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

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