Nitrates: Management of Headache

Availability

• Isosorbide Dinitrate 10mg
• Isosorbide mononitrate 30mg (Imdur)
• Isosorbide mononitrate 60mg (Imdex)

Headache

• most common adverse effects are headache (up to 57%) and dizziness (up to 11%), light-headedness (1% to 10%)
• Treatment with isosorbide mononitrate may be associated with light-headedness on standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol
• present results therefore suggest that NO may elicit a migraine attack in many healthy subjects if a high enough dose is given for several hours.
• A close temporal association between the disappearance of headache and the attenuation of the 5-ISMN induced dilatation of the superficial temporal artery was observed.
• In contrast, tolerance in the middle cerebral artery already appeared after 24 h, which was earlier than the development of tolerance to headache.
• If vasodilatation is the cause of headache the results point to extracerebral arteries.
• However, cytotoxic and pain modulating central nervous system effects of NO, the time courses of which are unknown, may also play a role, involving both intra- and extracranial arteries

Management

• In patients who get these headaches, the headaches are a marker of the activity of the drug.
• Patients should resist the temptation to avoid headaches by altering the schedule of their treatment with isosorbide mononitrate, since loss of headache may be associated with simultaneous loss of antianginal efficacy.
• Aspirin or acetaminophen often successfully relieves isosorbide mononitrate-induced headaches with no deleterious effect on isosorbide mononitrate's antianginal efficacy.
• headaches may gradually become less severe as you continue to use isosorbide mononitrate
• To reduce the risk of headache, your doctor may suggest starting with one-half tablet (30 mg) once daily each morning for the first 2 to 4 days.

Alternatives

• not much evidence available on alternative agents
• Calcium channel blockers are an alternative if there are side effects or other conditions that limit the use of beta blockers and nitrates. 
• Calcium channel blockers may also be used if nitrates and beta blockers do not control angina when used in combination
• Diltiazem dilates blood vessels (especially coronary arteries), decreases the heart's force of contraction, and slows the heart's conduction of electrical impulses.
• When compared to dihydropyridines and verapamil, diltiazem has a lower frequency of side effects and has a more balanced effect, neither markedly dilating blood vessels nor markedly depressing cardiac function.
• dihydropyridine calcium channel blockers and, in some cases, diltiazem can be used in combination with beta blockers for better control of angina. Verapamil, however, is usually not combined with beta blockers because combining the two drugs can markedly slow the heart rate.
• Beta blockers are more effective than calcium channel blockers for reducing the frequency of angina, but similar in terms of improving exercise tolerance and decreasing the need for nitroglycerin.

References:

1. www.drugs.com
2. https://www.ncbi.nlm.nih.gov/pubmed/11037739
3. Imdur and Imdex Product Leaflets
4. www.uptodate.com

Contrast Media Pre Medication

Non-emergent Pre-medication

• Methylprednisolone 32mg PO at 12 hours and 2 hours before contrast injection, plus diphenhydramine (Benadryl®) 50 mg PO/IV/IM 1 hour before contrast injection.
• Note: If oral medications cannot be taken, hydrocortisone 200 mg IV may be substituted for oral prednisone and given 4 – 6 hours before contrast injection Diphenhydramine 50 mg IV should also be administered 1 hour before contrast injection

Emergent Pre-medication (In Decreasing Order of Desirability)

• Methylprednisolone sodium succinate (Solu-Medrol®) 40 mg IV or hydrocortisone sodium succinate (Solu-Cortef®) 200 mg IV 4 – 6 hours before contrast injection, plus diphenhydramine 50 mg IV 1 hour before contrast injection.
• Dexamethasone sodium sulfate (Decadron®) 7.5 mg IV or betamethasone 6 mg IV 4 – 6 hours before contrast injection if there is a known allergy to methylprednisolone, aspirin, or non-steroidal anti-inflammatory drugs, especially if asthmatic. Diphenhydramine 50 mg IV should also be administered 1 hour before contrast injection.
• If the scan must be performed immediately, give diphenhydramine 50 mg IV. IV steroids have not been shown to be effective when administered less than 4 – 6 hours prior to contrast injection.
• Note: Diphenhydramine should not be given to a hypotensive patient.

