Cimetidine for Molluscum

Molluscum contagiosum: chronic poxvirus infection

·         Common disease of childhood but also can occur in adults

·         Transmitted by skin-skin contact anywhere on body

o   sexually or in contact sports

o   scratching or touching a lesion

o   only host is humans but can be spread by fomites on towels or swimming pools

·         Associated with immunocompromised states (HIV or immunosuppressive drugs)

·         May be associated with atopic dermatitis

·         Incubation period typically 2-6 weeks

·         Flesh-colored, dome-shaped papules usually 2-5 mm in diameter

·         Shiny surface with central indentation or umbilication

·         May be associated with pruritus

·         May occur anywhere on body except palms and soles

·         Most common areas: trunk, axillae, antecubital and popliteal fossae, and crural folds

·         Diagnose based on appearance but can do histology to confirm

·         Lesions usually resolve within 2 months but may take up to 1 year

·         Self-limited to technically do not need to treat (in immunocompetent patients)

·         First-line therapy:

o   Cryotherapy – liquid nitrogen

o   Curettage – may cause scars

o   Cantharidin – topical blistering agent, without scarring

o   Podophyllotoxin – antimitotic gel or cream

·         Second-line

o   Imiquimod – topical immunomodulator

o   Potassium hydroxide

o   Salicyclic acid

o   Topical retinoids

·         Oral cimetidine ***

o   H2 antihistamine

o   Immunomodulatory properties

§  Stimulate delayed hypersensitivity

§  T suppressor lymphocytes possess histamine receptors

§  Cimetidine enhances cell-mediated immunity by preventing histamine-induced stimulation of T suppressor activity but underlying mechanism is not clearly understood

§  Has been shown to benefit in varicella zoster, herpes simplex, mucocutaneous candidiasis, etc.

o   Dose studied: 40 mg/kg/day x 2 months – associated with clearance of all lesions

§  Dosage less than 40 mg/kg/day was inffective for viral warts

§  NOT a randomized placebo controlled trial

·         Need to prevent transmission  

o   Cover lesions with clothing or watertight bandage

o   Avoid sharing towels, sponges, etc

angioneurotic edema

A prescription came in to pharmacy electronically from an urgent care for a depo-Medrol injection with an icd10 code for angioneurotic edema

Angioneurotic Edema: a hereditary/genetic form of angioedema, also known as Quinke's disease

• genetic deficiency of C1 esterase inhibitor protein
• autosomal dominant inhereitance
• normally this protein prevents activation of a cascade leading to angioedema
• diagnosis suspected with severe recurrent angioedema
• most common areas: limbs, face, intestinal tract, and airway
• when occurs in larynx --> airway can be compromised
• when occurs in intestinal tract --> severe abdominal pain, nausea, vomiting 
• other symptoms may include fever, joint pain, mucus membrane swelling, brain swelling
• 1/3 of people with condition develop a non-itchy rash called erythema marginatum
• confirm diagnosis by low levels of C1 esterase inhibitor in blood
• attacks can occur every 1-2 weeks and last 3-4 days long
• can be triggered by minor trauma, stress, physical activity, certain medications (anti-hypertensives and heart failure drugs) but can also occur without a known trigger
• treatment & prevention options:
• antihistamines will not work
• androgen steroids may prevent
• C1 esterase inhibitor concentrate prevent attacks
• Cinryze, Ruconest, Berinert -- injected into veins
• encallantide (Kalbitor), icatibant (firazyr) -- injected under skin

There really isn't much evidence in the literature about using steroids for this condition. In fact, the literature I found stated that corticosteroids would not work. Androgen steroids such as danazol, oxandrolone, or methyltestostorone

• these agents work by increasing the level of aminopeptidase P which inactivates kinins which are responsible for angioedema

