Guidelines for topical steroids

Penetration differs at different sites:
High: axilla, groin, face, scalp, scrotum
Medium: limbs, trunk
Low: palm, sole, elbow, knee
Occlusive dressing enhance absorption (10 fold)
Absorption is greater in infants & Children
Absorption depends on nature of lesion:
High: atopic & exfoliative dermatitis
Low: hyperkeratinized & plaque forming lesions
More than 3 applications a day is not needed
Choice of vehicle is important
Lotions & creams: for exudative lesions
Sprays & gels: for hairy regions
Ointments: for chronic scaly lesions
(By Dr. Ahmad Najmi, Index Medical College, Indore)

Therapeutic uses of corticosteroids

(By Dr. Ahmad Najmi, Index Medical College, Indore)

1. Endocrine Disorders
Acute adrenal insufficiency
Primary adrenocortical insufficiency
Ad. Insufficiency second. to Ant. Pituitary
Congenital adrenal hyperplasia
2. Rheumatic carditis
Not responding to salicylates
Severely ill pts.
Prednisolone 40mg in divided doses
Salicylates given concurrently to prevent reactivation
3. Arthritis
Not the drug of first choice
Prednisolone 5 or 7.5 mg
Intra-articular injection
4. Renal diseases (Nephrotic syndrome)
Prednisolone 60 mg in divided doses for 3 – 4 weeks
If remission occurs continue for 1 year
Do not modify the course of disease; Some may benefit
5. Collagen diseases
DLE, pemphigus vulgaris, polyarteritis nodosa
Defect in connective tissue proteins in joints, various organs and deeper layer of skin
6. Allergic diseases
Anaphylactic shock, blood transfusion reaction, hay fever
Prednisolone (short course)
7. Bronchial asthma
Not routinely used except in Status asthmaticus
Methyl prednisolone sodium i.v. given followed by oral prednisolone
Inhaled steroids (Minimal HPA axis suppression
8. Ocular diseases
Outer eye & anterior segment: local application
Posterior segment: systemic use
Caution: bacterial, viral & fungal conjunctivitis
9. Dermatological conditions
Pempigus: Life saving therapy is steroids
Eczema, dermatitis & psoriasis: respond well
10. . Diseases of intestinal Tract
Ulcerative colitis: cortisol retention enema
11. Cerebral oedema
Questionable value in cerebral oedema following trauma, cerebrovascular oedema
Valuable in oedema associated with neoplasm and parasites
13. Malignancy
Part of multi drug regimens for acute lymphatic leukaemia (children), chronic lymphatic leukaemia (adult)

Prednisolone 1mg/Kg start; gradually reduce the dose

Contraindications of corticosteroids

Infections
Hypertension with CCF
Psychosis
Peptic ulcer
Diabetes mellitus
Osteoporosis
Glaucoma
Pregnancy : (prednisolone preferred)

Adverse effects of corticosteroids

Iatrogenic Cushing’s syndrome
Hyperglycaemia, glycosuria, diabetes
Myopathy (negative nitrogen balance)
Osteoporosis (vertebral compression fracture)
Retardation of growth (children)
Hypertension, oedema,CCF
Avascular necrosis of femur
HPA axis suppression
Behavioral toxicity: Euphoria, psychomotor reactions, suicidal tendency
Ocular toxicity: steroid induced glaucoma,posterior subcapsular cataract.
Others:
Superinfections
Delayed wound healing
Steroid arthropathy
Peptic ulcer
Live vaccines are dangerous
By Dr. Ahmad Najmi, Index Medical College, Indore

Finasteride

5-alpha reductase inhibitor

Orally active
used in BPH
Dose 5 mg/day
Decrease prostate volume
Decrease symptom score
Decrease DHT level in prostate
Also used for androgenic alopecia
ADR: loss of libido & impotense in 5 % patients

Antiandrogens

Danazol
Cyproterone acetate
Flutamide
Finasteride

Define briefly drug antagonism ?

