dermatotherapeutics - systemic prof. satyendra kumar singh department of dermatology and venereology...
DESCRIPTION
Introduction The current-day dermatologist is well equipped with an array of therapeutic tools in his/her armamentarium for the successful management of various dermatoses. A better understanding of diseases has resulted in the evolution of drugs that act more specifically with minimal risk to the patient. Drug interactions, resistance and side effects, however, pose challenge to the treating physician. Commonly used systemic agents in dermatological disorders will be discussed.TRANSCRIPT
Dermatotherapeutics - Systemic
Prof. Satyendra Kumar Singh Department of Dermatology and Venereology
Institute of Medical Sciences,B.H.U., Varanasi
Digital Lecture Series : Chapter 31
CONTENTS
Introduction
Sulfones
Antihistamines
Systemic Steroids
Antibacterial Agents
Antifungal Drugs
Antiviral Drugs
Antiparasitic Agents
Retinoids
Cytotoxic Agents
Antimalarials
Drugs Used During Pregnancy &
Lactation
MCQs
Photo Quiz
Introduction
The current-day dermatologist is well equipped with an array of
therapeutic tools in his/her armamentarium for the successful
management of various dermatoses.
A better understanding of diseases has resulted in the evolution of drugs
that act more specifically with minimal risk to the patient.
Drug interactions, resistance and side effects, however, pose challenge to
the treating physician.
Commonly used systemic agents in dermatological disorders will be
discussed.
Sulfone : Dapsone
Metabolized in liver and excreted by the kidneys Doses : 50 to 300 mg/day Drug interaction : with rifampicin, probenecid, omeprazole, and
trimethoprim Dapsone resistance : reported in leprosy (changes in DNA sequences in fol
P gene) Important indications : Leprosy, Dermatitis herpetiformis, erythema
elevatum diutinum Other indications : Bullous eruption in SLE, linear IgA disease,
actinomycetoma, bullous pemphigoid, subcorneal pustular dermatosis, chronic bullous disease of childhood, ITP, acne conglobata, pyoderma gangrenosum.
Dapsone : Adverse effects
Pharmacologic : hemolytic anemia and methemoglobinemia
GI system : Gastric irritation, nausea, anorexia, hepatitis, cholestatic
jaundice
Headache, fatigue, psychosis
Muco-cutaneous : morbilliform eruptions, erythema multiformae,
exfoliative dermatitis, SJS/TEN
Leukopenia, agranulocytosis
Peripheral neuropathy (almost always motor)
Antihistamines
Histamine receptors are of four types:-• H1 receptors : vasodilation of small vessels, smooth muscle
contraction and itching.• H2 receptors : gastric acid production.• H3 receptors : located in brain, & responsible for histamine production
& release. • H4 receptors : on immune active cells (eosinophils, neutrophils), in GIT
and CNS Antihistamines classification:-• Traditional/classic or First generation• Low-sedating or second and third generation• H2 type antihistamines
H1 antihistamines (H1 AH)
Both traditional & low sedating antihistamines are commonly used in dermatological disorders.
Low sedating AH are preferred in chronic urticaria. First generation antihistamines cause sedation as they cross blood brain
barrier. Most H1 AH are FDA category B or C Some AH (hydroxyzine, fexofenadine) cross the placenta while some
others (chlorpheniramine, cetrizine, loratadine) do not cross. Desloratadine and mizolastine are safe in renal disease patients. Cetrizine, fexofenadine and desloratadine are safe in hepatic patients
First generation antihistamines Doses
Chlorpheniramine maleate 25-50mg, 6-8 hourly
Diphenylhydramine HCl 25-50mg, 6-8 hourly
Promethazine 12.5-25mg, 6-8 hourly
Hydroxyzine HCl 10-25mg, 6-8 hourly
Cyproheptadine HCl 4-5mg, 8-12 hourly
First generation antihistamines
Second & third generation antihistamines have minimal sedative &
anticholinergic effects.
