A two year fate study of the anti psychotic drug thorazine

     Ninety-six chronically psychotic patients (26.2%) treated over a 2-year period with Thorazine have been released from the hospital. The stability of the release is indicated by the fact that only 11 of these patients have been returned from parole.2. Younger schizophrenics are more likely to respond to Thorazine to the extent that their release from the hospital is feasible.3. Of the patients remaining in the hospital, 65.5% are still receiving Thorazine.4. Behavioral improvement following Thorazine medication is maintained for at least 2 years.5. There appears to be evidence that prolonged administration of Thorazine does not lead to tolerance formation. Eighty-five point four per cent of the patients are receiving identical or smaller dosages of Thorazine than they were receiving a year ago.6. Some patients who responded minimally to Thorazine have shown a better response to one of the other tranquilizers.7. Eighteen of the Thorazine patients are showing a better response to combined therapy.8. Nursing personnel express conflicting opinions as to the efficacy of Thorazine medication.9. There is ample evidence of continued toxicity of Thorazine after 2 years of medication. This reinforces the concept that ataractic therapy must at all times be under medical supervision.10. Maintenence dosages are substantially smaller than the dosages necessary to obtain the initial therapeutic response.11. Blood studies (at monthly intervals) must be continued so long as the patient receives Thorazine.12. The need for routine liver-function tests is equivocal unless Thorazine medication is interrupted and then restarted.13. Side effects persist throughout the period of medication. All of them can be controlled, ameliorated or eliminated by the administration of proper antidote or discontinuation of Thorazine medication.

Behind: The Conjuring, and four other horror movies "based on a true story"

Last weekend, James Wan's paranormal thriller The Conjuring scared both moviegoers and its box-office competition with a hefty $41 million gross in the middle of summer — a time when we're all supposed to be watching movies about superheroes and giant robots. Made on a relatively thrifty budget of $20 million, The Conjuring outgrossed its far more expensive rivals like R.I.P.D. and Turbo on a marketing campaign that can be boiled down to five words: "Based on a true story."

It's a familiar promise to horror fans, who have been inundated with ghost stories making similar claims to veracity. But how much truth can there really be in stories about poltergeists and demonic possessions? Here, we fact-check The Conjuring and four other "based on a true story" horror movies:

1. The Conjuring

The movie:A family is beset by a series of wrathful wraiths after they move into a colonial farmhouse. When the ghosts begin to target their young daughters, they hire a pair of paranormal investigators to end the haunting once and for all.

The true story:The Conjuring's poster boldly proclaims that it's "based on the true case files of the Warrens." So who are the Warrens, anyway? The real-life couple, Ed and Lorraine (played in the film by Vera Farmiga and Patrick Wilson), were American paranormal investigators that founded the New England society for psychic research in 1952.

The Warrens' 10,000-plus career cases include the alleged haunting depicted in The Conjuring. In 1971, Roger and Carolyn Perron moved into a colonial farmhouse in Harrisville, R.I., with their five daughters, and quickly began experiencing what they described as both haunting and spiritual possessions. They invited the Warrens to the farmhouse to investigate. Over the nine years they lived in the house, the Perrons described spirits, both harmless and angry, that "stunk of rotting flesh" and routinely arrived at 5:15 a.m. to levitate their beds.

So how much of that is true? The real-life Perron family swears by their story, throwing their full weight behind the film and even appearing in some of The Conjuring's marketing materials. "Because I was the youngest and the most vulnerable, I was approached more than anyone, and I actually had a relationship with that [ghostly] boy," said April Perron in a trailer promoting the film.

Of course, there are plenty of people who doubt the story. Steven Novella, the president of the New England Skeptical Society, told USA Today that "there is absolutely no reason to believe there is any legitimacy" to the Warrens' reports on the Perron haunting — or, for that matter, to any of the Warrens' cases.

The Conjuring "is a fair reflection of the chaos and danger we faced at the farm," counteres Andrea Perron. "There are liberties taken and a few discrepancies, but overall, it is what it claims to be — based on a true story, believe it or not." Watch Perron describe her experiences in more details here:

2. The Devil Inside

The movie:A young woman hires a film crew to follow her to Italy, where she intends to investigate a triple homicide committed by her mother during an exorcism gone wrong.

The true story:The 2012 surprise megahit turned its paltry $1 million budget into a $100 million gross on the back of a marketing campaign that claimed the movie was "based on true events." What does that mean, exactly? Star Fernanda Andrade claimed that The Devil Inside was "inspired by several real accounts of possession," but doesn't specify which ones. A search for crimes committed by someone named Maria Rossi turned up a disturbing 1993 murder case — but that was a case without claims of satanic possession, and bearing no resemblance to the film's plot. Short answer: It's probably safe to file The Devil Inside under "very, very, very loosely based on true events."

3. The Haunting in Connecticut

The movie:When a family moves closer to a hospital to receive better care for their cancer-ridden teenage son, they discover that their new home used to be a funeral home — and that the spirits of the dead aren't exactly happy they moved in.

The true story:The Haunting in Connecticut — which, like The Devil Inside, was promoted as being "based on true events" — was purportedly based on the alleged haunting of the Snedeker family in Southington, Conn., in the 1980s. After renting a new home, Carmen Snedeker discovered that the house had once been a mortuary, and that the tools used on the corpses were still in the basement. The Snedekers were beset by "strange and disturbing phenomena," which they believed to be demons. They eventually contacted our old friends Ed and Lorraine Warren to investigate, and discovered that an employee of the mortuary had been convicted of necrophilia. Before The Haunting in Connecticut, their story formed the basis for a TV documentary and a book titled In a Dark Place: The Story of a True Haunting.

Pretty creepy, right? Just one problem: The book's author, Ray Garton, has since revealed that he didn't believe the story himself. In fact, he wanted In a Dark Place to be published as fiction, but was overruled by his editor. "Elements of Carmen Snedeker's story clashed with elements of Al Snedeker's story, and it seemed everyone was having a problem keeping their stories straight," said Garton in an interview with yahoo news. Garton also alleges that he approached the Warrens with his concerns, and that they urged him to just "make it up and make it scary."

In short: Yes, The Haunting in Connecticut is based on a "true story" — it's just a "true story" that has since been disowned by its author.

4. The Amityville Horror

The movie:A family experiences a series of strange, paranormal events after moving into a house in which a murder was committed less than a year earlier.

The true story:The Amityville Horror is based on Jay Anson's book of the same name — a best-seller that boldly proclaims itself to be a true story on its cover. The book tells the story of the Lutz family, who moved into 112 Ocean Ave. in Long Island, N.Y., 13 months after 23-year-old Ronald DeFeo Jr. murdered his parents and siblings there. The Lutzes stayed for just 28 days, citing a wide range of frightening paranormal activity, including swarms of flies, vivid nightmares, and the appearance of cloven hoof-prints in the snow outside the house.

Creepy stuff — but in the years since The Amityville Horror was published (and adapted for film), there have also been plenty of reasons to doubt its paranormal claims. Neighbors reported that they had witnessed nothing unusual at the house, and researchers discovered that there was no snow on the ground on the day the cloven hoof-prints were alleged to have appeared.

After a series of lawsuits related to the story, a judge said that the book is largely "a work of fiction," relying mostly on suggestions by DeFeo's defense attorney William Weber. Weber later admitted that the book was a "hoax" created with the Lutzes "over many bottles of wine." (George Lutz, for his part, has consistently maintained that the story is true.)

Of course, the controversy didn't stop filmmakers from turning The Amityville Horror into a franchise, nor from marketing the 2005 remake as being "based on a true story." As for the house, the current residents report that the the only weird thing they've experienced has been "people coming by because of the book and the movie."

5. The Exorcist

The movie:Two exorcists work to exorcize a demonic force called Pazuzu from a young girl.

The true story:William Blatty based both his novel and his screenplay for The Exorcist on the real life 1949 exorcism of a 13-year-old Maryland boy pseudonymously referred to as Roland Doe by the Catholic Church. In the days after the death of his aunt, Doe allegedly attempted to contact her with a Ouija board, which led to a series of seemingly supernatural events, including levitation. Multiple priests worked together to perform 30 exorcisms, during which Doe reportedly shied away from sacred objects and spoke in a guttural voice. One priest even reported seeing the word "hell," along with other strange markings, appear on Doe's body. At the end of the process, Doe returned to normal, and went on to have a perfectly normal life without any other supernatural behavior.

