Derm Pharm- Percutaneous Absorption & Di Skin Reactions

Front 1

Which layer of skin acts as the primary barrier to absorption?

Back 1

Stratum Corneum

Not all body sites are equally permeable. Variation in sratum corneum thickness can effect absorption.

Front 2

Is absorption faster or slower in cutaneous appendages (e.g. hair follicles, sebaceous glands, eccrine glands and apocrine glands)?

Back 2

FASTER. Areas rich in these appendages will have enhanced absorption.

Front 3

How does hydration play a role in percutaneous drug absorption?

Back 3

Hydration expands the skin surface area and will therefore enhance absorption.

Front 4

Order the following from most absorbing to least absorbing regions of skin:

Nail
Scrotum
Trunk/Extremities
Face/Scalp
Palm/Sole

Back 4

Main point is that not all regions are equal and this should be kept in mind when using dermal patches.

Nail<<Palm/sole<trunk/extremities<face/scalp<<Scrotum

Front 5

What is Fick's Law of Diffusion? Which variable is the only variable can we control?

Back 5

Fick’s law of diffusion J=KpC ; J= rate of absn
Kp = permeability constant
C= the concentration of the drug in the vehicle.

the only variable we can control is **concentration**!!!

Front 6

What characteristics could give percutaneous drugs more absorotion?

Back 6

small molecular size, small molecular weight, more lipid solubility = greater absorption.

Front 7

Transdermal delivery provides a controlled rate of delivery, reduces fluctuations in levels and bypasses 1st pass metabolism. What is the downfall of transdermal delivery?

Back 7

Absorption may vary widely

Front 8

Does the vehicle greatly impact efficacy of the drug?

Back 8

YES- It ties potency to efficacy.

Front 9

What are some things that can increase the likelihood of drug interactions?

Back 9

POLYPHARMACY (as in elderly, HIV/AIDs), Organ failure, lack of hepatic/renal perfusion (e.g., CHF, third spacing, dehydration) all can increase likelihood of interactions.

Front 10

How might genetics contribute to variability in drug reactions among patients?

Back 10

**Genetic polymorphisms** may contribute to variability in reactions - for example (FYI) slow acetylators are at higher risk of lupus-like symptoms with hydralazine, procainamide, isoniazid

Front 11

d

Back 11

d

Front 12

When evaluating a patient that may have a drug induced skin disease, what questions should you ask the patient?

Back 12

a. Description of lesion
b. Med history
c. Chronology of administration
d. Previous Hx of drug sensitivity?
e. Consider Excipients (e.g dyes, binders, etc. )

Also, Examine rash, describe, record as ADR with details (consider FDA MedWatch reporting)

Front 13

What type of patients are most at risk for Drug induced skin disease?

Back 13

Altered Immune Status
Organ Impairment (renal, hepatic)
Genetic Factors (Slow acetylaters)
Atopy (maybe, esp in pts with asthma, eczema)

Front 14

Chronology of Administration:
i. Initial dosing related to onset of rash
ii. Withdrawal - stop the drug!
iii. Rechallenge - not in severe type of reactions

Back 14

Chronology of Administration:
i. Initial dosing related to onset of rash***
ii. Withdrawal - stop the drug!
iii. Rechallenge - not in severe type of reactions

Front 15

The following 5 classes of drugs might cause adverse skin reactions, but it is very rare and you can often cross these off your list of differentials. What are some possible reasons why these DON'T cause reactions? (don’t memorize, but be able to use common sense- Babos)
Antacids
Antihistamines
Hormones
Steroids
Vitamins

Back 15

i. Antacids - locally acting (e.g., Mg(OH)2 OR antihistamine (e.g., H2 blockers)
ii. Antihistamines - d/t blocking histamine
iii. Hormones: insulin, OC, thyroid - endogenous substances
iv. Steroids - endogenous, used to TREAT rxns
v. Vitamins, Fe (needed to survive) (niacin can cause PG mediated flushing - prevent with ASA)

Front 16

What type of drug related eruption has a 7-14 onset, starts centrally and spreads outward, and is themost common type?

