ANTI HISTAMINES Receptor Distribution Response H1 Smooth Muscle Endothelium Brain H2 Gastric Mucosa Cardiac Tissue Mast Cells Brain H3 Presynaptic: Brain, Myenteric plexus H4 Eosinophils, Neutrophils, CD4-T cell H 1 -receptor antagonists It has been discovered that these H 1 -antihistamines are actually inverse agonists at the histamine H 1 -receptor, rather than antagonists per se. All H1 antagonists are reversible, competitive inhibitors of histamine receptors. Some of the first-generation H1-receptor blockers (eg, diphenhydramine, clemastine, promethazine) are also potent competitive inhibitors of muscarinic receptors and may cause anticholinergic syndrome (eg, sinus tachycardia, dry skin, dry mucous membranes, dilated pupils, ileus, urinary retention, agitated delirium). H1-receptor blockers may disrupt cortical neurotransmission and block fast sodium channels. These effects can exacerbate sedation, but they also can result in seizure activity.
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ANTI HISTAMINESReceptor Distribution Response
H1Smooth MuscleEndothelium Brain
H2
Gastric MucosaCardiac TissueMast CellsBrain
H3 Presynaptic: Brain, Myenteric plexus
H4 Eosinophils, Neutrophils, CD4-T cell
H1-receptor antagonists
It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se.
All H1 antagonists are reversible, competitive inhibitors of histamine receptors.
Some of the first-generation H1-receptor blockers (eg, diphenhydramine, clemastine, promethazine) are also potent competitive inhibitors of muscarinic receptors and may cause
Dosis : dws&anak≥12thn (1kaps atau 2sdt), anak 6-12thn (2sdt), 2-6thn – BB<30kg : 1sdt, 1-2thn (1/2 sdt). Semua dosis- 1x/hr.
H2 receptor antagonists tidak dibahas
block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells.
H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective proton pump inhibitors. In
the United States, all four FDA-approved members of the group—cimetidine, ranitidine, famotidine, and nizatidine—are available over the counter in
relatively low doses.
Pharmacology
The H2 antagonists are competitive antagonists of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells
and the meal-stimulated secretion of acid.
They accomplish this by two mechanisms: Histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors, which
stimulate acid secretion; therefore, other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells
when the H2 receptors are blocked.
Like the H1-antihistamines, the H2 antagonists are inverse agonists rather than true receptor antagonists.
Clinical use
Peptic ulcer disease (PUD)
Gastroesophageal reflux disease (GERD/GORD)
Dyspepsia
Prevention of stress ulcer (a specific indication of ranitidine)
People that suffer from infrequent heartburn may take either antacids or H2-receptor antagonists for treatment. The H2-antagonists offer several advantages over antacids,
including longer duration of action (6–10 hours vs 1–2 hours for antacids), greater efficacy, and ability to be used prophylactically before meals to reduce the chance of
heartburn occurring. Proton pump inhibitors, however, are the preferred treatment for erosive esophagitis since they have been shown to promote healing better than H2-
antagonists.
H2 antagonists are, in general, well-tolerated, except for cimetidine, wherein all of the following adverse drug reactions (ADRs) are common. Infrequent ADRs include
hypotension. Rare ADRs include: headache, tiredness, dizziness, confusion, diarrhea, constipation, and rash.[1] In addition, cimetidine may also cause gynecomastia in
males, loss of libido, and impotence, which are reversible upon discontinuation.
H3 receptors anatgonist
H3 receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine.
Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H1 receptors in the cerebral
cortex. Consequently unlike the H1 antagonist antihistamines which are sedating, H3 antagonists have stimulant and nootropic effects, and are being researched as potential
drugs for the treatment of neurodegenerative conditions such as Alzheimer's disease.
Examples of selective H3 antagonists include clobenpropit, ciproxifan.
Topical corticosteroid should only be used if there is a fast secondary eczematous (eczema-like) reaction, and used only in combination with the topical antifungal preparation.
Systemic therapy should be considered if the athletes foot infection features:
- If your toe nails are also involved- If its severe Moccasin type (fine scales on the soles of your feet with some redness)- If you do not respond to topical therapy
Jock itch (groin infection)
General advice as posted in the Prevention section Topical antifungal cream is usually sufficient. Apply on the affected area and
4-6 cm on the surrounding skin Use for 2 weeks after the rash has gone Also treat your feet if there is evidence of fungus infection If the infection spreads to the buttocks and/or abdomen, topical applications
may prove difficult; consider oral antifungal drugs instead
Ringworm (skin infection)
Localized infection Topical antifungal cream is usually sufficient. Apply on the affected area and
4-6 cm on the surrounding skin Use for 2 weeks after the rash has gone If the infection is extensive, and therefore makes topical applications difficult,
oral antifungal drugs may be the best method If fungal culture indicates that the fungus is animal in origin, a veterinarian
should be consulted
Nail infection
If your nail changes are asymptomatic (you have no symptoms), you may decide against treatment after weighing the risks. In the past prolonged oral treatment was the only option. For early nail fungal infection a new penetrating antifungal lacquer has provided another alternative with no risk of systemic side effects.
