clw 6 Flashcards
tb, aki, nutrition, seizure, med chem
what to check for TB tx initiation
- baseline liver enzymes
- (ethambutol) visual acuity, colour vision
- weight each visit
how are TB drugs dosed
by weight
first line TB tx drugs
rifampicin, isoniazid, pyrazinamide, ethambutol, streptomycin
common side effects of tb drugs
cutaneous rxn
photosensitivity
(PRI) gi s/e -> take after food
rifampicin metabolism
hepatic (monitor liver fx), cyp potent inducer
main ae associated with rifampicin
thrombocytopenia (feed mothers and neonates with VitK), SJS/TEN, flu-like syndrome
side effect of rifampicin to alert patients
ORANGE discoloration of bodily fluids eg. tears, sweat, urine
what to monitor for rifampicin
Renal fx - Rifampicin can cause acute renal failure
isoniazid metabolism
hepatic, N-acetyltransferase. kidney inactive metabolites excretion
isoniazid polymorphism
acetylation rate is related to genetic polymorphisms. chinese present rapid acetylator phenotype unlike indians
why can isoniazid exhibit hepatic toxicity?
toxic metabolite, hydrazine (not acetyl hydrazine)
isoniazid in pregnant patients / at risk of peripheral neuropathy give what
pyridoxine (vb6) for CNS function
avoid isoniazid with
carbs, tyramine, histamine
isoniazid inhibitor of
p450
main ae of isoniazid
peripheral neuropathy
importance of pyrazinamide
eliminates persistent bacilli responsible for relapse
which tb drugs can penetrate csf well
isoniazid, pyrazinamide
is pyrazinamide hepatotoxic
yes, avoid in patients with ALD
gout pts should be careful of pyrazinamide / ethambutol because
can lead to Increased uric acid levels
need adjust pyrazinamide / ethambutol for kidney pt?
yes, metabolites can accumulate. decrease dose
ethambutol ae
visual toxicity (esp kidney failure, elderly tx>2m)
gout
avoid ethambutol with
antacids, at least 2h
what can streptomycin replace
ethambutol
ae of streptomycin
ototoxicity, neuro, kidney toxicity
how to know if pt is cured of tb
negative sputum culture or smear in last month of tx and on at least one previous occasion
when patient has AKI and tb, what to remember to do?
adjust the tb dose according to the improving/worsening crcl
do hcps need to report tb
yes, to moh under infectious disease act
counselling points for tb drugs
- reinforce importance of compliance to medication to eradicate bacteria
- take after a light meal to reduce GI discomfort for PRI meds
- space antacids 2h apart
- cannot take concomitantly with tyramine and histamine-rich foods
- pyridoxine helps to prevent peripheral neuropathy
how to monitor effectiveness of tb treatment
CXR and clinical sample of smear after intensive phase (ie 2m)
how should airflow be for TB in hospital
- In airborne infection isolation room with special air handling & ventilation system
- Negative room pressure as compared to env: Unidirectional inward airflow frm the env to room → prevent contaminated air from pt’s room from flowing into env
do tb patients need to minimise contact with their household
nope, already exposed
non pharm for tb
- cough etiquette
- home should be well-ventilated
- after 2 weeks of tx, do not need to avoid others
- avoid allowing non-household contacts to visit
labs for aki
accumulation of waste products (urea and Cr)
drugs causing aki
NSAIDs
ACEi, ARB
Contrast media
Antimicrobials
(aminoglycosides,
amphotericin B, antivirals)
Chemotherapy
prerenal aki what is it
- sudden and severe drop in bp (shock)
- severe illness causing interruption of blood flow to kidneys
causes of prerenal aki
- volume depletion
(haemorrhage, overdiuresis, vomiting, diarrhoea)
decreased “effective” volume due to cirrhosis - heart failure
- acei/nsaid
prerenal aki urine type
Urine is highly concentrated (high SG) and low in Na (FeNa < 1%)
what to avoid in pre renal aki
use of diuretics: can reduce circulating volume excessively and add further insult, worsening aki
what is intrinsic aki
direct damage to kidneys due to drugs, inflammation, reduced blood supply
intrinsic aki causes
Acute Tubular Necrosis (ATN)