References:

1. Committee on Drugs and Contrast Media of the American College of Radiology. Manual on Contrast Media, Version 9.0

Paediatric Burn: Analgesia

MAJOR BURNS> 15%

• IV morphine 
• is the most widely used analgesia for burns.
• bolus administration dose: 0.1 mg/kg.
• IV morphine continuous infusion dose: <6months: 0-12.5ug/kg/hour,
• >6months: 0-25 ug/kg/hour.
• Paracetamol 
• 15mg/kg QID.
• Low dose ketamine infusion
• improve analgesia if standard doses of morphine do not provide adequate analgesia for pain.

Transition to oral analgesia

• Oral analgesics are started 1-2 hours before infusion/PCA ceased up.

Oral background	Oral breakthrough
MS Contin (suspension or tablets) l  Starting dose 0.6 mg/kg/dose 12 hourly regularly (for opioid naive) l  Consistent mechanism of delivery - avoids potential risk of over sedation when combined with other agents e.g dressing analgesia or sedating antihistamines	Oral morphine (syrup) l  0.2 mg/kg/dose 4 hourly PRN l  Preferred if nasogastric tube is used for administration Or Oral oxycodone (syrup or 5mg capsules) l  >1 year: 0.2mg/kg/dose 4 hourly PRN l  < 1year:0.1 mg/kg/dose 4 hourly PRN l  Preferred if no nasogastric tube used - more palatable

 MINOR BURNS <15%

•  Paracetamol
• 15 mg/kg/does 6 hourly regularly (all children)
• For breakthrough analgesia
• Oxycodone: 
• >1 year: 0.2 mg/kg/dose 4 hourly PRN, <1 year: 0.1 mg/kg/dose 4 hourly PRN
• Ibuprofen: 
• 10 mg/kg/dose 6-8 hourly PRN (cease 48 hours prior to surgery/grafting). Not to routinely prescribe for children <3 months
• Tramadol: 
• 1-2 mg/kg 6 hourly PRN
• For more extensive burns/adequate analgesia: 
• Morphine infusion or PCA with oral analgesia
• MS Contin: 
• 0.6 mg/kg/dose 12 hourly can be used to maintain comfort and facilitates in regular face care

References:

1. Guidelines for the Management of Paediatric Burns, Women’s and Children’s Hospital, 2010.
2. Gandhi, M., Thomson, C., Lord, D., & Enoch, S. (2010). Management of pain in children with burns. International journal of pediatrics, 2010.
3. Krishnamoorthy, V., Ramaiah, R., & Bhananker, S. M. (2012). Pediatric burn injuries. International journal of critical illness and injury science, 2(3), 128.

Availability : Antidiabetic medication

Insulin

Types of insulin	Name and dose	Brand
Rapid-acting	Insulin Glulisine 100iu/ml	Apidra SoloStar ®
Short-acting	Insulin Actrapid 100iu/ml	Actrapid®
	Insulin Actrapid 100iu/ml (3ml) Penfill	Actrapid Penfill®
	Insulin Insuman Rapid 100iu/ml (3ml) Penfill	Insuman Rapid®
Intermediate-acting	Insulin Insulatard 100iu/ml (10ml)	Insulatard®
	Insulin Insulatard 100iu/ml (3ml) Penfill	Insulatard Penfill®
Long-acting	Insulin Glargine 100iu/ml	Lantus SoloStar®
Premixed	Insulin Mixtard 100iu/ml (3ml) Penfill	Mixtard 30 Penfill®
	Insulin Insuman Combo30 100iu/ml (3ml) Penfill	Insuman Comb 30®
	Insulin Novomix30 100iu/ml	Novomix 30 Flexpen®

Oral Hypoglycaemic Agent (OHA)

Classification of OHA	Name and dose	Brand
Biguanide	Metformin 500mg	Glumet DC®
	Metformin XR 500mg	Proglutrol 500®
Sulphonylurea	Glibenclamide 5mg	Glibenclamide®
	Gliclazide 80mg	Gliclazide®
	Gliclazide Modified Release 30mg	Remicron MR®
α-glucosidase	Acarbose 50mg	Garbose®
Dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor)	Saxagliptin 5mg	Onglyza®
Biguanide + DPP-4 inhibitor	Metformin 1g + Vidagliptin 50mg	Galvus Met®