Antiemetics

This video shows Classification, Pharmacological actions, Mechanism of Action, Pharmacokinetics, Uses and Side effects of all Antiemetics.

Magnesium sulfate as the drug of choice for controlling eclamptic seizures

The drug of choice for controlling eclamptic seizures is

• A) hydralazine
• B) phenobarbital
• C) phenytoin
• D) diazepam
• E) magnesium sulfate

Answer and Discussion

The answer is E. 

In the United States, magnesium sulfate is considered the drug of choice for controlling eclamptic seizures. Fewer intubations are required in the neonates of eclamptic women who are treated with magnesium sulfate. In addition, fewer newborns require placement in neonatal intensive care units. In the treatment of eclampsia and preeclampsia, magnesium sulfate is often given according to established protocols. If serum magnesium levels exceed 10 mEq/L (5 mmol/L), respiratory depression can occur. This problem may be counteracted by the rapid intravenous infusion of 10% calcium gluconate. Magnesium sulfate should be used with caution in patients with impaired renal or cardiac status. It should not be used in patients with myasthenia gravis.

Simple Terms to learn about effect of drugs on CNS

- Sedation : Reduction of anxiety
- Addiction : The state of response to a drug whereby the drug taker feels compelled to use the drug and suffers anxiety when separated from it
- Anesthesia : Loss of consciousness associated with absence of response to pain
- Anxiolytic : A drug that reduces anxiety, a sedative
- Dependence : The state of response to a drug whereby removal of the drug evokes unpleasant, possibly life-threatening symptoms, often the opposite of the drug's effects
- Hypnosis : Induction of sleep
- REM : sleep Phase of sleep associated with rapid eye movements; most dreaming takes place during REM sleep
- Tolerance : Reduction in drug effect requiring an increase in dosage to maintain the same response

Azithromycin is the treatment of choice for Bordetella pertussis

Which of the following medications is considered the treatment of choice for Bordetella pertussis infection?

• A) Penicillin
• B) Ciprofloxacin
• C) Azithromycin
• D) Tetracycline
• E) Cefuroxime

Answer and Discussion

Recent epidemiologic studies have shown that the incidence and prevalence of Bordetella pertussis infection in adults are much greater than previously reported. In studies of adults with chronic cough, 20% to 25% were found to have serologic evidence of recent B. pertussis infection. However, pertussis is rarely considered in adults because the signs and symptoms are nonspecific.

Apart from a prolonged cough, there are no specific symptoms suggestive of pertussis in older individuals who have been immunized. With this in mind, pertussis should be considered in the differential diagnosis of persistent cough in previously immunized children and adults.

-Administration of erythromycin or other macrolide (azithromycin or clarithromycin) may be a consideration in patients presenting with persistent cough. Prophylaxis of exposed persons before culture or serologic results are available would be another consideration. Early treatment with a macrolide should limit the spread of infection to persons whose immunity has waned or in unimmunized children. The acellular vaccine may allow booster immunization, which can be a method of preventing B. pertussis infection after immunity from the pertussis vaccination has waned.
So;The answer is C.

Bleomycin-Induced Flagellate Hyperpigmentation

A 39-year-old woman with a long-standing vascular malformation of the posterior tongue underwent intralesional sclerotherapy with a single dose of bleomycin. Within 1 week after treatment, painless, nonpruritic, flagellate hyperpigmentation developed on her trunk. She had no alopecia and no changes in the appearance of nails or mucosa. She reported having no dyspnea or pulmonary symptoms.
Bleomycin is a glycopeptide antibiotic commonly used for chemical pleurodesis, the treatment of cutaneous warts, and the treatment of a variety of cancers. The rate of flagellate hyperpigmentation in patients who are treated with bleomycin may be as high as 20%. Most tissues contain a cysteine proteinase capable of hydrolyzing and inactivating bleomycin. The reduced concentration of bleomycin hydrolase in the skin and lung, as compared with other tissues, may explain the medication's adverse reaction profile.

The patient was counseled that the flagellate hyperpigmentation usually fades over a period of several months after the cessation of the medication. During the past year, the hyperpigmentation in this patient has faded but not yet resolved.

Beta2 Adrenergic Receptor Mnemonic

Beta2 Adrenergic Autonomic Receptor of the Sympathetic Nervous System presented in a pictorial mnemonic format . Key Point: Beta2 expands. For Medical learning.

Angioedema caused by angiotensin-converting enzyme (ACE) inhibitor

Swollen tongue caused by angiotensin-converting enzyme (ACE) inhibitor-associated

angioedema.

