Classification of Anti-emetic drugs and laxatives

Q:1. How do you classify anti-emetic drugs?

Ans.

(A) Central Anti-emetics:

(1) Dopamine D2-Receptor Antagonist:
Haloperidol

(2) Sedative-Hypnotics:
Barbiturates, Benzodiazepines

(B) Central and Peripheral Antiemetics:
(1) D2 receptor antagonists:
Metacloperamide, Domperidone

(2) 5-HT3 receptor antagonists:
Ondansetron, Granisetron

(3) Anti-muscarinics:
Scopolamine, Atropine

(4) H1 receptor antagonists:
Ceclizine, Meclizine, Dimenhydrinate

(C) Peripheral antiemetics:
(1) Demulcents:
Gum acacia, Gum tragacanth

(2) Adsorbents:
Kaolin, Aluminium hydroxide

(3) Gastric mucosal anesthetics:
Chlorbutanol

Q: 2. How do you classify anti-diarrheals?

Ans.
(1) Gastrointestinal protectives and adsorbents:
Bismuth subsalicylate, Attapulgite, Pectin, Kaolin

(2) Astringents:
Drugs that have the ability of releasing tannic acid e.g. catechin

(3) Anti-motility drugs
(a) Antimuscarinics:
Mepenzolate, Propantheline, Atropine

(b) Opioid derivatives:
Codeine, Loperamide

Q: 3. How do you classify bulk laxatives?

Ans.
(1) Hydrophilic colloids:
Agar, Psyllium seeds and husks, Bran

(2) Osmotic laxatives:
(a) Saline Cathartics:
Magnesium hydroxide, Magnesium citrate

(b) Lactulose

Q: 4. How do you classify Stimulant laxatives?

Ans.
(1) Mild stimulants
Figs, Prunes, Castor oil

(2) Moderate stimulants:
Phenolphthalein, Bisacodyl

(3) Severe stimulants:
Croton oil, Colocynth,

Q:5. Classify stool softeners?

Ans.

(1) Surface active agents:
Docusate sodium, Poloxamers such as poloxalkol

(2) Mineral oils:
Liquid paraffin

Viva from out of course of Pharmacology:

Q: 6. What is the effect of Quranic Recitation on Alzheimer’s disease (A. D.) ?

Ans.

Name of Journal:
Journal of Neurobiology of Aging

Article title:
The effect of voice of Holy QURAN to decrease aggressive behaviors in people with A. D.

Researchers and Year:
Abdollahzadeh et al. in 2000

Effects:
They have found that Quranic recitation after a 4 week observation period causes a

1. Decrease in aggressive behavior of patients with alzheimer’s disease.

2. General increase in remembrance of past memories.

Introduction of Pharmacology and Pharmacokinetics

Q: 1. What is the definition of drug?
Ans. Any substance intended for use in the diagnosis, cure, treatment, prevention or mitigation of disease in man or some other living things.

Q:2. What is the meaning of generic?
Ans. Any item or product that is sold without using brand name.

Q: 3. What do you mean by brand name?
Ans. It is also called as trade name. It is that name of the drug given to a drug or chemical, for sale, by a manufacturer in agreement with the regulating agencies.

Q: 4. What is pharmacopoeia?
Ans. It is an official book containing an authoritative list of medicines, formulae of these drugs, and standards appropriate for their strength such as USP is the Pharmacopoeia for Britain.

Q: 5. What is the difference between pharmacy and pharmacology?
Ans. The art or science, practice or profession of preparing, preserving, compounding, and dispensing drugs used as medical treatments is pharmacy whereas pharmacology talks with special reference to the mechanism of action of the drug on a (particular) disease.

Q: 6. What do you mean by liberation? Liberation is the process of drug release from the dosage form in which it is corporated.

Q: 7. What do you mean by Absorption?

Q: 8. What do you mean by Distribution?

Q: 9. What do you mean by Metabolism?

Q: 10. What do you mean by Excretion?

Q: 11. Briefly tell about the LADME scheme?

Q: 12. What are the input processes?

Q: 13. What are the output processes?
Q: 14. Shortly tell the factors affecting absorption?

Ans. (A) Factors related to Drug:
(1) Chemical Nature
(2) Dosage Form
(3) Degree of ionization
(4) Lipid water partition coefficient
(B) Factors related to Patient:
(1) Route of Administration
(2) State of health of the absorbing surface
(3) Rate of general circulation

Q: 15. Shortly tell the factors affecting drug distribution?
Ans. (A) Physical and Chemical Factors
(1) Molecular weight
(2) Ionization
(B) Capillary permeability
(C) Binding of drugs to plasma proteins
(D) Tissue affinity
(E) Blood flow

Viva from out of course of Pharmacology (Remember Ayah Number, Surah Number and What the Ayah wants to tell):

Q: 16. What ALLAH has said about arguments (discussion or talking)?
Ans. ALLAH has said in Holy Qur'an:

"Call to the way of your Lord with wisdom and fair admonition, and argue with them in the kindest way. Your Lord knows best who is misguided from His way. And He knows best
who are guided. (125)
(Surah An-Nahl (The Bee), Surah # 16: Ayah #125)"

Ans. Distribution, Metabolism and Excretion are considered as the processes for output.