Examples – Cetirizine (10mg), Levocetirizine (5mg), loratidine (10mg),
Desloratidine (5mg), Ebastine (10-20mg), Fexofenadine (30-180mg).
Traditional antahistimines need to be used in multiple daily dosages
while newer drugs are used in a once daily dose.
Presence of H2 receptors in the cutaneous vasculature justifies their
use in dermatology.
Second and third generation antihistamines
Mechanism of action
Act by competitive inhibition of the actions of histamine by receptor
blockade thereby reducing histamine mediated pruritus.
These drugs also prevent vasodilation, transdution and formation of
typical wheals on the vascular endothelial surface.
Indications
Indicated as first line treatment for pruritus, urticaria & angioedema.
Side Effects
Sedation & impaired concentration are the main adverse reaction
hence evening dosing is preferred.
Anti-cholinergic effects include mucosal dryness, urinary retention &
precipitation of Glaucoma.
Cutaneous side effects include photosensitivity & eczematous
dermatitis.
Precautions
One should always observe caution while using antihistamines in
hepatic diseases, epilepsy, BPH, Glaucoma, porphyria, &
concomitantly with CNS depressants.
Loratidine is currently approved as a safe drug to use in pregnancy &
lactation.
Chlorpheniramine and diphenhydramine are also considered safe in
pregnancy.
Systemic Steroids
Systemic steroids are used for their anti-inflammatory &
immunosuppressive effects in various dermatoses.
Mostly low doses are used over the shortest possible time period.
High doses of steroids are used in emergencies & in periods of stress
and trauma.
Mechanism of Action
At the Cellular Level
Steroids passively diffuse through the cell membrane.
Bind to intra-cytoplasmic soluble protein receptors to form a complex.
This complex enters the nucleus.
Regulates the transcription of a limited number of genes.
Decreased synthesis of pro-inflammatory molecules (ILs, cytokines, &
proteases).
Synthesis of lipocortin increases
Reduces phospholipase A2 activity
Reduces the concentration of PGs, & LTs.
Steroids reduce the no. of monocytes, lymphocytes & eosinophils and
increase the no. of neutrophils.
They modify cellular activation, proliferation & differentiation
Long Term Systemic Steroids – Pemphigus, bullous pemphigoid, SLE,
dermatomyositis, eosinophilic fasciitis, vasculitis, neutrophilic
dermatoses & lepra reaction.
Short Term Schedule – Atopic dermatitis, acute/disseminated
eczema of varying etiology.
Also used in Toxic epidermal Necrolysis, Erythema Nodosum ,
erythema multiforme, exfoliative dermatitis, Lichen planus and
Discoid lupus erythematosus.
Indications
FDA-approved indications of systemic steroids
Pemphigus vulgaris, pemphigus foliaceus
Bullous pemphigoid
Stevens Johnson Syndrome and TEN
Systemic lupus erythematosus
Dermatomyositis
Erythema multiformae minor
Severe urticaria
Pemphigus Vulgaris SLE
Equivalent Doses of Corticosteroids
Prednisolone/Prednisone 5 mg
Methylprednisolone 4 mg
Triamcinolone 4 mg
Deflazacort 6 mg
Betamethasone/Dexamethasone 0.75 mg
Hydrocortisone 20 mg
Side Effects
Adverse effects vary & depend on the type of steroid used, the dosage & duration and patient factors.
Low dose administration over a longer duration is more likely to precipitate side effects than a high dose over a short period.
Immunosuppression, precipitation of infection & suppression of the HPA axis.
Following lists the side effects in head to toe order :- raised ICT, psychosis, glaucoma, premature cataract, cushingoid features, activation of pulmonary TB, hypertension, gastritis, perforation, pancreatitis, worsening of diabetes, osteoporosis, premature closure of epiphysis, avascular necrosis of the femur.
