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

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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)"