Pharmacology

Question 1

Acquired resistance

Answer 1

mechanisms:

1. altered binding site: altered PBPs

2. enzyme modification: beta lactamase, aminoglycoside modifying enzymes

3. decreased access AB target: efflux pumps, decreased cell permeability

Question 2

Antibiotic mechanism of action

Answer 2

Beta-lactams: Time above MIC

• maxiumum kill rate MIC x2-4

Aminoglycosides: peak concentration ie. AUC/MIC

• maximum activity when MIC x10
• significant concentration dependent post AB effect

Question 3

Antibiotics Parameters

Answer 3

Question 4

Bioavailability

Answer 4

Question 5

Chloramphenicol

Answer 5

mechanism: inhibits bacterial protein synthesis by binding to 50S subunit

spectrum: broad against gram +ve/-ve bacteria and anaerobes

side effects: BM suppression, aplastic anaemia (1/180000-50000) and grey baby syndrome

grey baby syndrome: vasomotor collapse in neonates following high IV doses

• ashen grey skin, low body temperature, vomiting, irregular and rapid respiration, and lethargy

pathogenesis: ineffective liver glucoronidase in 1st weeks

Question 6

Clearance of Drug

Answer 6

clearance (L/min) = volume of blood cleared per unit of time

= rate of elimination/plasma concentration

Question 7

Codeine phosphate metabolism

Answer 7

enzyme: CYP450 2D6

decreased activity: 10% caucasians lack this enzyme making codeine inaffective

Question 8

Dihydroergotamine

Answer 8

class: ergot alkaloids

mechanism: agonist 5HT-1 causing arterial and venous vasoconstriction

contraindication: in migraines with local neurological signs

Question 9

Drug Loops

Answer 9

clockwise: tachyphylaxis with high effect initially with secondary drug tolerance

anti-clockwise: drug needs to be distributed in the plasma to it’s site of action eg. digoxin

Question 10

Drugs in uric acid metabolism

Answer 10

Question 11

half life

Answer 11

half-life: time required for the amount of drug to be reduced by half

t_1/2= 0.693V_d/CL

Question 12

Intrinsic resistance

Answer 12

definition: predictable resistance does not require testing

cause: cellular properties of organism

eg.

• vancomycin not effective gram -ve (no cell wall)
• cefotaxime low affinity pseudomonas (doesn’t bind PBP)
• cephalosporin low affinity enterococcus PBP

Question 13

MIC for penicillin

Answer 13

sensitive: <0.12 mcg/:

intermediate: 0.12-1mcg/L

resistant: >2mcg/L

Question 14

Mycophenolate

Answer 14

mechanism: prodrug converted to mycophenolic acid and selectively suppresses lymphocyte proliferation and antibody formation by inhibiting purine synthesis

common SEs: nasuea, vomiting, diarrhoea, thrombophlebitis/thrombosis

infrequent: oesophagitis, gastritis, GIT bleed, CMV tissue invasive disease, leucopenia, anaemia

carciongenesis: associated with post-transplant lymphoproliferative disease

Question 15

Steady State

Answer 15

steady state: achieved after 4.5 half lifes regardless of drug type or amount

Question 16

Therapeutic Index

Answer 16

TI = toxic dose/therapeutic dose

Question 17

Beta lactams

Answer 17

mechanism: bactericidal broad spectrum

resistance: b-lactamase, altered PBP, reduced entry, removal of drug

resistant organisms:

• GAS
• strep pneumo especially 19A (PRP)
• staph aureus
• E.coli
• haemophilus influenza
• ESBL with klebsiella/ecoli (only sensitive carbapenems)

CSF penetration: cefotaxime, vancomycin

Question 18

MRSA

Answer 18

resistance: altered transpeptidase PBP2a on mec gene

resistant drugs: all penicillin and cephalosporin

sensitive drugs:

• erythromycin (superficial infection, 25% resistant)
• clindamycin (superficial infection, resistance rapid)
• doxycycline (superficial, not <8yrs)
• cotrimoxazole (serious infection not endovascular)
• vancomycin (severe/complicated infection)
• gentamicin (synergy but needs to enter cell wall)

Question 19

CYP drugs

Answer 19