tetracyclines for blepharitis

tetracyclines for Chronic blepharitis

• one of the most difficult ocular diseases to treat
• 6 types: staphylococcal, seborrheic, seborrheic with staph infection, seborrheic with meibomian seborrhea, seborrheic with spotty inflammation of the meibomian glands, primary meibomianitis
• 2/3 of primary meibomianitis have associated skin condition, acne rosacea
• tetracyclines shown to be effective at treating primary meibomianitis 
• inhibit lipase activity and decrease the release of noxious free fatty acids
• minocycline given 50 mg daily x 2 weeks followed by 100 mg daily until end of study for 6 months
• also doses of 50 mg BID has been studied successfully showed symptom improvement compared to placebo
• meibum is the lipids that come from meibomian glands of patients with primary meibomianitis
• meibum was collected and contains wax and sterol esters, free cholesterol, triglycerides, and diglycerides
• minocycline had greatest effect on decreasing diglycerides, free fatty acids, and cholesterol
• fatty acids and diglycerides promote inflammation
• free cholesterol stimulates bacterial growth
• minocycline decreases fatty acids production and ROS produced by neutrophils
• tetracyclines reduce cytokine levels (IL-6, IL 1b, IL17a, TNFalpha)
• novel anti-inflammatory approach
• tetracyclines also used in ocular rosacea, corneal inflammatory disease, corneal infections
• effects not related to anti-biotic effects -- reduce the free fatty acids that are formed by bacteria on the eyelids
• should also recommend warm compresses 1-4 x day to increase flow of oil from the meibomian glands and help open clogged pores

acetazolamide

During case presentations, student presented that a patient was taking acetazolamide for hydrocephalus until she could get in for surgery, I was unaware of this use for it so needed to look into it more:

hydrocephalus: disorder of excessive amount of cerebrospinal fluid which accumulates in the ventricles and subarachnoid space

• CSF is produced by the choroid plexus -- epithelium and connective tissue in cerebral ventricles
• epithelial cells produce CSF using active transport which is dependent upon carbonic anhydrase
• CSF production is generally constant unless intracranial pressure is increased (absorption matches the production)
• production rate ~20mL/hour, complete turnover 3-4 time a day
• hydrocephalus results from imbalance between inflow and outflow
• obstruction of circulation
• inadequate absorption
• overproduction
• leads to increased intracranial pressure and ventricular dilation
• etiology: congenital, neural tube defects, CNS malformations, intrauterine infections, choroid plexus carcinoma, infections, tumors, post-hemorrhagic
• symptoms: headache, N/V, personality/behavior changes, lethargy
• bradycardia, hypertension, altered respiratory rate
• macrocephaly
• compression of cranial nerves
• Progressive (need to manage or will get worse)
• most effective treatment: surgical drainage using a ventriculostomy shunt (prevents excess accumulation of CSF, shunts CSF to either systemic circulation or peritoneum)
• Medical therapy:
• diuretics: furosemide and acetazolamide decrease CSF production
• used for short periods in slowly progressive hydrocephalus that is too unstable for surgery or until surgery can be done
• diuretics generally not effective for infants
• acetazolamide can be used for: acute mountain sickness, edema, glaucoma, retinal edema,
• need to dose adjust for renal impairment, caution in liver disease (can induce coma
• Mechanism of action: inhibits carbonic anhydrase from catalyzing the reversible hydration of carbon dioxide and dehydration of carbonic acid
• delays abnormal paroxysmal excessive discharge from CNS neurons and affects promotion of diuresis and urinary alkalinization
• adverse effects: metabolic acidosis, stevens Johnson syndrome, hepatic necrosis, agranulocytosis, thrombocytopenia, angle-closure glaucoma
• monitoring: CBC and electrolytes

prazosin for ptsd

PTSD: disorder that develops after exposure to traumatic event involving actual or threatened injury to themselves or others

• presents as: intrusive thoughts, nightmares, flashbacks, avoidance of reminders of the traumas, sleep disturbances
• leads to dysfunction in life
• 70% of patients with PTSD have sleep disturbances
• Mechanism unknown:
• increased central nervous system noradrenergic activity might contribute to pathophysiology
• elevated levels of norepinephrine disturb REM sleep and increase non-REM sleep
• prazosin decreases the arousal produced by norepinephrine in response to a stressor
• specific involvement of postsynaptic alpha 1 adrenoreceptor
• nightmares usually present during light sleep and disturb REM sleep
• prazosin has a role (mechanism unknown) in regulating REM sleep
• diagnosis made if having still having symptoms at least 4 weeks after traumatic event
• early initiation of treatment is best
• can be treated with SSRI's, SNRI's, TCAs, MAOIs, atypical antidepressants, second generation antipsychotics (augmentation).
• alpha-adrenergic receptor blocker: prazosin
• acts centrally (crosses BBB-highly lipophilic) and peripherally
• reduces nightmares
• improves sleep
• 1 mg at bedtime, gradually increase to 3-15 mg as tolerated
• avoid sudden d/c (can result in rebound hypertension)
• often used in conjunction with one of the antidepressant options (^ usually SSRIs)
• use in caution in patients with hypotension, prone to orthostatic hypotension
• studies show well-tolerated and successful improvement in symptoms of PTSD
• side effects: hypotension, dizziness, lightheadedness, orthostatic hypotension, sedation, syncope

