Prohibited classes of substances

Anabolic steroids e.g. nandrolone
Diuretics e.g. furosemide
Erythropoitin
Peptide hormones
Narcotics & analgesics e.g. heroin, morphine
CNS stimulants e.g. amphetamine, caffeine
Beta blockers
Agents with antiestrogenic activity e.g. aromatase inhibitors

What is doping ?

Accordiong to WADA, Doping is defined as the use of an artifice, whether substance or method, potentially dangerous to athletes' health and/or capable
of enhancing their performances, or the presence in the athlete's
body of a substance, or the ascertainment of the use of a method
on the list annexed to the Olympic Movement Anti-Doping Code

Therapeutic uses of androgens

Male hypogonadism
Enhancement of Athletic Performance
Male Contraception
Catabolic and Wasting States
Angioedema
Blood Dyscrasias

Methods of contraception

Female Contraception:
Inhibition of ovulation
Prevention of fertilization
Anti-zygotic drugs
Inhibition of implantation
use of spermicidal in vagina
IUCD
Male contraception:
Direct inhibition of spermatogenesis
Indirect inhibition of spermatogenesis
Immunological techniques (vaccine)

Uses of estrogens

As oral contraceptive pills
In hormone replacement therapy (HRT)
Osteoporosis
Treatment of postmenopausal hot flushes
Treatment of postmenopausal urogenital atrophy

Emergency Contraception

Mechanism: Multiple mechanisms are likely to contribute to the efficacy of these agents, but their precise contributions are unknown Some studies have shown that ovulation is inhibited or delayed, but additional mechanisms thought to play a role include alterations in endometrial receptivity for implantation; interference with functions of the corpus luteum that maintain pregnancy; production of a cervical mucus that decreases sperm penetration; alterations in tubular transport of sperm, egg, or embryo; or effects on fertilization. However, emergency contraceptives do not interrupt pregnancy after implantation.

Regimens: High doses of diethylstilbestrol and other estrogens once were used for postcoital contraception (the "morning-after pill") but never received FDA approval for this indication. The FDA has now approved two preparations for postcoital contraception. PLAN-B is two doses of the "minipill" (0.75 mg levonorgestrel per pill) separated by 12 hours. PREVEN is two 2-pill doses of a high-dose oral contraceptive (0.25 mg of levonorgestrel and 0.05 mg of ethinyl estradiol per pill) separated by 12 hours. This is sometimes referred to as the "Yuzpe" method after the Canadian physician who pioneered its use.

The first dose of such preparations should be taken anytime within 72 hours after intercourse, and this should be followed 12 hours later by a second dose. This treatment reduces the risk of pregnancy following unprotected intercourse by approximately 60% for the Yuzpe method and 80% for levonorgestrel alone. With either preparation, effectiveness appears to increase the sooner after intercourse the pills are taken

Adverse Effects: Nausea and vomiting are the main untoward effects, No changes in clotting factors have been reported for the combined regimen, but based on concerns with combination oral contraceptives, levonorgestrel alone might be considered for women who smoke or have a history of blood clots. Emergency contraceptive pills are contraindicated in cases of confirmed pregnancy.

Antidotes

Iron- Desferoxamine
Paracetamol- N acetylcysteine
Heparin-Protamine sulfate
Warfarin- Whole blood
Organophosphates- atropine / oximes
Dhatura- Physostgimine

How Transgenic animals help in research ?

Transgenic animals enable scientists to understand the role of genes in specific diseases.
By either introducing or inactivating particular genes, researchers can often for the first time discover the root causes of diseases associated with gene defects
Transgenic animals allow more effective treatments to be developed.
Transgenic animals help test the safety of new medicines and vaccines
Because transgenic models can highlight specific characteristics such as certain mechanisms involved in the formation of tumours, they can demonstrate more clearly the possible side effects of new therapies
Their use in early toxicity trials may also serve to prevent the subsequent use of a larger number of animals in the development phase
Transgenics may spare the use of higher animals
Transgenic animals can produce biological products.
It may be possible to use transgenic animals to make rare biological products for medical treatment
Human alpha-1-antitrypsin, a protein used to treat the rare genetic disorder of alpha-1-antitrypsin deficiency, is just one example

Role of transgenic animals in drug development

First, one can test whether it is reasonable to pursue a certain therapeutic approach. For example, if the researchers want to know if a disease could be treated by reducing the amount of a certain protein or the activity of a particular enzyme, they can produce transgenic animals missing the corresponding gene ("gene-knockout animals")
If symptoms of the disease are ameliorated without serious side effects, then it might be worth the time and expense of producing a drug that would have the same effect

How Transgenic animals are made?

To add a gene, called a transgene, to the normal chromosome set of an animal, researchers remove a one-cell embryo (the fertilized oocyte) from the oviduct of a pregnant animal and inject a cloned segment of DNA, including a gene of interest, into the male pronucleus.
The researcher then puts the embryo into the oviduct of a surrogate pregnant female who will carry the transgenic animal to term

What are transgenic animals

Neither science nor society may be ready for the direct manipulation of the human genome, but a technique for directing the genetic make-up of animals is being used in some of the most exciting biomedical research today
This technique involves inserting a foreign gene into the chromosome of an animal
The animal, called transgenic, then expresses that gene along with its normal genes
Transgenic animals are animals whose hereditary properties have been permanently modified by the introduction of recombinant DNA into their germ cells
In animals, transgenesis either means transferring DNA into the animal or altering DNA already in the animal.

Therapeutic query

A patient receiving prednisolone for one year developed oral thrush. He stopped taking prednisolone & took ketoconazole. After 24 hrs, he developed weakness, abdominal pain, fever, nausea, vomitting, diarrhoea, confusion & hypotension. A lot of fluid & electrolytes were supplemented but the condition got deteriorated.

1. What was the cause of symptom to patient ?

2. What should be the line of management in such case ?

3. What are the precautions to prevent it ?

Androgenic Alopecia (Male pattern baldness)

Clinical Features: Miniaturization of hairs along the midline of the scalp
Recession of the anterior scalp line in men and some women

Pathogenesis:Increased sensitivity of affected hairs to the effects of testosterone

Increased levels of circulating androgens (ovarian or adrenal source in women)

Treatment: If no evidence of hyperandrogen state, then topical minoxidil; finasteridea; hair transplant

Etiology of alopecia

I. Nonscarring alopecia
A. Primary cutaneous disorders
1. Androgenetic alopecia
2. Telogen effluvium
3. Alopecia areata
4. Tinea capitis
5. Traumatic alopeciaa

B. Drugs
C. Systemic diseases
1. Lupus erythematosus
2. Secondary syphilis
3. Hypothyroidism
4. Hyperthyroidism
5. Hypopituitarism
6. Deficiencies of protein, iron, biotin, and zinc
II. Scarring alopecia
A. Primary cutaneous disorders
1. Cutaneous lupus (chronic discoid)
2. Lichen planus
3. Folliculitis decalvans
4. Linear scleroderma (morphea)
5. Central centrifugal cicatricial alopecia
B. Systemic diseases
1. Lupus erythematosus
2. Sarcoidosis
3. Cutaneous metastases

Conjunctivitis

This is the most common cause of a red, irritated eye.This usually occurs in rainy season in tropical countries. This is also known as eye flu. It is contagious. It spread by close contact with infected cases. Pain is minimal, and the visual acuity is reduced only slightly. The most common viral etiology is adenovirus infection. It causes a watery discharge, mild foreign-body sensation, and photophobia. Bacterial infection tends to produce a more mucopurulent exudate. Mild cases of infectious conjunctivitis are usually treated empirically with broad-spectrum topical ocular antibiotics, such as sulfacetamide 10%, polymixin-bacitracin-neomycin, or trimethoprim-polymixin combination

Tocolytics

The drugs which relax the uterine smooth muscles are known as tocolytics.

