Pharmacology 3:

Include: 1. Chemotherapy of: a) Microbial diseases (anti microbial) b) Parasitic infestation (anti parasites) c) Neoplastic diseases (anti cancer) 2. Hormones and its antagonists: a) Pituitary hormones b) Thyroid hormones c) Insulin and oral hypoglycemics d) Estrogens and androgens e) Suprarenal hormones ====================================================================

Anti Microbial therapy Definition:

These are drugs used for treatment of microbial diseases

Classification:
These drugs include: 1. 2. 3. 4. 5. 6. 7. Antibiotics Sulfonamides Anti mycrobacterials Anti fungal Anti viral Anti protozoal Anti helmintics

SELEction

of antimicrobial drug may be according to : 2.empiric :In which we administer broad

1. Culture and sensitivity .

spectrum antibiotic until appearance of the result of culture and sensitivity and this empiric treatment is done in cases of severe illness as in meningitis and encephalitis to safe life of the patient . .

Factors that determine the choice of anti microbial drug depend on : 1:MICROBIAL FACTORS :
a. Identification of the organisms : by i. Gram stain microscopically ii. Culture iii. Microbial antigen iv. Detection of microbial RNA and DNA b. Susceptibility Microorganisms may be sensitive to bactericidal antibiotics which kill the organisms directly or to bacteriostatic antibiotics which inactivate the organisms and facilitate its killing by phagocytosis. i. MIC:Is the minimum inhibitory concentration of antibiotic which produce area of inhibition in culture of organisms. ii. MBC: Is the minimum bactericidal concentration of antibiotic that results in 99.9% killing of cultured organisms.

2: Patient factors:
a. Adequate amount of antibiotic must reach the site of infection b. Capillaries carry drugs to the body tissues through openings act as windows c. Barriers of the body:

i. Blood Brain Barrier... physiological barrier between blood and brain ii. Placental Barrier..anatomical barrier between maternal blood and foetal blood d. Drugs can pass B.B.B : should be : i. Lipid soluble ii. Small M.W iii. Poor attachment to plasma protein . e. Renal dysfunction delay execretion lead to accumulation of drugs with serious adverse effects f. Hepatic dysfunction: antibiotics which are eliminated by liver (e.g. tetracycline + erythromycin) should be avoided in patients with advanced liver diseases g. Bad local circulation at site of infection decrease antibiotic levels locally h. Age: extremes of age there are decreased renal and hepatic elimination of antibiotic . i. Pregnancy and lactation i. All antibiotics can pass placental barrier ii. Tetracycline have bone + dental effects).

F.D.A. categories of antibiotics:

A: Safeno human or animal risk. B: No studies, no human risk, but animals show potential risk C: Animal foetal risk developed, but undefined human risk D: Human foetal risk present, but benefits from the drug are more X: human foetal risk present

3 : FACTORS RELATED TO DRUG : a.

Drug safety :most antibiotics are among the least toxic drugs as penicillins.

b.Drug cost :always we prefer less coasty antibiotic if it is effective as others

Routes of administration of anti biotics :

usually antibiotics are given orally.But in some cases we need to give antibiotics by :
1. I.V. therapy to give rapid high conc. In blood but this should be followed by oral administration.as rapid as you can. 2. Parental administration : in the following cases... a. Mal absorption from G.I.T b. Serious infections

Determination of Dose

and frequency of administration :

Dosing of drugs based of: o Pharmacodynamics of antibiotic. o Pharmacokinetics of antibiotic. o Post antibiotic effects . Persistant suppression of microbe after the level of antibiotic become less than M.I.C

Antimicrobials used in bacterial infections

1. B- Lactames a. Penicillins b. Cephalosporins 2. Amiolglycosides 3. Tetracyclines 4. Macrolids 5. flouroqinoloues 6. Miscellaneous antibacterials

Spectra of antimicrobial

1. Narrow spectrum antibiotic: these are effective against one type of organism or limited group e.g. Isoniazide in T.B. 2. extended spectrum antibiotic: which are effective against gram +ve organism and some gram -ve organism e.g. Ampicillin 3. Broad spectrum antibiotic: which are effective against many types of microorganism e.g. Tetracyclines and chloramphenicol but lead to super infection by candida albicans.

Combination of antibiotics: Advantages:

Synergism More effective Lower dose Less side effects + toxicity Broader spectrum of antibacterial action

Disadvantages:
Bacteriostatics inactivate microorganism Bactericidal act effectively on active organisms only,

So dont combine Bacteriostatics drug whith Bactericidal agent.

Drug resistance:
1. Bacterial mutation due to genetic alterations of mutation of DNA which may be: a. Spontaneous DNA mutation b. DNA transfer from cell to another cell 2. Bacterial adaptation:

a. Modification of target cell b. Altered accumulation c. Enzymatic inactivation

Complications of Antibiotic:
1. Hypersensitivity and idiosyncrasy which may lead to anaphylactic shock. 2. Super infection by fungus infection in intestine (candida albicans) after broad spectrum antibiotics . 3. Blood dyscrasia like aplastic anemia after chloramphenicol . 4. Hepatic and renal damage . 5. Crainial nerve injury like aminoglycosides which lead to auditory vestibular (8th crainial) nerve damage lead to deafness and vertigo .

Sites and mechanisms of action of antibiotics

1. Inhibit metabolic pathways in organism: 2. Inhibit cell wall synthesis: a. B-lactames b. Vancomycin 3. Inhibit protein synthesis: a. Amino glycosides b. Tetracyclines c. Macrolides d. Chloramphenicol e. Clindamycin 4. Inhibit cell membrane function: a. Isoniazide b. Amphotericin B 5. Inhibit DNA function or synthesis a. Flouroquinolones b. Rifampcin like (a) sulfonamides b. trimethoprim