Antihypertensive Choices

Thanks to Rita for this post, based on a recent encounter with a difficult to control hypertensive clinic patient:

He was already on Lopressor 100mg BID, Amlodipine 10mg daily, HCTZ 25mg daily combined with an ARB at maximum dose, and hydralazine 100mg TID.  He is at very high risk as he has already had a hemorrhagic stroke.  He also notes morning HTN.  

Reviewing Up to Date, we reminded ourselves a few things:

• Chlorthalidone is a better choice for a thiazide diuretic as it is likely a more potent anti-hypertensive agent, is definitely longer acting, and was the thiazide diuretic used in the ALLHAT study that showed thiazide superior to all other agents in preventing events.  It is very helpful for AM hypertension as the HCTZ likely has already worn off.  There is a more potent hypokalemic effect with chlorthalidone then HCTZ so monitoring is important as is with all diuretics
• The ACCOMPLISH study showed that for combination therapy, Amlodipine/ Benazepril was superior to other agents in preventing events and specifically was superior to Benazepril/ HCTZ which showed increased event rates.  The Up To Date authors actually recommend switching patients well controlled on ACE/ HCTZ to Amlodipine/ Benazepril. 
• Also our patient had cost issues with his ARB so was switched to a long acting ACE.
• In general young patients should be started on ACE or ARB’s as monotherapy with Bblocker as an alternative.  Of course remember in women of child bearing age to caution regarding ACE use.  Otherwise BBlockers should never be used as monotherapy.   Of course if there is a specific indication (post MI, CHF) B Blockers are indicated but would usually be combined with ACE-I.  There have been increased events in older patients with BBlockers.
• Older patients and African American patients should be given long acting CCB’s (like amlodipine) or thiazide diuretics (chlorthalidone preferred as above) as monotherapy
• Initial therapy of course also guided by comorbidities (DM or proteinuria:  ACE or ARB, Post MI, CHF, LV Dysfunction:  ACE-I/ BBlockers, etc.)

Note: Click link for great summary (in physician reference card form) of JNC 7 hypertension guidelines. And since I know you're all waiting with baited breath for it, JNC 8 is due out in 2012!  Mark your calendars!  --sds

Identify the Image

An 8-year-old boy was referred for evaluation of a mass in the midline of the ventral surface of the anterior tongue. The lesion had fluctuated in size since it was first noted 4 months earlier. He was otherwise asymptomatic, and his medical history revealed that he habitually bit his tongue. Examination of the tongue revealed a nontender, smooth-walled, translucent, bluish, fluctuant mass of approximately 8 mm in diameter that was resting on an opalescent base.


What's the diagnosis?
[see first comment to reveal answer]

Oral Diabetes Agents

Class	Mechanism of Action	Benefits	Risks/Concerns
Sulfonylureas	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; long duration of action	Extensive clinical experience; improved microvascular outcomes in UKPDS; low cost; once-daily dosing possible	Hypoglycemia; weight gain; potential impairment of cardiac ischemic preconditioning
Glyburide Glipizide Glimepiride
Glinides (meglitinides)	Bind to sulfonylurea receptor on beta cells, stimulating insulin release; short duration of action	Target postprandial glucose; mimics physiologic insulin secretion	Hypoglycemia; weight gain; no long-term studies; expensive; frequent dosing (compliance an issue)
Repaglinide Nateglinide
Biguanides	Decrease hepatic glucose production	Extensive clinical experience; no hypoglycemia; weight loss or weight neutral; lipid and other nonglycemic vascular benefits; improved macrovascular outcomes; low cost; once-daily dosing available (sustained-release product)	Diarrhea, abdominal discomfort; many contraindications to consider, including serum creatinine >1.4 mg/dL (123.76 µmol/L) and lactic acidosis risk (rare); lowers vitamin B12 levels (without apparent effects on hematologic indices or neurologic function)
Metformin
α-Glucosidase inhibitors	Retard gut carbohydrate absorption	Target postprandial glucose; weight-neutral; nonsystemic	Flatulence, abdominal discomfort; frequent dosing (compliance); expensive
Acarbose Miglitol
Thiazolidinediones	Activate the nuclear receptor PPARγ, increasing peripheral insulin sensitivity. May also reduce hepatic glucose production	Address primary defect of T2DM; no hypoglycemia; lipid and other nonglycemic vascular benefits; probable decreased macrovascular outcomes with pioglitazone; greater durability of effectiveness; once-daily dosing	Edema and heart failure risk; weight gain; possible increased fracture risk in women; possible increased myocardial infarction risk with rosiglitazone; slow onset of action; expensive
Rosiglitazone Pioglitazone
Amylinomimetics	Activate amylin receptors, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	Weight loss	Nausea, vomiting; hypoglycemia risk when used with insulin; no long-term studies; injectable; expensive; frequent dosing (compliance)
Pramlintide
Incretin modulators	Activate GLP-1 receptors, increasing glucose-dependent insulin secretion, decreasing glucagon secretion, delaying gastric emptying, and enhancing satiety	No hypoglycemia; weight loss	Nausea, vomiting; possible pancreatitis (rare); no long-term studies; injectable; expensive
GLP-1 mimetics Exenatide
DPP-IV inhibitors	Inhibit degradation of endogenous GLP-1 and GIP, thereby enhancing the effect of these incretins on insulin and glucagon secretion	No hypoglycemia; weight neutral; once-daily dosing	Possible urticaria/angioedema (rare); no long-term studies; expensive
Sitagliptin
Bile acid sequestrants	Bind cholesterol within bile acid; unknown mechanisms of antihyperglycemic effect	No hypoglycemia; weight neutral; lowers LDL-cholesterol	Constipation; may increase triglycerides; no long-term studies; expensive
Colesevelam