Patients who have diabetes or peripheral vascular disease may be at increased risk of developing complications such as secondary bacterial skin infections from having persistent nail or skin fungal infection
Terbinafine is the oral treatment of choice. For the toenails a minimum of 3 months treatment is required, whereas 6 weeks may do for the fingernails. Severe liver reactions have been observed rarely with this drug. It is recommended that LFTs be measured before and one month into treatment. This drug can also alter your ability to taste.
Itraconazole is an alternative drug that can be used. It is effective if there is Candida or in the immunosuppressed patient with non-dermatphyte infection such as Aspergillus. Care must be taken with this drug in those at risk of heart failure, or in the elderly who are on negative inotropic drugs. Liver function tests are recommended if there is a history of liver disease or for treatment periods longer then 1 month . This drug can be taken daily for 1 week out of every month for 3 to 4 cycles.
Ciclopirox Nail Lacquer is a useful product in treating early nail fungus infection. It avoids the risks of oral medication, it is useful when the infection is limited to part of the nail, as well as for the superficial type of infection showing white nail changes. It has also been useful for treatment of chronic paronychia which causes the skin around the nail to become red and mushy, and can give the nail a green tinge
Scalp infection
If your child has a scalp infection, there is no need to stay away from school once they have started treatment
Shampoos containing antifungal ingredients such as Ketoconazole may be helpful in reducing risk of spreading infection.
Prevention of Fungal Infections
Check out these tips …
It's important to understand that although fungal infections are annoying and can cause some discomfort, you don't need to miss school or work. However, care should be taken to minimize skin-to-skin contact with others.
Wear flip-flops in changing areas. Use antifungal sprays or powders in shoes and feet. Dry the feet and between the toes last after a shower to prevent spread to
other parts of the skin. Avoid tight or closed footwear especially in warm climates. Change socks daily. Cotton socks keep the feet cooler. Wash towels daily.
Ringworm (skin infection)
Ringworm on the body can either spread from fungus elsewhere on the skin or from animals. It can also spread from contact with others.
Nail infection
An infected toenail is common but there won't always be symptoms. You may see a thickening of the nail, which can be uncomfortable when it
rubs against footwear. You may also see an infection of the skin, especially the web space between
the outer toes.
Jock itch (groin infection)
Wash the groin daily. Dry the skin carefully after bathing. Do not dry the feet before the groin to reduce the risk of spreading fungus
from the feet. Change underwear daily. Wash towels daily.
Scalp infection
An infection of the scalp would show an increase of fungus. It can be spread to others in the same family, or at school. There is no need to keep children out of school but combs and head wear
should not be shared with other children. There is always a risk of the infection being spread from pets.
Jock itch (groin infection)
Wash the groin daily. Dry the skin carefully after bathing. Do not dry the feet before the groin to reduce the risk of spreading fungus
from the feet. Change underwear daily. Wash towels daily.
Ketoconazole
It was originally developed in the late 1970's in the oral form and granted FDA acceptance in 1981. Shortly after the topical formulations were undergoing trials and proven effective. The 2% cream and 1% shampoo are now available over the counter. It is effective against yeasts and dermatophytes, both systemically and topically. It is now mainly used systemically in treating life-threatening fungal infections
Pityriasis versicolor Ketoconazole 200mg po daily x5-10d
Other antifungal indications Ketoconazole 200-400mg po daily.
Therapy to be continued for 1-2 weeks in candidal infections; for 1- 8 weeks in dermatophytes; and for 6 months or longer in systemic mycoses
Systemic
Safety and efficacy have not been established for systemic use in children < 2 years of age
> 2 years of age
Ketoconazole 3.3-6.6 mg/kg po daily
Topical
Dandruff Ketoconazole 1% shampoo every 3-4 days for up to 8 weeks
Seborrehic dermatitis
Ketoconazole 2% shampoo or cream twice a week for 2-4 weeks. Apply to the hair and scalp, leave for 5 minutes and wash off
Pityriasis versicolor
Ketoconazole 2% shampoo single application to the affected areas and surrounding skin. Leave for 5 minutes and rinse.