Back 16

Exanthematous Drug Eruptions

Front 17

What type of infection may worsen an Exanthematous Drug Eruption?

Back 17

Viral infections may worsen

FYI: Amp- and Amoxicillin not used in mononucleosis

Front 18

How do you treat an Exanthematous Drug Eruption?

Back 18

Less serious reaction, so less intensive Tx
1. Antihistamine
2. Topical steroid
3. Topical antipruritic

Front 19

What are the 5 common causes of Exanthematous Drug Eruptions?

Back 19

1. Allopurinol (Boards: causes MANY types of rash, most seriously SJS/TEN - educate pts to report rash immediately)
2. Antibiotics
3. Carbamazepine
4. Sulfonamide moiety: thiazides, loop diuretics, sulfa antibiotics. (Boards: celecoxib, sulfonylurea insulin secretogogues , dapsone)
5. Gold salts

Front 20

What type of drug related eruption has an onset of 36 hours, is usually hard to distinguish, and is the 2nd most common type of eruption?

Back 20

Urticaria

Front 21

What type of drug eruption is caused by increased permeability leading to fluid leakage that causes selling of the tongue, lips, eyelids, or genetalia?

Back 21

Angioedema

Treatment - systemic treatment needed
1. Resuscitation if needed (relatively rare)
2. Oral antihistamine
3. Oral corticosteroid if needed

Front 22

What are the most common causes of Angioedema?

Back 22

1. **ACEI** !!!→↑bradykinin levels
2. NSAIDS→↓COX activity→↑leukotriene production
3. Contrast media → mast cell degranulation
4. Monoclonal antibodies (e.g, infliximab, muromonab, abciximab)

Front 23

What type of eruption is characterized by a 7-10 day onset (duration may be lengthy), raised pupuric lesions on the legs, fever, utricaria, arthralgia, lymphadenopathy, maculopapular rash, & ↑PMNs near vasculature?

Back 23

Vasculitis

Front 24

How do you treat vasculitis?

Back 24

Treatment: systemic corticosteroids and/or NSAIDs (if not NSAID induced, of course)

Front 25

What drugs can cause vasculitis?

Back 25

1. Allopurinol
2. Antibiotics
3. Carbamazepine
4. NSAIDs
5. Sulfonamide moiety
6. Gold salts
7. Propylthiouracil

Front 26

Exfoliative dermatitis is a severe type of reaction that is characterized by exfoliation, fever, lymphadenopathy, edema.

What are come common causes of Exfoliative dermatitis? How do you treat it?

Back 26

Causes
1. Penicillins
2. Isoniazid (? More likely in slow acetylators)
3. Gold salts
4. Phenytoin
5. Sulfonamides

Treatment- antipyretics and fluids

Front 27

Stevens-Johnson and Toxic epidermal necrolysis (TEN) are EMERGENCIES and occur 1-3 weeks post exposure. Mortality can be high so proper treatment is imperative. How do you treat these?

Back 27

Treatment - give it your all! Corticosteroids, fluids, immunosuppressives, IVIG, etc.

Front 28

What are some common causes of SJS and TEN?

Back 28

1. Allopurinol
2. Anti TB drugs (isoniazid)
3. Antiepileptics (Barbiturates, carbamazepine, lamotrigine, phenytoin)
4. Gold
5. Sulfonamides
6. Tetracyclines

Front 29

< 10% epidermal detachment = _____
more severe = _______

Choose SJS or TEN

Back 29

< 10% epidermal detachment = SJS

more severe = TEN

Front 30

3 Common causes of Erythema Multiforme?

How do you treat it?

