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Pharmacology - NEETMDS- courses
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Pharmacology

Serotonin-norepinephrine reuptake inhibitors(SNRIs)

e.g. venlafaxine and duloxetine
- Inhibit the reuptake of both 5-HT and norepinephrine 
- Has a more favourable adverse effect profile than TCAs

Norepinephrine reuptake inhibitor

e.g. bupropion, reboxetine

Monoamine receptor antagonists

e.g. mirtazapine, trazodone, mianserin

Different Systems of the CNS & their functions

These systems are pathways formed of specific parts of the brain and the neurons connecting them. 

They include:
1.The pyramidal system 
2.The extrapyramidal system 
3.The limbic system 
4.The reticular formation 
5.The tuberohypophyseal system

The pyramidal system: 

It originates from the motor area of the cerebral cortex and passes through the spinal cord, therefore it is also known as the “corticospinaltract”. 
It is responsible for the regulation of the fine voluntary movements.

The extrapyramidal system: 

It also controls the motor functionbut involves areas other than the corticospinal tract. 
It is involved in the regulation of gross voluntary movements, thus it complements the function of the pyramidal system. 


The “basal ganglia” constitute an essential part of this system. 

Degenerative changes in the pathway running from the “substantianigra”to the “corpus striatum”(or nigrostriatal pathway) may cause tremors and muscle rigidity characteristic of “Parkinson’s disease”.


The limbic system: 

The major parts of this system are: the hypothalamus, the basal ganglia, the hippocampus(responsible for short term memory), and some cortical areas. 

The limbic system is involved in the control of “behavior”& “emotions”.


The reticular formation:

It is composed of interlacing fibers and nerve cells that run in all directions beginning from the upper part of the spinal cord and extending upwards. 
It is important in the control of “consciousness” and “wakefulness”.


The tuberohypophyseal system: 

It is a group of short neurons running from the hypothalamusto the hypophysis(pituitary gland) regulating its secretions.
 

Laxatives and cathartics (purgatives)

Constipation is a common problem in older adults and laxatives are often used or overused. Non drug measures to prevent constipation (e.g. increasing intake of fluid and high–fiber foods, exercise) are much preferred to laxatives.

Laxatives and cathartics are drugs used orally to evacuate the bowels or to promote bowel elimination (defecation). Both terms are used interchangeably because it is the dose that determines the effects rather than a particular drug. For example, Castor oil laxative effect = 4ml while Cathartic effect = 15-60ml

The term laxative implies mild effects, and eliminative of soft formed stool. The term cathartic implies strong effects and elimination of liquid or semi liquid stool. 

 Laxatives are randomly classified depending on mode of action as:
 
1. Bulk-forming laxatives: are substances that are largely unabsorbed from the intestine.
They include psyllium, bran, methylcellulose, etc. When water is added, the substances swell and become gel-like which increases the bulk of the faecal mass that stimulates peristalsis and defecation.

2. Osmotic laxatives such as magnesium sulphate, magnesium hydroxide, sodium phosphate, etc. These substances are not efficiently absorbed and cause water retention in the colon. The latter causes increase in volume and pressure which stimulates peristalsis and defecation.

Lactulose is a semisynthetic disaccharide sugar that also acts as an osmotic laxative. 
Electrolyte solutions containing polyethylene glycol(PEG) are used as colonic lavage solutions to prepare the gut for radiologic or endoscopic procedures

3. Stimulant (irritant) laxatives: these are irritant that stimulate elimination of large bowel contents. Individual drugs are castor oil, bisacodyl, phenolphthalein, cascara sagrada, glycerine, etc. The faeces are moved too rapidly and watery stool is eliminated. Glycerine can be administered rectally as suppositories.

4. Faecal softeners: they decrease the surface tension of the faecal mass to allow water to penetrate into the stool. They have detergent– like property e.g. docusate(docusate sodium, docusate calcium, and docusate spotassium. )

5. Lubricant laxatives e.g. liquid paraffin (mineral oil). It lubricates the intestine and is thought to soften stool by preventing colonic absorption of faecal water. They are used as retention enema. 

