Clinical pharmacology and toxicology Flashcards
how to differentiate drug induced lupus from normal lupus
Features: arthralgia, butterfly rash, pleurisy
don’t get neuropsych, rare to get renal (exc hydralazine)
liver enzyme inducers
Induction = PC BRAS Phenytoin Carbamazepine Barbituates Rifampicin Alcohol (chronic excess) St John’s wart
CYP450 inhibitors
CYP450 inhibitors: AODEVICCES allopurinol (xanthine oxidase inh) Omeprazole PPI Disulfiram aldehyde dehydrogenase erythromycin Valproate gaba transaminase Isoniazid [nucleic acid synthetase] & itiaconazole/fluconazole (ergosterol synth) Ciprofloxacin ****Cimetidine Ethanol (acute) Sulfonamide (dihydropteoate synthase)
nephrotoxics
Nephrotoxics Diuretics (esp high dose loops) ACEi/ARB/aminoglycosides/amphotericin NSAIDs incl high dose aspirin Cytotoxics eg cisplatin Calicneurin inh (cylcosporin, tacrolimus)
is rifampicin an inducer or inhibitor
inducer
haemodialysis doesn’t clear what (6)
but it does clear (5)
benzo's CCBs TCAs • dextropropoxyphene (Co-proxamol) • digoxin • beta-blockers
can be cleared -BLAST
• Barbiturate
• Lithium
• Alcohol (inc methanol, ethylene glycol)
• Salicylates
Theophyllines (charcoal haemoperfusion is preferable)
adrenaline doses in anaphylaxis and cardiac arrest
anaphylaxis: 0.5mg - 0.5ml 1:1000 IM
heart attack: 1mg - 10ml 1:10000 IV(or 1ml 1:1,000 IV)
SE of these common cytotoxics
- asparagine
- cisplatin
- vincristine/vinblastine
- bleomycin
- doxorubicin
- cyclophosphamide
- methotrexate
toxicity bear
- asparagine: neurotoxic
- cisplatin: ototoxic/nephrotoxic
- vincristine/vinblastine: christ my nerves, blast my bones - vincr = peripheral neuropathy, vinblas = myelosuppression
- bleomycin - pulmonary fibrosis
- doxorubicin - cardiotoxic
- cyclophosphamide - nephro/bladder toxic, SIADH
- methotrexate - nephrotoxic, myelosuppression
drinks bottle of anti freeze
- whats the toxin in it?
- tx?
ethylene glycol
tx: fomepizole (competitive inh of alcohol dehydrogenase in liver)
windshield washer fluid: methanol - also tx with fomepizole
lithium
- triggers of toxicity
- fts
- mx
Triggers of toxicity: dehydration, renal failure
- Diuretics (esp thiazides), ACEi/ARB/NSAID, metronidazole
Fts of tox:
- Coarse tremor (fine in therapeutic level) - Hyper-reflexia - Acute confusion - Polyuria - Seizure - Coma
Mx:
- Mild-mod NaCl - Severe: haemodialysis
st johns wort
- effect on p450?
- does it work? how does it work
- adverse effects 2
KEY BITS • Inducer of p450 NOTES · As effective as TCAs in mild-mod depression · Thought to act like SSRIs Adverse effects • profile in trials similar to placebo • can cause serotonin syndrome • inducer of P450 system (decreased levels of warfarin, ciclosporin. Reduced effectiveness of COCP)
DETAILS
mechanism: thought to be similar to SSRIs (although noradrenaline uptake inhibition has also been demonstrated)
NB ‘may be of benefit in mild or mod depression, but its use should not be prescribed or advised because of uncertainty about appropriate doses, variation in the nature of preparations, and potential serious interactions with other drugs’
paracetamol OD
- increased risk (2)
- protective (1)
single most important factor for prognosis?
