Saturday, May 23, 2009

Tuberculosis & TT technique

· Bacillary sub-populations in pulmonary TB:


B (persisters)



Site of bacilli

Extra-cellular in cavity

Intra-cellular in MQs

Extra-cellular in caseum

Dormant fatty

Responds to

S, H, R

Z, H, R

R only


Resistant to



H, Z, S, E


PH needed

Neutral or Alk.




O2 tension

Needs high


Needs low


Responsible for

Ttt failure

Relapse (must >2Ms ttt)



· Drugs used in TB:

a) 1st Line Drugs:








5-10mg/kg/d (max 300-600mg)

10-20mg/kg (max 600mg for >50kg, 450mg for <50kg)

25-40mg/kg (max 2gm for >50kg, 1.5gm for <50kg)

15-25mg/kg (0.8-1.2gm)

15mg/kg/d (max 1gm)


.Isocid 100

.I.forte 200

.Inhibex (50H+5Z)

.TBzide 50


.Riozid (300R+150H)

.Rifadin (v:600)(c:150/300)

.Rimactan (cap/syrup)

.Rifampin300 .Rifampicin

.P.T.B 500

.Pyrazide 500

.Pyraldina 500

.Rifater 2 (H,R,Z = 50,120,300)

.E.T.B 500, 100, 400

.Strept IM

(ineffective more than 2Ms and toxic as well)






-Inh. synth. of DNA, cell wall Mycolic acid.

-Acts on replicating bacilli (even in persisters they are slowly replicating not completely dormant.

-Competes pyridoxine (structure analogue).

-On empty stomach as R.


-IC/EC (kills intermittently, rapidly dividing org.)

-Dec.RNA synthesis through Dec. DNA depend. RNA polymerase.

-Also on: G+ve/-ve, pox virus, Chlamydia, Mycoplasma.


-IC only (acidic media)

-Change by pyrazinamidase of bacillus to pyrazinoic acid (wall).

-Must do pre-ttt sensitivity test.

-Main ttt in relapse and short course ttt (sterilizing)

-No effect in continuation phase.



-Dec. RNA synthesis to inhibit MB cell wall synthesis.


-EC only (alk. media)

-Binds to 30S ribosomal subunità prevents protein synthesis.

-Break polysomes to monosomes.

-Misreading in genetic code à abn. Protein.

-Inactivates initial complex of synthesis.


Peak conc


Half life




-2 hrs

-Acetylators (rapid/slow)

-1.5-3 hrs


- Crosses BBB

-In ½ hr

-3 hrs

-75% bound, partial deacetylation in liveràbile

-5 hrs

-Bile, less Urine (EHC).

-Inflamed meninges. only, well to other tissues.


-1-2 hrs

-50% bound,

hepatic deaminase changes it to active pyridazinoic acid then with xanthine oxidase to inactive metabolite.


-CSF=plasma conc.

-Dose decreased in renal failure.

-Inh. 'e ethanol , alumOH

-2-4 hrs

-Not altered with liver disease.

-must suspend at once.

-------------------Urine unchanged.

-No cross BBB even inflamed.

-Dose decreased in renal failure (drug level not>5ug/ml)

(not used in clearance <50)


-1 hr

-Cross-resistance with vio/ kanamycin

-----------------Urine completely.

-Inflamed meninges.

-Crosses placenta (1/2 mother's level).





.BM dep.









.Drug interact.


Follow up

-PN (slow A),

insomnia, restlessness, Ms twitches, Convulsions in epileptic pt.

-Atropine like (dry mouth, tinnitus, GIT)

-Rash, Fever, Pellagra (nicotinamide)

-Inhibit Histaminases (inc. histamin)


-Hemolytic anemia

-GIT upset

-Hepatitis (rapid A)

-D.M.(x B-cells)

-Lupus like




-Hydralazine, Procainamide, PAS inc. its toxicity.

-Carcinogenic in mice

-/4wks CBC, liver function,

-/3Ms urine test for compliance.

-Caution in epilepsy, alcoholics, pregnant


-Flushing, Acne form, Conjunctiv.

-Flu symp., asthma, purpra, ATN ('eintermittent ttt)

-----------------A.hemolytic anemia, thrombocytopenic purpra.


-Transient insig. inc. transaminases, Cholestatic jaundice.

-----------------Light chain protinuriaàRF, ATN

-Pseud crisis



-PAS inh. Its absorption.

-R is enzyme


-Turns fluids red.


-as INH

-as INH

-caution in pregnancy

-----------------Photosensitivity (Erythema with sunlt.)

-as eye

------------------Sideroblastic anemia.

-GIT upset

-Hepatitis (most hepatotoxic drug)



-Arthralgia, Gout (comp.'e uric A. excretion àPAS dec. it


-PAS decreases hyperuricemia


-as INH

-as INH

-uric acid


-Retro-bulbar neuritis (optic atrophy rev. dose depend., central>periph)

(given to >13yr pt only to detect abnormality)

-as others


-GIT upset









-examine each eye separately /4wks with CBC and urine and uric acid.

-caution in children, renal patients.

-----------------Vestibulo-cochlear damage (rev.)

(V1st then C)

-fetal Ototox.

-as others

-----------------Blood discariasis (an., tcp, agranulocyt.)

-low Ca, Mg, K -GIT upset


-----------------Renal tubular damage (irrev.) -------


+ve, cross R

-Curare like action (when used with D-tubocurarine topically)


-/4wks renal function

-as INH

-caution in renal, prev. hearing problem,preg.

b) 2nd Line Drugs: (reserve drugs)

Thioacetazone (not in WHO)

PAS acid


Ethionamide/ pro-ethiona.

