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Pharmacology - NEETMDS- courses
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Pharmacology

Dextromethorphan  
O-methylated dextrorphan,  Excellent oral antitussive,  No analgesic effect,  No GI effects,  No respiratory depression

Ofloxacin : It is a quinolone antibiotic and similar in structure to  levofloxacin. It is an alternative treatment to ciprofloxacin for anthrax.

DIURETICS

The basis for the use of diuretics is to promote sodium depletion (and thereby water) which leads to a decrease in extracellular fluid volume.
An important aspect of diuretic therapy is to prevent the development of tolerance to other antihypertensive drugs.

TYPES OF DIURETICS
A. Thiazide Diuretics examples include     chlorothiazide 
hydrochlorothiazide 
a concern with these drugs is the loss of potassium as well as sodium

B. Loop Diuretics (High Ceiling Diuretics) examples include 
furosemide (Lasix)
bumetanide
these compounds produce a powerful diuresis and are capable of producing severe derangements of electrolyte balance

C. Potassium Sparing Diuretics examples include
triamterene
amiloride 
spironolactone 
unlike the other diuretics, these agents do not cause loss of potassium

Mechanism of Action

Initial effects: through reduction of plasma volume and cardiac output.
Long term effect: through decrease in total peripheral vascular resistance.

Advantages

Documented reduction in cardiovascular morbidity and mortality.
Least expensive antihypertensive drugs.
Best drug for treatment of systolic hypertension and for hypertension in theelderly.
Can be combined with all other antihypertensive drugs to produce synergetic effect.

Side Effects
Metabolic effects (uncommon with small doses): hypokalemia,hypomagnesemia, hyponatremia, hyperuricemia, dyslipidemia (increased total
and LDL cholesterol), impaired glucose tolerance, and hypercalcemia (with thiazides).
Postural hypotension.
Impotence in up to 22% of patients.  

 Considerations
- Moderate salt restriction is the key for effective antihypertensive effect of diuretics and for protection from diuretic - induced hypokalaemia. 
- Thiazides are not effective in patients with renal failure (serum creatinine > 2mg /dl) because of reduced glomerular filtration rate.
- Frusemide needs frequent doses ( 2-3 /day ).Thiazides can be given once daily or every other day.
- Potassium supplements should not be routinely combined with thiazide or loop diuretics. They are indicated with hypokalemia (serum potassium < 3.5 mEq/L) especially with concomitant digitalis therapy or left ventricular hypertrophy.
- Nonsteroidal antiinflammatory drugs can antagonize diuretics effectiveness.

Special Indications

Diuretics should be the primary choice in all hypertensives.

They are indicated in:
- Volume dependent forms of hypertension: blacks, elderly, diabetic, renal and obese hypertensives.
- Hypertension complicated with heart failure.
- Resistant hypertension: loop diuretics in large doses are recommended.
- Renal impairment: loop diuretics

Fifth Generation:

These are extended spectrum antibiotics.

Ceftaroline, Ceftobiprole

DIAGNOSIS

Affective disorders:
I. unipolar depression – depression alone
bipolar affective disorder – alternating II. bipolar affective disorder – alternating depression and mania

Diagnosis is based on 

At least five of the following for 2 weeks
I. Depressed mood most of the day
II. Markedly diminished interest or pleasureII. Markedly diminished interest or pleasure
III. Significant weight loss or weight
IV. Insomnia or hypersomnia
V. Psychomotor agitation or retardation
VI. Fatigue or loss of energy
VII. Feelings of worthlessness or excessive guilt
VIII. Diminished ability to think or concentrate, 
IX. Recurrent thoughts of death

Underlying biological basis for depression is a deficiency of the monoamine neurotransmitters  norepinephrine and/or serotonin in the brain.

Gastric acid secretion inhibitors (antisecretory drugs):

 HCl is secreted by parietal cells of the gastric mucosa which contain receptors for acetylcholine (muscarinic receptors: MR), histamine (H2R), prostaglandins (PGR) and gastrin (GR) that stimulate the production, except PGs which inhibit gastric acid production.
 
Therefore, antagonists of acetylcholine, histamine and gastrin inhibit gastric acid secretion (antisecretory). On the other hand, inhibitors of PGs biosynthesis such as NSAIDs with reduce cytoprotective mechanisms and thus promote gastric mucosal erosion. Also, the last step in gastric acid secretion from parietal cells involve a pump called H+ -K+-ATPase (proton pump). Drugs that block this pump will inhibit gastric acid secretion. Antisecretory drugs include:

1. Anticholinergic agents such as pirenzepine, dicyclomine, atropine.
2. H2-receptors blocking agents such as Cimetidine, Ranitidine, Famotidine, Nizatidine (the pharmacology of these agents has been discussed previously).
3. Gastrin-receptor blockers such as proglumide.
4. Proton pump inhibitors such as omeprazole, lansoprazole.

Major clinical indications of antisecretory drugs:

• Prevention & treatment of peptic ulcer disease.
• Zollinger Ellison syndrome.
• Reflux esophagitis. 

Serotonin or 5-hydroxytryptamine (5-HT)

It is a neurotransmitter, widely distributed in the CNS, beginning in the midbrain and projecting into thalamus, hypothalamus, cerebral cortex, and spinal cord. CNS serotonin is usually an inhibitory neurotransmitter and is associated with mood, the sleep-wake cycle.

Serotonin is thought to produce sleep by inhibiting CNS activity. 

In the blood, 5-HT is present in high concentration in platelets (regulator of platelets function) and also high concentration in intestine

Pharmacological effects:

Smooth muscles. 5-HT stimulates the G.I smooth muscle; it increases the peristaltic movement of intestine.
Serotonin contracts the smooth muscle of bronchi; 

Blood vessels. If serotonin is injected i.v, the blood pressure usually first rises, because of the contraction of large vessels and then falls because of arteriolar dilatation. Serotonin causes aggregation of platelets. 

Specific agonists

- Sumatriptan a selective 5-HT1D used in treatment of acute migraine.
- Buspirone a selective 5-HT1A used in anxiety.
- Ergotamine is a partial agonist used in migraine. It acts on 5-HT1A receptor.

Nonspecific 5-HT receptor agonist

o Dexfenfluramine used as appetite suppressant.

Specific antagonists

o Spiperone (acts on 1A receptor) and
o Methiothepin (acts on 1A, 1B, 1D receptors)

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