Indications:

To delay or postpone labor

Arrest threatened abortion

Dysmenorrhoea

Delaying the labor is needed to allow foetus to mature, to initiate glucocorticoid therapy for foetal lung maturation, to transfer the mother in labor to a centre with proper facilities

The drugs used are

1. Selective beta 2 adrenergic agonist e.g. ritodrine, isoxsuprine

2. calcium channel blockers (CCB) e.g. nifedipine

3. Magnesium sulfate (i.v.)

4. Oxytocin antagonist, Atosiban

5. Misc. drugs e.g. nitrates, prgesterone, PG synthesis inhibitors (NSAIDS) , general anaesthetics (halothane) etc

Antidiabetic drugs

Antidiabetic drugs can be classified in various ways like hypoglycemics & euglycemics

Hypoglycemics drugs

Insulin

Sulfonylureas

Meglitinide

Euglycemic drugs are

Biguanides

Thiazolidinediones

Alpha glucosidase inhibitors

Oral hypoglycemic drugs

Sulfonylureas which can be further divided into first & second generation drugs e.g. Glipizide, Gliclazide

Biguanides e.g. metformin

Thiazolidinediones e.g. rosiglitazone, pioglitazones

Alpha glucosidase inhibitors e.g. Acarbose & Miglitol

Meglitinide/ Phenylalanine analogues e.g. Repaglinide, Nateglinide

Parenteral drugs e.g. insulin

Role of iodine in nuclear disasters

The amount of radioactive iodine uptake by thyroid is inversely proportional to concentration of iodide in blood. That is why iodide salts were given during nuclear disaster to prevent the chances of hypothyroidism & radiation induced thyroid cancer.Following the Chernobyl nuclear reactor accident in 1986, approximately 10 million children and adults in Poland were given stable iodine to prevent the development of thyroid cancers

Management of gestational diabetes

Counselling before pregnancy (for example, about preventive folic acid supplements) and multidisciplinary management are important for good pregnancy outcomes.
Most women can manage their GDM with dietary changes and exercise. Self monitoring of blood glucose levels can guide therapy.
Some women will need antidiabetic drugs, most commonly insulin therapy.
The goal of treatment is to reduce the risks of GDM for mother and child.
Scientific evidence is beginning to show that controlling glucose levels can result in less serious fetal complications (such as macrosomia) and increased maternal quality of life
Metformin has shown promising results. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease GDM levels

Test for gestational diabetes

Fasting blood glucose
Random blood glucose
Oral glucose tolerance test

Pathophysiology of gestational diabetes

The hallmark of GDM is increased insulin resistance. Pregnancy hormones and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor.Placental hormones, and to a lesser extent increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol and progesterone are the main culprits, but human placental lactogen, prolactin and estradiol contribute too.

Risk factors for gestational diabetes

* a previous diagnosis of gestational diabetes or prediabetes, impaired glucose tolerance, or impaired fasting glycaemia
* a family history revealing a first degree relative with type 2 diabetes
* maternal age - a woman's risk factor increases as she gets older (especially for women over 35 years of age)
* ethnic background
* being overweight, obese or severely obese increases the risk by a factor
* a previous pregnancy which resulted in a child with a high birth weight
* previous poor obstetric history

Geastational diabetes

Gestational diabetes (or gestational diabetes mellitus, GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy.
Babies born to mothers with gestational diabetes are at increased risk of problems typically such as being large for gestational age (which may lead to delivery complications), low blood sugar, and jaundice. Gestational diabetes is a treatable condition and women who have adequate control of glucose levels can effectively decrease these risks

Treatment of diabetic retinopathy

Regular, comprehensive eye examinations are essential for all individuals with DM. Most diabetic eye disease can be successfully treated if detected early. Routine, nondilated eye examinations by the primary care provider or diabetes specialist are inadequate to detect diabetic eye disease, which requires an ophthalmologist for optimal care of these disorders. Laser photocoagulation is very successful in preserving vision. Proliferative retinopathy is usually treated with panretinal laser photocoagulation, whereas macular edema is treated with focal laser photocoagulation

Monoamine oxidase Inhibitors

Monoamine oxidase enzyme is present in liver, intestines & MA releasing neurons
Inactivates monoamines
Inactivates dietary tyramine in liver
Foods rich in tyramine: cheese & red wine
Nonselective MAOI: e.g. Phenelzine & tranylcypromine, not used now a days because of frequent side effects & drug interactions
Selective MAOAI: Moclobemide, Clorgiline: used in depression
Selective MAOBI: Selegiline, used in parkinsonism

Other therapies of depression

Psychotherapy or talk therapy
Electroconvulsive therapy (ECT)
Light therapy for winter depression
Vagous nerve stimulation therapy
Transcranial magnetic stimulation

Other uses of SSRI

Obsessive compulsive disorder (OCD)
Panic disorder
Social phobias
Eating disorders
Premenstrual dysphoria
Post traumatic stress disorders
Anxiety disorders
Body dysmorphic disorders
Kleptomania

Examples of SSRI

Fluoxetine
Fluvoxamine
Sertraline
Citalopram

Selective serotonin reuptake inhibitors (SSRI)

Block only serotonin (not NE) reuptake
Elevate serotonin levels
Fewer side effects than TCA
No hypotension
No anticholinergic effects
No cardiotoxicity
Most common side effect
Nausea, insomnia, sexual dysfunction

Uses of Tricyclic antidepressant

Endogenous or major depression
Neuropathic pain like diabetic & postherpetic neuralgias
Attention deficit hyperactivity disorders in children
Nocturnal enuresis
Migraine
Pruritus e.g. atopic dermatitis, lichen planus

Antidepressant drugs

Depression ,in psychiatry, a symptom of mood disorder characterized by intense feeling of loss, sadness, hopelessness, failure and rejection.
Types :
1.Reactive : 60%
2.Endogenous 20-25%
3.Bipolar 15-20%
Pathophysiology
Amine hypothesis
Due to decrease functional amine dependent synaptic transmission
Medical evidence suggest that depressive states may be connected to deficiencies in the neurotransmitters norepinephrine and Serotonin. Serotonin is often referred to as the body’s natural mood altering drug & changes in serotonin levels can quickly alter mood
Classification of antidepressant drugs
Tricyclic antidepressant
Monoamine oxidase inhibitors (MAO-AI)
Selective serotonin reuptake inhibitors (SSRI)
Atypical antidepressant

Leukotriene Inhibitors- Zileuton, Montelukast, Zafirlukast

The formation of leukotrienes depends on lipoxygenation of arachidonic acid by 5-lipoxygenase.
Zileuton is a potent and selective inhibitor of 5-lipoxygenase activity and thus inhibits the formation of all 5-lipoxygenase products.
Thus, in addition to inhibiting the formation of the cys-LTs,
zileuton also inhibits the formation of leukotriene B4 (LTB4), a potent chemotactic autacoid
They are used only for prophylactic purpose in mild to moderate asthma

Triggers for bronchospasm in bronchial asthma

Antigens
Nonantigenic stimuli
• exercise
• cold air
• irritants (sulfur dioxide, smoke)
• sleep
• viruses
• Pharmacologic Stimuli: aspirin,coloring agents like tartrazine,Beta-blockers, & sufiting agents.

Ten Misconceptions about weight loss

1. High-protein/low-carbohydrate diets are a healthy way to lose weight
2. Starches are fattening and should be limited
3. Fad diets work for permanent weight loss
4. Herbal weight-loss products and slimming pills are safe and effective
5. Low-fat or fat-free means no calories:
6. Skipping meals is a good way to lose weight:
7. Eating after 8 p.m. causes weight gain:
8. Cutting out all snacks can help you lose weight:
9. Drinking water helps you lose weight
10.You burn more fat if you exercise on an empty stomach

Breast cancer- Prevention tips

1. Exercise regularly
2. Eat a healthy well- balanced diet: little or no red meat, and lots of fresh fruits and vegetables.
3. Stop Cigarette smoking
4. Maintain regular gynecological examinations: including Pap smears and Mammograms. 5. Perform monthly breast self exams

Breast cancer- Detection

Early detection of breast cancer, through monthly breast self-exam and particularly yearly mammography after age 40, offers the best chance for survival

Risk factors for breast cancer

Family history,
Atypical hyperplasia,
Delaying pregnancy until after age 30 or never becoming pregnant
Early menstruation (before age 12)
Late menopause (after age 55)
Current use or use in the last ten years of oral contraceptives
Daily consumption of alcohol

Routes of transmission of HIV

HIV is transmitted by both homosexual and heterosexual contact; by blood and blood products; and by infected mothers to infants either intrapartum, perinatally, or via breast milk
There is no evidence that HIV is transmitted by casual contact or that the virus can be spread by insects, such as by a mosquito bite

Breast cancer- Incidence & Prevalence

It is a scary statistic: one in every 30 Mumbai women stands the risk of developing breast cancer in her lifetime.Breast cancer, which has replaced cervical cancer as the leading cancer among women living in urban centres, is increasingly being viewed as a lifestyle disease.Its incidence is increasing because of late marriages, later age of bearing children, fewer children, shorter lactation period and lack of physical exercise.Availability of gene-based therapy has been the biggest change in the field of breast cancer. Monoclonal antibodies like Trastuzumab are used for treatment of breast cancer.The healthy lifestyle should be followed to prevent Ca breast like cutting down obesity, early motherhood and breast-feeding for a year.

Is depression causes weight gain ?

Weight gain can also occur as a side effect of antidepressant drugs.
Stress may be a cause of weight gain. Due to stress more stress hormones like cortisol releases, which increase appetite.
Depression and weight gain frequently co-occur. It becomes a vicious cycle when you eat out of boredom, loneliness, isolation or any number of emotional reasons and you gain weight

Parkinsons disease

Progressive degenerative disorder
Extrapyramidal dysorder charecterized by rigidity, tremor & hypokinesia with secondary manifestations like defective posture & gait, mask like face & sialorrhoea, dementia may occur
First described by James Parkinson in 1817

Etiology of Parkinsons disease

Primary or idiopathic
Secondary :
Environmental – toxins like MPTP, carbon monooxide, manganese
Repeated head injuries as in boxers
Free Radicals – there is a increase level of free radicals in post-mortem brain sections
Aging – age related decline in dopamine production
Genetic – possible, no single gene identified, mutation in the gene coding synuclein protein leading to formation of lewy bodies
Drug induced like antipsychotic drugs, reserpine, metoclopramide etc

Is alcohol beneficial in cardiovascular disease ??