So what happened? There are plenty of theories, but no one has definitively explained what happened to Roland Doe. Writer Mark Opsasnick interviewed the ministers involved and concluded that they'd exaggerated the more extreme supernatural elements of the case. The ministers always maintained that Doe had legitimately been possessed.

43 - Antitumor antibiotics ( Anticancer agents )

These drugs are also direct DNA-interacting agents . examples are :


1. bleomycin
2. actinomycin D
3. mitomycin C
4. etoposide ( VP16-213 )
5. topotecan
6. irinotecan ( CPT II )
7. doxorubicin and daunorubicin
8. idarubicin
9. epirubicin
10. mitoxantrone

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45 - Antimitotic agents ( Anticancer drugs )

These drugs are also indirect DNA-interacting agents . examples are :


1. vincristine
2. vinblastine
3. vinorelbine
4. paclitaxel
5. docetaxel
6. etramustine phosphate
7. NAB-paclitaxel ( protein bound )

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60 - Anti-Epileptic drugs

1. Hydantoin derivatives : Phenytoin, methotoin and ethotoin

2. Barbiturates : Phenobarbitone, primidone.

3. Iminostillbenes : Carbamazepine.

4. Succinimides : Ethosuximide, methosuximide

5. GABA transaminase inhibitors : Sodium valproate, Vigabatrin

6. GABA reuptake inhibitors : Tiagabine

7. GABA agonists : Gabapentin.

8. Benzodiazepines : Clonazepam, diazepam and clobazam.

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44 - Antimetabolites drugs ( Anticancer drugs )

These drugs are indirect DNA-interacting agents . examples are :


1. deoxycoformycin (pentostatin) ^

2. 6-mercaptopurine ^

3. 6-thioguanine ^

4. azathioprine ^

5. 2-chlorodeoxy adenosine (cladribine) ^

6. fludarabine phosphate ^

7. asparaginase
8. hydroxy urea
9. capacitabine "

10. cytosine arabinoside "

11. azacytidine "

12. gemcitabine "

13. 5-fluorouracil "

14. methotrexate ~

15. pemetrexed ~
---------------------------------
^ (1-6) Purine analogs and related inhibitors .
" (9-13) Pyramidine analogs
~ (14,15) Folic acid analogs 

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47 - Drugs causing Parkinsonism

Here is a list of drugs and toxins causing parkinsonism :

1. Fluoxetine
2. Valproate
3. Alpha methyl dopa
4. Neuroleptics
5. Dopamine depleting agents
6. Anti-emetics
7. Lithium carbonate
8. Some selective anti-psychotics

Toxins which cause parkinsonism are :

1. CO ( carbonmonoxide )
2. Cyanide
3. CS2
4. Manganese
5. Methanol
6. MPTP
7. N-Hexane

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52 - Drugs causing Fatty liver

1. Antiarrythmics - Amiodarone

2. Antibiotic - Tetracycline ( high-dose, intravenous )

3. Anticonvulsant - Valproic acid

4. Antiviral - Dideoxynucleosides ( eg: Zidovudine ), protease inhibitors ( indinavir, ritonavir )

5. Oncotherapeutics - Asparginase, Methotrexate .

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57 - Anti-arrhythmic agents classification

Ia
QuinidineProcainamideDisopyramideIb
LidocainePhenytoinMexiletineIc
FlecainidePropafenoneMoricizineII
PropranololEsmololTimololMetoprololAtenololIII
AmiodaroneSotalolIbutilideDofetilideE-4031

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62 - Adverse effects, Precautions and Contraindications of Chloroquine

Toxicity and Side Effects: 

Taken in proper doses, chloroquine is an extraordinarily safe drug; however, its safety margin is narrow, and a single dose of 30 mg/kg may be fatal (Taylor and White, 2004). Acute chloroquine toxicity is encountered most frequently when therapeutic or high doses are administered too rapidly by parenteral routes. Toxic manifestations relate primarily to the cardiovascular system and the CNS. Cardiovascular effects include hypotension, vasodilation, suppressed myocardial function, cardiac arrhythmias, and eventual cardiac arrest. Confusion, convulsions, and coma indicate CNS dysfunction. Chloroquine doses of more than 5 g given parenterally usually are fatal. Prompt treatment with mechanical ventilation, epinephrine, and diazepam may be lifesaving.

Doses of chloroquine used for oral therapy of the acute malarial attack may cause GI upset, headache, visual disturbances, and urticaria. Pruritus also occurs, most commonly among dark-skinned persons. Prolonged medication with suppressive doses occasionally causes side effects such as headache, blurring of vision, diplopia, confusion, convulsions, lichenoid skin eruptions, bleaching of hair, widening of the QRS interval, and T-wave abnormalities. These complications usually disappear soon after the drug is withheld. Rare instances of hemolysis and blood dyscrasias have been reported. Chloroquine may cause discoloration of nail beds and mucous membranes. Chloroquine can interfere with the immunogenicity of certain vaccines (Horowitz and Carbonaro, 1992; Pappaioanou et al., 1986).

Irreversible retinopathy and ototoxicity can result from high daily doses (>250 mg) of chloroquine or hydroxychloroquine that lead to cumulative total doses of more than 1 g of base per kilogram body weight, such as those used for treatment of diseases other than malaria. Retinopathy presumably is related to drug accumulation in melanin-rich tissues and can be avoided if the daily dose is 250 mg or less (see Rennie, 1993). Prolonged therapy with high doses of 4-aminoquinoline also can cause toxic myopathy, cardiopathy, and peripheral neuropathy; these reactions improve if the drug is withdrawn promptly (Estes et al., 1987). Rarely, neuropsychiatric disturbances, including suicide, may be related to overdose.

Precautions and Contraindications :

This topic has been reviewed by Taylor and White (2004). Chloroquine is not recommended for treating individuals with epilepsy or myasthenia gravis. The drug should be used cautiously if at all in the presence of hepatic disease or severe gastrointestinal, neurological, or blood disorders. The dose must be adjusted in renal failure. In rare cases, chloroquine can cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (see Primaquine below). Concomitant use of gold or phenylbutazone (no longer available in the United States) with chloroquine should be avoided because of the tendency of all three agents to produce dermatitis. Chloroquine should not be prescribed for patients with psoriasis or other exfoliative skin conditions because it causes severe reactions. It should not be used for malaria in patients with porphyria cutanea tarda but is used in smaller doses for treatment of the underlying disease . Chloroquine is an inhibitor of CYP2D6 and interacts with a variety of different agents. It should not be given with mefloquine because of increased risk of seizures. Most important, this antimalarial opposes the action of anticonvulsants and increases the risk of ventricular arrhythmias from coadministration with amiodarone or halofantrine. By increasing plasma levels of digoxin and cyclosporine, chloroquine also can increase the risk of toxicity from these agents. For patients receiving long-term, high-dose therapy, ophthalmological and neurological evaluations are recommended every 3 to 6 months.

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50 - Antimicrobial chemotherapy - Protein biosynthesis inhibitors

Pharmacology Mcqs Postgraduation entrance preparation: 50 - Antimicrobial chemotherapy - Protein biosynthesis inhibitorsPharmacology Mcqs Postgraduation entrance preparation

Friday, September 11, 2009 50 - Antimicrobial chemotherapy - Protein biosynthesis inhibitorsStreptomycin     30S ribosomal subunitBactericidalGentamicin     30S ribosomal subunit               
BactericidalTetracycline     30S ribosomal subunitBacteriostaticSpectinomycin     30S ribosomal subunitBacteriostaticChloramphenicol     50S ribosomal subunitBacteriostaticErythromycin     50S ribosomal subunitBacteriostaticClindamycin     50S ribosomal subunitBacteriostaticGriseofulvin     Microtubule functionFungistatic


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61 - Drugs potentially harmful in Porphyria

1. BARBITURATES : The effect of barbiturates on ALA synthetase can cause dangerous disease exacerbations in persons with intermittent porphyria.Because barbiturates enhance porphyrin synthesis, they are absolutely contraindicated in patients with acute intermittent porphyria or porphyria variegata.
2. ETHCHLORVYNOL: Ethchlorvynol may enhance the hepatic metabolism of other drugs such as oral anticoagulants, and it is contraindicated in patients with intermittent porphyria.
3. CHLOROQUINE : It should not be used for malaria in patients with porphyria cutanea tarda but is used in smaller doses for treatment of the underlying disease.

