Pharmacology and Medical Therapy Lecture Notes: Antibiotics, Gout, and RA

A comprehensive set of practice flashcards covering antibiotic classes, resistance mechanisms, gout pharmacological management, and Disease-Modifying Anti-Rheumatic Drugs (DMARDs) for Rheumatoid Arthritis based on lecture transcripts.

What are the four key points of Antimicrobial stewardship in Medication Therapy?

1. Take antibiotics only as needed; 2. Complete the full course of prescribed antibiotics; 3. Consult a doctor regarding antibiotic-related side effects; 4. Be aware of the importance of appropriate antibiotic use.

Name the three mechanisms of Drug Resistance discussed in the transcript.

1. Enzymatic inactivation (enzymes destroy or modify the antibiotic); 2. Alteration of Drug Target (active site configuration changes); 3. Efflux pump / Inhibition of drug uptake (drug is flushed out of cells).

How does the Mechanism of Action (MOA) differ between Beta-lactams and Glycopeptides regarding cell wall inhibition?

Beta-lactams inhibit transpeptidase to prevent peptide bond formation between NAM pentapeptides, while Glycopeptides bind to D-ala on NAM/NAG subunits to prevent transglycosylases from forming glycosidic bonds.

What are the components of Augmentin?

Amoxicillin and Clavulanate Acid.

Why should patients take Augmentin after food?

To manage GI intolerance and side effects like N/V/D and abdominal discomfort.

What role does the addition of different side chains to 7-aminocephalosporanic acid (7-ACA) play in Cephalosporins?

It broadens the spectrum of activity across the different generations of Cephalosporins.

What is a significant contraindication for all Cephalosporins and Penicillins?

Hypersensitivity to Beta-Lactams.

Which carbapenem-resistant mechanism involves Class A enzymatic inactivation?

Klebsiella pneumoniae Carbapenemase (KPC).

What is the specific Drug-Drug Interaction (DDI) between Carbapenems and Sodium Valproate?

Carbapenems decrease the concentration of Valproate, increasing the risk of seizure recurrence.

What is Red Man Syndrome and how is it caused?

An ADR associated with IV Vancomycin resulting from rapid infusion.

Why are Tetracyclines contraindicated in children $\leq 8$ years old?

Risk of growth retardation and permanent teeth staining due to chelation with Calcium.

What is the unique 'Post-antibiotic effect' associated with Aminoglycosides (AGs)?

The effect of the AG persists for several hours even after the drug level falls below the MIC or is renally eliminated.

How should a patient be counseled to use Tobramycin eyedrops?

Space 5 minutes from other eyedrops and 10 minutes from eye ointments; discard the bottle 4 weeks after opening.

Which Macrolide is the most preferred due to minimal CYP3A4 inhibition and fewer DDI risks?

Azithromycin.

What serious side effect is associated with the use of Linezolid for more than 2 weeks?

Thrombocytopenia.

What are the storage requirements for Chloramphenicol eye-drops?

Store in a refrigerator at $2-8^{\circ} C$.

Why is Bactrim contraindicated in patients with G6PD deficiency?

It can trigger hemolytic anemia.

What is the clinical implication of Fluoroquinolones (FQs) exhibiting concentration-dependent killing?

The Peak concentration must be significantly higher than the MIC to achieve a bactericidal effect.

What is the 'Disulfiram-Like Reaction' associated with Metronidazole?

An unpleasant reaction (abdominal pain, severe N/V, palpitations) if alcohol is consumed due to the accumulation of acetaldehyde.

Why is Nitrofurantoin not used to treat Pyelonephritis?

The drug does not distribute to renal tissue sufficiently to hit the MIC.

Which drug is used for chemoprophylaxis of influenza in the MTEMD syllabus?

Oseltamivir.

What is the mechanism of action of Colchicine in treating gout flares?

It disrupts tubulin, preventing the formation of microtubules and inhibiting the migration of WBCs in response to inflammatory mediators.

What does the 'RASHES' acronym stand for in identifying increased risk of Allopurinol-induced SCAR?

Renal impairment, Agent starting dose, HLA-B*5801 allele, Succession/Escalation, Seniority (older age).

How frequently is Methotrexate (MTX) dosed for Rheumatoid Arthritis (RA)?

Once weekly, at a dose between $7.5-25\,mg$.

What is the purpose of taking Folic Acid $2.5-5\,mg$ one day after Methotrexate?

To manage common side effects like mouth ulcers and hair loss and to improve tolerance.