(By Dr. Ahmad Najmi, Index Medical College, Indore)
When one drug decrease the action of another drug, they are k/a antagonist.Depending on mechanism involved antagonism may be
1. Physical e.g. charcoal adsorb alkaloids
2. Chemical e.g. Chelating agents complex toxic metals
3. Physiological e.g. Glucagon & insulin on blood sugar
4. Receptor is further divided into competetive & noncompetetive
In competetive type of antagonism, antagonist is chemically similar to agonist & bind to the same site.
In noncompetetive type of antagonism, the antagonist is chemically unrelated to the agonist, bind to a different allosteric site.

Adverse Drug Reaction

According to WHO, response to a drug that is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiologic function
excludes therapeutic failures, overdose, drug abuse, noncompliance, and medication errors
Adverse drug effects are classified on the basis of type, severity & onset
According to onset they are classified into
Onset of event:
Acute
within 60 minutes
Sub-acute
1 to 24 hours
Latent
> 2 days


According to severity
Severity of reaction:
Mild
bothersome but requires no change in therapy
Moderate
requires change in therapy, additional treatment, hospitalization
Severe
disabling or life-threatening
FDA Serious ADR
Result in death
Life-threatening
Require hospitalization
Prolong hospitalization
Cause disability
Cause congenital anomalies
Require intervention to prevent permanent injury
According to type

Type A
extension of pharmacologic effect
often predictable and dose dependent
responsible for at least two-thirds of ADRs
e.g., propranolol and heart block, anticholinergics and dry mouth

Type B
idiosyncratic or immunologic reactions
rare and unpredictable
e.g., chloramphenicol and aplastic anemia

Type C
associated with long-term use
involves dose accumulation
e.g., phenacetin and interstitial nephritis or antimalarials and ocular toxicity

Type D
delayed effects (dose independent)
Carcinogenicity (e.g., immunosuppressants)
Teratogenicity (e.g., fetal hydantoin syndrome)

Types of allergic reactions
Type I – immediate, anaphylactic (IgE)
e.g., anaphylaxis with penicillins
Type II – cytotoxic antibody (IgG, IgM)
e.g., methyldopa and hemolytic anemia
Type III – serum sickness (IgG, IgM)
antigen-antibody complex
e.g., procainamide-induced lupus
Type IV – delayed hypersensitivity (T cell)
e.g., contact dermatitis

Common causes of ADR
Antibiotics
Antineoplastics*
Anticoagulants
Cardiovascular drugs*
Hypoglycemics
Antihypertensives
NSAID/Analgesics
Diagnostic agents
CNS drugs*
*account for 69% of fatal ADRs

By Dr. Ahmad Najmi

Explain why morphine is contraindicated in head injury

Head injury is a traumatic , painful condition requiring analgesic.

Morphine in opoid analgesic.

1-It depresses respiratory drive.slowing of respiration leads to retention of co2

which will lead to increased intracranial tension.Head injury itself increases intracranial tension.

2-Raised intracranial tension leads to vomiting. Morphine also stimulates CTZ , LEADING TO nausea and vomiting.

3–Head injury assessment is done by pupillary constriction /dilataion.

Morphiune interferes wih this assessment/prognosis because it causes pupillary miosis- constriction of pupil.

Actions of Morphine

(By Dr. Ahmad Najmi, Index Medical College, Indore)
The main pharmacological effects are:

* analgesia

* euphoria and sedation

* respiratory depression-can lead to respiratory failure-apnoea.
* suppression of cough-is used as cough suppressent

* nausea and vomiting-Due to CTZ stimulation

* pupillary constriction-pinpoint pupil

* reduced gastrointestinal motility, causing constipation

* histamine release, causing bronchoconstriction-contraindicated in astmatics and hypotension.

* The most troublesome unwanted effects are constipation and respiratory depression.

