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Pharmacology - NEETMDS- courses
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Pharmacology

Antimania Drugs

MANIC SYMPTOMSMANIC SYMPTOMS

Elevated  or irritable mood
Increased activity or psychomotor agitation
Reduced need for sleep
Inflated self esteem or grandiosity
Increased or pressure of speech
Flight of ideas

These drugs are used to treat manic-depressive illness.

1. Lithium
2. Carbamazepine
3. Valproic acid

Mechanisms of action

1. Lithium works inside the cell to block conversion of inositol phosphate to inositol.
2. Carbamazepine blocks sodium channels 
3. Valproic acid blocks sodium and calcium channels

PHARMACOKINETICS

Absorbed readily and almost completely from the GI tract; peak concentrations in 1-2 hrs

Lithium toxicity

1. Nausea, diarrhea, convulsions, coma, hyperreflexia, cardiac arrhythmias, hypotension.
2. Thyroid enlargement; increases thyroid stimulating hormone (TSH) secretion; may cause hypothyroidism.
3. Polydipsia, polyuria (lithium inhibits the effect of antidiuretic hormone on the kidney).

Clinical applications concerning lithium 

- Patients must be warned against sodium-restricted diets because sodium restriction leads to greater retention of lithium by the kidney.
- Patients must have regular (e.g., monthly) blood checks because the margin of safety is narrow.

Endocrine Effects – Goitre and hypothyroidism commonly

Cardiac Effects:– ECG changes(common) - T-wave flattening/inversion and appearance of U wavesflattening/inversion and appearance of U waves

Li and Pregnancy -1st Trimester:Cardiovascular anomalies of the newborn, especially Ebstein's malformation
- 3rd Trimester: Neonatal goiter, CNS depression, hypotonia ("floppy baby" syndrome)

Drug–drug interactions of lithium
Diuretics and newer nonsteroidal anti-inflammatory drugs (NSAIDs) reduce lithium excretion and may cause lithium toxicity.

Helicobacter Pylori Agents

  Antimicrobial

• Amoxicillin,

• Clarithromycin,

• Metronidozole

• Tetracycline

 

 Antisecreteory agents accelerates symptom relief and yield healing (omeprozole)

  Bismuth subsalicylate

 

Therapy For H. Pylori

  Original

• Tetracycline

• Metronidazole (Flagyl)

• Bismuth subsalicylate

• Given for 14 days

• >90% effective in eradicating microorganisms

 

 New triple therapy

• Amoxicillin

• Clarithromycin

• Omeprazole (Prilosec)

• Given for 7 days

• >90% effective in eradicating microorganisms

 

Dual Therapy

  Amoxicillin or clarithromycin

  Omeprazole

  Given for 14 days

  60-80% effective in eradication of H. Pylori

BETA-LACTAM ANTIBIOTICS
β-lactam antibiotics are a broad class of antibiotics including penicillin derivatives, cephalosporins, monobactams, carbapenems and β-lactamase inhibitors; basically any antibiotic agent which contains a β-lactam nucleus in its molecular structure. They are the most widely used group of antibiotics available.

Mode of action All β-lactam antibiotics are bactericidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls.β-lactam antibiotics were mainly active only against Gram-positive bacteria, the development of broad-spectrum β-lactam antibiotics active against various Gram-negative organisms has increased the usefulness of the β-lactam antibiotics.

Common β-lactam antibiotics

Penicillins

Narrow spectrum penicillins:  

benzathine penicillin
benzylpenicillin (penicillin G)
phenoxymethylpenicillin (penicillin V)
procaine penicillin

Narrow spectrum penicillinase-resistant penicillins

methicillin
dicloxacillin
flucloxacillin

Moderate spectrum penicillins : 

amoxicillin, ampicillin

Broad spectrum penicillins :      

co-amoxiclav (amoxycillin+clavulanic acid)

Extended Spectrum Penicillins:    

piperacillin
ticarcillin
azlocillin
carbenicillin
 

On the basis of Receptors, drugs can be divided into four groups,

a. agonists

b. antagonists

c. agonist-antagonists

d. partial agonists

 

a. Agonist

morphine fentanyl pethidine

Action : activation of all receptor subclasses, though, with different affinities

b. Antagonist

Naloxone , Naltrexone

Action :  Devoid of activity at all receptor classes  

c. Partial Agonist: (Mixed Narcotic Agonists/Antagonists)

Pentazocine, Nalbuphine, Butorphanol , Buprenorphine

Action: activity at one or more, but not all receptor types

With regard to partial agonists, receptor theory states that drugs have two independent properties at receptor sites,

a. affinity

The ability, or avidity to bind to the receptor
Proportional to the association rate constant, Ka

b. efficacy

or, intrinsic activity, and is the ability of the D-R complex to initiate a pharmacological effect

Drugs that produce a less than maximal response and, therefore, have a low intrinsic activity are called partial agonists.

