NEET MDS Lessons
Pharmacology
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.
COAGULANTS
An agent that produces coagulation (Coagulation is a complex process by which blood forms clots).
ANTICOAGULANTS
An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting.
Anticoagulants:
Calcium Chelators (sodium citrate, EDTA)
Heparin
Dalteparin Sodium (Fragmin) -Low molecular-weight heparin
Enoxaparin - Low molecular-weight heparin
Tinzaparin Sodium - Low molecular-weight heparin
Warfarin
Lepirudin - recombinant form of the natural anticoagulant hirudin: potent and specific Thrombin inhibitor
Bivalirudin - analog of hirudin: potent and specific Thrombin inhibitor
Procoagulants:
Desmopressin acetate
Antiplatelet Drugs:
Acetylsalicylic Acid, Ticlopidine, Sulfinpyrazone, Abciximab , Clopidogrel bisulfate
Fibrinolytic Drugs:
Tissue Plasminogen Activator (t-PA, Activase), Streptokinase (Streptase),
Anistreplase, Urokinase
Antagonists:
Protamine sulfate, Aminocaproic acid
Pharmacological agents used to treat blood coagulation disorders fall in to three major categories:
1. Anticoagulants: Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of arterial thrombi and thromboembolic clots.
2. Antiplatelet agents: Substances that reduce the adhesion and aggregation of platelets.
3. Fibrinolytic agents: Substances that promote the destruction of already formed blood clots or thrombi by disrupting the fibrin mesh.
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.
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
Procaine penicillin Procaine penicillin is a combination of benzylpenicillin with the local anaesthetic agent procaine. This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin.
Indications
respiratory tract infections where compliance with oral treatment is unlikely ,syphilis, cellulitis
Neurophysiology
Nerve fibers exhibit wide range of sensitivity to nerve blockade-in order of increasing resistance to block are the sensations of pain, cold, warmth, touch, pressure, proprioception and motor function
Nerve Fibers:
|
Types |
Size |
Speed |
Occurrence |
|
A (α) |
20 µm |
80 - 120 |
Myelinated (Primarily for muscular activity). |
|
β |
8 - 15 µm |
|
Myelinated (Touch and pressure) |
|
γ |
4 - 8 µm |
|
Myelinated (Muscle spindle tone) |
|
δ |
3 - 4 µm |
10-15 |
Myelinated (Pain and temperature sensation) |
|
B |
4 µm |
10-15 |
Myelinated (Preganglionic autonomic) |
|
C |
1-2 µm |
1 - 2 |
Unmyelinated (Pain and temperature sensation) |
Myelinated = faster conducting
Unmyelinated = slower conducting
- Small non-myelinated fibers (C- pain fibers) and smaller myelinated pre-ganglionic B fibers are more readily blocked than are larger myelinated fibers responsible for muscle activity and touch [A-alpha and A-beta].
- Clinically, a person would notice complete lack of sensation to a pinprick, while at the same time still be able to move their fingers.
Roxithromycin
It is used to treat respiratory tract, urinary and soft tissue infections. Roxithromycin is derived from erythromycin, containing the same 14-membered lactone ring. However, an N-oxime side chain is attached to the lactone ring.
Roxithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Legionella pneumophilae.
When taken before a meal, roxithromycin is very rapidly absorbed, and diffused into most tissues and Phagocytes Only a small portion of roxithromycin is metabolised. Most of roxithromycin is secreted unchanged into the bile and some in expired air