Reference: MKSAP 15
http://mksap15.acponline.org/tables/en_t07

Hyperbilirubinemia in the Newborn

Excellent, concise summary of hyperbilirubinemia in the newborn from Pediatrics in Review.

Link to full text of PIR article.

Remember: http://bilitool.org/

 Summary

• Based on strong research evidence, breastfeeding, prematurity, significant jaundice in a previous sibling, and jaundice noted before discharge from the nursery are the most common risk factors associated with severe hyperbilirubinemia.
• Based on research evaluating benefit versus harm, jaundice in the first 24 hours after birth is not physiologic jaundice and needs further evaluation.
• All newborns should undergo a risk assessment for hyperbilirubinemia before discharge from the newborn nursery and have appropriate follow-up evaluation after discharge.
• Visual assessment of jaundice does not assess the TSB reliably; clinicians should check either a TSB or TcB when in doubt.
• The infant's age in hours is used when evaluating and managing bilirubin concentrations.

Fixed Drug Eruption

A 35-year-old man presented with a 10-day history of a cutaneous lesion on the left anterior chest. Examination revealed an annular, scaly, blistering, violaceous plaque, 5 cm in diameter, with an erythematous periphery. The lesion had appeared 24 hours after the patient began a self-prescribed course of oral trimethoprim–sulfamethoxazole for a respiratory tract infection. Six months earlier, an identical lesion had appeared in the same location after the patient had taken the same drug for 3 days. This first lesion healed after 3 weeks, but residual hyperpigmentation remained. On the basis of this characteristic presentation, a diagnosis of fixed drug eruption was made. Fixed drug eruptions are common, immune-mediated, cutaneous lesions that are typically of acute onset and appear as annular, edematous, sometimes blistering, reddish-brown to violaceous macules or plaques. Their diagnostic hallmarks include residual hyperpigmentation after healing and recurrence at previously affected sites, with subsequent antigenic challenges. This patient received a prescription for a 3-week course of topical glucocorticoids and was advised to avoid sulfonamides in the future.

Reference:

http://www.nejm.org/doi/full/10.1056/NEJMicm1013871

Cutaneous Warts

A 56-year-old man with type 2 diabetes mellitus presented with a 2-year history of slowly progressing, painless lesions on his fingertips. Physical examination revealed hyperkeratotic papules that were clinically diagnostic of common warts (Panels A and B). Warts are a manifestation of cutaneous infection with human papillomavirus (HPV). To limit the cost of the medical supplies required for fingerstick capillary blood glucose monitoring, the patient had been reusing the same lancet several times per day. Cycling from finger to finger resulted in the sequential inoculation of each fingertip with HPV. The patient was advised not to reuse the skin-prick lancets. After 6 weeks of topical treatment with fluorouracil and salicylic acid preparations, there was substantial improvement in the appearance of the lesions (Panel C).

Reference:
http://www.nejm.org/doi/full/10.1056/NEJMicm1009053