Fluorinated Quinolones


2-4 mg/kg (150mg/d)

150-300 mg/kg

15 mg/kg (1gm max)

15 mg/kg

(max 0.75-1)

800mg (tarivid 600)


+H = 150-300 + 50-100mg

500mg tab., IV in mening.

500mg tab.

.Trecator 250

.Isoprodian (proeth.+ H + Dapsone)


(best, safe, tolerable)





(less eff.on atypical MB)





carbazone gp.

-Used 1st line instead S or E

-Tolerated by africans.


-IC/EC caseum

-Delay Resist

-Like sulphonamides

-Competes with PABA for di-hydro-petroate synthetase in folic acid synth. Pathway.


-Effect. in non human TB

-Competes with D-alanine 4 synth. of cell wall peptidoglycans


-Effect. In bovine type

-Structural similarity to INH and same way of action.


-Used with MDR

-Inhibits DNA gyrase.



.Good absorb.


.Inactive in urine.

.Cross BBB if inflamed.

.No adjust. in RF /LCF.

-No cross R

-Cross BBB

-Excreted in kidney.


-Eth. à Eth. Sulphoxide (potent)

-Excreted in urine.

(Pro-eth. is less toxic)

-Excreted unchanged in urine.

-Safe in LCF.

-Adjusted in RF.


-Cerebral edema.

-Ototoxicity ofS

-GIT upset

-Liver toxicity


-Bl. discariasis

-Exfoliative dermatitis with HIV

-Chinese rash with cheese meals, fish.

-Cross R with Ethionamide/pro


-Glandulat like fever

-GIT upset,PU

-Liver damage

-Dec. glucose

-Bl. discariasis

-Allergy (rash/fever)

-dec.K, inc.Ca

-Crystalluria in kid.(not 'e S) (phenstix strips in urine)

-Drug interactions:

.R/H/Z (CB4)

.Probencid (inc. toxicity)

.'e Aspirin (salicylism).

-Psychosis, dep, tremors, convulsions, slurred speech, confusion (add B6 50mg)

-GIT upset


-Adjust in renal failure

-Psychosis, PN

-Dec. T4

-GIT upset

(metallic taste, sulpher eructation).

-Dec. glucose.


-Liver damage


-Gynecomastia, impotence, menstrual irregularities, acne.

-Cross R with thioacetazone

-Headache, insomnia, tremors.

-GIT upset.

-Liver enzymes high


-Damage articular cartilage (<16yrs)

-Drug interactions: (except oflo.)







Caution for S.Es and urine test/ 3Ms for compliance

*If sensitivity occurred à desensitization is done either:

Slow:à 1/10 dose à double every 12hrs à full dose.

Rapid: à ¼ dose à increase every day (1/2, ¾, full) then taper. + Steroids 20mg/d

c) New Drugs: (not in WHO except aminoglycosides)

- Clofazimine (Iminopherazine derivative):

.Action: anti-leprosy & antiTB in vitro

.Peak conc.: in 1M

.S.Es: à Crystalline deposits in organs (sp. In fat content)

à Brownish-black pigmentation of skin

à Severe life threatening abdominal pain

- B-lactam/ B-anti-lactamase: in vitro > in vivo so it has a limited use as it

poorly penetrates mammalian cells.

- Macrolides: Concentrated in MQs à antiTB effect (IC) so prevents

multiplication. (Azithro., Roxithro., Clarithromycins)

- Rifamycins: in vitro




Derived from




Activity on TB

>20 times than R

Intermediate between both

Used in R resistance

Used in M. avian complex > R

Half life

20 hrs


16 hrs, rapid abs.


600mg once/wk



150mg/d in new case

300mg/d in MDR

600mg/d in avian


Cross with R


Used in R resistance

- O xazolidinones (Linezolid):

.Used in: MDR and drug resistant G +ve coccal infections.

.S.Es: hematological, PN, expensive.

- Nitroimidazopyranes (Metronidazole derivative):

Bactericidal against Dormant TB & bacilli in anaerobic environment.

- Aminoglycosides:

.Action: Bactericidal

.Preparations: Amikin, Capreomycin, Kanamycin, Viomycin

.Dose: 15mg/kg/d or max. 0.75-1gm (all IM only except amikin can

be given IV too)

.S.Es: 1st 2 drugs à auditory = vestibular effects

2nd 2 drugs à auditory > vestibular effects

- Others: à Analogues of Z (but more active, no cross resistance)

à Drugs target iso-citrate lyase (enzyme that establishes latent TB)

à Immuno-modulation (improve effect of ttt):

.M. Vaccae (for protective cytokine release)

.Post-infection vaccine with LIBI

.Protective cytokines (INFg, IL12, GMCSF)


.Transfer factors

à Alternative drug delivery system:

.Implanted SC slow release Z, H

.Inhalation micro particles (dec. dose/toxicity)

(stimulates alveolar MQs)

.Liposomal encapsulation of antiTB (on MQs)

d) Steroids in TB:

.Indications: -Absolute: à Addison's disease

à Collagen disorders

à Sarcoidosis

à Transplanted organ

-Relative: à Severely ill (TB pneumonia, miliary)

à TB meningitis, pericarditis, peritonitis

(decrease adhesions)

à TB urethritis (dec. stricture)

à TB salpingitis and in vas

à Desensitization in drug sensitivity

à Suppress LN enlargement during

chemotherapy when symptomatizing

.Response: gives rapid improvement to fever, weight loss, ESR level,

exaudative lesion.

.Dose: 20mg/d (60 in pericarditis) à 4-6wks orally

then taper 5mg/d every wk (given under cover of anti-TB)


Thalidomide is used instead of steroids in TB meningitis when no response.

*For Full Text --> download from: Tuberculosis.pdf

Diagnosis of Tuberculosis Emerging trend

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