Ans. Liberation and absorption are considered as the processes for input of the drug.

Ans. It describes the pharmacokinetic processes and short form for Liberation, Absorption, Distribution, Metabolism and Excretion. After the drug is taken it is (1) liberated in the stomach, (2) absorbed by the stomach and intestine, (3) From there distributed in the blood (4) Metabolised in the liver and (5) Eliminated through the pulmonary, biliary or kidney processes.

Ans. It is the process of elimination of the drug either unchanged form or metabolites from the body.

Ans. It is the process in which drug is changed from one form to another which is comparatively easier to eliminate.

Ans. It is the process of diffusion or transfer of drugs from inside blood vessels to outside of blood vessels.

Ans. Absorption is the process of drug movement to the circulating blood from the administration site.

Ans.

Swine flu

Swine flu:
Swine flu was a respiratory disease of pigs. Its mutation in March 2009 has started the outbreak of new strain of Influenza virus (H1N1) that can cause infections in humans. 64 cases have been reported in United States in which 45 are only in New York to the date 28 April, 2009. (CDC)

Diagnosis and Treatment:
rRT-PCR Swine Flu Panel diagnostic test is used for the diagnosis of this virus. Relenza and Tamiflu antiviral products have been reported for the use against this virus. (Medline Plus)

Source:
Centers for Disease control and Prevention (CDC)

U. S. National Library of Medicine (Medline Plus)

Lectures on some Pharmacological Topics

1. Factors affecting drug distribution

2. G-Protein Receptor

3. G-Protein Receptor (Take II)

4. Diuretic action in Kidney

5. Agonists and Antagonists

6. Acid-Base Interaction

7. Inner workings of Enzyme Cytochrome P-450 2C9

8. Aspirin (Absorption and deprotonation)

9. Signal Transduction

Source:
University of Rhode Island

Parasympathomimetic Drugs

Q: 1. Classify parasympathomimetic drugs?
Ans:

(A)Direct acting:

(1)Muscarinic agonists:

(a)Choline Esters:

Bethanechol

(b)Alkaloids:

Muscarine, Pilocarpine, Oxotremorine

(2)Nicotinic agonists:

Alkaloids:

Nicotine, Lobeline

(3)Mixed agonists:

Choline esters:

Acetylcholine, Methacholine, Carbachol

(B)Indirect acting (Anti-Cholinesterase)

(1)Reversible:

(a)Quaternary alcohols:

Edrophonium

(b)Carbamate esters:

Neostigmine, Physostigmine, Ambenonium

(2)Irreversible:

Organophosphate compounds:

Echothiofate, Parathion, Melathoin

Q: 2. Classify Parasympatholytic drugs.

Ans.

(A)Anti-Muscarinic drugs:

(1)Natural alkaloids:

Atropine, Scopolamine (Hyoscine)

(2)Synthetic

(a)Mydriatic:

Homatropine, Eucatropine, Tropicamide

(b)Anti-Parkinsonism:

Benzhexol, Benztropine

(c)Anti-asthmatics:

Ipratropium

(d)Gastrointestinal and Genitourinary:

(i)Tertiary amines:

Pirenzepine, Dicyclomine, Oxybutynin

(ii)Quaternary amines:

Propantheline, Mepenzolate

(B)Anti-Nicotinic drugs:

(1)Ganglion blockers:

(a)Depolarizers:

Nicotine

(b)Competitive:

(i)Secondary amines:

Mecamylamine

(ii)Tertiary amines:

Pempidine

(iii)Quaternary amines:

Hexamethonium, Trimethaphan

(2)Neuromuscular blockers:

(a)Depolarizers:

Succinylcholine, Decamethonium

(b)Competitive:

Tubocurarine, Atracurium, Gallamine

(C)Cholinesterase regenerators:

Pralidoxime

Q: 3. What ALLAH has said about Seafood in Holy Qur’an?Ans: ALLAH has said in Holy Qur’an:“Anything you catch in the sea is lawful for you, and all food from it, for your enjoyment and that of travelers, but land game is forbidden for you while you are in the state of pilgrimage.So have fear of Allah, Him to Whom you will be gathered. (96)
(Surah Al-Ma’ida (The Table, The Table Spread), Surah # 5: Ayah # 96)”

Q: 4. What ALLAH has said about saying "Insha ALLAH"?
Ans:ALLAH has said in Holy Qur'an:

"Never say about anything, ‘I am doing that tomorrow,’(23) without adding ‘If Allah wills.’ Remember your Lord when you forget, and say, ‘Hopefully my Lord will guide me to something closer to right guidance than this.’(24)
(Surah Al-Kahf (The Cave), Surah # 18: Ayah # 23-24)"

Name of New Drugs approved in 2008

1. Almivopan (Entereg):It is used for the fast recovery of upper and lower GIT after resection surgery of small or large bowels.

2. Bendamustine Hydrochloride (Treanda):
It is an alkylating agent active against quiescent and dividing cells.

3. C1 inhibitor, Human (Cinryze):It works for complement and intrinsic coagulation pathways and resulates the fibrinolytic system.