Tinea corporis, cruris, pedis and cutaneous candidiasis
Ketoconazole 2% cream applied to the affected areas, and surrounding skin once a day until clear.
Vulvovaginal candidiasis
Ketoconazole 5-10 mg/kg po daily yx5d
Paronychia
Ketoconazole 5-10 mg/kg po daily
Topical
Safety and efficacy have not been established for topical use
Safety Information
Concurrent use with cisapride, aztemizole and terfenadine is contraindicated. Ketoconazole cream contains sulfites to which some patients may be allergic Hepatotoxicity may occur and has led to reported deaths. Ketoconazole may increase serum digoxin concentrations and lead to toxicity.
Side Effects
Local cutaneous effects may include itching, stinging, irritation or contact dermatitis.
Cutaneous effects may include hypersensitivity reactions including exfoliative dermatitis and Stevens-Johnson syndrome
Gastrointestinal effects may include nausea, abdominal pain, diarrhea, constipation, loss of appetite and rarely, hepatotoxicity.
Hematologic effects may include agranulocytosis or thrombocytopenia.
Other effects may include headache, dizziness and drowsiness. Azospermia, impotence, decreased libido in menstrual irregularities may occur as a result of corticosteroid
and testosterone suppression.
FDA Pregnancy Category C
Animal studies have shown teratogenicity and embryonic toxicity when given very high oral doses. Use of ketoconazole is not recommended during pregnancy or lactation.
Mechanism of Action / Pharmacokinetics
The azole antifungals interfere with cytochome P450 enzyme activity and inhibit demethylization of 14-alpha-methylsterolsterols to ergosterol. Since ergosterol is essential to the
fungal cell membrane, when it is depleted the fungal cells are destroyed.
Ketoconazole may also interfere with the conversion of lanosterol to cholesterol, affecting steroid hormone synthesis.
Systemic ketoconazole is well distributed, however it does not penetrate the CSF. Topical application does not result in significant systemic absorption.
Clotrimazole
Azole: a broad spectrum antifungal developed in 1967. It was one of the first azoles to be developed. Formulations are now generic in a number of countries. It is effective against Candida albicans and the dermatophytes. Its action is fungistatic or fungicidal, depending upon the concentration used. This azole drug is available in a variety of dosage forms, including oral lozenges and vaginal formulations. It is also available in a variety of combinations with antibiotics and corticosteroids.
Tinea corporis Tinea cruris Tinea pedis Pityriasis versicolor Cutaneous candidiasis Nail and skin infections, fungal or gram positive
Therapeutic Regimen
Adult Pediatric
Dermatomycoses
Clotrimazole 1% cream, solution, or lotion bid
x14-28d, apply in a thin layer to the affected
area and surrounding skin.
Topical preparations should not be used
in children < 2 years old
Vaginal preparations are not
recommended for children < 12 years
old
Lozenges should not be used in children
< 5 years old
Safety Information
Avoid applying dressings that seal the area Elevated liver function tests have been observed in patients using
Clotrimazole lozenges.
Side Effects
Local cutaneous effects may include irritation, hypersensitivity, burning, pruritus, erythema, fissuring, or swelling.
FDA Pregnancy Category COral formulation shows toxicity in animal trials. Use is not recommended during pregnancy or lactation.
Mechanism of Action / Pharmacokinetics
Clotrimazole damages the fungal cell wall and alters the permeability. It also inhibits the activity of intracellular enzymes, leading to a buildup of toxic concentrations of hydrogen peroxide within the fungal cell, causing death of the cell. Systemic absorption is minimal.
Ciclopirox
Antifungal, topical. Ciclopirox olamine is a hydroxypyridone antifungal that is
structurally unrelated to other antifungal agents.
It was first introduced in 1975 and has been accepted and used in Europe for many
years. It was approved by the FDA in 1982 for the treatment of superficial fungal
infections. A new lacquer formulation was approved in 1999.
Trade Name:
Penlac* Dermik
Loprox* Dermik
Dosage Forms:
Nail lacquer solution: Ciclopirox olamine 8% Penlac Nail Lacquer*
Topical Gel: Ciclopirox olamine 1% Loprox*
Cream: Ciclopirox olamine 1% Loprox*
Lotion: Ciclopirox olamine 1% Loprox*
The topical application of this drug was one of the first effective antifungals for
superficial dermatophyte, yeast, and fungal infections. The most recent formulation,
a lacquer, has made ciclopirox convenient in the treatment of nail infections.