Diagnosis:

Angioedema is a clinical diagnosis. If the patient presents with the characteristic swelling of the
mouth, lips, tongue, or pharynx and is also taking an ACE inhibitor, the diagnosis should be highly suspected.

Clinical Complication:
Airway compromise secondary to swelling of the tongue, uvula, soft palate, and larynx is a common and potentially life-threatening complication of ACE inhibitor-associated angioedema.

Management : Patients with impending airway compromise require the immediate establishment of a definitive airway. Those with less severe findings need early medical management with intravenous (IV) antihistamines, steroids, and subcutaneous epinephrine. After discontinuation of the ACE inhibitor and administration of the appropriate medications, most cases of ACE inhibitor-induced angioedema resolve within 12 to 48 hours.2 However, this angioedema can proceed rapidly to life-threatening airway closure and must be treated as a serious emergency.

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Side effects of Prostaglandin E1 on neonates

Prostaglandin E1 used in:
 Maintain patency or reopen ductus arteriosus in case of
1. Cyanotic Congenital Heart Disease

• Transposition of the Great Vessels
• Tricuspid atresia

2. Aortic Coarctation

# Side effects are common and potentially lethal

1. Flushing
2. peripheral edema
3. Hypotension
4. Apnea
5. Hyperpyrexia
6. Jitteriness
7. Diarrhea
8. Hypoglycemia
9. Hypocalcemia
10. Renal Failure
11. Rhythm disturbance
12. Coagulopathies

Note that : Start with "x" mg of Prostaglandin E1( Where "x" = 0.3 x WeightKg )
-Add enough D5W or NS to Prostaglandin for 50 ml total
At this dilution: Infusion rate of 0.5 ml/min provides 0.05 ug/kg

SLUG BAM: Muscarinic effects of Acetylcholine

Acetylcholine acts on two vastly different classes of receptors - nicotinic receptors (with two subtypes, one at the neuromuscular junction of skeletal muscle, the other within ganglia and the CNS), and muscarinic receptors (widely distributed within both peripheral and central nervous systems).

**Muscarinic effects SLUG BAM:

• Salivation/ Secretions/ Sweating
• Lacrimation
• Urination
• Gastrointestinal upset
• Bradycardia/ Bronchoconstriction/ Bowel movement
• Abdominal cramps/ Anorexia
• Miosis

propofol infusion syndrome: a simple name for a complex syndrome.

It was revealed just recently that Propofol, a short-acting, intravenously administered sedative agent is what might have caused the cardiac arrest of the King of Pop, Michael Jackson.

Propofol infusion syndrome (PRIS) is a rare and often fatal syndrome described in critically ill children undergoing long-term propofol infusion at high doses. Recently several cases have been reported in adults, too.

The main features of the syndrome consist of cardiac failure, rhabdomyolysis, severe metabolic acidosis and renal failure.
To date 21 paediatric cases and 14 adult cases have been described. These latter were mostly patients with acute neurological illnesses or acute inflammatory diseases complicated by severe infections or even sepsis, and receiving catecholamines and/or steroids in addition to propofol. Central nervous system activation with production of catecholamines and glucocorticoids, and systemic inflammation with cytokine production are priming factors for cardiac and peripheral muscle dysfunction. High-dose propofol, but also supportive treatments with catecholamines and corticosteroids, act as triggering factors.

At the subcellular level , propofol impairs free fatty acid utilisation and mitochondrial activity. Imbalance between energy demand and utilisation is a key pathogenetic mechanism, which may lead to cardiac and peripheral muscle necrosis. Propofol infusion syndrome is multifactorial, and propofol, particularly when combined with catecholamines and/or steroids, acts as a triggering factor.
The syndrome can be lethal and we suggest caution when using prolonged (>48 h) propofol sedation at doses higher than 5 mg/kg per h, particularly in patients with acute neurological or inflammatory illnesses. In these cases, alternative sedative agents should be considered. If unsuitable, strict monitoring of signs of myocytolysis is advisable.

Drugs administered in Status Epilepticus

A 21 year old is brought to your clinic in status epilepticus. What drug should be administered initially?

• A) Lorazepam


• B) Phenytoin


• C) Phenobarbital


• D) Pentobarbital


• E) Fosphenytoin

Answer and Discussion
The answer is A. Lorazepam should be administered intravenously and approximately 1 minute allowed to assess its effect. Diazepam or midazolam may be substituted if lorazepam is not available. If seizures continue at this point, additional doses of lorazepam should be infused and a second intravenous catheter placed in order to begin a concomitant phenytoin (or fosphenytoin) loading infusion. Even if seizures terminate after the initial lorazepam dose, therapy with phenytoin or fosphenytoin is generally indicated to prevent the recurrence of seizures.