Nicotinic acid/meclozine/hydroxyzine

Medroxyprogesterone + estrogenTestosterone, transdermal patch
Phenylpropanolamine + cinnarizinePseudoephedrine + dexbrompheniramine

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53 - Benzodiazepine interactions with other drugs

Benzodiazepine interactions with other drugs.

Decreased absorption of benzodiazepines
Increased half-life of diazepam and 
triazolam
Increased levels of diazepam and 
triazolam
Alprazolam and diazepam raise 
digoxin level
Increased duration of action of sedatives
Inhibition of antiparkinsonism effect
Impaired clearance of diazepam

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64 - AIPGME 2005 Pharmacology Mcqs with answers

1q: A highly ionized drug
a. Is excreted mainly by the kidney
b. Can cross the placental barrier easily
c. Is well absorbed from the intestine
d. Accumulates in the cellular lipids answera. Is excreted mainly by the kidney
2q: All of the following hormones have cell surface receptors except
a. Adrenaline
b. GH
c. Insulin
d. Thyroxine
3q: Which one of the following is true of adrenal suppression due to steroid therapy?
a. It is not associated with atrophy of adrenal glands
b. It does not occur in patients receiving inhaled steroids
c. It should be expected in anyone receiving greater than 5mg of prednisolone daily
d. Following cessation, the stress response normalizes after 8 weeks answerc. It should be expected .....
4q: With which of the following theophylline has an antagonistic interaction?
a. Histamine receptors
b. Bradykinin receptors
c. Adenosine receptors
d. Imidazoline receptors
5q: Which one of the following drugs increases gastrointestinal motility?
a. Glycopyrrolate
b. Atropine
c. Neostigmine
d. Fentanyl
6q: Which one of the following drugs has been shown to offer protection from gastric aspiration syndrome in a patient with symptoms of flux?
a. Ondansetron
b. Metaclopramide
c. Sodium citrate
d. Atropine
7q: The following drugss have significant drug interactions with digoxin except :
a. Cholestyramine
b. Thiazide diuretics
c. Quinine
d. Amlodipine
8q: One of the following is not true about nesiritide
a. It is a brain natriuretic peptide analogue
b. It is used in acutely decompensated heart failure
c. It has significant oral absorption
d. It has a short half life answerc. It has significant oral absorption.
9q: Dry mouth during antidepressant therapy is caused by blockade of
a. Muscarinic acetylcholine receptors
b. Serotonergic receptors
c. Dopaminergic receptors
d. GABA receptors answera. Muscarinic acetylcholine receptors.
10q: The major difference between typical and atypical antipsychotics is that
a. The latter cause minimal or no increase in prolactin
b. The former cause tardive dyskinesia
c. The former are available as parenteral preparations
d. The latter cause substantial sedation answerb. The former cause tardive dyskinesia.
11q: Antipsychotic drug induced parkinsonism is treated by
a. Anticholinergics
b. Levodopa
c. Selegilline
d. Amantadine
12q: Oculogyric crisis is known to be produced by all of the following drugs except
a. Trifluoperazine
b. Atropine
c. Perchlorperazine
d. Perphenazine
13q: Inverse agonist of benzodiazepine receptor is
a. Phenobarbitone
b. Flumazenil
c. Beta-carboline
d. Gabapentin
14q: All of the following are hallucinogens except
a. LSD
b. Phencyclidine
c. Mescaline
d. Methylphenidate
15q: All of the following are topically used sulphonamides except
a. Sulphacetamide
b. Sulphadiazine
c. Silver sulphadiazine
d. Mafenide
16q: One of the following is not pencillinase susceptible
a. Amoxicillin
b. Pencillin G
c. Piperacillin
d. Cloxacillin
17q: The group of antibiotics which possess additional anti-inflammatory and immunomodulatory activities is
a. Tetracyclines
b. Polypeptide antibiotics
c. Fluoroquinolones
d. Macrolides
18q: Which one of the following is best associated with Lumefantrine?
a. Antimycobacterial
b. Antifungal
c. Antimalarial
d. Antiamoebic
19q: Which one of the following is used in therapy of Toxoplasmosis?
a. Artensunate
b. Thiacetazone
c. Ciprofloxacin
d. Pyrimethamine
20q: Nevirapine is a
a. Protease inhibitor
b. Nucleoside reverse transcriptase inhibitor
c. NNRTI
d. Fusion inhibitor
21q: Which one of the following drugs is "Topoisomerase I" inhibitor?
a. Doxorubicin
b. Irinotecan
c. Etoposide
d. Vincristine
22q: Etanercept acts by one of the following mechanisms
a. By blocking Tumor necrosis factor
b. By blocking bradykinin synthesis
c. By inhibiting COX-2
d. By blocking lipoxygenase

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58 - Dexrazoxane

Dexrazoxane hydrochloride (Zinecard [Pfizer for USA & Canada]; Cardioxane [Novartis for EU & ROW]) is a cardioprotective agent.

It is used to protect the heart against the cardiotoxic side effects of anthracyclines, such as doxorubicin.

FDA has also approved a dexrazoxane hydrochloride drug, brand name Totect or Savene (developed by TopoTarget), for use as a treatment of extravasation resulting from IV anthracycline chemotherapy. Extravasation is an adverse event in which chemotherapies containing anthracylines leak out of the blood vessel and necrotize the surrounding tissue.

As a derivative of EDTA, dexrazoxane chelates iron, but the precise mechanism by which it protects the heart is not known.

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51 - Antimicrobial chemotherapy - Rest of drugs

Inhibitors of nucleic acid synthesisInhibitors of folate metabolismInhibitor of mycolic acid synthesisMycobacterial mycolic acid biosynthesisAlteration of cytoplasmic membraneBacterial membrane permeabilityFungal ergosterol biosynthesis

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46 - Molecularly targeted anticancer drugs

These drugs target a specific molecule and function as anticancer agents


1. imatinib
2. tretinoin
3. bexarotene
4. gemtuzumab ozogamicin
5. denileukin diftitox
6. gefitinib
7. erlotinib
8. dasatinib
9. sorafenib
10. sunitinib

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54 - Monoclonal antibodies approved for Hematological and Solid tumors

ANTIGEN AND TUMOR CELL TARGETS
ANTIGEN FUNCTION
NAKED ANTIBODIES
Tumor type: B-cell lymphoma and CLL
Tumor type: B-cell CLL and T-cell lymphoma
Tumor type: T-cell mycosis fungoides
Tumor type: acute myeloid leukemia
Tumor type: colorectal; NSCLC; pancreatic, breast

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48 - Atypical Antipsychotic drugs

Atypical antipsychotics are those drugs which act as antipsychotics but atypically have a very low risk of producing adverse extrapyramidal neurological side effects . These are

1. Risperidone

2. Quetiapine

3. Arisipiprazole

4. Clozapine

5. Olanzapine

6. Ziprasodine

Click here to read the mnemonic used to remember these drugs .

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55 - Drugs causing Megaloblastic anemia

1. Phenytoin (anticonvulsant)

2. Primidone (anticonvulsant)

3. Phenobarbitone (anticonvulsant)

4. Sulfasalazine

5. Nitrous oxide
6. Folate antagonists (inhibitors of Dihydrofolate reductase) like Methotrexate, Pentamidine,     Pyrimethamine, Triamterene, Trimethoprim and Cotrimoxazole.
7. Drugs that inhibit DNA synthesis may cause Megaloblastic anemia
example : 6a. Purine antagonists = 6-Mercaptopurine, Azathioprine.
6b. Pyramidine antagonists = 5 FU, Cytosine arabinoside .

6c. Others = Hydroxyurea, acyclovir and zidovudine (AZT, Azidothymidine).
8. Nitrofurantoin (less well documented)
9. Tetracycline (less well documented)
10. Anti-Tuberculosis drugs (less well documented)

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49 - Antimicrobial chemotherapy - Cell wall synthesis inhibitors

     SITE OF ACTION

     Peptidoglycan tetrapeptide side chain

     Formation of N-acetylmuramic acid
,     Peptidoglycan cross-linking
     Translocation of cell wall   intermediates

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56 - The Ceiling effect

*When the dosage of a drug is increased, its effect increases proportionally; but after a certain dosage, any amount of increase in the dosage of the drug shows no additional effect. This upper limit of the dosage, above which no additional effect is seen, is called the ceiling dose and this effect is called the CEILING EFFECT.

