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

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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