4. Certolizumab Pegol (Cimzia):
It is an inhibitor of tumor necrosis factor alpha (TNF-alpha).

5. Ciclesonide (Alvesco):Maintenance therapy of asthma for adult patients.

6. Clevidipine (Cleviprex):A calcium channel blocker.

7. Difluprednate (Durezol):
To reduce inflammation and pain after ocular surgery.

8. Eltrombopag (Promacta):To treat increased risk of bleeding in patients of thrombocytopenia.

9. Etravirine (Intelence):It is used in combination of anti-retroviral therapy for HIV-1.

10. Fesoterodine Fumarate (Toviaz):
Treatment of overactive bladder.

11. Lacosamide (Vimpat):
For partial onset seizure in epileptic patients.

12. Methylnaltrexone Bromide (Relistor):
For treating opioid induced constipation.

13. Plerixafor (Mozobil):
For non-Hodgkin's lymphoma and multiple myeloma.

14. Romiplostim (Nplate):
Increases platelet production in bone marrow.

15. Rufinamide (Banzel):
For patients of epilepsy.

16. Somatropin (Accretropin):
For pediatric patients who are showing growth failure due to inappropriate Growth Hormone secretion.

17. Tetrabenazine (Xenazine):
For the treatment of chorea from Huntington's disease.

References:
Erin Sears and Nicole Ladd, (2009), 2008 New drug approvals, Proceedings, 22 (2), 168-174

Free Books

Lots of Downloadable and Online books for free

Vaccine designed to lower blood pressure

CYT006-AngQb is a vaccine against angiotensin II. The 300 microgram dose of this vaccine has the ability of reducing the blood pressure in pateints of mild to moderate blood pressure. Moreover, it did not cause any serious side effects. (Tissot, A. C., et al.)

References:
Tissot, A. C., et al. (2008). Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. The Lancet, 371 (9615), 821-827

Important Websites

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Articles for Stress management, Memory improvement, Time management and many more.

Science Related:
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Search Engines:
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Sympathetic and Parasympathetic

Q: 1. How norepinephrine (neurotransmitter) is synthesized in the body?
Ans. Norepinephrine is found at most of the sympathetic neuro-effector synapses. It is synthesized by Tyrosine.
1) Tyrosine is hydroxylated to DOPA by the enzyme tyrosine hydroxylase
2) DOPA is decarboxylated to dopamine by the use of DOPA decarboxylase
3) Dopamine is hydroxylated to norepinephrine
4) Norepinephrine is methylated to norepinephrine.

Q: 2. How acetylcholine (neurotransmitter) is synthesized in the body?

Ans. It is stored in granules of synaptic vesicles. It is synthesized by Choline. Choline reacts with acetyl-CoA in the presence of choline acetyltransferase to form acetylcholine.

Q: 3. What is the structure of acetylcholine?

Ans.

Q: 4. What is the structure of Norepinephrine?

Ans.

Q: 5. Give classification of sympathomimetics.

Ans.

1) Alpha Selective:

a) Alpha-1 selective:

Phenylephrine, Cirazoline, Methoxamine

b) Alpha-2 selective:

Clonidine, Methylnorepinephrine, Guanabenz, Guanfacine

2) Beta selective:

a) Beta-1 selective:

Dobutamine, Prenalteral

b) Beta-2 selective:

Terbutaline, Albuterol, Salmeterol, Metaproterenol

3) Alpha and Beta Non-selective:

Epinephrine, Norepinephrine

4) Dopamine Selective:

Dopamine

Q: 6. Give classification of Sympatholytics.

Ans.

1) Alpha Adrenoceptor Antagonists:

a) Alpha-1 Antagonists:

Prazosin, Terazosin, Indoramin

b) Alpha-2 Antagonists:

Tolazoline, Yohimbine, Rauwolscine

c) Alpha-1 and -2 Antagonists:

Phentolamine, Ergot derivatives e.g. ergotamine, dihydroergotamine

2) Beta-Adrenoceptor Antagonists:

a) Beta-1 Antagonists:

Metoprolol, Atenolol, Alprenolol, Esmolol

b) Beta-2 Antagonists:

Butoxamine

c) Beta-1 and -2 Antagonists:

Propranolol, Sotalol, Timolol, Pindolol

3) Mixed (Alpha and Beta) Adrenoceptor Antagonists:

Labetolol

Viva from out of Course of Pharmacology (Memorise the Surah Number, Ayah Number and What the Ayah wants to tell?):

Q: 7. What ALLAH has ordered about Eyes and Chastity?

Ans. ALLAH has mentioned in Holy Qur’an:

“Say to the believers that they should lower their eyes and guard their chastity. That is purer
for them. Allah is aware of what they do. (30)

Say to the believing women that they should lower their eyes and guard their chastity and not display their adornments–except for what normally shows–and draw their head-coverings across their breasts. They should only display their adornments to their husbands or their fathers or their husbands’ fathers, or their sons or their husbands’ sons or their brothers or their brothers’ sons or their sisters’ sons or their women or those they own as slaves or their male attendants who have no sexual desire or children who still have no awareness of women’s private parts. Nor should they stamp their feet so that their hidden ornaments are known. Turn to Allah every one of you, believers, so that hopefully you will have success. (31)

(Surah Al Nur (The light), Surah # 24: Ayah #30-31)”

Introductory viva to some Pharmacological terms

Q: 1. What do you mean by placebo?
Ans. It is an inactive compound used for the patient’s satisfaction about the use of drug for the treatment of a (particular) disease.