Used for
Tinea corporis Tinea cruris
Tinea pedis Tinea versicolor Candidiasis, cutaneous Nail lacuer- Onychomycosis
Therapeutic Regimen
Adult Pediatric
Ciclopirox 1% lotion, gel or cream applied to the affected areas twice a day.
Ciclopirox 8% nail lacquer to be applied daily as directed and removed once a week. Continue up to 48 weeks if necessary.
PediatricSafety and efficacy have not been established for children < 10 years of age.
Safety Information
Adverse Effects Cutaneous effects may include local irritation or burning when first applied.
FDA Pregnancy Category B Adequate human studies have not been completed. Animal studies have not shown adverse fetal effects. It is not known if ciclopirox is distributed in breast mi
Terbinafine Hydrochloride
Antifungal, allylamine -one of the first antifungals of the allylamine class, discovered
in 1974. It was approved for systemic use in the UK in 1991, and for topical use in the
USA in 1992.
Terbinafine is an antifungal effective against Dermatophytes, Aspergillus sp., and
Candida and Pityrosporum yeasts. Terbinafine is only fungistatic against Candida,
however cure is possible after 2-4 weeks of treatment (-).
It is available in systemic and topical formulations. Systemic treatment is usually
reserved for infections of the nails, extensive cutaneous infections or those, which have
Itraconazole 100mg oral solution po daily x 3weeks
Onychomycosis
Itraconazole 200 mg twice a day po x1week, followed by 200 mg twice a day for the first week of each month. For toenail involvement, continue treatment x12 consecutive weeks
Safety and efficacy have not been established.
Patient Monitoring
Hepatic function tests should be monitored periodically during treatment. Serum potassium may be monitored as hypokalemia has lead to ventricular fibrillation in patients on itraconazole.
Drug Safety Information
!! Warnings & Contraindications !!
Concurrent use with cisapride, azemizole and terfenadine is contraindicated. Iatroconazole capsules not to be prescribed for onychomycosis in patients
with history of congestive heart failure. Hypokalemia has lead to ventricular fibrillation in patients on itraconazole
Adverse Effects
Cutaneous effects may include hypersensitivity reactions including exfoliative dermatitis and Stevens-Johnson syndrome
Gastrointestinal effects may include nausea, abdominal pain, diarrhea, constipation, loss of appetite and rarely, hepatotoxicity.
Other effects may include headache, dizziness and drowsiness.
FDA Pregnancy Category C Animal studies have shown itraconazole to be teratogenic and embryotoxic in dose-related studies. Iatroconazole is distributed in the breast milk.
Major Drug Interactions
Concurrent use of itraconazole anticholinergics, omeprazole, and antacids may reduce the absorption of itraconazole; with digoxin levels may be increased and should be monitored; lovstatin and simvastatin concentrations may be increased, and have been associated with rhabdomyolysis; Didanosene may decrease the absorption of itroconazole; antidiabetic agents can lead to hypoglycemia; cyclosporine and phenytoin plasma concentrations may be increased; triazolam and midazolam serum concentrations may be increased; isoniazid, rifampin metabolism may be affected; anticoagulant effects may be increased.
Fluconazole
Fluconazole is an antifungal azole. It is a broad spectrum antifungal, first approved
in Europe in 1988 and then in America in 1990.
It was the first single dose treatment approved for vaginal candidiasis. Fluconazole is
an effective agent in the treatment and prophylaxis of Candidal infection
Hepatic function tests should be monitored periodically during treatment. Transient increases in transaminases have rarely led to hepatotoxicity in patients receiving fluconazole.
Safety Information
Dose adjustment may be required in patients with renal function impairment.
Side Effects
Cutaneous effects may include hypersensitivity reactions including exfoliative dermatitis and Stevens-Johnson syndrome
Gastrointestinal effects may include nausea, abdominal pain, diarrhea, constipation, loss of appetite and rarely, hepatotoxicity.
Hematologic effects may include agranulocytosis or thrombocytopenia.
Other effects may include headache, dizziness and drowsiness.
FDA Pregnancy Category C
Animal studies report rare fetal abnormalities. Not recommended during pregnancy or lactation.
Major Drug Interactions
Concurrent use of antidiabetic agents can lead to hypoglycemia; cyclosporine and phenytoin plasma concentrations may be increased; anticoagulant effects may be increased.
Mechanism of Action / Pharmacokinetics
Fluconazole inhibits ergosterol synthesis in the cell wall of yeast and other fungi.
In Candida albicans, fluconazole may also inhibit the transformation of blastospores into the invasive mycelial form. Fluconazole is absorbed quickly after oral administration and