6. Chloride channel activators

Lubiprostone works by activating chloride channels to increase fluid secretion in the intestinal lumen. This eases the passage of stools and causes little change in electrolyte balances. Nausea is a relatively common side effect with lubiprostone.

Clinical indications of laxatives

1. To relieve constipation.
2. To prevent straining.
3. To empty the bowel in preparation for bowel surgery or diagnostic procedures.
4. To accelerate elimination of potentially toxic substances from the GI tract.
5. To accelerate excretion of parasite after anti-helmintic drugs have been administered. 

Carbapenems: Broadest spectrum of beta-lactam antibiotics.

imipenem with cilastatin

meropenem

ertapenem

Monobactams: Unlike other beta-lactams, there is no fused ring attached to beta-lactam nucleus. Thus, there is less probability of cross-sensitivity reactions.

aztreonam

Beta-lactamase Inhibitors No antimicrobial activity. Their sole purpose is to prevent the inactivation of beta-lactam antibiotics by beta-lactamases, and as such, they are co-administered with beta-lactam antibiotics.

clavulanic acid

tazobactam

sulbactam

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.

PHARYNGEAL DEMULCENTS 
Administered in the form of lozenges, cough drops and cough linctus. 
Produce soothing action on throat directly and by increasing the flow of saliva and provide symptomatic relief from dry cough.

EXPECTORANT

Expectorants are the drugs which increase the production of bronchial secretion and reduce its viscosity to facilitate its removal by coughing. 

ANTITUSSIVES

They are central cough suppressants and act centrally to raise the threshold of cough centre and inhibit the cough reflex by suppressing the coordinating cough centre in the medulla oblongata. 


Codeine - it depresses cough centre but is less constipating and abuse liability is low.


Pholcodeine is similar to codeine in efficacy and is longer acting. It has no analgesic or addicting property.

Noscapine is another opium alkaloid of benzylisoquinoline group. It is used as antitussive with no analgesic and drug abuse or drug dependence property. 

Dextromethorphan is a synthetic compound and its dextroisomer is used as antitussive and is as effective as codeine

Pipazethate is another synthetic compound of phenothiazine category used as antitussive with little analgesic and sedative properties.

ANTIHISTAMINICS
They do not act on cough centre but provide relief due to their sedative and anticholinergic action.

BRONCHODILATORS
Bronchodilators are helpful in individuals with cough and bronchoconstriction due to bronchial hyperreactivity. They help by improving the effectiveness of cough in clearing secretions.

Second Generation Cephalosporins

Prototype drug is CEFUROXIME (IV) and CEFUROXIME AXETIL (oral). CEFOXITIN has good activity vs. anaerobes.

1. Expanded activity against gram negative bacilli. Still have excellent activity against gram positive (Staph. and Strep.) bacteria.

Activity for Gram negative bacteria

Neisseria sp. (some gonococci resistant)
H. influenzae (including some ampicillin-resistant strains)
Moraxella catarrhalis (some resistance esp. to cefaclor)
E. coli
Proteus mirabilis
Indole + Proteus (some strains resistant)
Morganella morganii (some strains resistant)
Klebsiella pneumoniae
Serratia sp. (many strains resistant)

2. Anaerobic infections - CEFOXITIN & CEFOTETAN only

Moderate activity against Bacteroides fragilis group.

Good activity for other Bacteroides sp., Peptostreptococcus, Fusobacterium, Clostridium sp

Uses
1. Community-acquired pneumonia - Cefuroxime is widely used for empiric therapy. Has activity vs. many ampicillin-resistant H. influenzae strains.
2. Skin and soft tissue infection
3. Urinary tract infections
4. Upper respiratory tract infections (otitis media, sinusitis). Some resistance to H.influenzae to cefaclor (20-30%).
5. Mixed aerobic & anaerobic infections - Cefoxitin & Cefotetan. Resistance to B.fragilis is increasing.
6. Surgical prophylaxis - Cefoxitin or cefotetan are widely used in cases where mixed aerobic & anaerobic infections may occur, esp. intra-abdominal, colorectal, and gynecologic operations. For cardiovascular and orthopedic procedures, cefuroxime and others may be used, but cefazolin is cheaper and appears to work well.

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