Classification of Coagulants

Introduction:

These are the substances which are helpful in the coagulation of the blood.

Bleeding can be caused by
1. Fibrinolytic states arising after prostatectomy or gastrointestinal surgery.
2. Hemophilia

In this case, hemophilia can be caused due to decrease of plasma coagulation factors such as factor VIII or IX.

Classification of Coagulants:
Protamine sulfate, Vitamin K, Aprotinin

Fibrinolytic inhibitors:
Aminocaproic acid, Tranexamic acid

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Atorvastatin

Salt form of Atorvastatin is used i.e. atorvastatin calcium. It belongs to a drug calss of Statins.

Structure:

Credit: Drugbank.ca

Mechanism of Action:
It works by inhibiting the enzyme HMG-CoA (Hydroxymethyl glutaryl Coenzyme-A) reductase, which is present in the tissues of the liver and is responsible for the production of cholesterol in the body via mevalonate pathway.

Pharmacokinetics:
Maximum plasma concentrations is found within 1 to 2 hours. Absorption increases with increasing the dose of the drug. The absolute bioavailability is found to be 14%.

Uses:

It is used for the treatment of Cholesterol i.e. hyperlipidemia, dyslipidemia and hypercholesterolemia. It is used to reduce the risk of myocardial infarction, stroke and angina.

Side effects:
It may cause diarrhea, apin in extremeties and urinary tract infections.

Brand Names:

• Atogal (Ingers (Czech Republic))
• Atorpic
• Cardyl (Pfizer (Spain))
• Faboxim (Fabop (Argentina))
• Hipolixan (Pasteur (Chile))
• Lipitor (Pfizer, Elea (Argentina))
• Lipotropic (Drugtech (Chile))
• Lipovastatinklonal (Klonal (Argentina))
• Liprimar (Pfizer (Hungary, Ukraine), Goedecke (Russia))
• Lowden (Saval (Chile))
• Normalip (Quesada (Argentina))
• Sincol (Indeco (Argentina))
• Sortis (Pfizer (Austria, Czech Republic, Germany, Hungary, Poland, Portugal, Switzerland), Godecke (Germany), Parke, Davis (Germany))
• Sotis
• Torvacard (Zentiva (Czech Republic, Hungary, Poland, Russia, Ukraine))
• Torvast (Pfizer (Italy))
• Totalip (Guidotti (Italy))
• Tozalip
• Tulip (Lek (Czech Republic, Russia), Wermar (Mexico), Sandoz (Poland, Ukraine), Pharmacia (Spain))
• Vastina (Penn (Argentina))
• Xanator (Sieger (Greece))
• Xarator (Parke, Davis (Italy))
• Xavator
• Zurinel (Prater (Chile))

It is also available in the combination with amlodipine with the name of "Caduet".

Serotonin receptor blockers

5-HT3 serotonin receptor blockers include Ondansetron and granisetron.

Action:
It blocks 5-HT3 receptors in the periphery (visceral afferent fibers) and in the brain (chemorecptor trigger zone).

Pharmacokinetics:
• Orally or IV
• Prevents vomiting in 50 – 60% of patients treated with Cisplatin.

Clinical Uses:
It is used as prophylaxis of nausea and vomiting associated with cancer chemotherapy.

Side affects:
Headache.

5-HT1c and 5-HT2 receptor blockers include Ketanserin.

Action:

This drug potently blocks vascular α1-adrenoceptors resulting in hypotensive action. It antagonizes platelet aggregation caused by serotonin by blocking 5-HT2 receptors on platelets.

Uses:
It is used in hypertension and vasospastic conditions.

Serotonin

It is also known as 5-Hydroxy Tryptamine. It is an indole-ethylamine.
Synthesis:

Mechanism of action:
Seven families of 5-HT receptor sub-types (subscripts 1-7) are there. They act through a variety of cell membrane receptors that include:
1. Six involved G-protein coupled receptors.
2. One uses ligand gated ion channels.

Action:
It acts as a neurotransmitter causing strong inhibitory effect. It acts on chemosensitive endings causing bradycardia and hypotension. It can cause aggregation of platelets. It may cause hyperventilation due to chemoreceptor reflex.

Clinical uses of serotonin analogues:
1. Buspirone (a 5-HT1A agonist) is used as non-benzodiazepine anxiolytic.
2. Sumatriptan can be used in acute migraine and cluster headache.
3. Appetite suppression appears to be caused by the agonist action at 5-HT2C receptors in the central nervous system.
4. Cisapride (a 5-HT4 agonist) was used for gastroesophageal reflux disease and motility disorders.

Ergot Alkaloids

Ergot alkaloids are produced by Claviceps Purpurea.


Pharmacokinetics of Ergot Alkaloids:
It is effective in 50% of patients. The oral dose is about 10 times larger than IM dose although gastrointestinal absorption can be increased by caffeine.

Action of Ergot alkaloids:
As described of ergotism, some of the naturally occurring alkaloids are powerful hallucinogens. They constrict most human blood vessels which may be due to partial agonist effects at α-adrenoceptors. In very low doses, ergot preparations can evoke rhythmic contraction and relaxation of the uterus.

Clinical uses of ergot alkaloids:
1. Migraine.
2. Hyperprolactinemia.

Increased serum level of prolactin (Anterior pituitary hormone).

3. Postpartum Haemorrhage.
Oxytocin is usually used to control postpartum haemorrhage but if this is insufficient than ergonovine maleate can be used.

4. Senile Cerebral Insufficiency.
Once the headache starts, Analgesics or NSAIDs can be helpful in reducing the pain such as aspirin, naproxen, propoxyphene and caffeine.

Dihydroergotamine

Derivative of ergotamine, IV use, ≈ sumatriptan, nausea may occur.