Back 30

1. PCN
2. Barbiturates
3. NSAIDs

Tx: stop drug, systemic steroids?, watch for progression

Front 31

Fixed drug eruptions - not a high morbidity/mortality, caused by numerous agents (Allopurinol is always a good guess…)

Back 31

Fixed drug eruptions - not a high morbidity/mortality, caused by numerous agents (Allopurinol is always a good guess…)

Front 32

What are the most common causes of Angioedema?

Back 32

1. **ACEI** !!!→↑bradykinin levels
2. NSAIDS→↓COX activity→↑leukotriene production
3. Contrast media → mast cell degranulation
4. Monoclonal antibodies (e.g, infliximab, muromonab, abciximab)

Front 33

What type of eruption is characterized by a 7-10 day onset (duration may be lengthy), raised pupuric lesions on the legs, fever, utricaria, arthralgia, lymphadenopathy, maculopapular rash, & ↑PMNs near vasculature?

Back 33

Vasculitis

Front 34

How do you treat vasculitis?

Back 34

Treatment: systemic corticosteroids and/or NSAIDs (if not NSAID induced, of course)

Front 35

What drugs can cause vasculitis?

Back 35

1. Allopurinol
2. Antibiotics
3. Carbamazepine
4. NSAIDs
5. Sulfonamide moiety
6. Gold salts
7. Propylthiouracil

Front 36

Exfoliative dermatitis is a severe type of reaction that is characterized by exfoliation, fever, lymphadenopathy, edema.

What are come common causes of Exfoliative dermatitis? How do you treat it?

Back 36

Causes
1. Penicillins
2. Isoniazid (? More likely in slow acetylators)
3. Gold salts
4. Phenytoin
5. Sulfonamides

Treatment- antipyretics and fluids

Front 37

Stevens-Johnson and Toxic epidermal necrolysis (TEN) are EMERGENCIES and occur 1-3 weeks post exposure. Mortality can be high so proper treatment is imperative. How do you treat these?

Back 37

Treatment - give it your all! Corticosteroids, fluids, immunosuppressives, IVIG, etc.

Front 38

What are some common causes of SJS and TEN?

Back 38

1. Allopurinol
2. Anti TB drugs (isoniazid)
3. Antiepileptics (Barbiturates, carbamazepine, lamotrigine, phenytoin)
4. Gold
5. Sulfonamides
6. Tetracyclines

Front 39

< 10% epidermal detachment = _____
more severe = _______

Choose SJS or TEN

Back 39

< 10% epidermal detachment = SJS

more severe = TEN

Front 40

3 Common causes of Erythema Multiforme?

How do you treat it?

Back 40

1. PCN
2. Barbiturates
3. NSAIDs

Tx: stop drug, systemic steroids?, watch for progression

Front 41

Fixed drug eruptions - not a high morbidity/mortality, caused by numerous agents (Allopurinol is always a good guess…)

Back 41

Fixed drug eruptions - not a high morbidity/mortality, caused by numerous agents (Allopurinol is always a good guess…)

Front 42

What type of drug induced skin reaction is more common in drugs with aromatic ring structures/unsaturation?

Back 42

PHOTOSENSITIVITY
- electron cloud absorbs UV radiation

Front 43

What 4 classes of drugs commonly cause photosensitivity?

Back 43

i. Sulfonamide moiety
ii. Tetracyclines
iii. Fluoroquinolones
iv. Phenothiazines

Front 44

What are the most common causes of Angioedema?

Back 44

1. **ACEI** !!!Most common→↑bradykinin levels (don't re-challenge the pt)
2. NSAIDS→↓COX activity→↑leukotriene production
3. Contrast media → mast cell degranulation
4. Monoclonal antibodies (e.g, infliximab, muromonab, abciximab)

Front 45

What type of eruption is characterized by a 7-10 day onset (duration may be lengthy), raised pupuric lesions on the legs, fever, utricaria, arthralgia, lymphadenopathy, maculopapular rash, & ↑PMNs near vasculature?

Back 45

Vasculitis

Front 46

How do you treat vasculitis?