Calcium and Vit. D supplementation is essential in postmenopausal women & elderly patient.
Drug Interactions
Steroids increase the metabolism of barbiturates, phenytoin, rifampicin,
salicylates, antihypertensive, anti diabetic and increase in their dosage
during concomitant therapy is therefore essential.
Antibacterial Agents
PENICILLINS
Still the drug of choice for infections caused by gram-positive cocci.
Antistaphylococcal penicillins include oxacillin, dicloxacillin, flucloxacillin
and naficillin orally for mild infections or systematically.
Acute side effects-life-threatening angioedema and hypersensitivity
reactions such as urticaria, morbifilliform rashes, exfoliatve dermatitis,
drug fever, serum sickness or Stevens Johnson syndrome.
Injectable form are always preferred over oral forms for their proven
efficacy.
Other Penicillins
Aminopenicillins (ampicillin, amoxicillin) Carboxypenicillins (Carbenicillin, Ticarcillin) Ureidopenicillin (Mezlocillin, Azlocillin, Piperacillin) ß-lactam group of Monobactams (Aztreonam) & Carbapenems
(Imipenem, Meropenem). ß-lactamase inhibitors – Clavulanic acid, Sulbactam, Tazobactam NOTE : In combination formulations these restore the antibiotic
activity of Amoxicillin, Ticarcillin (Clavulanic acid), ampicillin (Sulbactam), Piperacillin & Cefoperazone (Tazobactam), against a spectrum of both gram positive & negative organisms.
Antibiotic allergic reactions and diarrhea are the main threat with combinations.
Cephalosporines
These broad spectrum antibiotics are best used as second line drugs
in bacterial infections.
Based on ß- lactamase stability & in vitro test these are classified as:-
Generation Drug details with adult dosingFirst generation(Gram Positive)
Cefadroxil (0.5-1gm BD orally), Cephalexin (0.5-1gm QID orally)
Second generation(Gram Positive)
Cefuroxime (1.5gm 6-8 hourly, I.V. )Cefoxitin (2gm 4-6 hourly, I.V. )Cefaclor (0.5-1gm TDS, orally)
Third generation(Nosocomial Gram Negative including Enterobactericeae & Ps. Aeruginosa)
Ceftriaxone (2gm, 12hourly, I.V. )Cefotaxime (1gm, 12hourly, I.V. )Cefpodoxime (200mg, BD orally )Cefixime (0.4gm BD orally)
Fourth Generation(Nosocomial Gram Negative including Enterobactericeae & Ps. Aeruginosa)
Cefipime ( 1-2gm, 8-12hourly, I.V.)
Aminoglycoside
The action spectrum of aminoglycosides is mainly against gram-
negative bacteria, and they act synergistically with penicillins against
staphylococci.
They should not be used alone in skin infections to avoid drug
resistance among gram-negative bacteria and Ps. aeruginosa.
Systemic : Tobramycin, Netilmicin, Amikacin, and Isepamicin.
Topical : Neomycin,
Both Topical & Systemic : Gentamicin
Side effects include Ototoxicity & Nephrotoxicity.
Tetracyclines
Based on their half-lives these are classified as follows:-• Short acting (oxytetracycline and tetracycline)• Intermediate acting (demeclocycline and methacycline)• Long acting- Doxycycline, Minocycline
Dosage Schedule
Tetracycline – 250-500mg QID daily Doxycycline - 200mg loading dose, f/b 100mg /day Minocycline -200mg loading dose, f/b 100mg BD Side effects - photosensitivity & gastrointestinal disturbances. Minocycline - Vertigo ( in females around day 2-4 of starting the drug).
Precautions
Avoid in pregnancy, lactation, & <8 yr. of age, as it causes teeth
anomalies & skeletal growth depression in foetus.
Tetracyclines should not be administered with food, antacids, milk or
iron containing compound.
Macrolides & Lincosamides
Macrolides - Erythromycin, Roxithromycin, Azithromycin,
Clarithromycin.