Q: 2. What do you mean by loading dose (LD)?
Ans. It is the amount of dose of a drug that will produce the required therapeutic effect by increasing the concentration of drug in plasma upto target concentration.

Q: 3. What is the formula for calculating the loading dose?
Ans. It is calculated by LD = Vd x TC

Where,
Vd = Volume of distribution
TC = Target concentration

Q: 4. What do you know about volume of distribution?
Ans. It is also known as “Apparent volume of distribution”. It is the volume of the fluid through which the drug is normally distributed in the body.

It can be calculated by
Vd = Total amount of drug in the body / Drug plasma concentration
= D / Co

Q: 5. What is the meaning of high value of volume of distribution?
Ans. It shows the high lipophilicity.

Q: 6. What are the formulae for the calculating the dosage for children?
Ans.
Young’s formula:
Child dose = Adult dose x Age in years / Age + 12

Dilling’s formula:
Child dose = Adult dose x Age in years / 20

Clark’s formula:
Child dose = Adult dose x Weight in pounds / 150

Q: 7. What are the different factors important in Drug distribution?
Ans.

1) Physical and Chemical characteristics of drug
a)                                       Molecular weight
          Ionization
2) Capillary permeability
3) Blood flow
4) Binding of drugs to plasma proteins
5) Tissue affinity

Q: 8. What do you mean by partial agonist and give example?
Ans. A partial agonist is that which activates a cell receptor, but does not produce as much of a physiological activity as does a natural full agonist e.g. pindolol at beta-adrenoceptors.

Q: 9. What do you know about inverse agonists and give example?
Ans. An inverse agonist binds to the receptors and produces opposite effects to those of agonists e.g. beta-carbolines on benzodiazepine receptors.

Q: 10. What is the difference between antagonist and inverse agonist?
Ans. Antagonists bind to the receptors without activating the receptors whereas inverse agonists bind to the receptors and produce exactly opposite effects to those of agonists.

Q: 11. What are the different types of antagonists?
Ans.
1) Pharmacological antagonist:
That antagonist which bind to receptors and stop the agonists from interacting with receptors to cause an activity.

2) Physiological antagonist:
The drugs, when act on different receptors and produce exactly opposite effects from one another, are said to be physiological antagonist.

3) Chemical antagonist:
Two drugs when combine with one another form an inactive compound and in the whole process no receptors are involved.

Q: 12. Give an example of Physiological antagonist.
Ans. Drugs acting on adrenergic receptors and cholinergic receptors are physiological antagonists.

Q: 13. Give an example of Chemical antagonist.
Ans. Protamine and Heparin.

Q: 14. What do you mean by synergistic effect?
Ans. It is a biological response to exposure to two or more than two drugs, which is more than the sum of the effects of the individual drugs. (can be symbolized as 1+1 = 3)

Q: 15. What do you know about potentiation?
Ans. A drug that normally lacks any effect of its own will increase the effect of another drug. (can be symbolized as 0 + 2 = 3)

Q: 16. What do you know about therapeutic index (TI)?
Ans. It is the ratio of median lethal dose of a drug to its median effective dose:

Therapeutic index = Median lethal dose/Median effective dose.
TI = LD50/ED50

Where,
median = the value or amount below which 50 % of the cases fall

Viva From Out of course of Pharmacology (Memorise the Surah Number, Ayah Number and What the Ayah wants to tell):

Q: 17. What ALLAH has said about hardwork in Holy Qur'an?

Ans: ALLAH has mentioned in Holy Qur'an:
" For truly with hardship comes ease; (5) truly with hardship comes ease. (6) Therefore, when thou art free (from thine immediate task), still labour hard, (7) And to thy Lord turn (all) thy attention. (8)

(Surah Al-Sharh or Al-Inshirah (The Expansion of the Breast), Surah # 94: Ayah # 5-8)"

Q: 18. What ALLAH has said about raising voices?

Ans. ALLAH has mentioned in Holy Qur'an:
"(Luqman said to his son,) ‘Be moderate in your tread and lower your voice. The most hateful of voices is the donkey’s bray.’ (19)

(Surah Luqman (Luqman), Surah # 31: Ayah # 19)"

Basic Pharmacology (Viva Preparation)

Q: 1. What is the difference between receptor and neurotransmitter?

Ans. Receptor is a structural protein molecule on the cell surface or within the cytoplasm that binds to a specific factor, such as a hormone, antigen, or neurotransmitter. Whereas neurotransmitters are the chemicals that carry messages between different nerve cells or between nerve cell and muscles.

Q: 2. What are adrenergic receptors?

Ans. These are reactive components of effector tissues. These receptors are activated by norepinephrine and/or epinephrine and by various adrenergic drugs. On activation, it results in a change of effector tissue function e.g. relaxation of bronchial muscles and contraction of arteriolar muscles.

Q: 3. What do you know about G proteins?