Alcohol exerts several effects on lipid levels, including raising the serum triglyceride and HDL cholesterol levels. Its effect on LDL cholesterol appears to be minimal. Since excessive alcohol causes numerous adverse effects, including hepatic toxicity, cardiomyopathy, motor vehicle crashes and extensive psychosocial consequences, it is not recommended for the prevention of coronary heart disease

Comorbid conditions associated with metabolic syndrome

Gout (Hyperuricemia)
Polycystic ovarian disease
Nonalcoholic fatty liver disease
Osteoarthritis
Obstructive sleep apnea

Which type of obesity is more dangerous- apple shaped or pear shaped ??

Differences in body-fat distribution (i.e., gynecoid versus android) associated with an altered metabolic profile were documented in the medical literature 50 years ago. Android or apple shaped obesity is more dangerous as compared to gynecoid or pear shaped obesity. Apple shaped obesity lead to more deposition of body fat in the visceral organs, that is why it is more dangerous

Is artificial sweetener used by diabetic safe ?

Saccharin: increase risk of cancer bladder
Sorbitol: produce diarrhoea
Aspartame: destroyed by heat so can not be used in baking or cooking
Acesulfame: can be used in cooking & baking
Fructose: is effective but can increase blood cholesterol
So artificial sweeteners should be avoided.

Are protein supplements safe ?

Protein supplements supplied by gym owners are very dangerous. They may contain steroids, heavy metals & other toxic ingredients. These can damage kidneys, bones & other vital organs if used for months.These products are promoted by gym owners for body building. Standard protein supplements may be used for some medical conditions like burns, malnutritions etc when prescribed by a qualified doctor.

New antidiabetic drugs

Insulin like growth factor-1 (Mecasermine): tried in patients with severe insulin resistance

Aldose reductase inhibitors- Alconil, Sorbinil. They prevent diabetes complications

Amylin analogue (Pramalinitide): It improve glycemic control

Incretins: GIP (glucose dependant insulinotropic polypeptide) & GLP-1 (glucagon like peptide-1) increase glucose dependant insulin secretion but rapidly metabolized by DPP IV (Dipeptidyl peptidase)

Exenatide is a GLP-I agonist that resist DPP IV & has a good glycemic control.
Sitagliptin & Vidagliptin are DPP IV inhibitors which prolong the effect of incretins

Circumcision:

Now it is confirmed scientifically that circumcised people have a very low incidence and prevalence of developing cancer penis. So circumcision has very protective role in the prevention of cancer penis. It was observed that cancer penis was very rare in Muslims and jews because they are circumcised at an early age.
Compelling evidence has shown that newborn circumcision prevents urinary tract infection (UTI) in infancy, balanoposthitis and phimosis in childhood and adolescence, human immunodeficiency virus (HIV) infection, and certain other sexually transmitted diseases (STDs) in young adults and invasive penile cancer (IPC) in middle and old age. (Reference:"Pediatrics-The Highly Protective Effect of Newborn Circumcision Against Invasive Penile Cancer")
According to a study published in NEJM, "Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners"

Hospital waste management

Hospital waste include all waste arising from healthcare establishments.
Large hospital’s generate 2.0 kg of waste, per bed per day. Of this, 0.5 kg can be categorized as biomedical risk waste.
Improper disposal practices results in reuse of discarded
syringes, IV tubes, blood bags and other equipment which
is not 0designed for either sterilization or reuse.
If hospital waste is not properly managed and disposed of,
it can result in injury by contaminated sharps and infection
with Hepatitis B, C, and
Hospital waste can be broadly be defined into 2 categories- risk & non risk waste.
Risk waste: Infectious, Pathological, Sharps, Pharmaceutical, Chemical & radioactive waste
Non- risk waste: Paper, Packaging, food waste
Methods:
Treatment:
• Incineration
• Chemical Disinfection
• Autoclaving
• Encapsulation
• Microwave irradiation etc.,
Final Disposal
• Landfill
• Burying inside Premises
• Discharge into Sewer etc.,
Waste not to be Incinerated
• Pressurized gas containers
• Large amounts of reactive chemical waste
• Radioactive waste
• Silver salts or radiographic waste
• Halogenated plastics (e.g. PVC)
• Mercury or cadmium
• Ampoules of heavy metals

How vultures become endangered species in india ?

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and as an analgesic reducing pain in conditions such as arthritis or acute injury. It can also be used to reduce menstrual pain, dysmenorrhea.
Diclofenac is available as a generic drug in a number of formulations. Over the counter (OTC) use is approved in some countries for minor aches and pains and fever associated with common infections.
Veterinary use of diclofenac has been linked to a crash in vulture populations across Asia, many of which are now endangered. A vulture will die of acute kidney failure within a few days of consuming meat from the carcass of livestock recently treated with the drug.
Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent, 95% decline in 2004, 99.9% decline as of 2008. The mechanism is probably renal failure, a known side-effect of diclofenac. Vultures eat the carcasses of livestock that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical. At a meeting of the National Wildlife Board in March 2005, the Government of India announced that it intended to phase out the veterinary use of diclofenac. Meloxicam is a safer candidate to replace use of diclofenac. It is more expensive than diclofenac, but the price is coming down as more drug companies begin to manufacture it.
"The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian subcontinent that pose a potential threat to human health. In many places, populations of feral dogs (Canis familiaris) have increased sharply from the disappearance of Gyps vultures as the main scavenger of wild and domestic ungulate carcasses. Associated with the rise in dog numbers is an increased risk of rabies" and casualties of almost 50,000 people The Government of India cites one of those major consequences as a vulture species extinction A major shift in transfer of corpse pathogens from vultures to feral dogs and rats can lead to a disease pandemic causing millions of deaths in a crowded country like India.
The loss of vultures has had a social impact on the Indian Zoroastrian Parsi community, who traditionally use vultures to dispose of human corpses in Towers of Silence, but are now compelled to seek alternate methods of disposal
Diclofenac has been shown also to harm freshwater fish species such as rainbow trout

(Reference: From Wikipedia, the free encyclopedia)

Health benefits of dark chocolates

Chocolate is made from plants, which means it contains many of the health benefits of dark vegetables. These benefits are from flavonoids, which act as antioxidants. Antioxidants protect the body from aging caused by free radicals
Two heart health benefits of dark chocolate are:
Lower Blood Pressure: Studies have shown that consuming a small bar of dark chocolate everyday can reduce blood pressure in individuals with high blood pressure.
Lower Cholesterol: Dark chocolate has also been shown to reduce LDL cholesterol (the bad cholesterol) by up to 10 percent
Other health benefits of dark chocolates
* it tastes good
* it stimulates endorphin production, which gives a feeling of pleasure
* it contains serotonin, which acts as an anti-depressant
* it contains theobromine, caffeine and other substances which are stimulants

Doesn't Chocolate Have a lot of Fat?
The fats in chocolate are 1/3 oleic acid, 1/3 stearic acid and 1/3 palmitic acid:

* Oleic Acid is a healthy monounsaturated fat that is also found in olive oil.
* Stearic Acid is a saturated fat but one which research is shows has a neutral effect on cholesterol.
* Palmitic Acid is also a saturated fat, one which raises cholesterol and heart disease risk.
That means only 1/3 of the fat in dark chocolate is bad for you.

Why chocolate should be avoided for those patients who are taking antidepressants ?

