Transcript Side Effects

Dermatotherapeutics - Systemic
Digital Lecture Series : Chapter 31
Prof. Satyendra Kumar Singh
Department of Dermatology and Venereology
Institute of Medical Sciences,
B.H.U., Varanasi
CONTENTS
 Introduction
 Retinoids
 Sulfones
 Cytotoxic Agents
 Antihistamines
 Antimalarials
 Systemic Steroids
 Drugs Used During Pregnancy &
 Antibacterial Agents
Lactation
 Antifungal Drugs
 MCQs
 Antiviral Drugs
 Photo Quiz
 Antiparasitic Agents
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
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
Second and third 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.
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
Indications
 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.
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
First generation
(Gram Positive)
Second generation
(Gram Positive)
Third generation
(Nosocomial Gram Negative including
Enterobactericeae & Ps. Aeruginosa)
Fourth Generation
(Nosocomial Gram Negative including
Enterobactericeae & Ps. Aeruginosa)
Drug details with adult dosing
Cefadroxil (0.5-1gm BD orally),
Cephalexin (0.5-1gm QID orally)
Cefuroxime (1.5gm 6-8 hourly, I.V. )
Cefoxitin (2gm 4-6 hourly, I.V. )
Cefaclor (0.5-1gm TDS, orally)
Ceftriaxone (2gm, 12hourly, I.V. )
Cefotaxime (1gm, 12hourly, I.V. )
Cefpodoxime (200mg, BD orally )
Cefixime (0.4gm BD orally)
Cefipime ( 1-2gm, 8-12hourly, I.V.)
Aminoglycoside
 The action spectrum of aminoglycosides is mainly against gramnegative 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
Primary and
secondary drug
resistance common,
Safe drug
Candidiasis (100-200 mg/day)
Pityriasis versicolar (400 mg single dose)
Dermatophytosis (150 mg/week)
Antifungals
Itraconazole
Common Indications
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
Comments
Expensive, effective
against most fungi
Extensive tinea
Kerion
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 antiinflammatory 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
Famiciclovir
Herpes 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
Isotretinoin
Nodulo cystic acne
Acitretin
Bexarotene
Severe Psoriasis
Cutaneous T cell
lymphoma
Dose
Onset of action
0.5-1 mg/kg/day
3-4 weeks
0.5-1 mg/kg/day
4-6 weeks
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.
POST
PRE
Treatment with Oral Isotretinoin
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.
Plaque Psoriasis
Methotrexate toxicity
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 antiinflammatory 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 the
Trimesters 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 the
Trimesters 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)
A.
B.
C.
D.
Which is known as curling factor?
Methotrexate
Interferones
Griseofulvin
None
Q.2)
A.
B.
C.
D.
Which of the following is incorrect about retinoids?
First generation-isotretinoin
Second generation-acitretin
Third generation-bexarotene
Fourth generation-etretinate
MCQ’s
Q.3) Fexofenadine is given in infants above?
A. 3 month of age
B. 6 month of age
C. 1 year of age
D. 2 year of age
Q.4) The dosage of intravevous methylene blue in the treatment of dapsoneinduced methaemoglobinemia?
A. 50-60mg/kg
B. 0.1-0.2mg/kg
C. 5mg/kg
D. 1-2mg/kg
Photo Quiz
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.
B.
C.
D.
Oral Steroids
Oral Acyclovir
Tetracycline
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 fungal
C. Scabies, topical permethrin
D. 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.
B.
C.
D.
Acne grade 2, oral antibiotics
Acne grade 3, topical antibiotics
Acne grade 4, topical steroids
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.
B.
C.
D.
Tinea corporis,oral antifungal
Lichen planus, topical steroid
Psoriasis, Oral methotrexate
Psoriasis, oral steroids
Thank You!