These drugs display certain pharmacological features,

a. the slope of the dose-response curve is less than that of a full agonist

b. the dose response curve exhibits a ceiling with the maximal response below that obtainable by a full agonist

c. partial agonists are able to antagonise the effects of large doses of full agonists

DIURETICS

Specific Therapeutic Objective

Clinical State(s)

Drug(s) (Class)

Draw fluid from tissue to vascular space reduce tissue edema

Cerebral edema
glaucoma

Mannitol (Osmotic)
Glucose (Osmotic)
Glycerin (Osmotic)

Decrease renal swelling
expand tubular volume

Renal shutdown

Glucose (Osmotic)
Mannitol (Osmotic)

Modest and/or sustained decrease in venous hydrostatic pressure

Congestive heart failure
Hepatic cirrhosis
Udder edema

Hydrochlorothiazide (thiazide)
Chlorothiazide (thiazide)

Aggressive and/or short-term decrease in venous hydrostatic pressure

Congestive heart failure
Hepatic cirrhosis
Udder edema

Furosemide (loop)

Inhibit aldosterone action

Hepatic cirrhosis
Congestive heart failure

triamterene (K+ sparing)
spironolactone (K+ sparing - competitive)

Reduce potassium wasting 2o to other diuretic

Hepatic cirrhosis
Congestive heart failure

triamterene (K+ sparing)
spironolactone (K+ sparing - competitive)

Inhibit ADH action

Inappropriate ADH secretion

lithium (aquaretic)
demeclocycline (aquaretic

Increase calcium secretion

Malignant hypercalcemia

  • Paraneoplastic
  • Hypervitaminosis D

Furosemide (loop)

Reduce urine output

Diabetes insidpidus

Hydrochlorothiazide (thiazide)
Chlorothiazide (thiazide)

Urine alkalinization

Various

Carbonic anhydrase inhibitors

 Sympathomimetics

Beta-Adrenergic Agonists

Beta1-adrenergic agonists (dopamine, dobutamine, prenalterol, xamoterol) have been used to treat acute and chronic heart failure, but have limited usefulness in chronic CHF because of their arrhythmogenic effects, short duration of action, the development of tolerance, and necessity of parenteral administration

Dopamine (i.v.) is used in acute heart failure (cardiogenic shock) to increase blood pressure and increase cardiac output

  • It has a short half-life (1 min)
  • At high doses dopamine has potent peripheral vasoconstrictor effects (alpha-receptor stimulation), in addition to its inotropic effects
  • Low dose dopamine has a renal artery dilating effect and may improve sodium and water excretion in patients refractory to loop diuretics
  • When systolic pressure is greater than 90 mm Hg, nitroprusside can be added to reduce ventricular filling pressure and reduce afterload
  • i.v. furosemide should also be administered to reduce edema

Levodopa and ibopamine, analogs of dopamine that can be administered orally, have been shown to improve symptoms in some patients, but can exhibit arrhythmogenic side-effects and tachyphylaxis

Dobutamine is a somewhat selective beta1-adrenergic agonist that lacks vasoconstrictor activity and causes minimal changes in heart rate

  • It is frequently added to nitroprusside when blood pressure is adequate to increase cardiac output
  • It is administered as an i.v. infusion to treat acute severe heart failure
  • It has a short half-life (2.4 min) and is only used on a short-term basis, although long-term beneficial effects on cardiac function have been noted
  • After 72 hours of therapy, tolerance can develop to dobutamine necessitating switch to other inotropic support (e.g. milrinone)
  • Dobutamine can enhance AV conduction and worsen atrial tachycardia

Prenalterol and xamoterol are partial beta1-adrenergic agonists that may simultaneously stimulate beta1-receptors and block the receptors from stimulation by endogenous catecholamines, thereby protecting against beta1-receptor down-regulation

CNS acting drugs are of major therapeutic and clinical importance. 

They can produce diverse physiologicaland psychologicaleffects such as:

•Induction of Anesthesia 
•Relief of Pain 
•Prevention of Epileptic seizures 
•Reduction of Anxiety 
•Treatment of Parkinsonism 
•Treatment of Alzheimer's disease 
•Treatment of Depression 
•Centrally acting drugs also include drugs that are administered without medical intervention like tea, coffee, nicotine, and opiates.
 

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