Antimicrobial prophylaxis general principles and drug used

General principles

01.Anti microbials cannot   eliminate all micro organisms in the host and cannot prevent all types of infection. hence prophylaxis should be directed against a specific pathogen or used to prevent infection at a specific site

02.Shorter the duration of prophylaxis the larger the range of pathogens affected. For prevention of all infections in leucopoenias

• Broad spectrum  anti microbials -> short term
• Long term use-> resistance
• Group “a” strep ->long term use  

03.Prophylaxis more effective against pathogens less likely to develop resistance 
       eg. penicillin for grp.”a” strep->effective not for gonococcus 

04.Drugs for therapy may not be good for prophylaxis

eg.penicillin in meningococcal meningitis not effective for prophylaxis

05.Prophylactic drugs should only be used when efficacy has been documented cost, toxicity, superinfection development of resistance

Surgical prophylaxis

• Antimicrobials must be efffective against majority of organisms causing post.op. infections
• Start therapy 1-2hours before and stop 12-48 hours after op.
•  A single pre op.dose gives maximal benefit
• Antimicrobials activity must be present in surgical wound before closure

Drugs

•  Cefazolin ->drug of choice  (first generation cephalosporin) 0.5gm -2gm i.v.        
• Cefepime 4^th generation cephalosporin more resistance to hydrolysis by beta lactamase

 eg. enterobacter that may    inactivate 3^rd generation ceph.

Drug combinations        

Indications

• Very ill patients with infections of unknown origin eg septicaemia anti staph (nafcillin-cloxacillin0 with gm –ve bacilli (gentamicin tobramycin amikacin)  immunocompromised
• Mixed infections peritonitis anaerobes– Metronidazole, Gram +ve bacteria- clindamycin coliforms –Aminoglycosides
• Prevent resistance eg : TB (isoniazid,ethambutol,rifampin)
• Enhance effect of single drug eg. sulphonamide with trimethoprim penicillin with aminoglysoide -> enterococcus faecalis

NSAID’s (Non Steroidal Anti Inflammatory Drugs)

Actions of NSAID’s

Anti-inflammatory effects of NSAIDs

This effect of NSAIDs is due to the inhibition of the enzyme COX, which converts arachidonic acid to prostaglandins, TXA2 and prostacyclin.

Acetylsalicylic acid irreversibly inactivates COX-1 and COX-2 by acetylation of a specific serine residue.

Other NSAIDs reversibly inhibit COX-1 and COX-2

Additional anti-inflammatory mechanism may include:

• Interference with the potentiative action of other mediators of inflammation – bradykinin, histamine, serotonin
• Modulation of T-cell function
• Stabilization of lysosomal membranes
• Inhibition of chemotaxis

Analgesic effect of NSAID s

This effect of NSAIDs is thought to be related to the peripheral inhibition of prostaglandin production, but it may also be due to the inhibition of pain stimuli at a subcortical site.

NDAIDs prevent the potentiating action of prostaglandins on endogenous mediators

of peripheral nerve stimulation ( e.g. bradykinin )

Antipyretic effect of NSAIDs

This effect is believed to be related to inhibition of the interleukin-1 and interleukin-6 induced production of prostaglandins in the hypothalmus and the “resetting” of the termoregulatory system, leading to vasodilation and increased heat loss

Clinical uses of NSAIDs

1) Analgesia

2) Inflammation

3) Antipyresis

4) Antiplatelet effect

5) Cancer preventive agents

Adverse effects of NSAIDs

• Gastrointestinal effects: abdominal pain, gastric and duodenal ulcer, diarrhea, pancreatis
• Gastrointestinal hemorrhage, hepatotoxicity
• Renal effect

- Disturbances of renal function with water and sodium retention

• Inhibition of platelet aggregation
• central symptoms: headache, decreased hearing, tinnitus, dizziness, confusion, depression
• Allergic reactions: asthma, rashes, photosensitivity

Pharmacodynamic  interaction NSAIDs with other drugs

• NSAIDs  + hypotensive drugs ( β-blockers, ACE-inhhibitors, diuretics ) = ↓ hypotensive effect
• NSAIDs + ehanol = ↑risk of bleeding from gastrointestinal tract
• NSAIDs  + ticlopidine or clopidogrel = ↑risk of bleeding
• NSAIDs  + lithium = ↑lithium toxicity  
• NSAIDs  + cylosporine or ACE-inhibitors or takrolimus= ↑nephrotoxicity of drugs
• NSAIDs  + fluoroquinolons = ↑ toxic action of fluoroquinolons on CNS
• NSAIDs  +oral antidiabetic drugs  =↑ risk of hypoglycemia
• NSAIDs  + cumarines = ↑risk of bleeding from gastrointestinal tract

Pharmacokinetic interaction NSAIDs with other drugs

• NSAIDs + oral antidiabetic drugs = ↑ risk of hypoglycemia
• NSAIDs  + cumarines =↑risk of bleeding
• NSAIDs  + corticosteroids = ↑risk gastropathy and bleeding from gastrointestinal tract
• NSAIDs  + aminogycosides = ↑ ototoxicity and  nephrotoxicity of aminogycosides
• NSAIDs  + fenytoine or valproinic acid  = ↑action of fenytoine or valproinic acid 
• NSAIDs   + metotrexat or digoxin = ↑action and ↑ toxicity metotrexat or digoxin
• NSAIDs   + tricycles antidepressive drugs  neuroleptics or antiarrhytmic drugs or
• selective serotonin reuptake inhibitors ( SSRI ) = ↑ action of drugs

