Download MBBS Dermatology PPT 28 Systemic Drug Therapy In Dermatology I Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Dermatology PPT 28 Systemic Drug Therapy In Dermatology I Lecture Notes

Systemic Drug Therapy in

Dermatology - I

Basic principles

? Medications ? Can target the skin by either topical/ intralesional/

systemic routes

? Intralesional administration ? Additional option for very localized

lesions e.g. IL steroids in keloids, AA etc.

? Topical application ? Often a very effective therapeutic modality

(frequently successful alone) for dermatological disease

? Will be ineffective if physical properties of drug leads to problem with

passive diffusion from the skin surface
? Systemic medications ? Distributed via the cutaneous vasculature
? Have the potential to exert pharmacological actions on all elements

of the skin ? therapeutic efficacy

? Not only the skin but also most of the other organs are exposed to

the drug

? Therefore, systemic therapies may have potential for significant

adverse effects

? Sometimes life-threatening

? One of the basic principles of medical ethics
? L. `primum non nocere', i.e. `first, do no harm'
? Before considering systemic options ? The clinician always to consider

possibility of unwanted consequences of any therapeutic intervention

? Clinician ? To use systemic medications safely
? Also ? Appreciate the patient's perspective
? Assess the detrimental impact of a skin disorder on the patient's

quality of life (QoL; DQLI)

? Assess the risk?benefit balance of a particular medication
? Best ? A shared & informed decision between patient &

dermatologist

Standards of care

? No perfect medical management plan in all cases
? The competent clinician ? Follow peerdetermined & approved

standards of care, e.g. in evidencebased/ National guidelines etc.

?The Indian Association of Dermatologists, Venereologists & Leprologists (IADVL)
?The British Association of Dermatologists (BAD)
?The American Academy of Dermatology (AAD)
?The National Institute for Health and Care Excellence (NICE)
?The European Academy of Dermadology & Venereology (EADV)
?For STIs: CDC guidelines etc.
Drug-drug interactions

? Clinicians ? To exclude potential interactions with the patient's

existing medication

? To provide the patient with a list of drugs that may interact with the

new drug

? To ensure the patient makes the prescribers of any future medication

aware of the medicines they are already taking

Immunomodulatory/ Immunosuppresive

drugs
? Many (but not all) of the systemic agents ? Immunomodulatory or

(potent) immunosuppressive

? Require Pretreatment screening & subsequent monitoring
? Prior to initiation ? Patients to be carefully counselled about the risk/

benefit aspects

? Written information Preferable
? Particular regard ? To infection, systemic & cutaneous malignancy,

bone marrow suppression & conceptionrelated issues
? Women ? Adequate contraceptive guidance if applicable
? Cervical cytology screening history if applicable
? A h/o malignancy in any organ Seek appropriate specialist advice
? The entire skin ? Examine to exclude the presence of dysplastic/

neoplastic lesions

? Minimize the risk of reactivation of infections ? Screen for latent

bloodborne viruses (e.g. hepatitis B and C & HIV), latent tuberculosis

? Review vaccinations
? Periodic followup visits ? Regular investigations with regard to

particular as per guidelines

? Occasional GPE ? With a view to excluding lymphoma & cutaneous

neoplasia

Antihistamines

? H1 antihistamines Mainstay of treatment for
?Chronic urticaria & angiooedema
?Physical urticarias,
?Urticarial vasculitis,
?Cutaneous mastocytosis,
?Insect bite reactions,
?Anaphylaxis & allergic reactions to drugs
? Effectiveness in atopic eczema ? Sedating H 1antihistamines - a role in

the management of nocturnal pruritus

? The combination of H1 & H2 antihistamines ? The treatment of

urticaria

Formula and structure

? H1 antihistamines ? 6 Structural classes:
?Alkylamines
?Ethanolamines
?Ethylenediamines
?Phenothiazines
?Piperidines
?Piperazines
? 1st generation of antihistamines ? Representatives in each structural

group

? Majority of 2nd generation antihistamines ? Piperidines or piperazines
? Doxepin ? Tricyclic antidepressant with antihistamine activity

Pharmacodynamics

? Traditionally, antihistamines ? Considered reversible competitive

inhibitors of histamine

? However, histamine receptors have an intrinsic level of activity
? H1 and H2 antihistamines are now best regarded as inverse agonists,
? Not just simply block the interaction of histamine with its receptors
? Also induce an opposite pharmacological response by decreasing the

constitutive activity of the receptors
Dose & regimens

? If recommended dose of individual antihistamines ? Not clinically

effective May prescribe higher doses i.e. updosing (limited

evidence for the efficacy & safety)

? Combination of two or more antihistamines ? Can be more effective

than monotherapy

? The combination of H1 & H2 antihistamines

Pregnancy

? Limited guidelines for use of H1 antihistamines in pregnancy
? Most ? Classified as Food & Drug Administration (FDA) pregnancy

category B or C

? Earlier reports ? Link H1 antihistamines to fetal malformations (e.g.

particularly cleft palate)

? Usually avoided in the first trimester of pregnancy
? Newer studies ? (including a meta-analysis of 200,000 first-trimester

exposures to first-generation antihistamines) ? No increased risk of

congenital malformations
Breastfeeding

? No formal studies ? During breastfeeding
? Theoretically ? May diminish milk supply via anticholinergic effects
? Many e.g. diphenhydramine, promethazine, cetirizine, loratadine,
? fexofenadine, levocetirizine etc. - Excreted in breastmilk
? However, effects on the nursing infants ? Not studied

Tricyclic antidepressants

? TCAs ? Bind to both H1 & H2 receptors
? TCA MC used in dermatology ? doxepin ? about 800 times more potent

than diphenhydramine

? Uses:
?Refractory CSU
?Physical urticarias
?Pruritus associated with systemic conditions
? Sedation is the most common adverse effect - some patients may develop

tolerance with regular use

? Oral doxepin - FDA as a pregnancy category C
? Use with caution in elderly - May be more susceptible to its anticholinergic

effects, including urinary retention & blurred vision
Antifungal drugs

? The systemic antifungal drugs ? Broadly classified by MoA
vAct on the fungal wall or cell membrane
vAct intracellularly

? The fungal wall/cell membrane agents Subdivided
?Inhibit ergosterol (integral part of fungal cell membrane) function
?Inhibit glucan synthase

? The ergosterol inhibitors
? Azoles (inhibit lanosterol 14 demethylase, essential for the synthesis of

ergosterol)

?Imidazoles (5membered aromatic ring with 2 nitrogen & 3 carbon atoms)

e.g. ketoconazole

?Triazoles (5membered aromatic ring with 3 nitrogen & 2 carbon atoms)

e.g. fluconazole, itraconazole, posaconazole, voriconazole

? Allylamines (inhibit squalene epoxidase, essential in ergosterol synthesis)

e.g. terbinafine

? Polyenes (bind to ergosterol & interfere with fungal cell membrane) e.g.

nystatin & amphotericin B
? glucan synthase inhibitors Interfere with the synthesis of glucan

(component of the fungal cell wall) e.g. echinocandin antifungals

caspofungin, micafungin

? Intracellular MoA
? Flucytosine A pyrimidine analogue, inhibits fungal DNA & RNA

synthesis

? Griseofulvin ? A spirobenzo[b]furan inhibits fungal mitosis by

binding to tubulin thus disrupting microtubule function


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