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      • amikacin
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      • verapamil
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      • vinorelbine
      • voriconazole
      • warfarin
      • zoledronic acid
  • Y-Site Incompatibility:
    • alteplase
    • dantrolene
    • daptomycin
    • MORE...
      • diazepam
      • hydroxycobalamin
      • levofloxacin
      • phenytoin
      • trimethoprim/sulfamethoxazole
  • Additive Incompatibility:
    • Manufacturer recommends that nitroglycerin not be admixed with other medications.

Patient/Family Teaching

  • Instruct patient to take medication as directed, even if feeling better. Take missed doses as soon as remembered unless next dose is scheduled within 2 hr (6 hr with extended-release preparations). Do not double doses. Do not discontinue abruptly; gradual dose reduction may be necessary to prevent rebound angina.

    • Caution patient to change positions slowly to minimize orthostatic hypotension. First dose should be taken while in a sitting or reclining position, especially in geriatric patients.
    • Advise patient to avoid concurrent use of alcohol with this medication. Patient should also consult health care professional before taking OTC medications while taking nitroglycerin.
    • Inform patient that headache is a common side effect that should decrease with continuing therapy. Aspirin or acetaminophen may be ordered to treat headache. Notify health care professional if headache is persistent or severe.
    • Advise patient to notify health care professional if dry mouth or blurred vision occurs.
  • Acute Anginal Attacks: Advise patient to sit down and use medication at first sign of attack. Relief usually occurs within 5 min. Dose may be repeated if pain is not relieved in 5–10 min. Call health care professional or go to nearest emergency room if anginal pain is not relieved by 3 tablets in 15 min.
  • SL Inform patient that tablets should be kept in original glass container or in specially made metal containers, with cotton removed to prevent absorption. Tablets lose potency in containers made of plastic or cardboard or when mixed with other capsules or tablets. Exposure to air, heat, and moisture also causes loss of potency. Instruct patient not to open bottle frequently, handle tablets, or keep bottle of tablets next to body (i.e., shirt pocket) or in automobile glove compartment. Advise patient that tablets should be replaced 6 mo after opening to maintain potency.
  • Lingual Spray: Instruct patient to lift tongue and spray dose under tongue ( Nitrolingual, NitroMist ) or on tongue ( NitroMist ).

Evaluation/Desired Outcomes

  • Decrease in frequency and severity of anginal attacks.

    • Increase in activity tolerance. During long-term therapy, tolerance may be minimized by intermittent administration in 12–14 hr or 10–12 hr off intervals.
  • Controlled hypotension during surgical procedures.
  • Treatment of HF associated with acute MI.

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