Valacyclovir Prophylaxis for wrestling

Question from provider --
Is there evidence to support using valacyclovir prophylactically for wrestlers? (prevention, NOT suppression)

Study analyzed the use of valacyclovir over a 10 year period (2003-2012) in participants at a 28-day wrestling camp in Minnesota for collegiate wrestlers
(Not a RCT) but looked at comparison of outbreaks of herpes gladiatorum from HSV-1 infection between subjects using valacylovir for prophylaxis or not using prophylaxis
3-4% had a known history of HSV-1 infection
29.8% seropositive for HSV-1
use of valacyclovir for prophylaxis --> ~87% reduction in outbreaks
started treatment 3 days before the start of camp and continued treatment through the end of the camp (28 days)
valacylcovir was dosed at 1 gm once daily
subjects also required to take other precautions such as daily skin checks and showers after physical contact
2793 total subjects over 10 years  --> 224-334 subjects annually
23. 1 outbreaks/year on average vs. 3.6 outbreaks/year during study (majority of outbreaks occurred in those not using antiviral prophylaxis)
~1 outbreak/year among the users of antiviral prophylaxis

of the total subject sample size, 2221 available for individual data assessment over 8 year period
71% on prophylactic antivirals
67 with a known history of HSV-1, of these, 9 had outbreak (13.4%)
only 1.1% of total had outbreak with no history of HSV infection

conclusion:
higher usage of prophylactic valacyclovir correlates with reduced number of outbreaks
valacyclovir suppresses seroconversion and reduces shedding of virus
team-wide usage of antiviral prophylaxis is appropriate
proven more efficacious than acyclovir 400 mg BID

Reference:
Prophylactic Valacyclovir to Prevent Outbreaks of Primary Herpes Gladiatorum at a 28-Day Wrestling Camp: A 10-Year Review

Anderson, B. J. MD; McGuire, Dennis P. PhD; Reed, Megan DC ATC; Foster, Monique M.Ed ATC; Ortiz, Deanna ATC

Clinical Journal of Sport Medicine  

Issue: Volume 26(4), July 2016, p 272–278

 

Recommendation: recommend antiviral prophylaxis with valacyclovir

dose --> unsure (the study used 1 gm once daily, but the FDA approved dose for SUPPRESSION is 500 mg once daily

vasopressin receptor antagonists

Vasopressin (ADH) Receptor Antagonists

• treatment of hyponatremia
• alternative or addition to fluid restriction and sodium chloride administration
• vasopressin receptors:
• V2: antidiuretic response
• V1a: vasoconstriction
• V1b: adrenocorticotropic hormone release
• selective free water diuresis (aquaresis) -- do not affect excretion of sodium or potassium
• increased urine output
• decreased urine osmolality
• restoration of serum sodium levels
• increases thirst significantly - limits sodium rise
• oral -- selective V2: tolvaptan (29:1 ratio, V2:V1a)
• IV -- blocks V2 and V1a: conivaptan
• tolvaptan: warnings -- should not be used longer than 30 days -- risk of hepatotoxicity, should not be used in liver disease
• conivaptan: concerns with V1a block leading to hypotension and increased risk of variceal bleeding in cirrhosis patients (vasopressin is used to treat active bleeds), also may worsen renal function in cirrhosis patients -- terlipressin (V1a agonist to treat hepatorenal syndrome)
• have been studied in hyponatremia due to SIADH, heart failure, and cirrhosis
• should NOT be used in patients who are hyponatremic and volume depleted (repletion with saline is primary therapy)
• do not correct sodium too quickly -->  osmotic demyelination of nerves
• no more than 8 mEq/L in 8 hours or 12 mEq/L in 24 hours
• slower rates in malnutrition, alcoholism, advanced liver disease
• only initiate in hospital setting to monitor serum levels
• adverse effects: increased thirst, dry mouth, polyuria
• substrate of cyp3A4 = many DDI's
• monitoring: serum sodium, rate of sodium increase, serum potassium, volume status, signs of hepatotoxicity/ hepatic function test
• half-life ~ 12 hours
• onset of action 2-4 hours, peak at 4-8 hours
• cost:
• 15 mg tablets (wty: 10) = $4293.70