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

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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)”