*Examples of drugs showing ceiling effect are :

- Loop diuretics (high ceiling diuretics)

- Ceiling effects for analgesia and respiratory depression are observed above 50 to 100 mg pentazocine. Pentazocine has opioid agonistic actions and weak opioid antagonistic activity. It is a type of opioid analgesic.

-  Nalbuphine exhibits a ceiling effect such that increases in dosage beyond 30 mg produce no further respiratory depression. However, a ceiling effect for analgesia also is reached at this point.
Nalbuphine is related structurally to naloxone and oxymorphone. It is an agonist–antagonist opioid with a spectrum of effects that qualitatively resembles that of pentazocine; however, nalbuphine is a more potent antagonist at MU receptors and is less likely to produce dysphoric side effects than is pentazocine.
- Buprenorphine is a semisynthetic, highly lipophilic opioid derived from thebaine. It is 25 to 50 times more potent than morphine. This drug is also believed to show the ceiling effect. Patients receiving methadone or buprenorphine will not experience the ups and downs experienced while on heroin. Drug craving diminishes and may disappear.  Buprenorphine, as a partial agonist, has a ceiling effect at about 16 mg of the sublingual tablet equaling no more than 60 mg methadone. If the patient has a higher level of physical dependence, methadone, a full agonist, must be used.
- The patient's ability to tolerate and absorb medicinal iron is a key factor in determining the rate of response to therapy. The small intestine regulates absorption, and with increasing doses of oral iron, limits the entry of iron into the bloodstream. This provides a natural ceiling on how much iron can be supplied by oral therapy.

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59 - Characteristics of antituberculous drugs

DrugMost Common Side EffectsTests for Side EffectsDrug InteractionsIsoniazid-
Bactericidal to both extracellular and intracellular organisms. Pyridoxine, 10 mg orally daily as prophylaxis for neuritis; 50–100 mg orally daily as treatment.Peripheral neuropathy, hepatitis, rash, mild CNS effects.AST and ALT; neurologic examination.Phenytoin (synergistic); disulfiram.Rifampin-
Bactericidal to all populations of organisms. Colors urine and other body secretions orange. Discoloring of contact lenses.Hepatitis, fever, rash, flu-like illness, gastrointestinal upset, bleeding problems, renal failure.Rifampin inhibits the effect of oral contraceptives, quinidine, corticosteroids, warfarin, methadone, digoxin, oral hypoglycemics; aminosalicylic acid may interfere with absorption of rifampin. Significant interactions with protease inhibitors and nonnucleoside reverse transcriptase inhibitors.Pyrazinamide-
Bactericidal to intracellular organisms.Hyperuricemia, hepatotoxicity, rash, gastrointestinal upset, joint aches.Ethambutol-
Bacteriostatic to both intracellular and extracellular organisms. Mainly used to inhibit development of resistant mutants. Use with caution in renal disease or when ophthalmologic testing is not feasibleOptic neuritis (reversible with discontinuance of drug; rare at 15 mg/kg); rash.Red-green color discrimination and visual acuity (difficult to test in children under 3 years of age).Streptomycin-
Bactericidal to extracellular organisms. Use with caution in older patients or those with renal disease.Eighth nerve damage, nephrotoxicity.Vestibular function (audiograms); BUN and creatinine.Neuromuscular blocking agents may be potentiated and cause prolonged paralysis.AST, aspartate aminotransferase; ALT, alanine aminotransferase; CBC, complete blood count; BUN, blood urea nitrogen.

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63 - Amiodarone

*Amiodarone is an iodine containing long acting antiarrythmic drug which belongs to class III.

*Mechanism of action : It prolongs actional potential duration and effective refractory period is also prolonged. Conduction is slowed. When the drug is given through oral route, it has minimal effect on cardiac contractility and BP. Amiodarone is categorized as a class III antiarrhythmic agent, and prolongs phase 3 of the cardiac action potential. It has numerous other effects however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV. Amiodarone shows beta blocker-like and potassium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects.
Amiodarone resembles thyroid hormone, and its binding to the nuclear thyroid receptor might contribute to some of its pharmacologic and toxic action

*Uses : It is used in resistant cases of VT and recurrent VF. It is used in resistant cases of AF when other drugs have failed.

*ADVERSE EFFECTS :
- It interferes with thyroid function : Both hypothyroidism and hyperthyroidism may be seen. It inhibits peripheral conversion of T4 to T3.
- Cardiac depressant action : This is seen on IV injection but not on oral dose. On IV administration fall in BP and myocardial depression occurs.
- Peripheral neuropathy
- Pulmonary alveolitis and fibrosis
- Photosensitization
- Corneal microdeposits.

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42 - Alkylating agents ( Anticancer drugs )

These drugs are direct DNA-interacting agents . examples are :


1. cyclophosphamide*
2. mechlorethamine*
3. chlorambucil*
4. melphalan(L-sarcolysin)*
5. ifosfamide*
 

6. lomustine ( CCNU ) %

7. carmustine ( BCNU ) %

8. streptozocin (streptozotocin) %


9. dacarbazine ( DTIC; dimethyltriazenoimidazole carboxamide ) =

10. temozolomide =


11. oxaliplatin -
12. cisplatin -
13. carboplatin -

14. altretamine ( formerly hexamethyl melamine ) +
15. thiotepa + 

16. procarbazine (N-methyl hydrazine, MIH) !

17. busulfan $
 -----------------------------

* (1-5) Nitrogen mustards 
%  (6-8) Nitrosoureas
=  (9,10) Triazenes
-  (11-13) Platinum coordination complexes
+ (14,15) Ethyleneimines and methylmelamines
! (16) Methylhydrazine derivative
$ (17) Alkyl sulfonate

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65 - Drugs causing CYP3A inhibition

1. HIV antivirals : Indinavir, nelfinavir, ritonavir, Saquinavir
2. Clarithromycin
3. Itraconazole and Ketaconazole
4. Nefazodone
5. Telithromycin
6. Aprepitant
7. Erythromycin
8. Grapefruit juice
9. verapamil, diltiazem
10. Cimetidine
11. Amiodarone
12. Chloramphenicol
13. Ciprofloxacin
14. Delaviridine
15. Diethyl-dithiocarbamate
16. fluvoxamine
17. gestodene
18. Imatinib
19. Mibefradil
20. Mifepristone
21. Norfloxacin
22. Norfluoxetine
23. Starfruit
24. Voriconazole

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Use of ACE Inhibitors & ARBs in Diabetic Nephropathy

1. How are ACE Inhibitors & Angiotensin Receptor Blockers (ARBs) useful in Diabetic Nephropathy?

Looking at a long term perspective, Angiotension II 2 by its vasoconstrictive effect increases the intra-glomerular pressure and hence renal hypertension. This induces glomerular hyperfiltration and glomerular injury. ACE inhibitors and ARBs reduce this parameter both by decreasing arterial blood pressure by opening up the blood vessel leaving the glomerulus (efferent arterioles). This reduces the pressure within the glomerulus so that less protein is forced across the blood vessel and into the urine (DIMINISH PROTEINURIA). This also protects the nephrons from hyper-filtration mode, that accelerates the glomerular injury and thus further diminishes proteinuria.
Other beneficial effects mediated by RAAS inhibitors in diabetic nephropathy include: ACE inhibitors increase the permeability selectivity of the filtering membrane, thereby diminishing exposure of the mesangium to proteinaceous factors that may stimulate mesangial cell proliferation and matrix production, two processes that contribute to expansion of the mesangium in diabetic nephropathy. Because Ang II is a growth factor, reductions in the intrarenal levels of AngII may further attenuate mesangial cell growth and matrix production.

This is why they are the drugs of choice for hypertensive patients with diabetes and are even being used in patients with diabetic nephropathy but are not hypertensive.

2. Why they are contraindicated in bilateral renal artery stenosis?

The entry of blood into glomerulus is regulated both by afferent and efferent arteriolar tone . Glomerular circulation is regulated by renal juxta glomerular apparatus.It modulates the glomerular blood flow by secreting renin which acts through Anigiotensin 2 on the efferent arteriole.
What happens in bilateral renal arterial stenosis?
When there is bilateral renal arterial stenosis the effective renal blood flow is not significantly reduced , but maintained at the cost of increasing the efferent arteriolar constrictor tone.
The reason is that the elevated circulating and intrarenal angiotensin II in this condition constricts the efferent arteriole more than the afferent arteriole within the kidney, which helps to maintain glomerular capillary pressure and filtration. It is like a check valve at the exit point of a dam , which is partially closed to maintain the adequate pressure ahead (Here, intra-glomerular pressure ahead)
What happens when ACEI are introduced ?
Removing this constriction by blocking circulating and intrarenal angiotensin II formation can cause an abrupt fall in glomerular filtration rate. This is not generally a problem with unilateral renal artery stenosis because the unaffected kidney can usually maintain sufficient filtration after ACE inhibition; however, with bilateral renal artery stenosis it is especially important to ensure that renal function is not compromised.
So once ACE inhibitors or ARBs are administered, the efferent arteriolar tone is removed , this triggers the intra glomerular pressure to drop suddenly and filtration pressure reduces.