Ans. These are intracellular membrane associated proteins stimulated by various receptors such as beta adrenergic receptors. They work as second messengers. Due to high affinity for guanine nucleotides, they are termed as G proteins.

Q: 4. Name some of the cholinergic antagonists.

Ans. Atropine, Botulinum toxin, Scopolamine, Tubocurarine, Erythroidin (nicotinic cholinergic antagonist)

Q: 5. Name some of the transmitter substances.

Ans. Acetylcholine, Norepinephrine, Dopamine, Serotonin, Gamma aminobutyric acid (GABA), Glutamate

Q: 6. What are the main types of receptors?

Ans. Four main types of receptors: 1) Ligand gated channels 2) G protein coupled receptors 3) Nuclear receptors 4) Kinase linked receptors

Q:7. What are ligand gated channels?

Ans. These are made up of subunits of protein that form a central core.

Q: 8. What are the main types of ligand gated channels?

Ans. 1) Nicotinic receptor 2) GABA receptor

Q: 9. What do you know about G protein coupled receptors?

Ans. They form a family of receptors with seven membrane spanning helices. They are associated with physiological responses by second messengers.

Q:10. What do you know about nuclear receptors?

Ans. They are used to regulate transcription and protein synthesis. These receptors for steroid hormones and thyroid hormones are located in the cell nucleus.

Q:11. What are kinase linked receptors?

Ans. These are surface receptors that have intrinsic tyrosine kinase activity. They include receptors for cytokines, insulin and growth factors.

Q: 12. What do you mean by second messenger?

Ans. An intermediate molecule produced as a result of hormone receptor interaction e.g. adenosine 3c,5c-cyclic monophosphate, Calcium and Inositide.

Q: 13. What do you know about baroreceptor?

Ans. Nerve endings those are sensitive to blood pressure changes.

Q: 14. What is pharmacology?

Ans. It is the science of drugs including their origin or sources, chemistry, production, composition, pharmacokinetics, therapeutic use, and toxicology.

Q: 15. What is the difference between pharmacy and pharmacology?

Ans. The art or science, practice or profession of preparing, preserving, compounding, and dispensing drugs used as medical treatments is pharmacy whereas pharmacology talks with special reference to the mechanism of action of the drug on a (particular) disease.

JNJ 7777120

Its full name is 1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine . (Thurmond et al.) It is developed by Johnson and Johnson Pharmaceutical R & D as an anti-inflammatory agent. It is better in the treatment of itching. (wikipedia.com, 2009)

It blocks the chemotaxis induced by histamine in mouse. (Thurmond et al.)

References:
1. JNJ 7777120 (2009). wikipedia, retrieved on 03. 03. 2009 from http://en.wikipedia.org/wiki/JNJ_7777120

2. Thurmond, R. L., Desai, P. J., Dunford, P. J., Leung, W. P. F., Hofstra, C. L., Jiang, W., Nguyen, S., Riley, J. P., Sun, S., Williams, K. N., Edwards, J. P., and Karlsson, L., (2004). Journal of Pharmacology And Experimental Therapeutics, 404-413.

SRT 1720

Action:
It is an activator of small molecule SIRT 1 (which is an NAD + dependent deacetylase and has the ability of removing acetyl groups from a variey of compounds). It has similar activity as that of resveratrol but is 1000 times more active than resveratrol. (wikipedia, 2009)

Uses:
It is under investigation for the treatment of obesity and diabetes.(wikipedia, 2009)

References:
Wikipedia, (2009). SRT 1720. Retreived on 27, February 2009 from http://en.wikipedia.org/wiki/SRT1720

Resveratrol

Its other name is 3,5,4′-trihydrostilbene. (1) Resveratrol is one the naturally occuring phytoalexin compound. This is found in grapes.

Actions:
Resveratrol has been found to increase the life span of yeast and worms. It is thought that it stimulates a deacetylase enzyme namely SIRT1. This enzyme have the ability of regulatin several transcriptional factors and enzymes which are responsible for the nutritional availability. (Mitchell D Knutson et al.)

Therapeutic uses:
It has found practical uses as an anti-cancer agent for breast cancer in both hormone dependent and hormone independent. (Hiroyuki Nakagawa et al.)
It has also been found that it has the ability of protecting against inflammatory arthritis. (N. Elmali et al.)

References:
(1) Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 2008, page 1684

Hiroyuki Nakagawa, Yasuhiko Kiyozuka, Yoshiko Uemura, Hideto Senzaki, Nobuaki Shikata, Koshiro Hioki and Airo Tsubura, 2001, Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator, Journal of Cancer Research and Clinical Oncology, Volume 127, 258-264

Mitchell D Knutson, Christiaan Leeuwenburgh, 2008, Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases, Nutrition reviews, volume 66, 591-596

N. Elmali , O. Baysal , A. Harma , I. Esenkaya and B. Mizrak, 2006, Effects of Resveratrol in Inflammatory Arthritis , Inflammation, volume 30, 1-6

Further reading:
A Cardiologist's Guide to Anti-Aging, Antioxidants & Resveratrol by M.D. Dr. William S. Gruss

Resveratrol in Health and Disease (Oxidative Stress and Disease) by Bharat B. Aggarwal and Shishir Shishodia

Resveratrol and Human Health by Debasis Bagchi

Effects of Naturally Occurring Compounds on HumanCancer Cells: Anticancer Activity of Resveratrol, Piceatannol,Gallic Acid & their Analogs by Philipp Saiko

Natural products:
Source Naturals Resveratrol, Tablets, 60 tablets (Read Nutrition facts)

Copyright (c), 2009, http://jeepakistan.blogspot.com

Tigliane

Structure of Tigliane:General Characteristics:
It has almost same system as that of daphnanes i.e. tricyclo tetradecane ring system. It has additional gem-dimethyl cyclopropane appended to the 6-membered ring. (Its most) famous (part) is Phorbol, which was named in about 25 BC by King Juba II of Mauritania. Wender, on one hand, and Cha, on the other hand, has completed its synthesis.