Lincosamides - Lincomycin, Clindamycin.
Cross-resistance amongst macrolides and lincosamides is the rule.
Their main Spectrum of action is against Gram-positive cocci.
Clarithromycin is effective against MRSA.
Telithromycin is a newer semisynthetic macrolide that acts against
Gram-positive bacteria.
Dosage Schedule
Erythromycin - 250-500mg, orally, 6 hourly Clarithromycin - 250-500mg, orally, 12 hourly Azithromycin - 500 mg, orally before food, 24 hourly Lincomycin - 500 mg, IV/orally, 8 hourly Clindamycin - 300-600mg, IV/orally, 8-12 hourly
SIDE EFFECTS Erythromycin may cause gastritis. Lincosamides may cause diarrhoea. 10% of patients may suffer from pseudomembranous colitis.
Quinolones
Quinolones (norfloxacin, ciprofloxacin, ofloxacin, moxifloxacin,
pefloxacin, enoxacin) have a wide range of action & good tolerability.
Their use in dermatology is limited to P. aeruginosa infections, UTI &
leprosy.
SIDE EFFECTS
GI disturbances are more frequent than CNS & phototoxic adversities.
Antifungal Drugs
Systemic antifungal drugs play an important role in the management of both superficial and systemic infections.
Indications for systemic antifungals Extensive superficial fungal infections Failure of topical therapy Recurrent attacks presence Involvement of hair & nails Poor compliance regarding topical application Presence of associated immunocompromised states Deep mycoses/systemic fungal infection
Systemic Antifungal : Azoles
Imidazoles – Ketoconazole, Miconazole
Triazoles- Itraconazole, Fluconazole, Voriconazole, Posaconazole.
Mechanism of action: by inhibiting 14 α demethylation affecting
ergosterol synthesis in the cell membrane
Drug interactions are more with these groups because of the
involvement of cytochrome P450 system
Antifungals Common Indications Comments
Ketoconazole Candidiasis (200-400 mg/day)Pityriasis versicolar (400 mg single dose or 200 mg/day for 5 days)Dermatophytosis, seborrhoeic dermatitis, mycetoma sporotrichosis and chromomycosis.
Hepatotoxic, gynaecomastia, and menstrual irregularities
Fluconazole Candidiasis (100-200 mg/day)Pityriasis versicolar (400 mg single dose)Dermatophytosis (150 mg/week)
Primary and secondary drug resistance common,Safe drug
Antifungals Common Indications Comments
Itraconazole Candidiasis (100-200 mg/day)Pityriasis versicolar (200 mg/day)Dermatophytosis (200 mg/day)Pulse therapy in onychomycoses (400 mg/day for 1 week every month for 2 or 3 months for finger & toenails, respectively) Deep fungal: mycetoma, sporotrichosis and chromomycosis., aspergillosis and histoplasmosis
Expensive, effective against most fungi
KerionExtensive tinea
Mycetoma Onychomycosis
Systemic antifungal : ALLYLAMINES
Terbinafine is highly effective against dermatophytoses
Mechanism Of Action Acts by inhibiting squalene epoxidase, results in the accumulation of
squalene and ergosterol
INDICATIONS Used to treat dermatophytoses, mould fungi such as Aspergillus,
dimorphic fungi and pigmented fungi Only the topical formulation acts against Candida species and
Malassezia Also used in sporotrichosis and chromomycosis
Terbinafine
Dosage Schedule
In tinea corporis – 250 mg/day for 1-2 weeks
Fingernail infections – 6 weeks
Toenail infections – 12 weeks
SIDE EFFECTS
Headache, GI symptoms and skin rash.
Caution is to be observed on concomitant usage of rifampicin and
warfarin.
Polyenes
The oldest of systemic antifungals, they are macrolides derived from
Streptomyces species.
Drugs in current usage include Amphotericin B, Nystatin and
Natamycin.