3. How ACE Inhibitors especially captopril may cause proteinuria in some patients although they generally decrease proteinuria?

Proteinuria is always a sign of kidney dysfunction/injury as may happen in case of acute renal failure/renal insufficiency
As mentioned above ACE inhibitors diminish proteinuria but in certain conditions they may cause proteinuria.
In patients who are hemodynamically unstable (e.g. due to hypovolemia) Captopril-induced hypotension may cause decreased renal blood flow and glomerular filtration in some patients. This decrease in GFR cant be compensated by the Renin Angiotensin Aldosterone system because it has been inhibited. Severe decrease in GFR may lead to acute renal failure with accompanying proteinuria.
Other risk factors for the development of captopril-induced renal insufficiency are hypovolemia, hyponatremia, concomitant use of other potentially nephrotoxic medications, and renal artery stenosis.

In addition, captopril may cause type 2 hypersensitivity drug reactions including interstitial nephritis (usually associated with rash, eosinophilia, fever, and azotemia), or a membranous glomerulopathy. The histological findings of membranous glomerulonephritis in some patients who have proteinuria suggest the possibility of an immune-complex glomerulopathy. These findings are similar to other cases of drug-induced glomerulopathy

For MCQs, SEQs, Quizzes, Tips, Mneumonics in #Pharmacology please visit daily http://www.facebook.com/pharma4all for MBBS, BDS, FCPS, USMLE, PLAB etc students with detailed answers/explanations

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GLP (Good Laboratory Practice) Summarized

Uniformity

Consistency

Reliability

Reproducibility

Quality

Integrity

Organization : Management, Sponsor, Study Director, PI, Researchers/Technicians

Quality Assurance

Test Facility

Test System

Study Design

Performance

SOPs

Data Collection

Data Analysis

Data Storage/Archiving

Planning

Performance

Monitoring

Recording

Reporting

Archiving

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66 - Beta blockers

*Beta blockers are drugs which act against the beta adrenergic receptors. There are three kinds of adrenergic receptors namely beta1, beta2 and beta3.

*First generation beta blockers (non-selective beta blockers) :
- Propranolol
- Nadolol
- Timolol
- Penbutalol
- Pindolol
- Oxprenolol
- Alprenolol

*Second generatin beta blockers ( Beta1 selective beta blockers = Cardioselective beta blockers ):
- Acebutalol
- Celiprolol
- Bisoprolol
- Metaprolol
- Nebivolol (most cardioselective beta blocker)
- Atenolol
- Esmolol
- Betaxolol

*Third generation beta blockers ( These are beta blockers which have additional vasodilator property ):
- Labetalol and Carvedilol ( act as vasodilators by antagonising alpha1 receptors on blood vessels)
- Tilosolol ( act as vasodilator by opening up potassium channels)
- Nebivolol and Nipradilol ( generate Nitric oxide )
- Bevantolol, Betaxolol, Carvedilol ( inhibit calcium channels )
- Bopindolol, Carteolol, Celiprolol ( agonists of beta2 receptors )

* Beta blockers with Membrane stabilising activity (local anaesthetic activity) :
- Propranolol (most effective)
- Labetalol
- Acebutolol
- Metaprolol
- Pindolol

* Beta blockers with intrinsic sympathomimetic activity :
- Oxprenolol
- Alprenolol
- Pindolol
- Celiprolol

* Beta blockers which are lipid insoluble ( so they are excreted by kidney and hence contraindicated in renal failure - LONG ACTING AGENTS ) :
- Nadolol
- Sotalol
- Acebutalol
- Atenolol
- Betaxolol
- Bisoprolol
- Celiprolol

* Longest acting beta blocker is Nadolol
* Shortest acting beta blocker is esmolol.

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Revolutionary Discovery in Medical Drug Delivery... Grapefruits!

Scientists uncover how grapefruits provide a secret weapon in medical drug delivery.

No, this is not a joke.  Recent research indicates that grapefruits may “revolutionize how medical therapies like anti-cancer drugs are delivered to specific tumor cells”.

Researchers used the natural lipids of grapefruit to create nanoparticle drug delivery systems which have been given the name grapefruit-derived nanovectors (GNVs).

Please view the article for more detailed information.

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Propanolol: LOL!

Get it?  LOL?  Bahahahaha!  Sigh.  Fine.  Well that’s a great way to remember beta blockers, because every last one of them has a generic name that ends in -lol.  This is a great example of why memorizing the generic names of things, instead of the trade names (these are the capitalized ones I put in parentheses), helps you immensely with categorizing drugs like lightning!

Propanolol (Inderal) is the prototype of 1st Generation Beta Blockers.  Propanolol is still prescribed for many things, including hypertension, angina pectoris, and stage fright.  Although it is very effective, it is not the number one drug of choice.  This is because, bless its heart, propanolol is non-selective. It likes both beta-1 and beta-2 just the same!  Can you think of a reason why this might be a problem?

Let’s start with the main therapeutic features of propanolol:

You already know it’s effects on the heart, because you know what the beta-1 receptors do:

1.  Negative Chronotropic (slows the heart rate)

2.  Negative Inotropic (eases the force of contraction)

3.  Negative Dromotropic (slows the rate of conduction)

And the effect of beta blockade on the blood vessels:

4.  Secondary Vasorelaxation (or reducing the amount of resistance from the blood vessels)

You may also remember that there are beta-1 receptors on the kidneys, so:

5. Renin inhibition (stop kidney/heart-controlled vasoconstriction)

But, propanolol also inhibits beta-2!

6.  Bronchoconstriction (anti-bronchodilation, to be more exact)

7.  Uterine relaxation (For our current purposes, just keep this one somewhere in your mind where you store those “fun facts”.  In general, no one gives much of a hoot about beta blockers’ effects on the uterus.  Sigh.)

Those are all the main effects of propanolol on your body!  In summary, they help relieve high blood pressure by loosening the blood vessel walls and stopping renin release, AND help make your heart a better pump by slowing it, letting it relax, and stopping its “go” signal.  All of this adds up to two main therapeutic uses:

1.  Reduced Cardiac Output, which with a little help, leads to…

2.  Antihypertension

But wait, what about the side effects?  For now, just think about that question.  See if you can come up with four possible adverse effects of propanolol, just by looking at what it does!

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Protamine Reaction

Protamine sulfate is a drug that reverses the anticoagulant effects of heparin by binding to it.

Protamine was originally isolated from the sperm of salmon and other species of fish but is now produced primarily through recombinant biotechnology. It is a highly cationic peptide. It binds to heparin to form a stable ion pair which does not have anticoagulant activity; on its own, protamine has a weak anticoagulant effect. The complex of heparin and protamine is then removed and broken down by the reticuloendothelial system.

I.    DESCRIPTION:

Following cardiopulmonary bypass with heparin anticoagulation, protamine sulfate is used to neutralize the effects of heparin and reverse anticoagulation.  Currently protamine is the only drug available in the United States that can be used for this purpose. Hexadimethrine bromide (Polybrene) and toluidine blue are for laboratory use only.

II.    ADMINISTRATION:

The method of determining protamine dose varies from center to center, but it is known that 1.0 mg protamine reverses 100 units of heparin. The method of determining how much heparin is on board at the termination of bypass also varies.  Some centers will use a standard 1 to 1 reversal of total heparin given.  Protamine titration is a more specific test and can be used if bleeding persists after protamine has been given.  Protamine should be administered over 5 minutes and slower if the patient has any signs of adverse reaction.

III.    ADVERSE EFFECTS:

A.        Hypotension:

Most common side effect is hypotension due possibly to a histamine release and is accompanied by venodilation, reduced cardiac filling, and decreased systemic vascular resistance.

B.    Thrombocytopenia:

Studies have shown decreases in platelet count upon protamine administration.  Excessive amounts of protamine are not recommended due to increased postoperative blood loss.