Some foods like cheese, bear, wines, yeast extracts & chocolates have high content of tyramine & other catecholamines. If these foods are taken by those patients who are taking some antidepressant drugs like monoamine oxidase inhibitors (MAOI), it will lead to sudden rise in blood pressure, tachycardia & palpitations. This is known as cheese reaction. So those patients who are taking these medication should avoid these foods.If this cheese reaction happen, it should be treated by giving i.v. injection of some alpha blockers like phentolamine, prazocin etc

Obesity

Obesity is a multifactorial disorder of energy balance in which chronic calorie intake is greater than energy output
Body mass index (BMI) The BMI is body mass (kg) divided by the square of the height (metres); it is highly correlated with body fat. 'Healthy' people have a BMI of 20-25, those with a BMI of 25-30 are deemed to be 'overweight', those with a BMI of >30 are said to be obese and those with a BMI >40 to be morbidly obese.
In our body there are two types of hormones which affect food intake
1. Hormones which decrese food intake (anorexigenic peptide) e.g. leptin, MSH etc
2. Hormones which increase food intake (orexigenic peptide) e.g. neuropeptide Y & agouti related protein which increase food intake

Pharmacological approaches for obesity
Orlistat is a pancreatic lipase inhibitor, preventing the breakdown of dietary fat to fatty acids and glycerols

Sibutramine, originally intended to be used as an antidepressant, has recently been shown to have anti-obesity action. Sibutramine is an inhibitor of neuronal 5-hydroxytryptamine (5-HT)/noradrenaline reuptake at the hypothalamic sites that regulate food intake
POTENTIAL NEW ANTI-OBESITY DRUGS
mazindol (adrenergic agonist
sertraline (a selective serotonin uptake inhibitor
pegylated leptin
β3-adrenoceptor agonist

Some other uncategorized antiarrhythmics

Atropine: for sinus bradycardia
Adrenaline: for cardiac arrest
Isoprenaline: for heart block
Digoxin: for atrial fibrillation
Adenosine: for PSVT
Calcium chloride: for ventricular tachycardia due to hyperkalemia
Magnesium chloride: for ventricular fibrillation, digoxin toxicity, & torsade de pointes

Classification of antiarrhythmic drugs (Vaughan & Williams)

Class I – sodium channel blocker
Ia: Procainamide, quinidine, disopyramide, moricizine (PQDM)
Ib: Lignocaine, mexilitine, phenytoin (LMP)
Ic: Propafenone, Flecainide (PF)
Class II: Beta Blockers (BB) e.g. metoprolol, propanolol, esmolol, sotalol
Class III: K channel blockers e.g. amiodarone, bretylium, dofetilide (BAD)
Class IV: Calcium channel blockers (CCB) e.g. verapamil

Factors that precipitate arrhythmias

Ischemia
Hypoxia
Acidosis
Alkalosis
Electrolyte imbalance
Sympathetic overactivity
Digitalis toxicity
Overstretching of cardiac fibres
Presence of scarred or diseased tissue

Etiology of cardiac arrhythmias

MI- commonest cause
Cardiomyopathy
Congenital e.g. congenital long QT syndrome d/t mutation in the gene encoding K channels
Myocarditis
Cardiac dilatation
Thyroid disorders
Electrolyte imbalance e.g. hypo or hyperkalemia
Drug induced e.g. cisapride, terfenadine etc

Approach to a patient of erectile dysfunction

The physical examination is an essential element in the assessment of ED. Signs of hypertension as well as evidence of thyroid, hepatic, hematologic, cardiovascular, or renal diseases should be sought. An assessment should be made of the endocrine and vascular systems, the external genitalia, and the prostate gland. The penis should be carefully palpated along the corpora to detect fibrotic plaques. Reduced testicular size and loss of secondary sexual characteristics are suggestive of hypogonadism. Neurologic examination should include assessment of anal sphincter tone, the bulbocavernosus reflex, and testing for peripheral neuropathy.
The other test may be done to rule out common causes

1. studies of nocturnal penile tumescence and rigidity;
2. psychological diagnostic tests.
3. vascular testing (in-office injection of vasoactive substances, penile Doppler ultrasound, penile angiography, dynamic infusion cavernosography/cavernosometry)
4. neurologic testing (biothesiometry-graded vibratory perception; somatosensory evoked potentials)
Depending upon cause following steps should be taken
1. Patient counselling & education
2. Oral agents: Sildenafil, tadalafil, and vardenifil are the only approved and effective oral agents for the treatment of erectile dysfunction
3. Androgen therapy
4. Vacuum Constriction Devices: Vacuum constriction devices (VCD) are a well-established, noninvasive therapy.
They are a reasonable treatment alternative for select patients who cannot take sildenafil or do not desire other interventions.
VCD draw venous blood into the penis and use a constriction ring to restrict venous return and maintain tumescence.
Adverse events with VCD include pain, numbness, bruising, and altered ejaculation. Additionally, many patients complain that the devices are cumbersome and that the induced erections have a nonphysiologic appearance and feel.
5. Intraurethral Alprostadil: If a patient fails to respond to oral agents, a reasonable next choice is intraurethral or self-injection of vasoactive substances. Intraurethral prostaglandin E1 (alprostadil), in the form of a semisolid pellet (doses of 125–1000 g), is delivered with an applicator
6. Intracavernosal Self-Injection: Injection of synthetic formulations of alprostadil is effective in 70–80% of patients with ED, but discontinuation rates are high because of the invasive nature of administration.
Surgery: A less frequently used form of therapy for ED involves the surgical implantation of a semirigid or inflatable penile prosthesis. These surgical treatments are invasive, associated with potential complications, and generally reserved for treatment of refractory ED. Despite their high cost and invasiveness, penile prostheses are associated with high rates of patient and partner
satisfaction.
7. Sex therapy : A course of sex therapy may be useful for addressing specific interpersonal factors that may affect sexual functioning. Sex therapy generally consists of in-session discussion and at-home exercises specific to the person and the relationship. It is preferable if therapy includes both partners, provided the patient is involved in an ongoing relationship.

Common causes of erectile dysfunction

Vasculogenic
Neurogenic
Endocrinological
Diabetes
Psychogenic
Drugs e.g. thiazides, methyldopa, calcium channel blockers, SSRI, Cimetidine, estroge, progesterone, cytotoxic drugs, ethanol, coccaine, marijuana etc.

Sildenafil

Inhibits PDE5 in the corpus cavernosa of the penis
50mg, p.o. 1 h before sexual activity
potentiate nitrate’s hypotension activity
ketoconazole & erythromycin increases its level
renal & hepatic disease increases its level
Side effects: headache, flushing, dyspepsia, myalgia

Classification of purgatives

Purgative are drugs that induce defecation
They are divided into
Laxative & cathartics
Laxative: help in production of soft, formed stool
Cathartics: help in rapid, intense fluid evacuation of bowel
Ther are classified into following groups (BOSS)
B-Bulk forming e.g. methylcellulose, psyllium
O-Osmotic purgatives e.g. lactulose, magnesium salts
S-Stimulant e.g. castor oil, bisacodyl,
S- Surfactant e.g. bile acid, docusate salts

Comorbid conditions associated with metabolic syndrome

Nonalcoholic Fatty Liver Disease
Hyperuricemia (Gout)
Polycystic Ovary Syndrome
Obstructive Sleep Apnea
Osteoarthritis

Pathogenesis of metabolic syndrome

Insulin resistance
Inflammation
Prothrombotic state
Endothelial dysfunction
Obesity & abnormal body fat distribution

Monoclonal Antibodies

Both polyclonal and monoclonal antibodies against cell-surface antigens are widely used for prevention and treatment of various diseases

The advent of hybridoma technology to produce monoclonal antibodies was a major advance in immunology
Both polyclonal and monoclonal products have a place in immunosuppressive therapy
Based on origin, monoclonal antibodies may be murine, humanized, human or chimeric
Following is the list of some monoclonal antibodies

Trastuzumab- used in Ca breast

Rituximab- used in Non Hodgkins lymphoma (tu for tumour)

Infliximab- used in rheumatoid arthritis

Omalizumab- used in bronchial asthma ((li suffix for monoclonal antibodies, used in disorders of immunity)

Absciximab- used as antiplatelet antibody in thromboembolic disorders (Ci suffix for circulatory system)

Tefibazumab- for staphylococcal infections (ba suffix for bacterial disease)

Natalizumab- multiple sclerosis

Denosumab- osteoporosis (os suffix for osteoporosis)

Palivizumab- for respiratory syncitial virus infection (vi suffix for viral infection)

Daclizumab- to prevent graft rejection

Ezetimibe

Ezetimibe: inhibit intestinal absorption of cholesterol & phytosterols

Interfere with specific cholesterol transport protein in intestinal mucosa

Reduce absorption of both dietary & biliary cholesterol

Compensatory ↑ in cholesterol synthesis, which can be blocked by statins

Statins + ezetimibe: synergistic CH lowering effect

Weak hypocholestrolemic drug

no major side effects

Fibrates

stimulate the beta-oxidative degradation of fatty acids
- liberate free fatty acids for storage in fat or for metabolism in
striated muscle

- increase the activity of lipoprotein lipase,
hence increasing hydrolysis of triglyceride in chylomicrons
and VLDL particles

reduce hepatic VLDL production and increase hepatic LDL
uptake
The fibrates act through paroxysome proliferator activated receptor (PPAR-alpha) which is gene transcription regulating receptor
PPAR-alpha are present in liver, adipocytes & muscle cells.
Activation of PPAR alpha enhances lipoprotein lipase synthesis & fatty acid oxidation
PPAR alpha also mediate enhanced LDL receptor expression in liver
Compare from PPAR gamma agonist glitazones, on which insulin sensitizer act
LDL ↓5-20 %, may ↑ LDL when TG is high
HDL ↑ 10-20 %
TG ↓ 20-50 %
With clofibrate there is risk of gall stones, so not used now a days
Gemfibrozil + statin ↑the risk of myopathy
Fenofibrate is most suitable fibrate for combining with statins
O t h e r e f f e c t s :
improve glucose tolerance
inhibit vascular smooth muscle inflammation
A d v e r s e e f f e c t s:
In patients with renal impairment myositis (rhabdomyolysis) myoglobulinuria, acute renal failure
Fibrates should be avoided in such patients and also in alcoholics)
Mild GI upset
Uses: Mixed dyslipidemia
Diabetic dyslipidemia
Patients with low HDL & high risk of atheromatous disease

Metabolic Syndrome

The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III) identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention
The various synonyms exist for metabolic syndrome are insulin resistance syndrome, Syndrome X, Beer Belly syndrome, Dysmetabolic syndrome, Reaven syndrome

ATP III Definition of Metabolic Syndrome

1. Abdominal obesity, given as waist circumference (Men > 40 in or women >35 in)
2.TG > 150 mg %
3. HDL cholesterol < 40 mg % in males & < 50 mg % in females 4. BP > 130/85 mmHg
5. Fasting blood glucose > 110 mg%
When ≥ 3 out of 5 listed characteristics are present, with or without treatment, a diagnosis of metabolic syndrome can be made.