Mechanism of action
These binds on to the cell membrane and cause cell leakage.
Amphotericin B
Effective against systemic mycoses such as Candidiasis & aspergillosis.
Amphotericin B is available in four parenteral forms:
• Amphotericin B deoxycholate (0.5-1 mg/kg/day)
• Liposomal amphotericin B (AmBisome) (3mg/kg/day)
• Amphotericin B lipid complex (Abelcet)
• Amphotericin colloid dispertion (Amphotec, Amphocil)
S/E : Nephrotoxicity , which is countered to a certain extent by
tagging liposomes to the drug.
Griseofulvin
Derived from Penicillium griseofulvum.
Mechanism of Action
It is fungistatic and acts by the inhibition of intracellular
microtubules and so inhibits the formation of mitotic spindles.
The defective fungal filaments dehydrate and curl; hence
griseofulvin was also called – curling factor.
It is also known to inhibit leucocyte movement and has an anti-
inflammatory action.
Griseofulvin
Indications
Effective only against dermatophytes and is currently used in tinea
capitis.
The oral dose is 6-8 mg/kg/day in two divided doses.
SIDE EFFECTS
Nausea, gastritis, intolerable headache, photosensitivity and
antabuse-like effects with alcohol.
Drug interactions with phenytoin and phenobarbitone are known.
Antiviral Drugs
There is limited array of antiviral drugs for
dermatological disorders.
The early use of antivirals is advisable to
reduce viraemia and fulminant infection
and to minimize nerve damage.
In herpes simplex, varicella and herpes
zoster antiviral drugs should be used within
24, 48 and 72 hours of skin eruption
respectively.Herpes Zoster
Acyclovir
Synthetic purine analogue used orally, intravenously, and topically.
It is converted by thymidine kinase to acyclovir triphosphate which
subsequently inhibits viral DNA polymerase. Resistance due to
alteration to or deficiency of thymidine kinase.
Commonly used orally to treat herpes simplex and varicella zoster
virus infection
Intravenous acyclovir is used in fulminant infections, the occurrence
of CNS complications and in immunocompromised patients.
Dosage schedule of antivirals
Aciclovir Valaciclovir FamiciclovirHerpes simplex
Primary 200mg, 5 times a day for 7-10 days
1g, twice a day for 7-10 days
250mg, orally 3times a day for 7-10 days
Recurrence 400mg, 3times a day for 5days
500mg, twice a day for 5days
125mg, twice a day for 5 days
Suppressive 400mg, twice a day 500mg, twice a day 250mg, twice a day
Herpes zoster 800mg, 5times a day for 7 days
1g, 3times a day for 7 days
500mg, 3times a day for 7days
Interferons
Interferone α, β and γ belong to the cytokine network and are
implicated in host defense.
They have antiviral, antiproliferative and immunomodulatory
properties.
α-interferon is frequently used in dermatology in subcutaneous (HSV
and HPV) or intralesional form (HPV infection ).
Dosing : daily or pulse basis 5-10IU/kg/day for 7-10days.
Side effect: flu-like system and fatique.
Caution: cardiac disease and psychiatric illness.
Antiparasitic Drugs
Ivermectin Originally approved for strongyloidisasis and onchocerciasis, this
drug is often used in the treatment of scabies and pediculosis capitis.
A single dose of 200µg/kg is advocated on an empty stomach. It block blocks glutamate-gated chloride ion channels,causing
neuromuscular paralysis in the parasite.Thiabendazole It is antihelmenthic and acts by inhibition of the enzyme fumarate
reductase. It is useful in larva migrans and currens Dosage:1.5g/day for 2 days GIT discomfort is frequent on oral administration.