Major non-antibiotics Teratogenic drugs

Before that we will talk about some principles, first adapted by James Wilson, highlight the nature of teratogens:

Principle 1: Susceptibility to teratogenesis depends on the genotype of the embryo

Principle 2: Susceptibility to a teratogenic agent depends on the developmental stage when the exposure occurs

Principle 3: Different teratogenic agents effect developing cells and tissues in various ways

Principle 4: The final manifestations of abnormal development are death, malformation, growth retardation, and functional disorder

Principle 5: The nature of the detrimental environmental agent impacts its access to the fetus.

Principle 6: As dosage increases the manifestations of abnormal development increase in degree from the no-effect to the lethal level

TAP CAP : Is the word that collct some of the most Major non-antibiotics Teratogenic drugs

Thalidomide Androgens Progestins Corticosteroids Aspirin & indomethacin Phenytoin

Melatonin and it`s uses

Melatonin is a hormone secreted by the pineal gland in the brain. It helps regulate other hormones and maintains the body's circadian rhythm. The circadian rhythm is an internal 24-hour “clock” that plays a critical role in when we fall asleep and when we wake up. When it is dark, your body produces more melatonin; when it is light, the production of melatonin drops. Being exposed to bright lights in the evening or too little light during the day can disrupt the body’s normal melatonin cycles. For example, jet lag, shift work, and poor vision can disrupt melatonin cycles.

It also helps determine when a woman starts to menstruate, the frequency and duration of menstrual cycles, and when a woman stops menstruating (menopause).And has strong antioxidant effects.

Some researchers also believe that melatonin levels drop as we age(as in the diagram).Some people think lower levels of melatonin may explain why some older adults have sleep problems and tend to go to bed and wake up earlier than when they were younger.


Uses:
1-Insomnia
Melatonin supplements may help people with disrupted circadian rhythms (such as people with jet lag or those who work the night shift) and those with low melatonin levels (such as some seniors and people with schizophrenia) to sleep better. A review of clinical studies suggests that melatonin supplements may help prevent jet lag, particularly in people who cross five or more time zones.

A few clinical studies suggest that when taken for short periods of time (days to weeks) melatonin is more effective than a placebo in reducing the time it takes to fall asleep, increasing the number of sleeping hours, and boosting daytime alertness. It’s not clear how well melatonin works, however – some studies suggest that it only reduces the amount of time to fall asleep by a few minutes.


2-Menopause
Melatonin supplements may help with sleep problems associated with menopause. However, it does not appear to relieve other symptoms of menopause, such as hot flashes. Peri- or postmenopausal women who use melatonin supplements should do so only for a short period of time since long term effects are not known.

3-Benzodiazepine Withdrawal
Some clinical research has found that melatonin may help elderly people with insomnia who are tapering off or stopping benzodiazepines such as diazepam (Valium), alprazolam (Xanax), or lorazepam (Ativan). Taking controlled-release melatonin improved sleep quality in those stopping benzodiazepine use.

4-Breast Cancer
Several studies suggest that melatonin levels may be associated with breast cancer risk. For example, women with breast cancer tend to have lower levels of melatonin than those without the disease. Laboratory experiments have found that low levels of melatonin stimulate the growth of certain types of breast cancer cells, while adding melatonin to these cells slows their growth. Preliminary evidence also suggests that melatonin may strengthen the effects of some chemotherapy drugs used to treat breast cancer. In a study that included a small number of women with breast cancer, melatonin (given 7 days before beginning chemotherapy) prevented the lowering of platelets in the blood. This is a common complication of chemotherapy that can lead to bleeding.

In another small study of women who were taking tamoxifen for breast cancer but seeing no improvement, adding melatonin caused tumors to modestly shrink in more 28% of the women. Women with breast cancer should ask their doctors before taking melatonin.

5-Prostate Cancer
Studies show that people with prostate cancer have lower melatonin levels than men without the disease. In test tube studies, melatonin blocks the growth of prostate cancer cells. In one small-scale study, melatonin -- combined with conventional medical treatment -- improved survival rates in 9 out of 14 men with metastatic prostate cancer. More research is needed before doctors can make recommendations in this area.

6-Attention Deficit Hyperactivity Disorder (ADHD)
Some evidence suggests that melatonin may help promote sleep in children in ADHD, although it does not seem to improve the behavioral symptoms of ADHD.

Beta Receptor: Mechanism of Activation in Cardiac Muscle

1.The agonist binds to the myocardial beta1-adrenergic receptor. which is a typical G-protein coupled receptor.