Complementry & Alternative Medicines for Dyslipidemias

Gugulipid
Omega-3-fatty acids
Policosanol
Plant stanols sterols
Flaxseed
Red yeast rice
Garlic fiber
Almonds
Soy
Black seed (Nigella sativa)

Statins

HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors. The reductase catalyses the conversion of HMG-CoA to mevalonic acid
Simvastatin + pravastatin + atorvastatin decrease hepatic CHO synthesis
LDL ↓20-55%
HDL ↑ 5-15 %
TG ↓ 10-35 %
All statins produce peak LDL CH lowering after 1-2 weeks of therapy
Statins are effective in both primary & secondary dyslipidemias
Statins are given at bed time to obtain maximum effect.
Not necessary for atorvastatin & rosuvastatin which have long plasma half life
All statins except rosuvastatins are metabolized by CYP3A4
Pleiotropic actions:
improved endothelial function
reduced vascular inflammation and platelet aggregability
antithrombotic action
stabilisation of atherosclerotic plaques
increased neovascularisation of ischaemic tissue
enhanced fibrinolysis
immune suppression
osteoclast apoptosis and increased synthetic activity in
osteoblasts
Pharmacokinetics
well absorbed when given orally
extracted by the liver (target tissue), undergo extensive presystemic biotransformation

Simvastatin is an inactive pro-drug
C l i n i c a l u s e s
Secondary prevention of myocardial infarction and stroke in patients who have symptomatic atherosclerotic disease (angina, transient ischemic attacks) following acute myocardial infarction or stroke
Primary prevention of arterial disease in patients who are at high risk because of elevated serum CHO concentration, especially it there are other risk factors for atherosclerosis
Atorvastatin lowers serum CHO in patients with homozygous familiar hypercholesterolemia
A d v e r s e e f f e c t s:
mild gastrointestinal disturbances

increased plasma activities in liver enzymes

severe myositis (rhabdomyolysis), muscle tenderness & rise in Creatine phosphate kinase (CPK) levels, myopathy
and angio-oedema (rare), myopathy is more common when enzyme inhibitors are used simultaneously

Calcineurin inhibitors

Cyclosporine:
cyclic polypeptide, obtained from fungus
Highly selective immunosuppressant which markedly increased the success of organ transplantation
Selectively inhibit T lymphocyte proliferation, IL-2 & other cytokine production without affecting suppressor T cells
Tacrolimus
Sirolimus
Mechanism
Cyclosporine enter target cells, bind to cyclophilin
The complex then bind & inactivate calcineurin
Calcineurin is membrane associated serine/ threonine phosphatase enzyme, present in T lymphocytes
Calcineurin help in transcription of cytokine genes, leading to production of IL-2, GM-CSF, TNF alpha & interferons
Selectively suppress CMI, humoral immunity remains intact
Recipient is able to deal with bacterial infection
No toxicity of bone marrow & RES
Adverse effects
Nephrotoxicity
Hypertension
Precipitate diabetes
Impair Liver functions
Hyperkalemia
Gum hyperplasia
Opportunistic infections
Hirsutism
Anorexia, lethargy
Tremor
seizures
Therapeutic uses
Kidney, liver, heart, and other organ transplantation (First line drug) along with other immunosuppressant
Second line drug in autoimmune disorders, when not controlled by primary drugs
Severe rheumatoid arthritis
Psoriasis
Behcet’s acute ocular syndrome
Endogenous uveitis,
Atopic dermatitis,
Inflammatory bowel disease
Nephrotic syndrome, when standard therapies have failed

Toxicity of Imatinib

The most frequently reported drug-related adverse events are nausea, vomiting, edema, and muscle cramps
Most events are of mild-to-moderate grade, and only 2% to 5% of patients permanently discontinue therapy, most commonly because of skin rashes and elevations of transaminases
Edema can manifest at any site, most commonly in the ankles and periorbital tissues. Severe fluid retention (pleural effusion, pericardial effusion, pulmonary edema, and ascites) is reported in 1% to 2% of patients taking imatinib.
Neutropenia and thrombocytopenia are consistent findings in all studies in leukemia patients, with a higher frequency at doses ³750 mg.
(Reference : Goodman & Gillmans 11th edition)

Imatinib- Mechanism of action

Imatinib has inhibitory activity against ABL and its activated derivatives v-ABL, BCR-ABL, and EVT6-ABL
Cellular studies showed that imatinib specifically inhibited the proliferation of myeloid cell lines that express the BCR-ABL fusion protein associated with CML
Similar concentrations of imatinib inhibit the proliferation of cells dependent on KIT or PDGFR for proliferation. This includes cells expressing mutant KIT isoforms associated with gastrointestinal stromal tumors (GISTs)

Terbutaline

Terbutaline is beta 2 agonist adrenergic drug. It is used as a bronchodialtor drug. Given by oral, s.c. & inhalational route.
Uses of terbutaline
1. Bronchial asthma
2. Refractory asthma
3. Status asthmaticus
Adverse effects: Tremors, palpitation & rarely arrythmias

Therapeutic uses of metoclopramide

1. As antiemetic in postoperative, drug induced, disease associated, radiation induced vomitting
2. As gastrokinetic agent in emergency GA, before giving spinal anesthesia for cesarian operation, postvagotomy or diabetes associated gastric paresis, to facilitate duodenal intubation
3. Dyspepsia
4. Gastroesophageal reflux disease

How beta blocker propanolol is effective in hypertension ?

1. Reduction of cardiac output (CO) leads to reduce total peripheral resistance (TPR). Due to reduction in TPR both systolic & diastolic BP falls.
2. Decrease renin from kidney leading to decrease plasma renin activity
3. Decrease NA release from sympathetic nerves
4. Decreased central sympathetic outflow

How haloperidol is effective in schizophrenia ?

According to dopamine theory of schizophrenia, it occurs due to overactivity of dopaminergic neurones in the limbic area of brain. Haloperidol antagonize dopaminergic activity in brain by blocking D2 receptors in brain which are located in corpus striatum & limbic system.In this way haloperidol is effective in schizophrenia.

Similarities in insulin & sulfonylureas

1. Both cause weight gain.
2. Both are secretogogue.
3. Both cause hypoglycemia.

Difference between insulin & sulfonylurea

1. Insulin is given by subcutaneous route while sulfonylureas are given orally.
2. Insulin is used predominately in type I diabetes, while sulfonylureas are used predominately in type II patients.
3. Insulin is a peptide hormone synthesized in body by beta cells of pancreas, while sulfonylureas are synthetic sulfa group of drugs.
4. Insulin stimulate glucose transport across the cell by ATP dependent translocation of glucose transportes GLUT 1 & GLUT 4, while sulfonylureas release insulin by blocking ATP dependent K channels in beta cells of pancreas.