Retinoids
First generation (non-aromatic) - isotretinoin and tretinioin (all-trans
retinoic acid)
Second generation (monoaromatic) - etretinate and acitretin
Third generation (polyaromatic) – bexarotene
FDA-Approved indications :
• Severe acne (isotretinoin)
• Severe psoriasis (acitretin)
• Cutaneous T-cell lymphoma (bexarotene)
Retinoids : Dosing and Onset of Action
Retinoid Dermatological condition Dose Onset of action
Isotretinoin Nodulo cystic acne 0.5-1 mg/kg/day 3-4 weeks
Acitretin Severe Psoriasis 0.5-1 mg/kg/day 4-6 weeks
Bexarotene Cutaneous T cell lymphoma 300 mg/m² 3-6 months
Retinoids : Mechanism of action
It include all synthetic and natural compounds that have activity
similar to vit-A.
At the cellular level, the cytosolic RBP transfers it to the nucleus.⟹ Retinoids activate the nuclear recepters and regulate gene
transcription.
They induce cellular differentiation, and have anti-inflamatory and
antproliferative action.
In the skin they have an anti-keratinising effect, and in sebaceous
glands, they reduce sebum production and decrease maturation of
sebocytes.
Retinoids : Mechanism and Indications
They induce cellular differentiation, and have anti-inflamatory and
antproliferative action.
In the skin they have an antikeratinising effect, and in sebaceous
glands, they reduce sebum production and decrease maturation of
sebocytes.
Indications
Retinoids are the drugs of choice for nodulocystic acne. Off label uses
are rosacea, hydradenitis suppurativa, Darier’s disease,icthyosis and
keratodermas.
Retinoids : Dosage Schedule
Acitretin (25-75mg/day) is the chosen retinoid for psoriasis, although
uses is limited to pustular and palmoplanter psoriasis.
Acitretin with PUVA is termed Re-PUVA.
Isotretinoin (0.5-1 mg/day) is used in acne.
An initial response is seen within 8 weeks and improvement continues
through 20-24 weeks,
Intermittent pulse therapy 0.5 mg/day for 7 days/month for 6 months
is also used in acne.
Treatment with Oral Isotretinoin
PRE POST
Methotrexate
Dosage Schedule It can be taken orally, IV or IM. Oral dose commonly used is 2.5-15 mg/week in single dose. The ‘Winstein-Frost’ schedule recommends usage in 3 divided
doses, given at an interval of 12 hours, on a weekly basis.SIDE EFFECTS Side effects infrequent when used as per standard therapeutic
guidelines. Hepatotoxicity, pneumonitis, diffuse interstitial fibrosis,
pancytopenia, gastritis. MTx is a potential teratogen and abortifacient.
Methotrexate toxicityPlaque Psoriasis
Methotrexate
Monitoring Guidelines
Includes complete haemogram, LFT and USG scan of the liver.
Test are best done at 0,1,2,4,8, & 12 weeks, and later regularly every
third month in long term therapy.
Baseline liver biopsy is indicated at a cumulative dose of 1.5 g of total
MTx usage in high risk patients while in others at 4g.
Patients with grade I and II disease- can continue therapy
Grade IIIA-can continue with repeat biopsy after 6 months.
Grade IIIB and IV- calls for total discontinuation of therapy.
Azathioprine
It derived from 6-mercaptopurine, and considered a safer
immunosuppressant because of infrequent toxicity.
Indications
Used for its both immunosuppressive and anti-
inflammatory effects.
Commonest indication is pemphigus vulgaris.
Other indications include vasculitis, neutrophilic
dermatoses,CTD and recalcitrant photodermatoses.Pemphigus vulgaris
Azathioprine
Absolute contraindications include pregnancy, TPMT (thiopurine methyltransferase) levels of <5 U and the presence of fulminant infections.
Dosage Schedule 0.5-2.5mg/kg/day, while the commonly used dosage 50-100 mg/day.
SIDE EFFECTS Pancytopenia, precipitation of infections and drug hypersensitivity
syndromes. A TPMT assay prior to starting treatment is always advisable.