Action:
It primarily acts on protein kinase C (PKC, which is important for regulating cellular growth and differentiation).

Isolation of tiglianes:
It has been isolated from Euphorbia and Thymelaceae as esters.

Therapeutic uses:
It was primarily used for tumors, parasites, migraines, venereal diseases and as purgatives.
It has been found that C12 deoxy derivative blocks formation of the tumor.

Adverse effects:
Its most important tumor promoting example is Tetradodecanoyl phorbol acetate.

Further reading:
Naturally Occurring Phorbol Esters by Evans

Terbutaline

It is a member of the family of medications which is in use for
1. stopping the contractions of preterm labor (tocolytics)
2. asthma

It is a beta 2 adrenergic receptor agonist.

Pharmacokinetics:
The inhaled form of terbutaline starts working in 10-15 minutes and lasts for about 5-6 hours.

Side effects:
It may cause tachycardia, pulmonary edema, hypokalemia and in fetus it may also cause hypoglycemia.

Further reading:
Beta 2-agonists in Asthma Treatment (Lung Biology in Health and Disease) by Romain Pauwels and Paul O. Byrne

Fragmentation

In cell biology, fragmentation is the breaking apart of cells or cell organelles into smaller parts. Fragmentation may serve as a normal function for the cell, but may also be the result of a disorder.

Functions of cell fragmentation include:
Reproduction
Apoptosis

Disorders:
Microangiopathic diseases results in red blood cell fragmentation into schistocytes.

Further reading:
Biology: A Self-Teaching Guide, 2nd edition by Steven Daniel Garber

Lorentz force law

It is equal to a force on a point charge due to electromagnetic fields.

It is given by the following equation in terms of electromagnetic fields:

F = q [E + (v x B)]

where,
F = force (in newtons)
E = electric field (in volts per meter)
B= magnetic field (in teslas)
q = electric charge of the particle (in coulombs)
v = instantaneous velocity of the particle (in meters per second)

Dissociation

It is a process in which there is separation of ionic compounds into smaller parts (molecules or ions).

It is usually a reversible process.

It is the opposite of association and recombination.

pKa

pKa is an acid dissociation constant.

Definition:
It is the negative logarithm of the acid dissociation constant i.e., Ka

Equation:
Its equation is:
pKa = -log10 Ka

Importance:
1. It shows the extent of dissociation. As the value of pKa increases, the extent of dissociation will decrease.
2. It has the ability of telling the acidic or basic properties of a substance.

Mass analyzer

Mass analyzer is a technique used for the separation of the ions according to mass/charge ratio.

Equation for the Mass analyzer:

1. Lorentz force law:
F=Q(E+v*B)

Where
F = force applied to the ion
Q = ion charge
E = electric field
v*B = the vector cross product of the ion velocity and the magnetic field

2. Newton's second law of motion:
F=ma

Where
F = force applied to the ion
m = mass of the ion
a = acceleration

By combining the above two equations, we get:

Q(E+v*B) = ma

=> E+v*B = a(m/Q)

where m/Q denotes mass to charge ratio.

Types of mass analyzers:

There are various types of mass analyzers:

1. Scanning Mass Analyzers

2. TOF - Mass Analyzers

3. Trapped Ion Mass Analyzers

Ion Source

It is a type of an electro-magnetic instrument, primarily used to create charged particles.

It is used in ion implanters, ione engines, mass spectrometersand particle accelerators.

Mass spectrometry

Introduction:
Mass spectrometry is a technique used in analysis.

It is a form of spectrometry in which, usually, high energy electrons are bombarded onto a sample and this produces charged particles of the parent sample; these ions are then focused by electrostatic and magnetic fields to produce a spectrum of the charged fragments which is helpful in establishing the ratio of charged to mass of the particles.

Essential parts:
The design of a mass spectrometer has three essential modules:

1. An ion source:
This transforms the molecules in a sample into ionized fragments.

2. A mass analyzer:
This causes the sorting of the ions by their masses by applying electric and magnetic fields

3. A detector:
This measures the value of some indicator quantity and thus provides data for calculating the abundances of each ion fragment present.

Uses and applications:
The technique has both qualitative and quantitative uses, such as

1. Identifying unknown compounds,
2. Determining the isotopic composition of elements in a compound,
3. Determining the structure of a compound by observing its fragmentation. Its use is there in the identification and structural determination of the flavonoid glycosides. ( Maciej Stobiecki)
4. Quantifying the amount of a compound in a sample,
5. Studying the fundamentals of gas phase ion chemistry
6. Determining other physical, chemical, or biological properties of compounds.

