Cyclosporine is an immunosuppressive drug that was originally isolated from fungi in 1970 and approved by the FDA for transplant rejection in 1983. It is a cyclic polypeptide consisting of 11 amino acids that acts by inhibiting T cell activation through the calcineurin/NFAT pathway. It has since been approved for treating various dermatological conditions like psoriasis, atopic dermatitis, and pyoderma gangrenosum. While effective, cyclosporine use can cause nephrotoxicity, hypertension, and increased risk of infection and skin cancer with long term use. It can also interact with various other drugs that are metabolized through the CYP3A4 pathway.
The drugs included in the presentation are Methotrexate, Cyclosporine, Azathioprine, Cyclophosphamide, Mycophenolate mofetil and Intravenous Immunoglobulin.
It is useful mainly for dermatologists.
The drugs included in the presentation are Methotrexate, Cyclosporine, Azathioprine, Cyclophosphamide, Mycophenolate mofetil and Intravenous Immunoglobulin.
It is useful mainly for dermatologists.
It's about how toxins affect our body and how our body build as defense mechanism to fight it. Biotransformation is a process when these toxins are converted into useful metabolites.
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Approach to a case of diffuse hair loss in females
. Anagen effluvium-
(a)Dystrophic
(b)Loose anagen hair
2. Telogen effluvium –
(a)acute telogen effluvium
(b)Chronic telogen effluvium
3. Female pattern hair loss
Primary CTE –represents a primary disorder and is a diagnosis of exclusion.
Secondary CTE- secondary to variety of systemic disorders.
Iron deficiency
Other deficiency –protein calorie malnutrition ,zinc deficiency
Thyroid diseases
Metabolic diseases-chronic liver or renal failure, advanced malignancy, pancreatic disease and upper GI disorder with malabsorption
SLE and other connective tissue disorders.
HIV infection
Drug induced
1. Cutaneous T-cell pseudolymphomas
A) Primarily with stripe-like infiltration (the majority of cases)
Lymphomatoid drug eruption (most cases);
Lymphomatoid contact dermatitis;
Actinic reticuloid;
Nodular scabies (individual cases);
Idiopathic forms;
Clonal cutaneous T-cell pseudolymphomas.
B) Primarily with nodular infiltration (a small percentage
of the cases)
Drug-induced – mainly by anti-convulsive drugs
Persistent nodules after insect bites;
Nodular scabies (the majority of cases).
2. Cutaneous B-cell pseudolymphomas (with nodular infiltration)
Cutaneous lymphocytoma from Borrelia burgdorferi;
Cutaneous lymphocytoma after antigens injection;
Cutaneous lymphocytoma resulting from tattoo;
Cutaneous lymphocytoma after Herpes zoster;
Idiopathic forms;
Clonal cutaneous B-cell pseudolymphomas
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
2. o 1970, isolated as narrow antifungal
from Tolypocladium inflatum Gams
o 1976, found to be a potent immunosuppressive
o 1983, FDA approval for transplant rejection.
o 1997, FDA approval for Rx of psoriasis
o Approved for atopic dermatitis in other
countries.
3. › Cyclic polypeptide
› Consist of 11 amino acids
› Produced as a metabolite by Beauveria nivea.
4. Pharmacokinetics
Absorption and bioavailability
• Before meal higher absorption
• Widely distributed
• Ideal body weight should be
used to calculate dose
Elimination
First-order kinetics
Peak levels
(hr)
Bioavailabl
e (%)
Protein
binding (%)
Half-life
(hr)
Metabolism Excretion
2-4 30 90 5-18 CYP3A4 and
CYP3A5 in liver
Efflux p-
glycoprotein
pump (PGP),
in GI tract and
liver
Primarily
hepatobilia
ry
Renal 6%
5. o Sandimmune (cyclosporine, USP)
o Gengraf (cyclosporine, USP – Modified)
o Neoral (cyclosporine, USP – Microemulsion)
6. o Twice the bioavailability
o Less intraindividual and interindividual
variability
o Reduced time (more than 30 percent) to
maximal concentration (Tmax)
o Absorption and drug levels are less susceptible
to effects of food (particularly fatty foods),
o Not dependent upon bile salts for absorption.