nephrotoxins (AG, contrast dyes, amphotericin B)
ischemia
penicillins, cipro, sulfonamides
what is postrenal aki
obstruction of urine flow due to enlarged prostate, kidney stones
GOT of AKI
- Minimize or remove insult to kidney
- Reduce extrarenal complications
- Restore patient’s renal function to pre-AKI baseline
how do NSAIDs and ACEi cause AKI
NSAID inhibits prostaglandin, cause afferent to constrict, inhibiting blood flow into the glomerulus
ACEi inhibits ag2, results in loss of constriction of efferent, intraglomerulus pressure drops
reduced pressure causes reduced urine formation
four phases of ATN
initiating, oliguric, diuretic, recovery
managing AKI
- diuretics for fluid management to prevent fluid accumulation
- 2g of Na a day
- managing electrolytes to prevent hyper K,Mg,P
diagnosing AKI
- Increase in SCr by ≥ 26.5 μmol/L within 48 h
- Increase in SCr to ≥ 1.5x baseline, within 7 days
- Urine vol < 0.5 ml/kg/h for ≥ 6h
what kind of aki is most common in hospitalised patients
prerenal - decreased perfusion in kidneys
seizure non pharm
keto diet
limit alcohol consumption
adequate sleep
manage stress
drug inhibitor effects vs inducer effect
drug inhibition (3-4d) vs peak effect of inducer (up to 2w later)
what is a carrier-linked prodrug
carries a pro-moiety which is subsequently hydrolysed to the active drug
what is a bioprecursor prodrug
converted to active forms via oxidation or reduction, do not have promoieties
properties of drugs with carrier linked prodrugs
physicochemical deficiencies that do not allow it to pass cross cellular barrier
advantages of bioprecursors
achieves site specific targeting by taking advantage of enzymes at that location
what kind of drugs are most likely to be converted to prodrugs
- low solubility, high permeability
- high solubility, low permeability
aim of prodrugs
- Improve solubility for parental and oral delivery
- Improve passive permeability
- Improve metabolic stability
- Improve targeting and reduce side effects.
succinate chemical formula
c4h404(2-)
solubility of succinate due to
ionised terminal carboxylate
why are succinate esters easy to hydrolyse
intramolecular catalysis easy
- terminal carboxylate is nucleophilic
- side chain sufficient length to allow intramolecular reaction
what is the intestinal brush border rich with
membrane bound phosphatases to hydrolyse phosphate prodrug
what is Pe (permeability coefficient)
rate at which a cpd transverses a lipid barrier by passive diffusion (ie lipophilicity of solute)
adefovir/tenofivir (anti-hepatitis drugs) are activated by?
kinases - phosphorylated via introduction of two phosphate groups
what is phase 1 metabolism
Phase I: Yields a polar, water-soluble, metabolite that is often still active. Many of the products in this phase can also become substrates for phase II.
Oxidation with cytochrome P450 (most common)
Reduction
Hydrolysis
what is phase 2 metabolism
Phase II: Yields a large polar metabolite by adding endogenous hydrophilic groups to form water-soluble inactive compounds that can be excreted by the body.
Methylation
Glucuronidation (most common)
Acetylation
Sulfation
Conjugation with glutathione
Conjugation with amino acids (glycine, taurine, and glutamic acid)
glycine chemical structure
NH₂‐CH₂‐COOH
main enzymes for phase 1 rxn
oxidase, reductase, hydrolase
what is amidase
catalyze the hydrolysis of an amide, leading to the formation of carboxylic acid and ammonia,
main enzymes for phase 2 rxn
glutathione S-transferases,
N-acyltransferases,
N-acetyltransferases
sulfotransferase (S04)
glutathione chem form
C10H17N3O6S
acyl vs acetyl
An acetyl is a type of acyl group. An acyl group can have any R group attached to the carbonyl (C=O).
An acetyl has a methane group attached to the carbonyl.
esterase
Esterases hydrolyze the compounds that contain ester, amide, and thioester bonds, which cause prodrug activation or detoxification.
crcl calculate
CrCl mL/min (males) = (140 - age) x weight(kg) / 0.814 x serum creatinine (micromol/L), for females, multiply result by 0.85.
