Metoprolol masks the adrenergic symptoms of overnight/between-meal hypoglycaemia induced by NPH insulin (4–12 h peak).
The NPH peak often occurs overnight; beta-blockade suppresses the tachycardia warning and reduces hepatic β2 glycogenolysis (Prontuário 8.4.1).
Overnight glucose, sweating, morning neurological status (headache).
Nightmares, morning headache, sweat-soaked clothing (nocturnal hypoglycaemia).
Regular overnight glucose monitoring; educate on "silent" hypoglycaemia; adjust basal insulin and bedtime snack.
INFARMED Prontuário Terapêutico (11th ed., 2012), 8.4.1 Insulins; DailyMed — Humulin N (NPH) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6edd793-440b-40c2-96b5-c16133b7a921
Lithium can alter insulin sensitivity and destabilise the basal glycaemic control provided by NPH insulin.
Lithium-induced insulin resistance increases basal insulin requirements (hyperglycaemia); in combination, NPH peaks become unpredictable.
Fasting glucose, serum lithium, HbA1c.
Polydipsia/polyuria, weight loss (hyperglycaemia).
Reassess fasting glucose 1–2 weeks after lithium dose changes; adjust basal insulin; educate on hypoglycaemia.
INFARMED Prontuário Terapêutico (11th ed., 2012), Lithium Carbonate entry; DailyMed — Humulin N (NPH) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6edd793-440b-40c2-96b5-c16133b7a921
Diabetic patients treated with NPH (isophane) insulin — insulin bound to protamine — have an increased risk of severe anaphylactic reactions to IV protamine given as a heparin antidote.
NPH insulin is an insulin-protamine suspension (Prontuário 8.4.1); prior exposure generates anti-protamine antibodies; IV protamine can cause severe hypotension and anaphylaxis (Prontuário 4.3.1.1: "anaphylactic reactions in diabetic patients who received protamine zinc insulin"; EMC Prosulf 4.4).
Anaphylaxis signs (sudden hypotension, bronchospasm, urticaria) during infusion; aPTT/ACT.
Sudden blood pressure drop, breathing difficulty, cardiovascular collapse.
ALWAYS ask about NPH/protamine-zinc insulin exposure before IV protamine; slow infusion (≤ 5 mg/min, max 50 mg/dose) with resuscitation team available; consider alternatives (heparin withholding, bexatra).
EMC-UK — Prosulf (Protamine Sulfate) 10mg/ml SmPC [Wockhardt], sec. 4.2/4.4: https://www.medicines.org.uk/emc/product/8/smpc; INFARMED Prontuário Terapêutico (11th ed., 2012), 4.3.1.1 Heparins: anaphylactic reactions in diabetics on protamine zinc insulin; DailyMed — Protamine Sulfate Injection label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c76876da-b9a8-45d0-9278-7df3288d3a06
Combining NPH insulin (basal) with gliclazide (sulfonylurea) increases the risk of hypoglycaemia (NPH peaks 4–12 h overlapping the sulfonylurea effect), requiring dose adjustment.
Both lower glucose through different mechanisms (SU increases insulin secretion + exogenous insulin; the NPH peak 4–12 h may overlap the SU peak) (labels; Prontuário 8.4).
Capillary glucose (including overnight), HbA1c, weight.
Night sweats, morning headache, confusion (hypoglycaemia).
Careful titration of the sulfonylurea and basal insulin; capillary glucose especially overnight; consider sulfonylurea reduction when introducing insulin.
DailyMed — Glipizide Tablet [Apotex] (sulfonylurea class) and Humulin N (NPH) labels: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dcf426b8-bcdc-8214-a1b6-6388bd3399a0
Non-selective propranolol blocks hepatic glycogenolysis and masks the hypoglycaemia symptoms of the NPH insulin peak, especially overnight.
Hepatic β2 blockade prolongs and worsens hypoglycaemic episodes; β1 blockade removes the tachycardia warning (Prontuário 8.4.1; NPH label).
Overnight glucose, neurological status, sweating.
Morning confusion, headache, profuse night sweats.
Prefer a cardioselective beta-blocker; overnight glucose; consider NPH dose reduction if recurrent episodes.
DailyMed — Humulin N (NPH) and Inderal (propranolol) labels: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6edd793-440b-40c2-96b5-c16133b7a921; INFARMED Prontuário Terapêutico (11th ed., 2012), 8.4.1.
Alcohol inhibits hepatic gluconeogenesis and potentiates nocturnal hypoglycaemia induced by NPH (intermediate-acting insulin).
Avoid alcohol at dinner/before bed; monitor night-time glucose.
Prontuário Terapêutico INFARMED, 8.4.1; site monograph (NPH insulin — monitor night-time glucose).
Alcohol potentiates NPH insulin-induced hypoglycaemia (inhibits hepatic gluconeogenesis); risk is higher with intermediate-acting insulins.
Advise avoiding alcohol while fasting; reinforce glucose self-monitoring and hypoglycaemia awareness education.
Prontuário Terapêutico INFARMED, 8.4 Insulins: "special concern... alcoholics".
Hypoglycaemia in patients with coronary or cerebrovascular disease can precipitate ischaemia/arrhythmia.
Less aggressive glycaemic targets; avoid documented hypoglycaemia; enhanced surveillance.
Prontuário Terapêutico INFARMED, 8.4: "individuals with coronary or cerebrovascular disease".
Like regular insulin, NPH is the antidiabetic of choice in pregnancy — the intermediate peak covers basal needs and it is the most studied basal insulin in gestation. Annex 1 records use with frequent assessment of requirements; severe maternal hypoglycaemia is the main risk to monitor (neuroglycopenia can harm the fetus).
Compatible and indicated; in gestational diabetes the typical regimen is NPH basal + regular pre-meals; monitor maternal hypoglycaemia, especially in the 1st trimester.
Compatible (see regular insulin, l. 42790).
Prontuário Terapêutico INFARMED — Annex 1: "Insulins" (l. 40605, 40619-23); Annex 2 (l. 42790). EMC-UK (MHRA) — Insulin Human SmPC (Insulatard).
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Basal-profile blood glucose lowering; onset 1–2 h, peak 4–12 h, duration 18–24 h (SC).
Same receptor as regular insulin; ionic binding to protamine delays dissociation and diffusion in subcutaneous tissue, prolonging absorption (isophane crystal depot). The depot protamine is also a clinically relevant allergen: patients on NPH can develop anti-protamine antibodies, which increase the risk of anaphylactic reaction to IV protamine (the heparin antidote).
SC only: prolonged and variable absorption from crystal depot (never IV — risk of severe hypoglycaemia and embolisation).
Identical to regular insulin (IDE degradation); protamine is degraded by peptidases.
~ 12–18 h (SC; dependent on isophane depot absorption).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