7. o 1. Action on the calcineurin / NFAT
pathway
o 2. Action on JNK and p38 signaling
pathways
o 3. Action by Induction of TGF-b
9. o JNK and p38 act in stress responses,
(inflammation and apoptosis),
o Activated when T cell responses are triggered
through both TCR and CD28 co-stimulatory
receptor
o Are sensitive to CsA (Su et al., 1994;Matsuda
et al., 1980) .
o JNK and p38 with ERK leads to activation of
transcription factors including AP-1 (Karin,
1995)
10. o CsA induces synthesis of TGF-b in vitro and in
vivo (Li et al., 1991; Khanna et al., 1994; Wolf et
al.,1995; Shihab et al., 1996)
o TGF-b is known to stimulate cells to increase their
extracellular matrix ECM composition
o Decreases production of ECM-degrading
proteases,
o Thereby inducing a profibrogenic state
(Massague,1990) .
o TGF-b produced by CsA administration directly
promotes cancer progression (Hojo et al., 1999) .
11. o US FDA approved
› Psoriasis
› Severe Psoriasis
› Recalcitrant, treatment resistant Psoriasis
› Disabling Psoriasis
o Approved in other countries
› Psoriasis
› Atopic dermatitis
12. Disease CsA dose Duration of
Rx
Response Time to relapse
after discontinued
Other
drugs
Comm
ents
Psoriasis 12-16 wks,
12 mos
maximum
Excellent Average 111 days; however,
30% had no relapse 6 mos
after CsA discontinued
A. Intermittent
short-term
therapy
2.5-5 mg/kg/day for 12-16 wks,
course repeated when relapse occurs
B. Rescue
therapy
5 mg/kg/day for 12-16 wks for
flaring of disease
C. Long term
therapy
<5 mg/kg/day for up to 1 y; reducing
dose to lowest effective
D.
Combination
therapy
Corticosteroids, anthralin, or vitamin D3 analogues for an
improved response. MTX, fumaric acid esters, and
mycophenolate mofetil in severe cases
E. Rotational
therapy
Can minimize
CsA toxicity
13. Disease CsA
dose
Duratio
n of
treatme
nt
Response Time to relapse
after discontinued
Other
drugs
Comments
Psoriatic
arthritis
3-4
mg/kg/da
y, max 5
mg/kg/da
y
6-12 mos Very good MTX
15
mg/wk,
occasio
nally
50% reduction in joint
complaints required 24
wks of CsA monotherapy,
CsA-MTX combination
therapy given to patients
with partial MTX response
Atopic
dermatitis
2.5-3
mg/kg/da
y, max 5
mg/kg/da
y
12-16
wks, 12
mos max
Excellent 2 wks (50%), 6
wks (80%)
Used for short treatment of
severe, AD that cannot be
controlled with topical
therapy. Approved for this
in Europe and UK
Pyoderma
gangrenosu
m
5
mg/kg/da
y
>6 mos Excellent Methylprednisolo
ne (0.5-1
mg/kg/day, or
pulse treatment 1
g/day for 1-5
days) usually
given concurrently
14. Disease CsA dose Duration of
treatment
Response Time to relapse
after
discontinued
Other
drugs
Comments
Dyshidrotic
eczema
2.5-3
mg/kg/day
6 wks, up to
16 wks
Equivalent 77% of patients
continued to have a 54%
improvement at 1 y
CsA equivalent to
BDP cream
Behçet
disease
5 mg/kg/day >6 mos Very good Prednisone, occasionally Used for refractory
eye disease, topical
steroid–resistant
mucocutaneous
disease, and arthritis.
Poor prevention of
neurologic
involvement
Chronic
urticaria
4 mg/kg/day 12-16 wks Very good 33% at 3-6 mos, relapse
less severe
Cetirizine 10 mg/day,
occasionally concurrently
Used as a steroid
sparing agent or in
cases refractory to
corticosteroids
15. Disease CsA dose Duration
of
treatment
Response Time to relapse
after
discontinued
Other
drugs
Comments
Pityriasis
rubra
pilaris
3-5
mg/kg/day,
maintenance
dose 2
mg/kg/day
>8 mos Mixed Used in erythrodermic
classic adult and
erythrodermic juvenile
PRP
Dermato -
myositis
1-1.8
mg/kg/day,
>200
mg/day
Very good Prednisone 40 mg/day Used in cases not responsive
to prednisone combined with
MTX or azathioprine.