* Morphine may be given by injection (intravenous or intramuscular) or by mouth, often as slow-release tablets.

* Acute overdosage with morphine produces coma and respiratory depression.- is treated by naloxone- antidote

* Morphine is metabolised to morphine 6-glucuronide (M6G), which is more potent as an analgesic.

* Morphine and M6G, are the active metabolites of diamorphine and codein

WHO analgesic ladder

(By Dr. Ahmad Najmi, Index Medical College, Indore)
WHO has formulated certain guidelines for the use of analgesic drugs in various painful conditions. These guidelines are known as WHO analgesic ladder. According to these guidelines :
1. For mild degree pain, simple nonopioid analgesic drugs like paracetamol or acetamenophen should be used
2. For moderate degree of pain weak opioid analgesic like codeine should be used with or without NSAIDS
3. For severe degree of pain, strong opioid should be used for e.g. morphine with or without non opioids

Ivabradine

(By Dr. Ahmad Najmi, Index Medical College, Indore)
It is new drug for the treatment of chronic angina which is resistant to conventional drugs.
It reduce cardiac work load by selectively reducing heart rate.
It is selective sinus node channel inhibitor.
It has got no negative inotropic effect

Mnemonics

Hepatic necrosis: drugs causing focal to massive necrosis
“Very Angry Hepatocytes”:
Valproic acid
Acetaminophen
Halothane
Adrenoceptors: vasomotor function of alpha vs. beta
ABCD:
Alpha = Constrict.
Beta = Dilate.
Amiodarone: action, side effects
6 P’s:
Prolongs action potential duration
Photosensitivity
Pigmentation of skin
Peripheral neuropathy
Pulmonary alveolitis and fibrosis
Peripheral conversion of T4 to T3 is inhibited -> hypothyroidism
Antiarrhythmics: class III members
BIAS:
Bretylium
Ibutilide
Amiodarone
Sotalol
By Dr. Ahmad Najmi,Asst. prof., Index Medical College, Indore

Mneumonics- Antiarrythmic drugs classification-MBA College

In order of class I to IV:
Membrane stabilizers (class I)
Beta blockers(Class11)
Action potential widening agents(Class 111)
Calcium channel blockers (IV)
By Dr. Ahmad Najmi, IMCHRC, Indore

Why Linezolid Should not be used with tyramine containing food like cheese etc ?

Linezolid belongs to glycopeptide group of antibiotics. It is available for the treatment of VRSA, VRE & many other resistant type of organisms. Because linezolid inhibit the enzyme monoamine oxidase (MAOI), interaction with adrenergic, serotonergic & tyramine containing food may occur.

By Dr. Ahmad Najmi, Asst. prof. Index Medical College, Indore

Therapeutic uses of testosterone

(By Dr. Ahmad Najmi, Index Medical College, Indore)

1. Testicular failure: Primary & Secondary
2.Osteoporosis
3. Burns
4. Chronic illness
5. Long term corticosteroid therapy
6. Pituitary dwarfism
7. Carcinoma of breast
8. Hereditary angioneurotic oedema
9. Anaemia (refractory)
10. Menopausal syndrome

Sildianafil

(By Dr. Ahmad Najmi, Index Medical College, Indore)


1.It is used in erectile dysfunction
2. Inhibits (phosphodiesterase -5 ) PDE5 in the corpus cavernosa of the penis, thus increasing the level of c-AMP
3. 50mg, per orally 1 h before sexual activity
4. potentiate nitrate’s hypotension activity
5. ketoconazole & erythromycin increases its level
6. renal & hepatic disease increases its level
7. Side effects:

headache, flushing, dyspepsia, myalgia

Benefits of OCP's other than contraception

Dr. Ahmad Najmi, Index Medical College, Indore
There is reduced risk of :