Why must Sulfasalazine (SSZ) tablets be swallowed whole without chewing or crushing?

They are enteric-coated; premature release in the stomach due to pH changes (e.g., from antacids) causes GI intolerance.

What is the function of the 'wash-out' drug Cholestyramine for female patients who have taken Leflunomide?

It adsorbs teriflunomide in the intestine to prevent enterohepatic recycling, significantly reducing the drug's half-life for those planning pregnancy.

What is the first-line therapy for a healthy patient with Pneumonia and no co-morbidities using Doxycycline?

$100\,mg$ BD for 7 days.

Describe the dosage for Fosfomycin in the treatment of Acute, Uncomplicated Cystitis.

A single $3\,g$ dose.

What are the four key principles of Antimicrobial Stewardship in Medical Therapy?

1. Take antibiotics as needed, 2. Complete the full course of prescribed antibiotics, 3. Consult a doctor regarding any related side effects, and 4. Be aware of the importance of appropriate antibiotic use.

Identify and describe the three main mechanisms of antibiotic drug resistance mentioned in the transcript.

(1) Enzymatic inactivation: Bacteria produce enzymes to destroy or modify the antibiotic. (2) Alteration of Drug Target: Modification of the enzymatic active site prevents antibiotic binding. (3) Efflux pump/Inhibition of drug uptake: Efflux Transporters flush antibiotics out of bacterial cells to prevent them from reaching target sites.

What is the mechanism of action (MOA) for Beta-lactam antibiotics?

They inhibit transpeptidase, which prevents the formation of peptide bonds between pentapeptides of adjacent $NAM$ subunits in the bacterial cell wall.

What is the composition of Augmentin and how is its spectrum of activity classified?

Augmentin consists of Amoxicillin and Clavulanate Acid (a Beta-lactamase inhibitor) and is classified as a Broad Spectrum Amino-Penicillin.

Which bacterial enzyme can hydrolyze the lactam ring in Penicillin, rendering it inactive?

Beta-lactamases.

What specific mechanism allows 1st Generation Cephalosporins to overcome drug resistance in bacteria like E. Coli?

They are produced from $7-aminocephalosporanic\,acid\,(7-ACA)$ with the addition of different side chains to broaden the spectrum across generations.

Under what condition should a patient be advised to seek immediate medical attention while taking antibiotics like Augmentin or Cephalosporins?

If they experience severe diarrhea, which can indicate a Clostridioides difficile ($C.\,difficile$) infection.

How do Carbapenems like Imipenem-Cilastatin resist bacterial resistance?

They resist hydrolysis by most bacterial strains, though they can still be inactivated by Carbapenem-Resistant Enterobacteriaceae (CRE) via carbapenemase production.

Identify the four classes of Carbapenemase-producing CRE mentioned in the notes.

Class A: Klebsiella pneumoniae Carbapenemase (KPC); Class B: NDM-1 Carbapenemase; Class C: AmpC Beta-Lactamases; Class D: OXA-48 Carbapenemase.

What is the mechanism of action for Vancomycin?

It inhibits transglycosylase and prevents $D-ala-D-ala$ formation and polymerization, thereby blocking bacterial cell wall synthesis.

What infusion-related adverse reaction is associated with rapid IV administration of Vancomycin?

Red Man Syndrome.

Why are Tetracyclines contraindicated in children $\le 8$ years old and pregnant women?

They cause chelation with $Ca^{2+}$ in the gastrointestinal tract, leading to growth retardation and permanent teeth staining.

What is the 'Post-antibiotic effect' (PAE) unique to Aminoglycosides?

The effect of Aminoglycosides persists for several hours after the drug concentration has dropped below the minimum inhibitory concentration (MIC) or has been renally eliminated.

Which Aminoglycosides adverse effects require therapeutic drug monitoring due to a narrow therapeutic index?

Nephrotoxicity (tubular necrosis leading to acute kidney injury) and Ototoxicity (disruption of vestibular/auditory systems leading to tinnitus).

How should a patient be counseled to take Erythromycin, and why?

Swallow whole and take AFTER food to prevent GI intolerance and prevent inactivation by gastric acid, as it is formulated with an enteric coating.

Describe the mechanism of action of Linezolid.

It binds to the $23S$ ribosomal RNA subunit of the $50S$ subunit to prevent the formation of the $70S$ ribosome, interfering with bacterial translation.

What serious adverse reaction can occur when Linezolid is taken with other drugs that increase serotonin levels (e.g., SSRIs)?

Serotonin ($5-HT$) Syndrome.