It is now applicable in the field of proteomics. (Christine C. Wu et al.)

References:
Christine C. Wu and John R. Yates III, The application of mass spectrometry to membrane proteomics, Nature Biotechnology 21, 262 - 267

Maciej Stobiecki, 2000, Application of mass spectrometry for identification and structural studies of flavonoid glycosides , Phytochemistry, 54, 237-256

Further reading:
Mass Spectrometry: Principles and Applications by Edmond de Hoffman and Vincent Stroobant

Mass Spectrometry: A Textbook by Jürgen H. Gross

Metabolism

Metabolism is essential for maintaining life by certain chemical reactions. In the result of these reactions and phenomenon, organisms develop ability to grow and reproduce, while maintaining their structures and adopt itself according to the environment.

Types of Metabolism:
There are two types of metabolism:
1. Catabolism:
Catabolism catabolyze or breaks the organic matter and produce heat or energy as a result.

2. Anabolism
Anabolism utilize the energy produced by the catabolism of organic matter.

Factors important in metabolism:
1. Chemicals
Chemicals are important for the metabolic pathways.

2. Enzymes
These enzymes catalyze a reaction involving the chemicals. They make the environment favourable for a reaction to proceed.

Distribution

Distribution in pharmacology is a branch of pharmacokinetics which describes the reversible transfer of drug from one location to another within the body. It is the movement of molecules of drugs from blood into general body (compartments) and peripheral tissues.

The distribution of a drug between tissues is dependent on permeability between tissues (between blood and tissues in particular), blood flow and perfusion rate of the tissue and the ability of the drug to bind plasma proteins and tissue. pH parturition plays a major role as well.

Once a drug enters into systemic circulation by absorption or direct administration, A drug has to be distributed into interstitial and intracellular fluids.

The lipid solubility, pH of compartment, extent of binding with plasma protein and tissue proteins, cardiac output, regional blood flow, capillary permeability are associated for distribution of the drug through tissues.The drug is easily distributed in highly perfused organs like liver, heart, kidney etc in large quantities & in small quantities it is distributed in low perfused organs like muscle, fat, peripheral organs etc. The drug can be moved from the plasma to the tissue until the equilibrium is established (for unbound drug present in plasma).

The volume of distribution (VD) of a drug is a property that quantifies the extent of distribution.

Further reading:
Comparative Pharmacokinetics: Principles, Techniques, and Applications by Jim E. Riviere

Pharmacokinetics : Principles and Applications by Mehdi Boroujerdi

Clinical Pharmacokinetics Handbook by Larry Bauer

Pharmacokinetics

Pharmacokinetics (in Greek: “pharmacon” meaning drug and “kinetikos” meaning putting in motion, the study of time dependency; sometimes abbreviated as “PK”) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. It is the study of what the body does to a drug.
In practice, this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism, such as nutrients, metabolites, hormones, toxins, etc.
Pharmacokinetics is often studied in conjunction with pharmacodynamics.

Pharmacokinetics includes the study of the mechanisms of absorption and distribution of an administered drug, the rate at which a drug action begins and the duration of the effect, the chemical changes of the substance in the body (e.g. by enzymes) and the effects and routes of excretion of the metabolites of the drug.

ADME
Pharmacokinetics is divided into several areas which includes the extent and rate of Absorption, Distribution, Metabolism and Excretion. This is commonly referred to as the ADME scheme. However recent understanding about the drug-body interactions brought about the inclusion of new term Liberation. Now Pharmacokinetics can be better described as LADME.

Liberation is the process of release of drug from the formulation.

Absorption is the process of a substance entering the body.

Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body.

Metabolism is the irreversible transformation of parent compounds into daughter metabolites.

Excretion is the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in a tissue in the body.

Pharmacokinetics describes how the body affects a specific drug after administration. Pharmacokinetic properties of drugs may be affected by elements such as the site of administration and the concentration in which the drug is administered. These may affect the absorption rate.

AnalysisPharmacokinetic analysis is performed by noncompartmental (model independent) or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Compartment-free methods are often more versatile in that they do not assume any specific compartmental model and produce accurate results also acceptable for bioequivalence studies.


Noncompartmental analysis
Noncompartmental PK analysis is highly dependent on estimation of total drug exposure. Total drug exposure is most often estimated by Area Under the Curve methods, with the trapezoidal rule (numerical differential equations) the most common area estimation method. Due to the dependence of the length of 'x' in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer your time points are, the closer the trapezoids are to the actual shape of the concentration-time curve.

Compartmental analysis
Compartmental PK analysis uses kinetic models to describe and predict the concentration-time curve. PK compartmental models are often similar to kinetic models used in other scientific disciplines such as chemical kinetics and thermodynamics. The advantage of compartmental to some noncompartmental analysis is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper model. Compartment-free modeling based on curve stripping does not suffer this limitation. "PK Solutions" is an easy to use, industry standard software that produces both noncompartmental as well as compartment-free results suitable for research and education. The simplest PK compartmental model is the one-compartmental PK model with IV bolus administration and first-order elimination. The most complex PK models (called PBPK models) rely on the use of physiological information to ease development and validation.