Effective for lung and
esophageal involvement
Pemphigus
vulgaris
1-3
mg/kg/day
8 mos ±
11.8 mos
Good, but
better
treatment
options
available
43% free of relapse
after combination
therapy with
cyclosporine and
prednisone 5 y after
discontinuation of
therapy
Prednisone,
usually given
concurrently
Used as a
steroid
sparing agent
16. Disease CsA
dose
Duration
of
treatment
Response Time to relapse
after
discontinued
Other drugs Comments
Epidermolysis
bullosa
acquisita
4-5
mg/kg/d
ay
1-24 mos Good, but better
treatment options
available
Prednisone, u
sually given
concurrently
Used as
steroid
sparing agent
Photodermatoses
A. Chronic
actinic
dermatitis
4-4.5
mg/kg/day
Good
B.
Polymorphic
light
eruption
3-4
mg/kg/day
May be given 1 wk
before sun exposure,
and discontinued
upon return
Good
C. Solar
urticaria
4.5
mg/kg/day
Short courses during
summer months
Flares once cyclosporine
discontinued
17. Disease CsA
dose
Duration
of
treatment
Response Time to relapse
after discontinued
Other
drugs
Comments
Lichen
planopilaris
3-5
mg/kg
/day
3-5 mos Good Symptom free,
stable disease at 12
mos
postcyclosporine
CsA may be
effective in the
initial phases
before severe
follicular damage
occurs
Prurigo
nodularis
3.5-4
mg/kg
/day
6-9 mos Good
Lichen
planus
3-4.5
mg/kg
/day
2-3 mos Good Prednisone,
occasionally
topical
steroids
Used for disseminated ,
erosive LP, and LP
resistant to systemic
corticosteroids and
retinoids. Topical CsA
may be effective in
treatment of oral LP
18. Disease CsA dose Duration
of
treatment
Response Time to relapse after
discontinued
Other drugs Comments
Severe
alopecia
areata
5
mg/kg/da
y
2-12 mos Mixed 33%-86% with
>70% hair
regrowth, 76%
with maintained
hair regrowth at
12 mos follow-
up
Methylpredn
isolone
(pulse and
daily
dosing),
prednisone
Eight case reports of
patients who developed
alopecia areata while on
CsA for solid organ
transplant, and atopic
dermatitis
Hailey-Hailey
Ds.
1.2-3.4
mg/kg/da
y
6-8 mos Good Acitretin 10 mg/day,
occasionally
Eosinophilic
pustular
folliculitis
100-150
mg/day
2-12 wks Good
Hidradenitis
suppurativa
4-4.5
mg/kg/da
y
Good Prednisolone,
broad spectrum antibiotics
Scleroderma May potentially worsen hypertension or renal disease associated with systemic
sclerosis
19. o Pemphigoid
o Linear IgA bullous dermatosis
o Lupus erythematosus
o Granuloma annulare
o Sarcoidosis
o Kimura’s ds.
o Morphea
o Papular erythroderma of ofuji
o Purpura pigmentosa chronica
o Reiter’s syndrome
o Scleromyxedema
o Sezary’s syndrome
o Mycosis fungoides
20. o Department of Dermatology, Health
Waikato, New Zealand.
o Abstract
o A patient developed toxic epidermal
necrolysis while on carbamazepine, 80% of
her skin surface being involved. She also
developed a pancytopenia with a
neutropenia of 0.77 x 10(9)/l (normal range
2-7.5 x 10(9)/l), but was treated with
cyclosporin and granulocyte colony
stimulating factor and made a full recovery.
o Int J Dermatol. 1989 Sep;28(7):441-4.
21. Drug-induced toxic epidermal necrolysis
treated with cyclosporin.
Renfro L, Grant-Kels JM, Daman LA.
Division of Dermatology, University of
Connecticut Health Center, Farmington.