C.    Idiosyncratic reactions:

Severe anaphylactic reactions may occur in some patients resulting in profound vascular collapse.

IV.    TREATMENT OF CARDIOVASCULAR COLLAPSE:

A.    Primary Therapies:

1.    Stop protamine administration

2.    Maintain airway with 100% O2

3.    Stop all inhalational anesthetics

4.    Start intravascular volume expansion with crystalloid, colloid or blood

5.    500 mg to 1.0 g calcium chloride

6.    0.1 to 1.0 mg epinephrine IV bolus

7.    Evaluate heart rate and rhythm.  May use pacer, ephedrine or atropine if bradycardic

8.    For hypotension without bradycardia, may use phenylephrine 50-100 mcg IV bolus

9.    Reinstitute cardiopulmonary bypass if no response to pharmacologic interventions

B.    Secondary Therapies:

1.      Antihistamines  May be given prior to protamine administration:

Diphenhydramine 0.5-1.0 mg/kg, Cimetidine 300 mg, Famotidine 20 mg or Ranitidine 50 mg.

2.      Catecholamine infusions:

Epinephrine 2-4 mcg/min, norepinephrine 2-4 mcg/min, or isoproterenol 0.5-1.0 mcg/min as a drip, titrated as needed.

3.      Aminophylline

5-6 mg/kg over 20 minutes with persistent bronchospasm.

4.      Corticosteroids 

0.25-1 g hydrocortisone during rewarming on cardiopulmonary bypass

V.    HIGH RISK PATIENTS:

A.    Patients with higher risk include:

Diabetics on NPH insulin, patients allergic to fish, pregnant women, nursing women, children, previous protamine exposure and men who have had vasectomies.

B.    High Risk patients

(or those patients placed back on CPB after cardiopulmonary collapse may be offered any or all of the following options:)

1.    After loading with steroids, discontinue CPB.  Modified Ultrafiltration should very effective for this patient to remove cytokines and activated complement prior to attempting heparin reversal for the second time..

2.    The heparin reversal may be attempted or allowed to be broken down over time and the ACT allowed to come back to normal naturally.

3.    Protamine may be given by the surgeon into the left atrium thus allowing dilution and dissemination systemically prior to the AT III-Heparin-Protamine complexes entering the pulmonary vascular system.

4.    Concomitant Calcium Chloride administration may be useful during the administration of the protamine.

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Oxidative stress: the mystery continues

Extensive research work done during last three decades gives a detailed account of the oxidative stress, a condition where oxidants, within the body, outnumber endogenous antioxidants or the latter’s level is, somehow, depleted in order to allow the oxidants to freely damage cells and tissues. This condition is reported to cause or lead to development of a variety of diseases including cardiovascular diseases (CVDs), neurological disorders, lung diseases, cancer and many more. There are so many published reports indicating an axial role of oxidants in the development of diseases. However, oxidative stress condition does not emerge spontaneously, rather it needs a stimulus to create destructive endogenous environment where oxidants prevail over the normal physiology. Body, itself, monitors and assures a perfect balance between oxidants and antioxidants. In order to induce an imbalance, a stimulus needs to assist in and increase the generation of free radicals within the body and/or suppress the expression or activities of endogenous antioxidants. Such kind of stimulus may include any of the physical, chemical or biological agents, normally categorised as ‘toxicants’ or ‘xenobiotics’. (Note: for most of the xenobiotics a particular mechanism of action is reported that is involved in induction of a specific condition, e.g. consumption of ethanol, carbontetrachloride (CCl4) or paracetamol (Acetaminophen) primarily induces hepatotoxicity; Cigarette smoke, automobile exhaust or suspended particulate matter (SPM) commonly induce lung toxicity. However, oxidative stress is reported to remain a common and integral part of the whole damaging mechanism).

Two points apparently becomes clear that (i) oxidative stress is not spontaneous, and (ii) it needs some stimulus to reach up to the level of causing oxidative damages. But the phenomenon is not so much simple as it appears through these two points. To understand the complexity of the event one needs to understand the very nature of the oxidants, which are mainly free radicals generated by essential physiological processes, the ways of their generations and the mechanism behind the macromolecular damages to the cells. The one also needs to understand the physico-chemical properties of the xenobiotics.

While going through the literature an ambiguity arises whether its oxidative stress which is an interface between xenobiotics exposure and the consequent toxicities or xenobiotics itself causes the toxicity and the oxidative stress condition arise as an effect. However, various recent published reports indicates that exposure to certain chemicals and consequent injuries is not just a matter of oxidant-antioxidant imbalance and it goes beyond that notion with an alteration in genetic material and gene expression, enzyme inhibition and ultimately affecting the normal physiology. But at the very same time oxidative stress arise and appear to play a crucial role in the development of toxicities. These two separately defined events are interwoven in such a way that it’s not easy to conclude whether the effect includes toxicities and oxidative stress or the cause includes chemical exposure and the oxidative stress.  Oxidative stress seems at either side creating a mystery that continues.

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New Educational Practices Improving Patient Care In Sacramento

Bill Hammontree is no dummy, but he works with plenty every day at the UC Davis Health System. As the program manager for the Center for Virtual Care, he uses ultra-sophisticated mannequin patient simulators and surgical robots to train health care professionals.

Bill Hammontree, program manager, UC Davis Health System with medical practice dummy (photo courtesy of Bill Hammontree)

Hammontree earned his registered nurse and emergency medical technician licenses, and then got a bachelor of science degree in nursing, but it did not happen overnight. “School took longer because I was learning so much in the field,” he says, in the U.S. Navy, as an emergency medical technician and on the hectic floor of an emergency room in a level-one trauma center. But school gave Hammontree the foundation on which to build and he is currently moving ahead with his dream of a post-graduate degree.

What is the most exciting part of your current job?

Hammontree had to think for a moment to narrow it down to even a few things. “Getting mannequins to mimic reality, making them behave like people,” he says, adding, “teaching others and sharing the experience with them is great.”

The patient simulators talk, breathe, blink their eyes and even have a heartbeat and pulse points. Med students and current health care professionals use them to practice skills from anesthesia to neonatal resuscitation and surgical techniques. Hammontree even takes a gowned mannequin to a hospital bed and calls a code blue, a critical event to which the hospital staff must fully respond.

Which classes were particularly helpful?

Pharmacology courses, especially because Hammontree had a great instructor. “He was so good at breaking down how medicines work. He really brought it home for me.” That background serves him well now, as the patient simulators are designed to respond to drug treatments.

Why are you applying for a master’s program now when you are already so successful?

Furthering his education can help “get a leg up to higher functions of management within the hospital,” says Hammontree. Advancing his career and education go hand in hand, even when the “hand” in question belongs to a state-of-the-art mannequin or robot.

Valerie Heimerich is a freelance writer out of Sacramento. She typically covers animals and community issues. She has volunteered and worked for many organizations helping animals and people.
Her work can be found at Examiner.com.

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Morphine: Haven't Got Time for the Pain

Morphine is the prototype for opioid analgesics.  This baby is a pure mu receptor agonist, so it has some amazing pain-killing properties!

Pharmacokinetics:

Morphine can be absorbed tons of ways.  It can be given IV, SubQ, IM, PO, intrathecally, and rectally.  You can also snort it but I wouldn’t recommend suggesting that to a patient. It is distributed via the blood stream to the mu receptors in your spinal cord, brain, and small intestine.  That last part is important to remember! The liver metabolizes it and the kidneys excrete it.

Morphine is an example of a drug that does not have a ceiling.  Some drugs have a point of concentration when they actually stop working.  Adverse effects can sometimes still worsen (great, huh?) but with no more nice analgesia.  Morphine can just keep building and building, and it will relieve more and more pain.  This doesn’t mean that people can’t overdose, of course, but it does mean that although it may require more morphine to relieve the pain, more can be given and with good effect.

You may remember that opioid analgesics produce euphoria and reduce pain. They are also CNS depressants, which means we have to be VERY careful to watch patients after they are given morphine.  Why, you ask?  I’m glad you did!

Because CNS depression…

1.  Reduces the respiratory rate.  You want it between 12-20 breaths per minute, but morphine can drop that really quickly.  It also reduces air hunger (your gasping reaction when you are out of breath) so it’s difficult to see unless you are counting breaths.

2. Reduces level of consciousness.  If you patient immediately falls into a deep sleep and their respiratory rate drops, this is a problem.

