Name Tandiwe Chuma

Module/ Course. Phamarcology ll

Tutor Mrs Hebene

Date of Submission 25/02/2025

 Isoniazid (INH): Isoniazid is a bactericidal drug that inhibits the synthesis of mycolic
acid, an essential component of the mycobacterial cell wall. This results in the inhibition
of cell wall formation, leading to the death of the Mycobacterium tuberculosis ([Link])
organism.
 Rifampicin (RMP): Rifampicin is a bactericidal drug that inhibits bacterial RNA
synthesis by binding to the bacterial DNA-dependent RNA polymerase, preventing
transcription. It has a broad spectrum of activity, including against [Link], and helps in
reducing bacterial load.
 Ethambutol (EMB): Ethambutol inhibits the synthesis of arabinogalactan, an essential
component of the mycobacterial cell wall. This action disrupts the integrity of the cell
wall, impairing cell division and leading to bacterial death.
 Pyrazinamide (PZA): Pyrazinamide is a prodrug that is converted to its active form,
pyrazinoic acid, in acidic environments. It inhibits the enzyme fatty acid synthase I,
which is involved in mycobacterial lipid biosynthesis, disrupting the integrity of the cell
membrane and reducing bacterial viability, particularly in acidic areas such as within
macrophages.

2. Dosage and Administration:

 Isoniazid (INH): The recommended dosage for an adult patient is 5 mg/kg body weight
daily, up to a maximum of 300 mg per day. For this patient (55 kg), the dose would be
approximately 300 mg daily.
 Rifampicin (RMP): The standard dose for an adult patient is 10 mg/kg body weight,
with a maximum dose of 600 mg daily. For this patient (55 kg), the dose would be 550
mg daily.
 Ethambutol (EMB): The usual dose is 15 mg/kg body weight daily, with a maximum
dose of 1,200 mg daily. For this patient (55 kg), the dose would be 825 mg daily.
 Pyrazinamide (PZA): The usual dose is 25 mg/kg body weight daily, with a maximum
dose of 2,000 mg daily. For this patient (55 kg), the dose would be 1,375 mg daily.

3. Common Side Effects and Adverse Reactions:

 Isoniazid (INH): Common side effects include hepatotoxicity (liver damage), peripheral
neuropathy (especially in patients with predisposing factors such as diabetes or
malnutrition), rash, and fever. Severe side effects can include hepatitis and seizures.
 Rifampicin (RMP): Common side effects include gastrointestinal symptoms (nausea,
vomiting), hepatotoxicity, rash, and discoloration of body fluids (e.g., urine, sweat, tears
may turn orange). Rare side effects include thrombocytopenia, hepatotoxicity, and flu-
like syndrome.
 Ethambutol (EMB): Common side effects include visual disturbances (such as optic
neuritis), nausea, vomiting, and joint pain. Severe side effects can include permanent
vision loss or impairment due to optic neuritis.
  Pyrazinamide (PZA): Common side effects include hepatotoxicity, joint pain,
hyperuricemia (which may lead to gout), and gastrointestinal symptoms (nausea,
vomiting). Severe side effects can include hepatotoxicity and acute gout attacks.

4. Resistance Patterns and Strategies to Overcome Resistance:

 Drug Resistance: [Link] can develop resistance to any of the first-line drugs, particularly
when treatment regimens are not followed properly. Resistance to Isoniazid
(INH) and Rifampicin (RMP) are the most common, and their occurrence leads
to multidrug-resistant tuberculosis (MDR-TB).
 Strategies to Overcome Resistance:
o Directly Observed Treatment (DOT) to ensure patients adhere to their treatment
regimen.
o Use of Combination Therapy: To prevent resistance, all TB patients should be
treated with a combination of drugs, not monotherapy.
o Susceptibility Testing: Regular monitoring and testing (e.g., GeneXpert, sputum
culture) to detect resistance patterns and adjust treatment regimens accordingly.
o TB Infection Control: Isolating patients with drug-resistant TB to prevent
transmission to others.

5. Second-Line Medications According to Zambia National TB Treatment

Second-line drugs are used when resistance to first-line drugs occurs, including:

 Fluoroquinolones (e.g., Levofloxacin, Moxifloxacin)

These drugs are used based on the susceptibility patterns of the [Link] strain and under strict
monitoring due to potential side effects.

6. Role in First-Line and Second-Line TB Treatment Regimens:

 First-Line Drugs:
o Isoniazid (INH), Rifampicin (RMP), Ethambutol (EMB), and Pyrazinamide
(PZA) are the cornerstone of first-line treatment for drug-sensitive TB. The
combination of these four drugs is used to achieve a high cure rate and prevent the
development of resistance.
 Second-Line Drugs:
o Second-line drugs are used when there is drug resistance, particularly in MDR-
TB (resistance to at least INH and RMP) or XDR-TB (resistance to INH, RMP,
and additional drugs). These drugs are typically more toxic and less effective than
 first-line agents, which is why early detection of drug resistance and appropriate
use of second-line agents are crucial.

Summary:

Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide are the first-line drugs used in
treating pulmonary [Link] for side effects, adherence, and resistance
patterns is critical in managing TB [Link] drug-resistant TB, second-line
medications such as fluoroquinolones and injectables are used based on susceptibility
testing.

References:

1. World Health Organization (WHO). (2020). Global tuberculosis report 2020. World
Health Organization. Link to WHO TB report.
2. Zambia National TB Guidelines (2020). National Tuberculosis, Leprosy and Lung
Disease Program (NTLP), Ministry of Health, Zambia.
3. Donald, P. R., & Khan, M. (2019). The role of first-line and second-line drugs in
tuberculosis treatment and their impact on global tuberculosis control. Tuberculosis,
113, 77-90.
4. Mistry, N. F., & Saran, S. (2016). Management of drug-resistant tuberculosis: An
overview of clinical strategies and treatment regimens. Journal of Clinical Tuberculosis,
11(1), 10-21.
5. Gonzalez, R., & Stojanovic, J. (2018). Managing multidrug-resistant tuberculosis:
Pharmacological considerations and clinical approaches. European Respiratory Journal,
51(4), 123-130.