Further reading:
Pharmacokinetics Made Easy by Donald Birkett

Clinical Pharmacokinetics: Concepts and Applications by Malcolm Rowland and Thomas N. Tozer

Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring by William E. Evans, Leslie M. Shaw, Jerome J. Schentag and Michael E. Burton

Absorption

In pharmacology (and more specifically pharmacokinetics), absorption is the movement of a drug into the bloodstream.
Absorption involves several phases. First, the drug needs to be administered via some route of administration (oral, via the skin, etc.) and in a specific dosage form such as a tablet, capsule, and so on.
In other situations, such as intravenous therapy, intramuscular injection, enteral nutrition and others, absorption is even more straight-forward and there is less variability in absorption and bioavailability is often near 100%.
Absorption is a primary focus in drug development and medicinal chemistry, since the drug must be absorbed before any medicinal effects can take place. Moreover, the drug's pharmacokinetic profile can be easily and significantly changed by adjusting factors that affect absorption.
The Processes by which the concentration of the drug at any moment and in any region can be determined is done by translocation of drug molecule. The drug is translocated in the body by bulk flow and diffusion. If the drugs chemically differ, still the transfer by bulk flow can occur by the same mechanism but if the drugs are moving by diffusion, it means that their movement is markedly different. The transfer of a drug is highly dependent on its solubility in either lipid or water.
For movement of the drug from the GIT to the system the sink condition is playing a vital role. Sink condition means, the drug is always in circulation due to blood circulation. So, the conc. of drug is not reaching at equilibrium. Thus, the drug can be diffused due to no equilibrium state.
The smaller molecules can move faster than larger ones.

Dissolution
In the most standard situation, a tablet is ingested and passes through the esophagus to the stomach. Because the stomach is an aqueous environment, this is the first place where a tablet will dissolve.
The rate of dissolution is a key target for controlling the duration of a drug's effect, and as such, several dosage forms that contain the same active ingredient may be available, differing only in the rate of dissolution. If a drug is supplied in a form that is not readily dissolved, the drug may be released more gradually over time with a longer duration of action. Having a longer duration of action may improve compliance since the medication will not have to be taken as often. Additionally, slow-release dosage forms may maintain concentrations within an acceptable therapeutic range over a long period of time, as opposed to quick-release dosage forms which may result in sharper peaks and troughs in serum concentrations.
The rate of dissolution is described by the Noyes-Whitney equation as shown below:

Where:
dW/dt is the rate of dissolution.

A is the surface area of the solid.
C is the concentration of the solid in the bulk dissolution medium.
Cs is the concentration of the solid in the diffusion layer surrounding the solid.
D is the diffusion coefficient.
L is the diffusion layer thickness.

As can be inferred by the Noyes-Whitney equation, the rate of dissolution may be modified primarily by altering the surface area of the solid. The surface area may be adjusted by altering the particle size (e.g. micronization). The rate of dissolution may also be altered by choosing a suitable polymorph of a compound. Specifically, cystalline forms dissolve slower than amorphous forms.
Also, coatings on a tablet or a pellet may act a barrier to reduce the rate of dissolution. Coating may also be used to modify where dissolution takes place. For example, enteric coatings may be applied to a drug, so that the coating only dissolves in the basic environment of the intestines. This will prevent release of the drug before reaching the intestines.
Since solutions are already dissolved, they do not need to undergo dissolution before being absorbed.

IonizationThe gastrointestinal tract is lined with epithelial cells. Drugs must pass through these cells in order to be absorbed into the circulatory system. One particular cellular barrier that may prevent absorption of a given drug is the cell membrane. Cell membranes are essentially lipid bilayers which form a semipermeable membrane. Pure lipid bilayers are generally permeable only to small, uncharged solutes. Hence, whether or not a molecule is ionized will affect its absorption, since ionic molecules are considered charged molecules by definition.
The Henderson-Hasselbalch equation offers a way to determine the proportion of a substance that is ionized at a given pH. In the stomach, drugs that are weak acids (such as aspirin) will be present mainly in their non-ionic form, and weak bases will be in their ionic form. Since non-ionic species diffuse more readily through cell membranes, weak acids will have a higher absorption in the highly-acidic stomach.
However, the reverse is true in the basic environment of the intestines-- weak bases (such as caffeine) will diffuse more readily since they will be non-ionic.
This aspect of absorption has been targeted by medicinal chemistry. For example, a suitable analog may be chosen so that the drug is more likely to be in a non-ionic form. Also, prodrugs of a compound may be developed by medicinal chemists-- these chemical variants may be more readily absorbed and then metabolized by the body into the active compound. However, changing the structure of a molecule is less predictable than altering dissolution properties, since changes in chemical structure may affect the pharmacodynamic properties of a drug.

Other factors
factors which affecting bioactivity, resonance, inductive effect, isosterism, bio-isosterism, spatial consideration.

Further reading:
Pharmacokinetics Made Easy, Revised by Donald Birkett

Basic Clinical Pharmacokinetics (Basic Clinical Pharmacokinetics (Winter)) by Michael E. Winter
Applied Clinical Pharmacokinetics by Larry Bauer