Advantages of clarithromycin over erythromycin

1. Clarithromycin covers Mycobacterium avium complex (MAC), other atypical mycobacteria, M. leprae & some anaerobes.It also covers Legionella, M.pneumonae & H. pylori, while erythromycin is not active against these microbes.
2. Clarithromycin is more acid stable than erythromycin, rapidly absorbed, better gastric tolerance as compared to erythromycin
3. Clarithromycin has better tissue penetration.
4. Erythromycin is given four times a day while clarithromycin is given twice daily

Immunomodulators

Immunomodulators include both immunosuppressants as well as immunostimulants.
The important group of immunosuppressants are glucocorticoids, calcineurin inhibitors, antiproliferative and antimetabolic agents and antibodies.
Among the group of immunostimulants, the main drugs are Levamisole, thalidomide, BCG vaccine, recombinant cytokines, interferons & interleukin-2.
Clinical role of Immunosuppressants
Glucocorticoids:
1. To prevent and treat transplant rejection
2. autoimmune disorders like rheumatoid and other arthritides, systemic lupus erythematosus, systemic dermatomyositis, psoriasis and other skin conditions
3. Treatment of graft-versus-host disease in bone-marrow transplantation. asthma and other allergic disorders
4. inflammatory bowel disease,
5. inflammatory ophthalmic diseases
6. autoimmune hematologic disorders
7. acute exacerbations of multiple sclerosis
Calcineurin inhibitors
Cyclosporine suppresses some humoral immunity, but is more effective against T-cell-dependent immune mechanisms such as those underlying transplant rejection and some forms of autoimmunity
Therapeutic uses:
1. kidney, liver, heart, and other organ transplantation
2. Rheumatoid arthritis
3. Psoriasis
4. Behcet’s acute ocular syndrome
5. endogenous uveitis,
6. atopic dermatitis,
7. inflammatory bowel disease, and
8. Nephrotic syndrome, when standard therapies have failed
Antiproliferative agents
Sirolimus is an antiproliferative agent.
Sirolimus is a macrocyclic lactone produced by Streptomyces hygroscopicus
Sirolimus inhibits T-lymphocyte activation and proliferation downstream of the IL-2 and other T-cell growth factor receptors
Sirolimus is indicated for prophylaxis of organ transplant rejection in combination with a calcineurin inhibitor and glucocorticoids
Azathioprine is a purine antimetabolites
Azathioprine was first introduced as an immunosuppressive agent in 1961, helping to make allogeneic kidney transplantation possible
Severe rheumatoid arthritis
Other antiproliferative & cytotoxic agents
Many of the cytotoxic and antimetabolic agents used in cancer chemotherapy are immunosuppressive due to their action on lymphocytes and other cells of the immune system. Other cytotoxic drugs that have been used as immunosuppressive agents include methotrexate, cyclophosphamide thalidomide, and chlorambucil
Methotrexate is used for treatment of graft-versus-host disease, rheumatoid arthritis, and psoriasis, as well as in anticancer therapy
Cyclophosphamide and chlorambucil are used in treating childhood nephrotic syndrome and a variety of malignancies

Antibody
Both polyclonal and monoclonal antibodies against lymphocyte cell-surface antigens are widely used for prevention and treatment of organ transplant rejection
The advent of hybridoma technology to produce monoclonal antibodies was a major advance in immunology
Both polyclonal and monoclonal products have a place in immunosuppressive therapy.
The important antibodies which are used in immunosuppression are
Antithymocyte Globulin: used for treatment of acute renal transplant rejection
Anti-CD3 Monoclonal Antibodies: (Muromonab-CD3) is indicated for treatment of acute organ transplant rejection
Anti-TNF Reagents.
Infliximab Infliximab is a chimeric anti-TNF-? monoclonal antibody used in rheumatoid arthritis

Immunostimulants:
Levamisole. Levamisole was synthesized originally as an anthelmintic but appears to “restore” depressed immune function of B lymphocytes, T lymphocytes, monocytes, and macrophages.
Its only clinical indication is as adjuvant therapy with 5-fluorouracil after surgical resection in patients with Dukes’ stage C colon cancer where it occasionally has been associated with fatal agranulocytosis

Thalidomide. Thalidomide is best known for the severe, life-threatening birth defects it caused when administered to pregnant women
Thalidomide should never be taken by women who are pregnant or who could become pregnant while taking the drug.
Nevertheless, it is indicated for the treatment of patients with erythema nodosum leprosum and also is used in conditions such as multiple myeloma.
Its mechanism of action is unclear
Alternatively, it has been suggested that the drug affects angiogenesis
The anti-TNF-? effect has led to its evaluation as a treatment for severe, refractory rheumatoid arthritis

Bacillus Calmette-Guerin (BCG)
It is live attenuated vaccine for tuberculosis.
By unclear mechanisms, this preparation is active against tumors and is indicated for treatment and prophylaxis of carcinoma in situ of the urinary bladder
Interferons.Although interferons (alpha, beta, and gamma) initially were identified by their antiviral activity, these agents also have important immunomodulatory activities
Interleukin-2: Human recombinant interleukin-2 (aldesleukin) is indicated for the treatment of adults with metastatic renal cell carcinoma and melanoma
(Reference: Goodman & Gillman’s, The Pharmacological Basis of Therapeutics 11th edition)

Drugs used in epilepsy

Antiepileptic drugs are
Hydantoin e.g. Phenytoin
Iminostilbene e.g. Carbamazepine
Aliphatic carboxylic acide e.g. Valproate
Barbiturates e.g. Phenobarbitone
Deoxybarbiturates e.g. Primidone
Succinimide e.g. Ethosuximide
Benzodiazepines e.g. Clonazepam, Diazepam, Lorazepam
Phenyltriazine e.g. Lamotrigene
GABA analogue e.g. Gabapentin
Newer drugs e.g. Vigabatrin, Levetiracetam, Topiramate, Tiagabine

Antidepressant drugs

I. Tricyclic antidepressants :
A. Predominately Noradrenaline reuptake inhibitor : Desipramine, Nortriptyline
B. Noradrenaline + Serotonin reuptake inhibitor : Imipramine, Amitryptyline, Doxepin, Clomipramine
II. Selective serotonin reuptake inhibitor (SSRI) : Fluoxetine, Fluvoxamine, Sertraline, Citalopram, Paroxetine
III. Atypical antidepressants: Trazodone, Mianserin, Venlafaxine, Bupropion
IV. Reversible inhibitor of MAO-A (mono amine oxidase A): Clorgyline, Moclobemide

Osteoporosis

Osteoporosis, which comes from Greek meaning porous bone, is a condition or disease process that is marked by structural deterioration of bone tissue and low bone mass. Low bone mass can lead to bone fragility and increase risk of fractures
Clinical Features
a "silent disease" (i.e., there are frequently no symptoms) until a fracture has occurred. As the disease progresses, symptoms may include
back pain,
fractures,
loss of height,
skeletal deformity (kyphosis or kyphoscoliosis),
neck strain (due to an exaggerated cervical lordosis),
midabdominal pain (caused from the ribs resting on the iliac crest),
alterations in bowel function,
Risk factors
Postmenopausal women
Elderly age
Personal Medical History and Family History
Hormonal abnormalities, such as hyperthyroidism, and hyperparathyroidism can impair the bone-making process
Individuals with a history of neoplastic disorders, such as multiple myeloma,
Nutritional deficiencies,inadequate calcium or vitamin D intake,
Lifestyle Factors
Pharmacologic Risk Factors
Phenytoin sodium (Dilantin)
Glucocorticoids
Medroxyprogesterone acetate (Depo-Provera)
Nonpharmacologic Interventions

Lifestyle modification
Weight-bearing exercises
Nutrition

Pharmacological interventions
hormone replacement therapy
bisphosphonates,
calcitonin,
selective estrogen receptor modulators,
fluoride supplementation

ERT/HRT
ERT/HRT has been shown to prevent osteoporosis by decreasing the bone loss that is common after menopause,
new studies have indicated that although ERT/HRT may prevent bone loss, there is no concrete evidence to support its use as a treatment modality because of unacceptable increased incidence of breast cancer noted in the women who used HRT
women with osteoporosis, other pharmacologic interventions may be preferred
Bisphosphonates
Alendronate,Etidronate,Pamidronate

Mechanism of action:
Inhibits bone resorption by binding to hydroxyapatite crystals
Accelerated apoptosis of osteoclasts
Disruption of cytoskeleton and ruffled border of osteoclasts
Inhibits osteoclasts differentiation by suppressing IL-6

Precaution needed with BPN Prevent conatct with oesophageal mucosa

Second/third generation BPN Zolendronate,Risedronate

Enfavirtide

It is fusion inhibitor, used in HIV.
It is an antiretroviral drug(for HIV/HTLV-3 virus)
It act by binding to HIV-1 envelope glycoprotein (gp41) & prevent the fusion of viral & cellular membranes.
Entry of virus into cell is blocked.
It is not active against HIV-2.
It is given by s.c. route
It is used as add on drug.

Selective estrogen receptor modulators (SERM)

Nonsteroidal synthetic agents
Selective estrogen receptor modulators, which are sometimes referred to as partial estrogen agonist/antagonists
Modulates activity of estrogen receptors
Unique profile of aginistic/antagonistic actions(agonist in bone and CVS but antagonist in endometrium and breast)
statistically significant improvement in bone mineral density
extreme caution for perimenopausal because the drug is contraindicated in pregnancy

good choice of therapy for women with a history of breast or uterine cancer or for women with concerns about taking estrogen
Adverse effects are vasomotor symptoms
Other side effects of leg cramps and venous thrombohemolytic events have been reported.
It may also be a better choice of therapy for women with severe gastrointestinal symptoms and for those who have difficulty tolerating the bisphosphonates.

