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Pharmacology

Antianginal Drugs

Organic Nitrates :
Short acting: Glyceryl trinitrate (Nitroglycerine, GTN), Amyl Nitrate
Long Acting: Isosrbide dinitrate (Short acting by sublingual route), Erythrityl tetranitrate, penta erythrityl tetranitrate

Beta-adrenergic blocking agents : Propanolol, Metoprolol
Calcium channel blockers Verapamil, Nifedipine, Dipyridamole
 
Mechanism of action 
– Decrease myocardial demand 
– increase blood supply to the myocardium

Miconazole

Miconazole is an  imidazole antifungal agent commonly used in topical sprays, creams and ointments applied to the  skin to cure fungal infections such as Athlete's foot and Jock itch. It may also be used internally to treat vaginal  yeast infection.

When used by a person taking the anticoagulant medication warfarin, Miconazole may cause an adverse reaction which can lead to excessive bleeding or bruising.

Sympatholytics (Antiadrenergic Agents)

PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent 

It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension. 
It increases the cardiac output and decreases the total peripheral resistance.

It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.

Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.

ERGOT ALKALOIDS

 Ergotamine is an  important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.

METHYSERGIDE

It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine. 

SUMATRIPTAN

It is a potent selective 5-HT 1D  receptor agonist used in the treatment of migraine.

PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1  receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.

TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½

DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.

TAMSULOSIN
It is uroselective α1A  blocker and has been found effective in improving BPH symptoms.

Other drugs used for erectile dysfunction

Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.

Codeine

Codeine is methyl morphine, with a methyl substitution on the phenolic hydroxyl group of morphine. It is more lipophilic than morphine and thus crosses the blood–brain barrier faster.

  • classified as a simple, or mild analgesic, codeine is often used in low doses as an oral analgesic has a much better oral/parenteral absorption ratio than morphine.
  • Effective for mild to moderate pain.
  • Constipation occurs
  • Dizziness may occur in ambulatory patients.
  • More potent histamine-releasing action than does morphine.
  • Should not be administered by IV injection.
  • Extremely effective antitussive agent and is used therapeutically for suppressing cough.
  • In contrast to morphine, codeine overdose can occasionally lead to the production of seizures.
  • Seizures can be treated with barbiturates.
  • Respiratory depression can be counteracted with Naloxone.
  • orally, 30 mg of codeine is equi-analgesic to 600 mg of aspirin, however, the effects of the two are additive, and occasionally synergistic

Sympatholytics And Alpha Adrenergic Blockers 

Types 
1.    Alpha 1-receptor blockers: prazocin,doxazocin. 
2.    Centrally acting alpha 2- agonists: methyldopa, clonidine. 
3.    Peripherally acting adrenergic antagonists: reserpine. 
4.    Imidazoline receptor agonists: rilmenidine, moxonidine. 
 
Advantages 

- Alpha1- receptor blockers and imidazoline receptor agonists improve lipid profile and insulin sensitivity. 
- Methyldopa: increases renal blood flow. Drug of choice during pregnancy. 
- Reserpine: neutral metabolic effects and cheap. 

Indications: 

- Diabetes mellitus: alpha1- receptor blockers, imidazoline receptor agonists. 
- Dyslipidemia: alpha 1- receptor blockers, imidazoline receptor agonists. 
- Prostatic hypertrophy: alpha 1- receptor blockers. 
- When there is a need for rapid reduction in blood pressure: clonidine. 

Side Effects 

- Prazocin: postural hypotension, diarrhea, occasional tachycardia, and tolerance (due to fluid retention). 
- Methyldopa: sedation, hepatotoxicity, hemolytic anemia, and tolerance. 
- Reserpine: depression, lethargy, weight loss, peptic ulcer, diarrhea, and impotence
- Clonidine: dry mouth, sedation, bradycardia, impotence, and rebound hypertension if stopped suddenly. 

Considerations 
- Prazocin, methyldopa, and reserpine should be combined with a diuretic because of fluid retention. 

Direct Arterial Vasodilators 

Types: hydralazine, diazoxide, nitroprusside, and minoxidil

Macrolide

The macrolides are a group of  drugs (typically antibiotics) whose activity stems from the presence of a macrolide ring, a large  lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, are attached. The lactone ring can be either 14, 15 or 16-membered. Macrolides belong to the polyketide class of natural products.

The most commonly-prescribed macrolide antibiotics are:  

Erythromycin,  Clarithromycin, Azithromycin, roxithromycin,

Others are: spiramycin (used for treating  toxoplasmosis), ansamycin, oleandomycin, carbomycin and tylocine.

There is also a new class of antibiotics called ketolides that is structurally related to the macrolides. Ketolides such as telithromycin are used to fight respiratory tract infections caused by macrolide-resistant bacteria.

Non-antibiotic macrolides :The drug Tacrolimus, which is used as an

immunosuppressant, is also a macrolide. It has similar activity to  cyclosporine.

Uses : respiratory tract infections and soft tissue infections.

Beta-hemolytic  streptococci,  pneumococci, staphylococci and enterococci are usually susceptible to macrolides. Unlike penicillin, macrolides have shown effective against mycoplasma, mycobacteria, some rickettsia and chlamydia.

Mechanism of action: Inhibition of bacterial protein synthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl-tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations

Resistance : Bacterial resistance to macrolides occurs by alteration of the structure of the bacterial ribosome.

Uses of NSAIDs

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions, such as cancer and cardiovascular disease.

NSAIDs are generally indicated for the symptomatic relief of the following conditions.

rheumatoid arthritis, osteoarthritis, inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome), acute gout, dysmenorrhoea, metastatic bone pain ,headache and migraine, postoperative pain, mild-to-moderate pain due to inflammation and tissue injury, pyrexia, renal colic

Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation; an indication useful in the management of arterial thrombosis and prevention of adverse cardiovascular events.

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