Abstract
A 35-year-old woman developed toxic
epidermal necrolysis secondary to
phenytoin. Because the life-threatening
eruption was resistant to prednisone and
high-dose methylprednisolone therapy,
cyclosporine therapy was initiated. Within
24-48 hours, the eruption stabilized and the
patient improved.
22. o ABSOLUTE
• Uncontrolled
hypertension,
• Significant renal
impairment,
• Serious infections,
• Previous
history of malignancy,
excluding BCC
• High cumulative
dose of previous
psoralen and ultraviolet
A light phototherapy
• Cutaneous T-cell
lymphoma
o RELATIVE
23. o Drugs that inhibit or stimulate
cytochrome P450
o Nephrotoxic drugs should be avoided
o A full drug history should be taken at
every visit
24. o Calcium channel blockers
Diltiazem, nicardipine,
verapamil, and mibefradil
o Antifungals
Ketoconazole >
itraconazole >
Fluconazole, and
voriconazole
o Antibiotics
Erythromycin,
clarithromycin, and
josamycin, Doxycycline,
Gentamicin and
tobramycin, Ticarcillin,
Ciprofloxacin
o Oral contraceptives
o Amiodarone
o Cimetidine
o Protease inhibitors
o Warfarin
o Grapefruit juice
o SSRIs (sertraline)
By other mechanism
o Methylprednisolone
o Allopurinol
o Thiazide diuretics
o Furosemide
26. Drug Type Comments
Nephrotoxic agents
NSAIDs
Vancomycin
Ganciclovir
Aminoglycosides
Monitor renal function
NSAIDs may have increased nephrotoxicity
with hepatic impairment
Potassium-sparing diuretics Hyperkalemia has been reported
Antacids Magnesium and aluminum antacids may inhibit
absorption of CNIs
If necessary, should be taken 2 hours after CNI
dose
HMG-CoA reductase inhibitors
(statins)
Increased risk of rhabdomyolysis, bone marrow
suppression
27. o Are leading cause of its limited use in
dermatology.
o Depend on dose and duration of therapy
o Reversible on discontinuation,
o Structural renal abnormalities may be
persistent.
o Mitochondrial dysfunction (ion channel
regulation)
o Inhibition of immunophilins may play a role
28. Event Comments
•Renal dysfunction
o Functional
Vascular
dysfunction
Tubular
dysfunction
o Structural
Vasculopathy
Tubulopathy
Prolonged therapy (>2 yrs) or dose >5 mg/kd/day
C/b vasoconstriction of afferent glomerular
arterioles → ↓GFR
↓ magnesium reabsorption, ↓ uric acid excretion,
↓ K+ & H+secretion, and distal tubular acidosis.
↓HCO3-, and hyperkalemia
Glomerular or arteriolar thrombi, arteriolopathy,
and interstitial fibrosis with tubular atrophy
Vacuolization of PCT, giant mitochondria in
tubular epithelial cells, single cell necrosis, and
microcalcification of Tamm–Horsfall protein in
DCT
Malignancy
Skin cancers,
Cervical cancer,
Lymphoproliferative
Incidence appears to be a function of overall
amount and duration
29. Event Comments
Gastrointestinal
Nausea, abdominal pain, diarrhea,
vomiting, Hyperbilirubinemia,
cholelithiasis
If serum bilirubin or transaminases rise
to twice the normal value, a dose
reduction of 25% is necessary
Neurologic
Headaches, tremor, seizures,
psychosis, paraesthesias, and sleep
disturbance, Pseudotumor cerebri,
Decrease in high-energy phosphate
metabolism and a reduction in
intracellular
concentrations of neurotransmitters
hypertension (S>140 or D>90 mm Hg) Dose reduction of 25% to 50% or start
CCBs amlodipine have vasodilating
effect on afferent arteriole
Hyperlipidemia (hypertriglyceridemia
)
Normalizes on discontinuation of drug
30. Event Comments
Cutaneous
Hypertrichosis, epidermal cysts,
keratosis pilaris, acne, folliculitis,
and sebaceous hyperplasia.