New emerging therapies of osteoporosis

Statins:
great interest in actions of statins unrelated to their main effect of lowering LDL
Promotes osteoclasts apoptosis
Increase osteoblast activity
Increase gene expression for BMP-2
r-PTH(recombinant PTH Teriparatide)
PTH in low and intermittent doses increase bone formation without stimulating bone resorption
Subcutaneous route 25 mg/day

Cephalosporins

The first-generation cephalosporins, epitomized by cephalothin and cefazolin, have good activity against gram-positive bacteria and relatively modest activity against gram-negative microorganisms.
The second-generation cephalosporins have somewhat increased activity against gram-negative microorganisms but are much less active than the third-generation agents
Third-generation cephalosporins generally are less active than first-generation agents against gram-positive cocci, but they are much more active against the Enterobacteriaceae, including b-lactamase-producing strains
Fourth-generation cephalosporins, such as cefepime, have an extended spectrum of activity compared with the third generation and have increased stability from hydrolysis by plasmid and chromosomally mediated b-lactamases
The first-generation cephalosporins are excellent agents for skin and soft tissue infections owing to S. aureus and S. pyogenes
The second-generation cephalosporins generally have been displaced by third-generation agents. They have inferior activity against penicillin-resistant S. pneumoniae compared with either the third-generation agents or ampicillin and therefore should not be used for empirical treatment of meningitis or pneumonia. The oral second-generation cephalosporins can be used to treat respiratory tract infections
The third-generation cephalosporins, with or without aminoglycosides, have been considered to be the drugs of choice for serious infections caused by Klebsiella, Enterobacter, Proteus, Providencia, Serratia, and Haemophilus spp
The fourth-generation cephalosporins are indicated for the empirical treatment of nosocomial infections where antibiotic resistance owing to extended-spectrum b-lactamases or chromosomally induced b-lactamases are anticipated.

Patient-Controlled Analgesia (PCA)

With this modality, the patient has limited control of the dosing of opioid from an infusion pump within tightly mandated parameters.
PCA can be used for intravenous or epidural infusion.
This technique avoids any delays in administration and permits greater dosing flexibility than other regimens, better adapting to individual differences in responsiveness to pain and to opioids.
It also gives the patient a greater sense of control.
With shorter-acting opioids, serious toxicity or excessive use rarely occurs.
An early concern that self-administration of opioids would increase the probability of addiction has not materialized.
PCA is suitable for adults and children, and it is preferred over intramuscular injections for postoperative pain control

Hematological Toxicity of Chloramphanicol

Dr. Ahmad Najmi, Index Medical College, Indore
The most important adverse effect of chloramphenicol is on the bone marrow. Chloramphenicol affects the hematopoietic system in two ways: a dose-related toxicity that presents as anemia, leukopenia, or thrombocytopenia; and an idiosyncratic response manifested by aplastic anemia, leading in many cases to fatal pancytopenia.
Pancytopenia seems to occur more commonly in individuals who undergo prolonged therapy and especially in those who are exposed to the drug on more than one occasion.
A genetic predisposition is suggested by the occurrence of pancytopenia in identical twins. Although the incidence of the reaction is low¾1 in approximately 30,000 or more courses of therapy¾the fatality rate is high when bone-marrow aplasia is complete, and there is an increased incidence of acute leukemia in those who recover.
Aplastic anemia accounts for approximately 70% of cases of blood dyscrasias due to chloramphenicol, while hypoplastic anemia, agranulocytosis, and thrombocytopenia make up the remainder.
The exact biochemical mechanism has not yet been elucidated but is hypothesized to involve conversion of the nitro group to a toxic intermediate by intestinal bacteria.

The risk of aplastic anemia does not contraindicate the use of chloramphenicol in situations in which it may be life-saving. The drug should never be used, however, in undefined situations or in diseases readily, safely, and effectively treatable with other antimicrobial agents.

Dose-related, reversible erythroid suppression probably reflects an inhibitory action of chloramphenicol on mitochondrial protein synthesis in erythroid precursors, which in turn impairs iron incorporation into heme.
Leukopenia and thrombocytopenia also may occur. Bone marrow suppression occurs regularly when plasma concentrations are 25 mg/ml or higher and is observed with the use of large doses of chloramphenicol, prolonged treatment, or both. Dose-related suppression of the bone marrow may progress to fatal aplasia if treatment is continued, but most cases of bone marrow aplasia develop suddenly, without prior dose-related marrow suppression.
Some patients who developed chronic bone marrow hypoplasia after chloramphenicol treatment subsequently developed acute myeloblastic leukemia.

The administration of chloramphenicol in the presence of hepatic disease frequently depresses erythropoiesis. About one-third of patients with severe renal insufficiency exhibit the same reaction.
Reference: Goodman & Gillmans Pharmacological Basis of Therapeutics , 11th edition

Daptomycin

By Dr. Ahmad Najmi, Index Medical College, Indore
Daptomycin is a cyclic lipopeptide antibiotic derived from Streptomyces roseosporus It is bactericidal effective against vancomycin-resistant gram-positive bacteria. Also active against aerobic, facultative, and anaerobic gram-positive bacteria
Daptomycin binds to bacterial membranes resulting in depolarization, loss of membrane potential, and cell death
Daptomycin is poorly absorbed orally and should only be administered intravenously
Daptomycin is indicated for treatment of complicated skin and skin-structure infections caused by methicillin-susceptible and methicillin-resistant strains of S. aureus, hemolytic streptococci, and vancomycin-susceptible E. faecalis
Skeletal muscle damage occurs in dogs given daptomycin at doses above 10 mg/kg. Peripheral neuropathic effects with axonal degeneration occurred at higher doses
Reference: Goodman & Gillmans Pharmacological Basis of Therapeutics, 11th edition

Gray baby syndrome

by Dr. Ahmad Najmi, Index Medical College, Indore
Neonates, especially if premature, may develop a serious illness termed gray baby syndrome if exposed to excessive doses of chloramphenicol
This syndrome usually begins 2 to 9 days (average of 4 days) after treatment is started
Within the first 24 hours, vomiting, refusal to suck, irregular and rapid respiration, abdominal distention, periods of cyanosis, and passage of loose, green stools occur
The children all are severely ill by the end of the first day, and in the next 24 hours turn an ashen-gray color and become flaccid and hypothermic
A similar "gray syndrome" has been reported in adults who were accidentally overdosed with the drug
Death occurs in about 40% of patients within 2 days of initial symptoms.
Those who recover usually exhibit no sequelae.

Two mechanisms apparently are responsible for chloramphenicol toxicity in neonates: (1) a developmental deficiency of glucuronyl transferase, the hepatic enzyme that metabolizes chloramphenicol, in the first 3 to 4 weeks of life; and
(2) inadequate renal excretion of unconjugated drug. At the onset of the clinical syndrome, chloramphenicol concentrations in plasma usually exceed 100 mg/ml, although they may be as low as 75 mg/ml.
Children 2 weeks of age or younger should receive chloramphenicol in a daily dose no larger than 25 mg/kg of body weight; after this age, full-term infants may be given daily quantities up to 50 mg/kg.
Toxic effects have not been observed in the newborns when as much as 1 g of the antibiotic has been given every 2 hours to the mothers during labor.
Chloramphenicol is removed only minimally from the blood by either peritoneal dialysis or traditional hemodialysis.
Thus, exchange transfusion and charcoal hemoperfusion have been used to treat overdose with chloramphenicol in infants
Reference: Goodman & Gillmans Pharmacological Basis of Therapeutics 11th edition

QUINUPRISTIN/DALFOPRISTIN

By Dr. Ahmad Najmi, Index Medical College, Indore
Quinupristin/dalfopristin is a combination of quinupristin, a streptogramin B, with dalfopristin, a streptogramin A, in a 30:70 ratio
These compounds are semisynthetic derivatives of naturally occurring pristinamycins, produced by Streptomyces pristinaespiralis
Quinupristin/dalfopristin is active against gram-positive cocci, including S. pneumoniae, beta- and alpha-hemolytic strains of streptococci, E. faecium (but not E. faecalis), and coagulase-positive and coagulase-negative strains of staphylococci
Quinupristin and dalfopristin are protein synthesis inhibitors that bind the 50S ribosomal subunit
The combination of quinupristin/dalfopristin is administered only by intravenous infusion over at least 1 hour. It is incompatible with saline and heparin and should be dissolved in 5% dextrose in water
Quinupristin/dalfopristin is approved in the United States for treatment of infections caused by vancomycin-resistant strains of E. faecium and complicated skin and skin-structure infections caused by methicillin-susceptible strains of S. aureus or S. pyogenes
Quinupristin/dalfopristin should be reserved for treatment of serious infections caused by multiple-drug-resistant gram-positive organisms such as vancomycin-resistant E. faecium
The most common side effects are infusion-related events, such as pain and phlebitis at the infusion site and arthralgias and myalgias
Quinupristin/dalfopristin inhibits CYP3A4
(Reference Goodman & Gillmans, The Pharmacological Basis of Therapeutics, 11th edition)

Mechanism of resistance in macrolide antibiotics

Resistance to macrolides usually results from one of four mechanisms: (1) drug efflux by an active pump mechanism (encoded by mrsA, mefA, or mefE in staphylococci, group A streptococci, or S. pneumoniae, respectively);
(2) ribosomal protection by inducible or constitutive production of methylase enzymes, mediated by expression of ermA, ermB, and ermC, which modify the ribosomal target and decrease drug binding;
(3) macrolide hydrolysis by esterases produced by Enterobacteriaceae
(4) chromosomal mutations that alter a 50S ribosomal protein (found in B. subtilis, Campylobacter spp., mycobacteria, and gram-positive cocci).