2.In the unstimulated state the G-protein is complexed with GDP.

3. The receptor promotes exchange of GTP for GDP and release of G"/GTP.

4.The G"/GTP complex activates adenylate cyclase.

5.Intracellular cAMP increases and activates cAMP dependent protein kinase (PKA).

6.PKA phosphorylates the Ca2+ channel promoting Ca2+ influx.

7.Intracellular Ca2+ increases activating the contractile proteins.

8.PKA phosphorylates the sarcoplasmic reticulum leading to an increase in Ca2+ uptake and release.

9.PKA phosphorylates troponin changing its calcium binding kinetics

10.G" directly activates the Ca2+ channel.

11.Prolonged stimulation can lead to receptor down regulation via PKA and other protein kinases which phosphorylate the receptor. The other protein kinases which are involved in phosphorylation are referred to as G-protein coupled receptor kinases or GRKS. These phosphorylation steps lead to internalization of the receptor.

Drugs in Allergic Rhinitis

#H1 antihistamines are effective for treating nasopharyngeal itching, sneezing, watery rhinorrhea, and ocular itching, tearing, erythema.

*Side effects associated with older H1 antihistamines include sedation, visual disturbance, urinary retention, and arrhythmias

#Newer H1 antihistamines:( terfenadine (Seldane) astemizole (Hismanal))

*These agents exhibit less sedation associated with their reduced ability to cross the blood brain barrier.
*However, there are very important drug-drug interactions associated with this category.

• For example, macrolide antibiotics such as erythromycin, clarithromycin (Biaxin), ketoconazole-class broad-spectrum antifungal drugs, inhibit terfenadine (Seldane) or astemizole (Hismanal) metabolism.
• Toxic levels of terfenadine (Seldane) or astemizole (Hismanal) may induce potentially fatal cardiac arrhythmias.
• These new H1 antihistamines are contraindicated for concurrent use with macrolide antibiotics and ketoconazole-class and fungal drugs or in the presence of impaired hepatic function or inpatients predisposed to arrhythmias.

#Topical alpha-adrenergic agonists:

*Phenylephrine (Neo-Synephrine) or oxymetazoline (Afrin) reduce nasal congestion/obstruction.

• Efficacy duration: limited due to rebound rhinitis and systemic effects which may include insomnia, irritability, and hypertension -- the latter which is seen more commonly with oral alpha adrenergic agonists.

#Oral alpha-adrenergic agonists may be useful in diminishing antihistamine-mediated sedation while improving antihistamine efficacy in relieving congestion. However, there is a concern that these agents due to their potentially hypertensive effects, may precipitate adverse cardiovascular effects, such as stroke. Recently, there has been an effort to remove such "pressor" agents from common over-the-counter cold medications.

#Cromolyn sodium: This agent is a liquid provided as a nasal metered-does spray. Cromolyn sodium (Intal) is not associated with side effects and typically is used prophylactically to reduce episodic allergen nasal mast cell activation. This agent may be used as part of a anti-asthma drug regimen.

#ntranasal glucocorticoids:

*Intranasal glucocorticoids are the most potent drugs available for management of established rhinitis (seasonal or perennial) and including vasomotor rhinitis

• Topical-to-systemic activity greater for: flunisolide (AeroBid) or budesonide (Rhinocort), compared to beclomethasone (Banceril) or triamcinolone (Aristocort).

*Despite the different route of administration, intranasal-administered glucocorticoids exhibit the same efficacy but with reduced systemic side effects compared to same agent administered orally.
*Side effects include local irritation, which is the most frequent side effect to Candida over-growth which is an unusual side effect
*Topical high potency glucocorticoids exhibit superior efficacy compared antihistamines during pollen season.

#Immunotherapy (hyposensitization): This approach is based on repeated, subcutaneous injections of gradually increasing allergen (specific for the symptom complex) over a period of 3-5 years.

*Contraindications include significant cardiovascular disease and unstable angina
*Cautious use applies to patients receiving beta adrenergic blockers (due to difficulty in managing possible anaphylactoid responses to treatment)

**Clinical Management Sequence:

1.Identification of allergens confirmed by allergens-specific IgE skin testing and/or serum assay.
2.Avoidance of offending allergen
3.Mild symptoms: prophylaxis with topical cromolyn sodium or single (bedtime) dose of chlorpheniramine (Chlor-Trimeton) or astemizole (Hismanal) or terfenadine (Seldane) (decision based on side effects and presence of other concurrent medications or disease.
4.Prominent symptoms: Topical beclomethasone (Banceril) or if needed budesonide (Rhinocort) or flunisolide (AeroBid)
5.Management failure: immunotherapy

Challenges for Drug Discovery in a Postgenomic World

Jeffrey Conn, Ph.D.