Back 46

Treatment: systemic corticosteroids and/or NSAIDs (if not NSAID induced, of course)

Front 47

What drugs can cause vasculitis?

Back 47

1. Allopurinol
2. Antibiotics
3. Carbamazepine
4. NSAIDs
5. Sulfonamide moiety
6. Gold salts
7. Propylthiouracil

Front 48

Exfoliative dermatitis is a severe type of reaction that is characterized by exfoliation, fever, lymphadenopathy, edema.

What are come common causes of Exfoliative dermatitis? How do you treat it?

Back 48

Causes
1. Penicillins
2. Isoniazid (? More likely in slow acetylators)
3. Gold salts
4. Phenytoin
5. Sulfonamides

Treatment- antipyretics and fluids

Front 49

Stevens-Johnson and Toxic epidermal necrolysis (TEN) are EMERGENCIES and occur 1-3 weeks post exposure. Mortality can be high so proper treatment is imperative. How do you treat these?

Back 49

Treatment - give it your all! Corticosteroids, fluids, immunosuppressives, IVIG, etc.

Front 50

What are some common causes of SJS and TEN?

Back 50

1. Allopurinol
2. Anti TB drugs (isoniazid)
3. Antiepileptics (Barbiturates, carbamazepine, lamotrigine, phenytoin)
4. Gold
5. Sulfonamides
6. Tetracyclines

Front 51

< 10% epidermal detachment = _____
more severe = _______

Choose SJS or TEN

Back 51

< 10% epidermal detachment = SJS

more severe = TEN

Front 52

3 Common causes of Erythema Multiforme?

How do you treat it?

Back 52

1. PCN
2. Barbiturates
3. NSAIDs

Tx: stop drug, systemic steroids?, watch for progression

Front 53

Fixed drug eruptions - not a high morbidity/mortality, caused by numerous agents (Allopurinol is always a good guess…)

Back 53

Fixed drug eruptions - not a high morbidity/mortality, caused by numerous agents (Allopurinol is always a good guess…)

These are solitary, sometimes multiple well demarcated lesions, can develop blisters in the center. Color varies. Appropriate to orally challenge to confirm is appropriate.

Front 54

Take home points for DI Skin disease

Back 54

recognize severity; think about mechanism to help remember (e.g., angioedema, which drugs aren’t likely to cause eruptions, etc), for TEN/SJS: allopurinol, sulfonamide moiety drugs, isoniazid, tetracyclines are always good board guesses. Drug induced SLE is a likely board question, too. PTU causes ↑ANCA in up to 50% of patients, so remembering this cause of vasculitis might be a good idea. DON”T MEMORIZE THIS CHART or lists of drugs, but get a feel for which drugs are likely culprits, and keep your eye on the biggies, especially any you see emphasized in your board reviews.

Front 55

Don't memorize, good for reference and boards

Back 55

Don't memorize, good for reference and boards

Front 56

What type of skin reaction occurs commonly with drugs that have an aromatic ring/unsaturation?

Back 56

Photosensitivity
- electron cloud absorbs UV radiation

Front 57

What drugs commonly case photosensitivity?

Back 57

i. Sulfonamide moiety
ii. Tetracyclines
iii. Fluoroquinolones
iv. Phenothiazines

Front 58

What drug induces skin necrosis and causes "purple toe"?

Back 58

Warfarin induces skin necrosis = “purple toe” - Boards: mechanism: Factors II, VII, IX, and X and Proteins C and S require reduced vitamin K to be activated; when vitamin K epoxide reductase is inhibited by warfarin, proteins C and S do not get activated; persons with deficiencies of C and/or S will get CLOTTING and subsequent necrosis when warfarin is initiated

Front 59

BOARDS

What drugs can cause Systemic Lupus Erythematosus-like syndrome (SLE)?

Back 59

1. Drugs that undergo N-acetylation, more common in slow acetylators
2. Isoniazid, hydralazine, procainamide