The MLSB (macrolide-lincosamide-streptogramin B) phenotype is conferred by erm genes, which encode methylases that modify the macrolide binding of the ribosome. Because macrolides, lincosamides, and type B streptogramins share the same ribosomal binding site, constitutive expression of erm confers cross-resistance to all three drug classes

KETOLIDES (TELITHROMYCIN)

Ketolides and macrolides have very similar antibacterial properties
Ketolides and macrolides have the same ribosomal target site
The principal difference between the two is that structural modifications within ketolides neutralize the common resistance mechanisms that make macrolides ineffective
Introduction of the 3-keto function converts a methylase-inducing macrolide into a noninducing ketolide
This moiety also prevents drug efflux, probably because it generates a less-desirable substrate

Types of beta lactamase enzyme

Bacteria also can destroy beta-lactam antibiotics enzymatically.
b-Lactamases are capable of inactivating certain of these antibiotics and may be present in large quantities
Different microorganisms elaborate a number of distinct beta-lactamases, although most bacteria produce only one form of the enzyme. The substrate specificities of some of these enzymes are relatively narrow, and these often are described as either penicillinases or cephalosporinases.
Other "extended spectrum" enzymes are less discriminant and can hydrolyze a variety of b-lactam antibiotics.
b-Lactamases are grouped into four classes: A through D.
Class A b-lactamases include the extended-spectrum b-lactamases (ESBLs) and degrade penicillins, some cephalosporins, and, in some instances, carbapenems
Class A and D enzymes are inhibited by the commercially available b-lactamase inhibitors, such as clavulanate and tazobactam
Class B b-lactamases are Zn2+-dependent enzymes that destroy all b-lactams except aztreonam,
class C b-lactamases are active against cephalosporins
Class D includes cloxacillin-degrading enzymes (Bush, 2001)

Adverse effects of morphine (MBBS DAV April 2010 paper)

Dr. Ahmad Najmi, Index Medical College, Indore
Respiratory depression
Nausea & vomiting
Dizziness
Mental clouding
Dysphoria,
Pruritus,
Constipation
Increased pressure in the biliary tract
Urinary retention
Hypotension
Morphine causes histamine release, which can cause bronchoconstriction and vasodilation
Morphine and related opioids must be used cautiously in patients with compromised respiratory function
Anaphylactoid reactions

Drugs for acne vulgaris

Acne vulgaris is a self-limited disorder primarily of teenagers and young adults. It occurs due to increase in sebum production by sebaceous glands after puberty. Small cysts, called comedones , form in hair follicles due to blockage of the follicular orifice by retention of keratinous material and sebum. The activity of bacteria (Proprionobacterium acnes) within the comedones releases free fatty acids from sebum, causes inflammation within the cyst.
The drugs can be given by either topical route or by systemic route
Topical therapy includes Benzyl benzoate, retinoic acid, Adapalene, topical antibiotics & azelaic acid
Benzyl benzoate:
It gradually liberate oxygen which kills bacteria
Keratolytic
Comedolytic
Induce mild desquamation
Adverse effects: Burning & stinging sensation, dryness of skin, scaling, erythema etc
Avoid contact with eyes, lips & mucous membranes
It is used in the form of cream, gel or lotion
Retinoic acid:
Comedolytic
Keratolytic
epidermal cell turn over is stimulated resulted in peeling
response is delayed
Adverse effects are warmth, stinging, redness, crusting & edema
used in form of cream or gel
It is teratogenic, so should be avoided during pregnancy
retinoic acid & benzoyl peroxide should not be applied together because benzyl peroxide promote degradation of retinoic acid

Adapalene: It is newer synthetic tretinoin like drug
It act by binding to nuclear retinoic acid receptor
Comedolytic
Keratolytic
Antiinflammatory
less irritating as compared to tretinoin
can be combined along with benzyl peroxide

Topical Antibiotics: Clindamycin, erythromycin & tetracyclines can be used topically in the form of cream, gel or lotion. Nadifloxacin is a newer topical quinolone broad spectrum antibiotic which can be used in inflammed acne & folliculitis
Azelaic acid:
Natural product from Pityorosporum ovale
Many Aerobic, anaerobic organism & P. acnes are inhibited
reduces bacterial density
reduces free fatty acid content of skin
reduces proliferation of keratinocytes
used in the form of cream
response is delayed
also used in melasma

Systemic therapy:
Indicated in severe cases with cyst & pustules
Antibiotics: Tetracycline, doxycyclines, Minocyclines & erythromycin are used
Isotretinoin or cis retinoic acid:
It is an orally administered retinoid
decrease production of sebum
correct abnormal keratinization
Adverse effects are dryness of skin, eyes, nose , mouth, chelitis, epistaxis, pruritus, rise in serum lipids & intracranial tension.
It is highly teratogenic, strictly contraindicated during pregnancy & one month after

Unwanted effects and pharmacokinetics of local anaesthetics (LAs)

LAs are either esters or amides. Esters are rapidly hydrolysed by plasma cholinesterase, and amides are metabolised in the liver. Plasma half-lives are generally short, about 1-2 hours.
Unwanted effects result mainly from escape of LAs into systemic circulation.
Main unwanted effects are:
CNS effects, agitation, confusion, tremors progressing to convulsions and respiratory depression
cardiovascular effects, namely myocardial depression and vasodilatation, leading to fall in blood pressure
occasional hypersensitivity reactions.
LAs vary in the rapidity with which they penetrate tissues, and in their duration of action. Lidocaine penetrates tissues readily and is suitable for surface application; bupivacaine has a particularly long duration of action.

Mechanism of action of local anaesthetics

Action of local anaesthetics (LAs)
LAs block action potential generation by blocking sodium channels.
LAs are amphiphilic molecules, with a hydrophobic aromatic group and a basic amine group.
LAs probably act in their cationic form but must reach their site of action by penetrating the nerve sheath and axonal membrane as unionised species; they, therefore, have to be weak bases.
Many LAs show use-dependence (depth of block increases with action potential frequency). This arises:
because anaesthetic molecules gain access to the channel more readily when the channel is open
because anaesthetic molecules have higher affinity for inactivated than for resting channels.
Use-dependence is mainly of importance in relation to antidysrhythmic and antiepileptic effects of sodium channel blockers.
LAs block conduction in the following order: small myelinated axons, non-myelinated axons, large myelinated axons. Nociceptive and sympathetic transmission is thus blocked first.

Therapeutic uses of NSAIDS

As an analgesic
As antipyretic
As an anti-inflammatory
Rheumatic fever
Prophylaxis & treatment of MI & DVT
PDA
Bartters syndrome
High risk pregnancy to reduce the risk of preeclampsia & PIH
Prophylaxis of Ca colon & rectum
Radiation induced diarrhoea
Niacin induced flushing
ACEI induced cough
Systemic mastocytosis
Hypercalcemia of some tumours
Alzheimers disease

Selective COX 2 Inhibitors

Parecoxib, Rofecoxib, Celecoxib, Valdecoxib
They do not depress TXA 2 production by platelets (COXI dependent), but reduce PGI2 production by vascular endothelium (COX2 dependant)
Only in patients at high risk of peptic ulcer, perforation or bleeds
They should be given in lowest dose for shortest period of time
Avoided in patients of cardiovascular risk factors

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

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

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

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)

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

Sildenafil

(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

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

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

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

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

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

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

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

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.

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

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.

Antiandrogens

Danazol
Cyproterone acetate
Flutamide
Finasteride

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

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

Contraindications of corticosteroids

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

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

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)

OSTEOPOROSIS

Osteoporosis is a serious public health issue. The past 10 years have seen great advances in our understanding of its epidemiology, pathophysiology, and treatment, and further advances are rapidly being made. Clinical assessment will probably evolve from decisions mainly being made on the basis of bone densitometry, to use of algorithms of absolute fracture risk. Biochemical markers of bone turnover are also likely to become more widely used. Bisphosphonates will probably remain the mainstay of therapy, but improved understanding of the optimum amount of remodelling suppression and duration of therapy will be important. At the same time, other diagnostic and therapeutic approaches, including biological agents, are likely to become more widespread. Strontium ranelate is a fairly new antiosteoporotic agent that has been approved in the European Union for thetreatment of postmenopausal osteoporosis. Although postulated to increase bone formation while reducing bone resorption, its mechanism of action remains unclear.