Cyclophosphamide
It is derivative of nitrogen mustard acts by damaging the DNA molecule through its active metabolites.
It is cell cycle nonspecific and depresses B cell functions more than T cells.
Acrolein, an inactive metabolite, is the responsible for bladder toxicity. Hence proper hydration and good urinary output is needed
Indications Used in severe pemphigus alone or as a constituent of
Dexamethasone-Cyclophosphamide pulse therapy.
Advanced mycosis fungoides, lupus erythematosus and Wegener’s
granulomatosis.
Cyclophosphamide
Dosage Schedule It is used orally in a dose of 1-5 mg/kg/day in equal divided doses or as
a single dose of 50-200 mg/day. Parental usage is in dose of 5-9mg/kg/day in lupus nephropathy and
serious lupus vasculitis.
SIDE EFFECTS
Haemorrhagic cystitis, bladder carcinoma, leucopenia, anagen
effluvium are common toxicities. The risk of transitional cell bladder
cancer is 8-10 fold higher in these patients.
Hydroxyurea
This affects DNA synthesis & repair and gene regulation through inhibition of ribonucleotide reductase.
Withdrawal of drug results in a rapid reversal of its effect. Oral tab are used in a dose of 1-1.5 g/day in divided doses. It is used infrequently in recalcitrant psoriasis.
Adverse Reactions Marrow suppression, elevated transaminases, altered renal function
and poikiloderma.
Cyclosporine-A
Acts by decreasing T-cell & keratinocyte proliferation. It also reduces levels of ILs & TNF. It is used in wide spread erythrodermic or pustular psoriasis. It’s a rapid ‘cooldown’ of the inflammatory component of a florid psoriasis. Also used in atopic dermatitis, recalcitrant urticaria & pyoderma
gangrenosum. Dose : 3-5 mg/kg/day.
SIDE EFFECTS Renal dysfunction, hypertension, tremors, dysaesthesia & gingival
hyperplasia.
Mycophenolate Mofetil
MPA was used widely in psoriasis in previous years and mycophenolate mofetil, an esterified form with greater bioavailability is now used in atopic dermatitis, lupus erythematosus, psoriasis, refractory P.G. and bullous diseases.
Mycophenolate mofetil gets cleaved to MPA after absorption. It acts by inhibiting de novo purine synthesis.
It affects T & B- cells predominantly.
SIDE EFFECTS include nausea, diarrohea, strangury and an increased incidence of
viral & bacterial infections.
Antimalarials : Hydroxy chloroquine (HCQ)
Metabolized in liver but only 15 to 25 % of total clearance is through
kidney
Usual dose : 400 mg/day
Photoprotective effects: high concentration in epidermis because of
their affinity for pigment
Immunologic and anti-inflammatory effects: decrease in T cell release
of IL-1, IL-6, TNF and interferon gama
Dermatologic indications : SLE, Discoid lupus, porphyria cutanea
tarda, PMLE, Chronic cutaneous vasculitis, solar urticaria.
Drugs Used During Pregnancy and Lactation
Antihistamines
Safer-diphenhydramine, chlorpheniramine, cyproheptadine and
loratidine
Avoid-hydroxyzine, fexofenadine and cetirizine
Antihistamines may suppress lactation and create infantile irritability.
Systemic Steroids
Systemic steroids are avoided in the first trimester because of a risk
of multiple-organ anomalies
Short-term therapy is best advocated in the second and third
trimesters.
Drugs Used During Pregnancy and Lactation
A short-term usage of topical steroids is also preferred; Potent and superpotent steroids are avoided because of the risk of
systemic absorption.
Antibacterial Agents SAFE : macrolide, penicillins and cephalosporins. AVOID : quinolones, tetracycline. Silver suphadiazine is not advised in
the third trimester because of foetal haemorrhage.
Drugs Used During Pregnancy and Lactation
Antifungal Drugs
Single-dose fluconazole is safe, while prolonged use is best avoided.