Classification of NSAIDs According to mechanism of action

1) COX-1 selective inhibitors

    - Acetylsalicylic acid at low dosage

2) Non selective  COX  inhibitors

    - Acetylsalicylic acid at high  dosage

    - Diclofenac

    - Ibuprofen

    - Ketoprofen

    - Flurbiprofen

    - Indomethacin

    - Piroxicam

    - Naproxen

3) More COX-2 selective inhibitors

    -Nimesulid

   - Etodolak

   - Meloxicam

   - Nabumeton

4) COX-2 selective inhibitors

    - Celecoxib

    - Etorcoxib

    - Valdecoxib

Chemical classification of Non-steroidal anti-inflammatory Drugs (NSAIDs)

A: Salicylates

Acetyl salicylic acid (aspirin), sodium salicylate, Mg salicylate, choline salicylate,

Na thio salicylate, salicyl salicylate

B: Propionic acid derivatives

Ibuprofen, ketoprofen, naproxen, oxaprozin, flurbiprofen

C:Indole acetic acid

Indomethacin, sulindac,

D: Substituted anthranilic acids (Rarely used)

Mefenamic acid, meclofenamate Na

E: Pyrrole alkanoic acid (Rarely used)

Tolmetin

F: Oxicams

Piroxicam, meloxicam

G: Difluorophenyl derivatives

Diflunisal

H: Phenyl acetic acid

Diclofenac

I:Acetic acid derivatives

Etodolac

J: Naphthyl acetic acid prodrugs

Nabumetonre

K: Para-amino phenol derivatives

Acetaminophen

Theraputic classification of NSAID s

A: Analgesics

Aspirin, paracetamol

B: Anti-inflammatory

Indomethacin, naproxen, ibuorofen

C: Anti-coagulants

Aspirin

D: Anti-pyretics

Aspirin, paracetamol, indomethacin, celecoxicv, ibuprofen

E: Inflammatory bowel disease

Sulfasalazine, infiximab

F: Anti-cancer drugs

Methotraxate

G: Anti-malarial

Chloroquine, hydroxychloroquine

H: Tissue transplantation

Cyclosporine

I: Chelating agents in wilson’s disease

Penicillamine

J: Anti-gout drugs

Indomethacin, ibuprofen

W.H.O Classification

A: Drugs with weak anti-inflammatory effect

Acetaminophen

B: Drugs with mild to moderate anti-inflammatory effect

Propionic acid derivatives, anthranilic acid derivatives

C: Drugs with marked anti-inflammatory effects

Salicylates, acetic acid derivatives, oxicams, diclofenac, etodolac

Drugs Affecting the Cardiovascular System PowerPoint Presentation Free Download

This PowerPoint Point Presentation Includes

— Name the main classes of Anti anginal and anti hypertensive drugs

— Describe the principles of drug action in the treatment of Angina and Hypertension

— Describe the mechanism of action of the above drugs

— Name the adverse effects of each of the drugs

Click here to Download the
"Drugs Affecting the Cardiovascular System"

Elimination Of a Drug

Elimination of a Drug

Termination of drug effect > biotransformation > inactive > excreted

Organs of Excretion

Kidney, Liver.Lungs,Skin (sweat)

Kidney > Glom.Filtration,Tubular secretion Re-absorption by passive diffusion

o Glom. Filtration > passive process

o Removes mols. Size of small proteins

o Protein bound drug > less Glom.Filtration

o Free drug more filtration > rate approximates cratinine clearance

o Tubular secretion > actively secreted by proximal convoluted tubule

o Lipid membrane of nephron reabsorbs lipid soluble mol.

o Water soluble mol. excreted

Liver

o Actively secreted into bile after metabolism

o Enters G.I.T & may be reabsorbed into the blood > entero hepatic circulation

o E.g/ cardiac glycosides and some anti microbials

o Gastro Intestinal Tract > passive diffusion

o Drugs > blood>lipid membrane > lumen of G.I.T.

Clinical importance of excretion into lumen of gut

o Weakly basic drugs like morphine in high concentrations diffuses into acidic environment of stomach > poorly re absorbed as it is 100% ionized. Hence can be removed by gastric lavage.

o If not removed, it is re absorbed in the small intestine

Other organs of excretion

o LUNGS > Gaseous anaesthetics

o SWEAT

o SALIVARY GLANDS

o MILK

DRUG CLEARANCE

o Rate of elimination is relative to the conc. Of drug any biological fluid e.g. plasma, blood.

CL= Rate of elimination

Plasma conc.

o CL(renal) =

Rate of elimination(Kidney)

conc.in plasma (Cp)

o CL(liver) =

Rate of elimination(liver)

Cp

o Rate of elimination

o For an organ =QxC(in) – Qx C(o)

Q = rate of bl.flow

C(in) = amt of drug entering

C(o) = amt of drug leaving

o Bioavailability(F) = 1 – ER(extraction ratio)

o Dosing Rate = CL x Css (IV infusions)

o Half life proportional to VD & CL

o t1/2 =

0/693VD or 0.7VD

CL

Loading Dose = VD x Cpss

o Used for long t1/2 drugs > raise conc of drug to steady state value > amt. of drug in the body when steady state is reached

o E.g. If reqd. ss conc is 15microgms/ml and VD is 35L Then LD = 15 x 35 = 525mg

Dosage Regimen

o 1. Dose of drug

o 2. Route of administration

o 3. Dosing interval

o 4. Period of administration

o Clinical significance of dosing rate

o Eg. Desired Pl.conc of drug A is 15microgms/ml CL = 48ml/min/70Kg

o Dosing rate = 48 x 15 = 720mugm/min =0.72mg/min = 43.2mg/hour = rate of IV infusion