Cyclosporine modulates protein kinase C
expression and translocation in hair
epithelial cells and promotes
proliferation of these cells
Gingival hyperplasia Caused by fibrous hyperplasia and has been
reported in up to 30% of patients
on cyclosporine, with a higher incidence
reported in children
Infections Rare and seldom severe,
treatment of the infection or
withdrawal of the drug led to resolution
Other side effects Slight NC, NCr anemia
Fatigue, lethargy, and flu-like symptoms
are common
joint pain and muscle aches in 10% to
40%
31. o Patients should be instructed to attend their
dentist at 6-month intervals
o National malignancy screening programs
should be adhered to
o Where possible Vaccination should take
place before initiation of treatment
32. Investigation Details
Full history Previous infections: TB, hepatitis B/C;
history of hypertension, kidney disease,
liver disease, or malignancy; full
medication history, which should be
repeated at every subsequent visit
Blood pressure Baseline (2 separate measurements,
should be <140/90 mm Hg); taken again
at weeks 2, 4, 6, and 8, then monthly
Physical examination Actinic damage/cutaneous malignancies;
herpes simplex; viral warts
33. Investigation Details
Serum creatinine Baseline (mean of 2 separate fasting
measurements; if discrepancy of >10%, repeat
again);taken again at weeks 2, 4, 6, and 8, then
monthly
Blood urea nitrogen Baseline and at weeks 2, 4, 6, and 8, then monthly
Complete blood cell count Baseline, then monthly
Potassium Baseline, then monthly
Bilirubin, liver enzymes Baseline, then monthly
Fasting lipid profile Baseline, then monthly
Uric acid Baseline, then monthly
Magnesium Baseline, then monthly
Urinalysis Baseline, then monthly
34. Investigation Details
Tuberculin test Baseline
Glomerular filtration rate After 1 y of continuous therapy
Screening Programs Cervical, breast, and colon cancer
screening as per national guidelines
Vaccinations Annual pneumococcal and influenza
vaccinations
35. o Typically monitored in transplant patients
to avoid toxicity
o Minimum of 0.5 mL ( ½ cc) whole blood,
collected in purple-top tube.
o Sample should not be centrifuged.
o Sample may be frozen or kept cold in
refrigerator until analysis.
o Samples are stable for 30 days at -20°C
(frozen).
36. Low risk Mod Risk High risk
0-6 m 150-250 ng/ml 175-325 ng/ml 200-350 ng/ml
6-12 m 100-200 ng/ml 125-225 ng/ml 150-250 ng/ml
> 12 m 50-150 ng/ml 75-175 ng/ml 100-200 ng/ml
S Hariharan. Am J Kidney Dis. 2006. 47(S2):S22-S36.
Trough or C0 level (samples are collected
immediately before next scheduled dose)
37. Cyclosporin: C2 Level (two-hour sample)
< 6 months: 1000-1500 ng/ml
> 6 months: 800-900 ng/ml
› Little evidence from prospective studies to
support theoretical benefits of C2 monitoring.
Potential dose reductions in stable patients may
reduce costs, but no short-term clinical benefit is
seen.*
*Knight, S R. et al. Transplantation 2007 Jun; 83(12):1525-1535
38. o Crosses placental, category C drug in
pregnancy
o Pregnancy registries show no increase in
risk of teratogenicity,
o Although there were trends towards low
birth weight and prematurity
o Excreted in breast milk
39. o Decreased bioavailability in children
o Children are less susceptible
to cyclosporine-induced nephropathy
than adults
40. o Use in psoriasis changed entire field of psoriasis
research
o From that of a hyperproliferative, keratinocyte-
driven disorder to that of an ―immune-driven‖
disease,
o Provided a way for biologic revolution in
psoriasis.
o Useful in treatment of significant
flares of cutaneous disease — especially
psoriasis and atopic dermatitis
o Bridging agent during induction of other
maintenance agents.
41. o Combination or rotational therapy can be
used to minimize cumulative dosage and
long-term side effects.
o Treatment for more than 1 year should be
avoided where possible.
o Side effects are dose and
duration dependent, reversible on
discontinuation
o It is a drug that should be an integral
part of our therapeutic armamentarium
o Provided that guidelines are closely
followed.