Ketoconazole, terbinafine and griseofulvin are not advised in
pregnancy and lactation.
Antiviral Drugs
Systemic antivirals are safe in all trimesters.
An assessment of the risk-benefit ratio is done, and their usage is
reserved for severe cases or near the end of the pregnancy.
Drugs Used During Pregnancy and Lactation
Antiparasitic Drugs
Topical antiscabetics are considered safe, but large dose of lindane is
not advised in pregnancy.
Retinoids
Systemic retinoids are totally contraindicated during pregnancy and
lactation.
Topical retinoids are avoided in the first trimester, whereas benzyol
peroxide and azelaic acid are considered safe.
Effect of Drug with respect to theTrimesters of Pregnancy & Lactation
Before Conception (contraception Failure) The use of azathioprine, mtx, NSAIDs, Griseofulvin, Itraconazole,
Tetracycline and rifampicin may result in contraceptive failure either directly or though hepatic enzyme induction
First Trimester Drugs at this stage affect all cell equally, and cell death often results in
spontaneous abortion. Differentiating cells, when affected, result in defective organogenesis
and congenital anomalies. Hence, FDA pregnancy Category X and D drugs are totally avoided;
they include retinoids, finasteride, methotrexate, thalidomide,
colchicine, spironolactone, griseofulvin and cyclophosphamide.
Effect of Drug with respect to theTrimesters of Pregnancy & Lactation
Second Trimester Metabolism of drugs may be at a slower pace in the foetus compared to
the mother, for example, foetal hypothyroidism with maternal iodine use. Drug excretion into the amniotic fluid results in a prolonged contact of the
foetal skin with the drug.Third Trimester Non-teratogenic conditions occur; for example, sulphonamide-induced
kernicterus, rifampicin-related foetal haemorrhage and immunosuppression and NSAIDs causing oligohydroamnios.
Lactation Teratogenic drugs are best avoided. This include anti-neoplastics which
may induce immunosuppression or a possible carcinogenesis.
MCQ’s
Q.1) Which is known as curling factor?A. MethotrexateB. InterferonesC. GriseofulvinD. None
Q.2) Which of the following is incorrect about retinoids?E. First generation-isotretinoinF. Second generation-acitretinG. Third generation-bexaroteneH. Fourth generation-etretinate
MCQ’s
Q.3) Fexofenadine is given in infants above?A. 3 month of ageB. 6 month of ageC. 1 year of ageD. 2 year of age
Q.4) The dosage of intravevous methylene blue in the treatment of dapsone-induced methaemoglobinemia?
E. 50-60mg/kgF. 0.1-0.2mg/kgG. 5mg/kgH. 1-2mg/kg
A 23 yr old male presented with grouped vesicles on a erythematous base in a dermatomal distribution for 2 days, drug of choice for this patient is :
A. Oral SteroidsB. Oral AcyclovirC. TetracyclineD. Topical Steroids
Photo Quiz
A 10 month old male brought by mother with ruptured bullae and erosions with honey crust for 3 days. Identify the condition and its treatment :
A. Bullous impetigo,oral antistaphylococcal
B. Tinea faciei, oral anti fungalC. Scabies, topical permethrinD. Psoriasis, topical steroid
Photo Quiz
A 19 yr old male with nodulocystic lesions on face for 10 months, identify the lesions, its grade and best treatment :
A. Acne grade 2, oral antibioticsB. Acne grade 3, topical antibioticsC. Acne grade 4, topical steroidsD. Acne grade 4, oral retinoids
Photo Quiz
A 35yr old female presented with erythematous itchy plaques with silver white scaling all over body(BSA=12%). Identify the condition and best treatment for patient :
A. Tinea corporis,oral antifungalB. Lichen planus, topical steroidC. Psoriasis, Oral methotrexateD. Psoriasis, oral steroids
Photo Quiz
Thank You!