The other big problem with morphine is that it makes you VERY CONSTIPATED.  You know why?  Because mu receptors are all over your gut!  Morphine slows the digestive tract and can pretty much bring it to a halt.

So when you have a patient that needs morphine, remember you always have to check their respiratory rate and level of consciousness BEFORE you give it to them (to make sure they aren’t already having issues) and AFTER (to make sure they don’t get any issues).

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Pharmatrollogy

We were given an assignment on our first day —  answer the Pharma lab manual. The professor said she was still thinking if we will submit it the following day. A later announcement indicated that our assignment would just be a seatwork, therefore we did not have to finish it before class.

I was sleeping when our Pharma class started (the class started 15 minutes earlier). I woke up to the sound of our professor’s voice saying something I was not able to comprehend immediately. She then handed out pieces of paper (along with her assistant who had red hair and kinda look liked Hayley Williams haha) which turned out to be a quiz. The quiz was about prescription writing. I was quite relieved at first, but when I realized I did not have my calculator with me, things turned ugly. I was not able to finish all of the items.

After passing our papers, I was preparing for the lecture. The professor then started handing out another set of papers. It was another quiz. I later found out that while I was sleeping, the professor announced that she would be giving two quizzes that day. Oh well. The exam type was multiple choice, but there were several items which had more than one correct answer. We had to encircle all of the correct answers (and nothing but the correct answers) to gain a point in each item. The questions and choices did not help us either, since they were very confusing.

When we were done with the second quiz, we were then dismissed. I was like, “Huh??”.

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Oblivion 2013

This film was totally brilliant! I love it!

It was released on 19th April here in Poland. Back then, I saw the ads on some small billboards in Warsaw, but I couldn’t figure out what the title was because the title was in Polish, Niepamiec. And I have not seen a lot of trailers like I used to, lately. So that’s one of the reason for not knowing about this movie in advance hahah. Blame it all on Pharmacology

Oblivion 2013

Oblivion 2013

Jack & Julia Harper – Oblivion 2013

Watch online

****

By the way, I’m now doing Paediatrics clinics. Today, my group went to see an 8-year-old boy, Marcin, who is suffering from Haemophilia type A. He was admitted to the hospital for physiotherapy session. He currently receives infusion of factor VIII concentrate.

Our doctor mentioned that before the factor infusion was introduced as management for Haemophilia, plasma and cryoprecipitate (Cryoprecipitated Antihaemophilic Factor) or “cryo” for short was used. Nowadays, they are largely replaced by the factor concentrates.

Marcin is going to stay in the ward for another two weeks. Our doctor said that he has no parents, he is an orphan so it might be another reason for him not being really cheerful. When our doctor said that, my heart sank. He was cute, a little bit shy and all but by looking at his face I knew (or felt like I knew) that he is lonely.

He was very well-behaved though. He was cooperative and didn’t mind us doing the whole body examination on him. It took quite a while but he was very patient with us. At the end of the interview, our doctor asked him to show his “treasures” which he kept inside the drawer of the side table. He showed us some cards of some football players.

I hope that he would be healthy for all his life. And hopefully the factor concentrate would prevent him from getting crippled in the future. I hope that he will be happy

Tags: 2013, Andrea Riseborough, clinics, colony, cryo, cryoprecipitate, drones, Factor VIII, factor VIII concentrate, film, Haemophilia, haemophillia, julia harper, Julia Rusakowa, Morgan Freeman, Niepamiec, Oblivion, Olga Kurylenko, orphan, paediatrics, pharmacology, Poland, Sally, sci-fi, space, Tet, Tom Cruise, Victoria, Warsaw

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Administration - Part 1 of what seems like 1,000,000 things to remember

As I said, I’m using a ton of resources but truly am leveraging Mosby’s Memory Cards to help me stay organized.

Today’s topic is all about Medication Administration.

Six Rights of Medication Administration and Routes of Medication

The Six Rights of Medication Administration are:

MedicationRouteTimePatientDosageDocumentation

Routes of Administration

Enteral or oral (most common) – ingested into gastrointestinal tract.- Liquid or pillParenteral – injected into blood or body tissues (intravenous (IV), intramuscular (IM), subcutaneous (SC).  – Think of a shotTopical – absorbed across skin or mucous membrane – Think of a patch or a creamInhalation – inhaled directly into the lung to elicit local effects – Think of an inhalerRectal or vaginal suppository – inserted for local effects – Thinking you figured this out.

 Well, this is only Day 1 of many more and I am thinking this may not be as bad as I thought…..hang in there and just learn these items.   Tomorrow we’ll take on the Nursing Implications!

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Naloxone: The Antidote (aka The Cruel Awakening)

This drug is the OPPOSITE OF FUN.  For real.  You do NOT want naloxone (Narcan) unless you absolutely, positively need it.  Naloxone is an opioid receptor antagonist.  Think about it.  Owwwwww.

The most important thing to know about naloxone is that it is the best way to rescue someone that has either overdosed on or had a bad reaction to morphine/heroin/any opioid.  The reason it is NOT a fun drug is that it actually kicks morphine (and other opioid agonists) off the mu receptors, essentially reversing the peaceful, pain-free, near-death experience and throwing it into the complete opposite.

It’s certainly a nice thing to have around, and an absolute necessity when you are giving an opioid analgesic, but please, use it with care!

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“We’re evolving towards systems pharmacology”

A theoretical chemist by training, Jordi Mestres started up the chemogenomics lab of the IMIM, currently part of the GRIB, in 2003. The structure of the group, made up of graduates and doctors in chemistry, biology, biotechnology and computer science, perfectly reflects its three main lines of research: molecules, proteins and programming to predict the interaction between them.

“We apply our predictions to both drug discovery and chemical biology”, summarises Mestres. This last discipline consists of using small molecules to sound out biology, for example inhibiting a protein to understand its function. According to the scientist from Girona the optimisation of these chemical probes is just as important as that for drugs. “They have been used for years as if they were selective for a single target protein, but now we are beginning to understand that they are not.”

In fact, drugs do not owe their effectiveness to the fact that they are very selective for a single target, rather to their affinity for a whole group of proteins. “We are evolving towards systems pharmacology, where the drug is placed in the context of all of the proteins with which it can potentially interact, the organs it can reach, the polymorphisms of the person that takes the drug, and so on”, explains the head of the group.

 A multitude of projects

The laboratory is involved in several European projects, including Open PHACTS, where they have developed an interactive tool to show ligand-protein interactions via the web (www.pharmatrek.org), and eTOX coordinated by Ferran Sanz (GRIB), where they design new methods to predict drug safety profiles. “Drug safety profiles are not really known until they are on sale and the drug is exposed to millions of users. If we were able to anticipate any adverse effects before entering the market and we understood the mechanisms, we could modify the structure of the drug in advance”, reasons Mestres.

They also look at ethnopharmacology, and try to explain how medicinal plants work. “We have made predictions for 109 plants and we are trying to rationalise their use for cardiovascular disease.”

In collaboration with Pilar Navarro (IMIM) they have found molecules inhibiting the formation of b-amyloid plaques that work as well or better than memantine, an Alzheimer’s drug. The research was funded by a pharmaceutical company and has generated two patents. In total, the group has four patents in collaboration with companies and one with the CSIC.

The creation of a spin-off

In some cases, they are asked by companies or other groups to prioritise which molecules to use at the beginning of a research project or to predict the proteins of active molecules in phenotypic trials. This was the origin of Chemotargets, in 2006, where currently three people work. “The students who were doing this could not publish anything, so we created this spin-off service”, explains the head of the group.

Chemotargets is still going and has quite a lot of work. They are currently designing the screening collection for the Karolinska Institute in Stockholm, with more than 10,000 molecules. They did something similar for the CRG, creating a list of small molecules that interact with proteins of interest to the researchers. Lately, they have also been contracted by the Swiss foundation ‘Medicines for Malaria Venture’ (MMV) to investigate the action of 400 antimalarials identified in phenotypic tests. “Chemotargets predicts targets for each molecule. Afterwards it is necessary to confirm the predictions experimentally, and this work is usually outsourced”.

It is, according to Mestres, the future of drug design. “Everything will be done from an office in a skyscraper in Manhattan or London, outsourcing molecule design to companies like Chemotargets, synthesis to a chemical company in China, and the trial to a pharmacology firm in India”, he predicts. “In fact it is already happening with the big pharmaceutical companies -they close their research centres, but do not abandon projects: they subcontract them out”.