Professor of Pharmacology and Director of the Vanderbilt Institute for Chemical Biology Program in Drug Discovery, Vanderbilt University School of Medicine

The lecture was part of Vanderbilt Medical's Discovery Lecture Series, featuring the nation's most eminent scientists, speaking on the highest-impact research and policy issues in science and medicine today.

Alpha1 Autonomic Receptor Mnemonic

Alpha 1 Adrenergic Autonomic Receptor of the Sympathetic Nervous System presented in a pictorial mnemonic format. Key Point: Alpha1 Constricts. For Medical learning.

When man becomes Reddish !!

What is Red man syndrome??
It is an infusion-related reaction peculiar to vancomycin.Typically it consists of pruritus, an erythematous rash that involves the face, neck, and upper torso.
Less frequently, hypotension and angioedema can occur. Patients commonly complain of diffuse burning and itching and of generalized discomfort. They can rapidly become dizzy and agitated, and can develop headache, chills, fever, and paresthesia around the mouth.
In severe cases, patients complain of chest pain and dyspnea. In many patients, the syndrome is a mild, evanescent pruritus at the end of the infusion that goes unreported.

It would appear about 4–10 min after an infusion started or may begin soon after its completion.
Vancomycin can cause two types of hypersensitivity reactions, the red man syndrome and anaphylaxis. Red man syndrome has often been associated with rapid infusion of the first dose of the drug and was initially attributed to impurities found in vancomycin preparations. Even after improvement in vancomycin's purity, however, reports of the syndrome persist.

Other antibiotics (e.g. ciprofloxacin, amphotericinB, rifampicin and teicoplanin) or other drugs that stimulate histamine release can result in red man syndrome.

Discontinuation of the vancomycin infusion and administration of diphenhydramine can abort most of the reactions. Slow intravenous administration of vancomycin should minimize the risk of infusion-related adverse effects.

Chloroquine-Induced Hair Hypopigmentation

A 16-year-old, blonde-haired patient was evaluated for a new band of lighter-colored hair located approximately 3 cm from the scalp. The patient first noted the change in hair color 1 week after returning from a 2-week vacation in Costa Rica, during which she took chloroquine phosphate for malaria prophylaxis.

Instead of taking 500 mg weekly, the recommended dose for prophylaxis, the patient took 500 mg of chloroquine phosphate daily, starting 1 week before the trip, during the 2 weeks in Costa Rica, and for 1 week after returning home. She had taken the first dose 3.5 months before presentation. Hair hypopigmentation is a rare but reversible side effect of chloroquine.
Although most cases occur after 3 consecutive months of treatment with daily doses of more than 500 mg of the drug, rapid onset is also possible.

Antimalarial medications overdose

A woman on antimalarial medications takes an overdose .
Which of the following is the most consistent feature of antimalarial overdose?

• a) ventricular arrhythmias
• b) hypokalemia
• c) methaemoglobinaemia
• d) Thrombocytosis
• e) blindness

The correct answer is B

Explanation
Quinoline derivatives, particularly quinine and chloroquine, are highly toxic in overdose. The toxic effects are related to their quinidine-like actions on the heart and include circulatory arrest, cardiogenic shock, conduction disturbances and ventricular arrhythmias.

Additional clinical features are obnubilation, coma, convulsions, respiratory depression. Blindness is a frequent complication in quinine overdose.
Hypokalaemia is consistently present, although apparently self-correcting, in severe chloroquine poisoning and is a good index of severity. Recent toxicokinetic studies of quinine and chloroquine showed good correlations between dose ingested, serum concentrations and clinical features, and confirmed the inefficacy of haemodialysis, haemoperfusion and peritoneal dialysis for enhancing drug removal. The other quinoline derivatives appear to be less toxic. Amodiaquine may induce side effects such as gastrointestinal symptoms, agranulocytosis and hepatitis.
The main feature of primaquine overdose is methaemoglobinaemia. No cases of mefloquine and piperaquine overdose have been reported. Overdose with quinacrine, an acridine derivative, may result in nausea, vomiting, confusion, convulsion and acute psychosis. The dehydrofolate reductase inhibitors used in malaria treatment are sulfadoxine, dapsone, proguanil (chloroguanide), trimethoprim and pyrimethamine. Most of these drugs are given in combination. Proguanil is one of the safest antimalarials. Convulsion, coma and blindness have been reported in pyrimethamine overdose. Sulfadoxine can induce Lyell and Stevens-Johnson syndromes.