* Ovarian cysts

* Ovarian & endometrial cancer

* Benign breast diseases

* Lower incidence of ectopic pregnancy

There is less common chances of

* iron deficiency
* rheumatoid arthritis
* Pre-menstrual tension
* Dysmenorrhea
* Endometriosis
* Acne
* Hirsutism

Adverse effects of OCP's

Most serious:
A-CVS side effects:
1-Thrmobophlebitis (due to O & P)
2-Thromboembolism ( due to oestrogen)
3-Hypertension
4-Cerebral & coronary thrombosis
5-Increased incidence of M.I. and stroke

B-Cancer: Ca. breast, vagina and cervix ?
Benign hepatoma:
Gall stones: biliary cholesterol secretion
C-Less serious:
Weight. gain
Pigmentation of cheeks, nose and forehood
Pruritus vulvae
Diabetes,
Mood swings, abdominal discomfort
D-Non- serious:
Nausea, vomiting
Breakthrough bleeding
Breast discomfort
Suppression of lactation (very rare)
(Dr. Ahmad Najmi, Index Medical College, Indore)

Types of OCP's

Types of methods
A-Oral
1-Combined pill-contain estrogen(ethinyl estradiol) and progestin(norgestrel)

2-Sequential pill-
3-Phased regime-initial phase(proliferative) estrogen

then in secretory(luteal) phaseesrtrogen plus progesterone-recommended for women over 35 years age

4-Mini pill-progesterone only pill-where estrogen is contraindicted

5-Post-coital pill-emergency pill-

1-levonorgestrel plus ethinyl estradiol

2 tablets within 72 hour of unprotected intercourse

2-levonorgestrel alone 2 tablets within 72 hours

3-mifepristone alone within 72 hours
B-Injectable

1-Long acting
a-progest. alone-DMPA-150 mg at 3 monthly interawal

b-Norethindrone enanthate-200mg-at 2 months interwa

2-Long acting
progest. + Oestrog.
C-Implants:
Norplant-levonorgestrel 6 capsules subcutaneous

Dr. Ahmad Najmi, Index Medical College, Indore

What is the mechanism of action of oral contraceptive pills ?

1. Decrease Gonadotropin release from pituitary leading to absence of FSH & LH peaks

2. Decrease Follicular development & ovulation

3. Thick cervical mucus hostile to sperms

4. Decrease Implantation of blastocyst in endometrium

5. Contractions of uterus & Fallopian tubes are modified

Dr. Ahmad Najmi, Index Medical College, Indore

What is centchroman / Saheli ?

Dr. Ahmad Najmi, Index Medical College, Indore
•Non-steroidal oral contraceptive (CDRI, Lucknow)
•Oestrogen antagonist
•Anti-implantation agent
•Safer free from OCS side effects; menstrual cycle not disturbed – may be lengthened in 6-10% women
•For all age group of women
•Failure rate: 1 – 3 %
•Side effects: enlargement of ovary
•C/I: polycystic ovarian disease, cervical hyperplasia,

renal or hepatic disease, tuberculosis & lactating mother
•Dose: 30mg tablet twice a week; 30mg once a week till needed

Dr. Ahmad Najmi, Index Medical College, Indore

Adverse effects of oral contraceptive pills (OCP)

Most serious:
A-CVS side effects:
1-Thrmobophlebitis (due to O & P)
2-Thromboembolism ( due to oestrogen)
3-Hypertension
4-Cerebral & coronary thrombosis
5-Increased incidence of M.I. and stroke

B-Cancer: Ca. breast, vagina and cervix ?
Benign hepatoma:
Gall stones: biliary cholesterol secretion
C-Less serious:
Weight. gain
Pigmentation of cheeks, nose and forehead
Pruritus vulvae
Diabetes,
Mood swings, abdominal discomfort
D-Non- serious:
Nausea, vomiting
Breakthrough bleeding
Breast discomfort
Suppression of lactation (very rare)

Dr. Ahmad Najmi, Index Medical College, Indore