How must Chloramphenicol eye-drops be stored?

They must be stored in a refrigerator at $2-8^{\circ} C$.

What is the mechanism of action of Bactrim (Sulfamethoxazole-Trimethoprim)?

It acts as a folate synthesis inhibitor, disrupting nucleic acid formation by depriving bacteria of raw materials needed to produce nucleic acid.

In which specific patient population is Bactrim contraindicated due to the risk of hemolytic anemia?

Patients with $G6PD$ (Glucose-6-Phosphate Dehydrogenase) Deficiency.

What is the primary mechanism of action for Fluoroquinolones (FQs)?

They inhibit DNA gyrase, which relaxes supercoiled DNA, eventually leading to DNA breakdown and truncated transcription and translation.

What musculoskeletal adverse effect is a unique risk of Fluoroquinolone use?

Tendonitis or Tendon Rupture and Arthralgia (joint pain).

Explain the interaction between Metronidazole and Alcohol.

Metronidazole inhibits gut aldehyde dehydrogenase, leading to the accumulation of acetaldehyde, which causes abdominal pain, severe N/V, palpitations, and tachycardia (Disulfiram-Like Reaction).

What is the duration and dosage for a single-dose treatment of Fosfomycin for a lower UTI?

A single dose of $3g$ is sufficient because the drug stays above the MIC for $2-4$ days.

Which natural remedy is noted for reducing the risk of symptomatic UTI by $40\%$ by preventing bacterial adhesion?

Cranberry Juice ($750\,mL$ daily intake).

Differentiate the use of NSAIDs for acute gout flares versus chronic gout management.

NSAIDs provide analgesia and anti-inflammatory effects by inhibiting $COX-2$ enzymes to prevent the conversion of arachidonic acid to Prostaglandins ($PG$).

What specific CNS side effects are associated with the non-selective NSAID Indomethacin?

Drowsiness and Dizziness.

Describe the mechanism of action of Colchicine in treating gout.

It causes tubulin disruption to prevent the formation of microtubules, which inhibits the migration of WBCs in response to inflammatory mediators and prevents phagocytosis.

What is the Uricosuric mechanism of action for Probenecid?

It inhibits the Organic Anion Transporter (OAT) at the Proximal Convoluting Tubule (PCT), preventing the reabsorption of urate back into systemic circulation so it can be renally excreted.

How does Prednisolone act on a molecular level to reduce inflammation?

It forms a drug-receptor complex with glucocorticoid receptors ($GR$), migrates to nucleic acids to alter transcription, and increases production of proteins that inhibit phospholipase $A_2$, thereby reducing arachidonic acid and prostaglandin formation.

Why must patients on high-dose Prednisolone ($> 30\,mg/day$) for more than $2$ weeks taper the dose instead of stopping abruptly?

Abrupt discontinuation leads to a sudden drop in cortisol levels, resulting in withdrawal symptoms like fever, fatigue, and N/V/D because physiological cortisol production was suppressed.

What is the mechanism of action of Allopurinol?

It competitively inhibits Xanthine Oxidase ($XO$), preventing the hydrolysis of purines into uric acid, thus lowering serum urate production.

Name the mnemonic for factors that increase the risk of SCAR/TEN when starting Allopurinol.

RASHES: Renal impairment, Agent starting dose, HLA-B*5801 allele, Escalation, Seniority (older age).

What is the mechanism of action for Methotrexate (MTX) in Rheumatoid Arthritis?

It competitively inhibits Dihydrofolate Reductase ($DHFR$) to prevent the conversion of folic acid into thymidylic acid and purines, reducing RA-related inflammation.

What are the auxiliary handling instructions for Methotrexate, and why?

It is Cytotoxic; patients should avoid direct contact, wash hands immediately if touched, and use a medicine cup to avoid touching tablets, as it can kill healthy cells.

How does Sulfasalazine (SSZ) reduce inflammation in the joints for RA patients?

It is metabolized by intestinal bacteria into sulfapyridine and $5-aminosalicylic\,acid\,(5-ASA)$; sulfapyridine modulates local chemical mediators of the inflammatory response.

Which DMARDS drug has a 'wash-out' procedure involving Cholestyramine for patients wishing to family plan?

Leflunomide ($LEF$).

Explain the role of Cholestyramine in the 'wash-out' of Leflunomide.

It is not absorbed in the body but stays in the GIT, where it adsorbs teriflunomide that has re-entered the intestine via enterohepatic recycling; the complex is then excreted faecally.