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Tobacco Products..... A Desire for Unwanted Death

WHO Framework Convention on Tobacco Control (FCTC) defines tobacco product as completely or partially made from tobacco. Actually, these products are small, nicotine delivery devices which are categorized as follows:

Rolls: These are the products that are made by rolling tobacco in a wrapper (paper, tobacco leaf, tendu leaf etc.). This category includes Cigar, Cigarette, Bidi, Kretek, Roll-your-own cigarettes etc.Pipes: these are made by metals or glass and hold a small amount of tobacco at one end where it is ignited in order to inhale smoke from the other end. Water pipe (Hookah) is also included in this category.Snuffs: This category includes powdered tobacco specially made for inhaling through the nose.Chewable: these are made by processing the tobacco with lime and other flavoring substances for chewing or sucking purpose. Gutkha, Khaini etc. are the popular forms included in this category.

Cigarette is the most popular form, of all above mentioned products, worldwide. However in India, Bidis constitute more than 50% of total tobacco consumption. Bidis out sale cigarettes by 8/1. Bidis are made by rolling crude, unprocessed tobacco in tendu or tamburni leaf that gives it peculiar taste and a disguising natural look. Various surveys indicate that natural appearance is one of the major reasons for consumption of this tiny Indian cigarette among a large fraction of population. Kreteks are manufactured in Indonesia and mainly contain cloves along with tobacco. Cigar is made by rolling the tobacco in a tobacco leaf itself.

Tobacco product manufacturers are focusing on allurement of the tobacco users by changing the information about their products to more appealing with a safety point of view. Mild/low tar cigarettes or herbal cigarettes are good examples of that misleading, though effective, way of marketing the very same lethal product.

Manufacturers put their business ahead of public health despite having undisputed data on toxic effects of tobacco. They are very much aware about the nature of highly addictive component of tobacco that is Nicotine. Once you start getting a high with these products you become addicted to it with an alarmingly fast rate. This starting point is what manufacturers keep in mind when they launch a product in the market. Their prime target is young population as they can pay money for these nicotine delivery devices for an expected longer period.

Interesting fact is that all types of tobacco products are consumed for nicotine only, which has pharmacological activities. It is the only component that has stimulatory effects on nervous system. However, people might not be aware about those more than 4,000 chemicals that are released when a cigarette is smoked, or those cancer causing agents (around 100) present in all types of tobacco either smoked or smoke less.

Is it perceptible to get yourself exposed to highly noxious agents just for a single stimulatory one? Which itself is causing various kinds of debilities. Cigarettes are known to cause a great number of morbidity and mortality by developing cardiovascular diseases (CVDs), Lung Inflammatory diseases (Chronic Obstructive Pulmonary Disease, Bronchitis, Pulmonary Fibrosis, Asthma, Emphysema), Lung cancer and cancers of other organs. If, on a crude level, we combine the number of deaths caused by cigarettes, it can outnumber the deaths caused by other reasons.

   It is a preventable cause of such kind of deaths and we can avoid this danger to our lives. We just need to be aware about the toxic manifestations of tobacco products and the misleading promotion of these products by manufacturers.

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Parkinson's Disease Drugs

Point: Parkinson’s Disease is due to loss of dopaminergic neurons with an excess of cholinergic activity resulting. The goal of therapy is to increase CNS dopaminergic activity. Dopamine can’t cross the BBB until it reacts with tyrosine to form Levodopa. Levodopa is administered with other  agents (illustrated below) to prevent its degradation and improve its bioavailability.

Visual Aid: The picture helps  demonstrate the agents administered to improve dopamine delivery. Think of the BBB as the front door to the house (brain). Notice the stop sign turning dopamine away as it tries to enter. Outside the front door  there is a CARport with a DOBerman pinscher (Carbidopa). It scares off DOPA-decarboxylase and protects dopamine from degradation in the periphery. Also notice that the COMeT monster (COMT) is kept at bay by AL CAPONE (Tolcapone) who prevents COMT from degrading levodopa. Once in the CNS, levodopa is converted to dopamine. Officer SLY GLEEN (Selegiline) prevents MAO-B from degrading dopamine in the CNS thereby increasing its bioavailability.

Summary of drugs and their target:

Carbidopa-DOPA-decarboxylase
Tolcapone-COMT
Selegiline-MAO-B

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Muscarinic Receptors: Blood Vessels, Sweat*, and Tears**

Sit back and relax after a meal, recline and let your heart slow down, feel the warmth of your extremities…and secrete those fluids!

Ewwwwww…secretions!!  Diaphoresis, urination, vasodilation, lactation, and all kinds sweaty gooey things coming out and doing their thing!  In a very crude and stunted way, this is a main function of the parasympathetic nervous system. 

Muscarinic receptors are usually what we are talking about when we refer to anything “cholinergic”.  This is because their function works to balance the agonism of adrenergic (sympathomimetic!) receptors, thus allowing our body to essentially work “normally”.  So if you remember nothing else at all about muscarinic agonists (or “cholinergic drugs”), do remember the words REST and WET.  Now, to delve into more detail.  Woot!

There are 5 subtypes of muscarinic receptor, and they are all G Protein Coupled Receptors (if you don’t know what I’m talking about see “Our Friends the Receptors” in the basic pharmacology section).  Let’s make that easier and cut out the last two, because they are mostly in the CNS and the jury is still out on what exactly they do.  Actually, the jury is still out on almost every receptor type, but researchers have dedicated their work to studying them and make new discoveries every day!

Anyway, for our purposes there are 3 muscarinic subtypes: M1, M2, and M3.  I recommend remembering them as head, heart, and trunk.  While not entirely encompassing, it’s a start!

1.  M1:  Head.  These guys are in the CNS, on salivary glands, and surrounding your esophagus.  So they help regulate parasympathetic signals from the CNS, help to begin the digestive process (which starts with salivation!), signal the stomach to secrete digestive “juices”, and speed along signals to your organs.

2. M2:  Heart.  These are the important receptors that help regulate the conduction speed and contractile force of the atria in your heart.  They, too, are in the CNS and on the heart itself!  In the atria, they counter the effect of sympathetic stimulation by relaxing how hard those amazing atrial cardiomyocytes are pumping…Negative Inotropic! They also monitor signals from the CNS to ease up on the stimulation given to the AV node and slowing the conduction…Negative dromotropic!

3.  M3:  Trunk (and Eye…I know, this messes it up).  These guys are in the CNS, on the ciliary bodies in your eye (remember the little guys that control your pupil?), on your bronchioles, on your blood vessels, and all over your digestive system, from start to finish!  The most important thing to remember is that they help you digest by enhancing secretions from the salivary glands down to the colon.  Pretty amazing, huh?  In your lungs, they actually cause a bit of bronchoconstriction, which is why we have to be very careful using muscarinic agonists.  One of the coolest (IMHO) features of M3 receptors is how they affect the blood vessels.  I will nerd out on this in another post, so for now, just remember vasodilitation!  In the eyes, they cause myosis, or pupillary constriction.

Can you guess what the opthamologist drops in your eyes to make your pupils HUGE?

So there you go.  Secretions and rest (mostly). Here is a summary of what muscarinic receptors are in charge of:

1.  Secretions along the digestive tract

2. Reduced contractility and conduction of the atria

3. Vasodilitation

4. Myosis

5. Speeding along autonomic signals

6. Bronchoconstriction

There was a lot of information in this post!  I needed help too (one can only pack so much into the Rolodex), so I consulted the humongous bag of notes I have.  These notes came from two lecturers:

Robert Mouton at Concordia University, Austin, TX.  He is a cell biologist and incredible professor of pharmacology and physiology.

Dr. Sue Greenfield at Columbia University, New York, NY.  She is a nurse practitioner and PhD who has a vast clinical knowledge of drugs and has the amazing ability to put their use into simple terms!

*But…why didn’t we talk about sweat??  Well, as I was writing this, I realized that the simplest way to remember muscarinic drugs is by their parasympathetic activity.  So…diaphoresis is indeed a muscarinic activity, but it is modulated by the sympathetic nervous system.  I know, I know!!  It’s very complicated.  If I were you, I’d just remember that most things wet come from M receptors.

**But…why didn’t we talk about tears??  Lacrimation is one of those tricky things that happen via the CNS, more specifically the cranial nerves.  The “tear signal” from that good old cranial nerve VII is modulated by muscarinic receptors.  Again, don’t cry over it.  Just assume that wet is muscarinic and if you are very curious then look it up!

So I sacrificed complete accuracy for a good title.

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