Mx incl criteria for liver transplant
metabolic reason for overdose
Enzyme inducers»_space; increase risk of hepatotoxicity
- Chronic alcohol - Rifampicin - Carbamazepine - St john's wort
Other increased risk: malnourished pt (anorexia) or not eaten for a few days
prognosis: arterial pH
Acute alcohol intake - may be protective
Mx
1. Present <1hr: charcoal 2. NAC - Indications: Staggered OD (taken over a period >1h), doubt over time of ingestion; Nomograph - Anaphylactoid reaction common - stop and restart at slower rate 3. Liver transplant - Arterial pH <7.3 (24h after ingestion) - All of: PT >100s, Cr >300 + grade 3 or 4 encephalopathy
NAC = cysteine = precursor of glutathione
OD occurs when glutathione runs out»_space; increase in NAPQI
cocaine - abdo pain/PR bleeding, think? - 1st line mx? mx of CP, of HTN? - ABG pic mechanism effects on preg (2)
Mx: generally benzos 1st line
- MI due to cocaine: give IV benzo + ACS tx
Abdo pain or PR bleeding in coke pt = ischaemic colitis
Metabolic acidosis
NOTES
Mx
- Chest pain: benzo + GTN (if MI: go for PCI)
- HTN: benzo + sodium nitroprusside
Middle
Mech: Blocks uptake of dopamine, noradrenaline and serotonin
preg: IUGR, prem labour
metformin - acts by? 2 main effects CI (2) SE (3) does it cause hypos or wt gain? what do you do if giving contrast
Metformin
- Acts by activation of AMP-activated protein kinase - Increases insulin sensitivity, decreases hepatic gluconeogenesis - Leave at least 1 week between increasing doses
Metformin
- CI CKD - review dose if Cr>130 (eGFR <45), stop If >150 (eGFR <30)
○ Periods of tissue hypoxia eg recent MI/sepsis/aki/dehydration - if give metformin > lactic acidosis
- SE
○ GI upset (nausea/anorexia/diarrhoea)
○ Reduced vit B12 abs
○ lactic acidosis w severe liver/renal disease
- Uptitrate the dose slowly (reduce chance of GI SE)
- If unacceptable SE consider MR metformin
Extra
- Biguanide
- Doesn’t cause hypoglycaemia or wt gain
- Tx t2dm, nafld, pcos
- Improve glucose tolerance; may reduce GI abs of carbs
Discontinue metformin on day of contrast and for 48h after
allopurinol - mech - most sig adverse effects (3) - whos most at risk? what should they be screened for interactions w 3 drugs how to start it indications
Key bits
- Inhibits xanthine oxiase (oxidates 6-mercaptopurine > 6-thiouric acid)
NOTES
Adverse effects
Most sig: derm - warm to stop allopurinol immediately if they develop a rash:
• severe cutaneous adverse reaction (SCAR)
• drug reaction with eosinophilia and systemic symptoms (DRESS)
• SJS
Certain ethnic groups (Chinese, Korean and Thai): increased risk of these reactions
- Pts at a high risk of severe cutaneous adverse reaction should be screened for HLA-B *5801 allele.
Interactions
Azathioprine
• metabolised to active compound 6-mercaptopurine
• xanthine oxidase is responsible for the oxidation of 6-mercaptopurine to 6-thiouric acid
• allopurinol»_space; high levels of 6-mercaptopurine
• much reduced dose (e.g. 25%) must therefore be used if the combination cannot be avoided
Cyclophosphamide
• allopurinol reduces renal clearance, therefore may cause marrow toxicity
Theophylline
• allopurinol causes an increase in plasma concentration of theophylline by inhibiting its breakdown
DETAILS
Starting it
• Wait until inflam settled so pts not making choices in pain
• initial dose: 100 mg od (lower if low eGFR); titrate every few wks to aim for uric acid of < 300
• Consider colchicine cover when starting. If not tol, consider NSAIDs - take for 6 months
Indications for allopurinol
• all patients after their first attack of gout
• esp if: >= 2 attacks in 12 months, tophi, renal disease, uric acid renal stones, prophylaxis if on cytotoxics or diuretics
patients with Lesch-Nyhan syndrome often take allopurinol for life
actions of these adrenoreceptors - a1 a2 b1 b2 b3
Alpha-1 • vasoconstriction • relaxation of GI smooth muscle • salivary secretion • hepatic glycogenolysis Alpha-2 • mainly presynaptic: inhibition of transmitter release (inc NA, Ach from autonomic nerves) • inhibits insulin • platelet aggregation Beta-1 • mainly located in the heart • increase heart rate + force Beta-2 • vasodilation • bronchodilation • relaxation of GI smooth muscle Beta-3 • Lipolysis
Pathways • all are G-protein coupled • alpha-1:activate phospholipase C → IP3 → DAG • alpha-2: inhibit adenylate cyclase • beta-1: stimulate adenylate cyclase • beta-2: stimulate adenylate cyclase beta-3: stimulate adenylate cyclase
quinolones
- eg abx?
- SE (4), CI (3)
- mech
= ciprofloxacin
SE - Lower seizure threshold in epilepsy - Tendon damage (increased on steroids - MUM) - Cartilage damage - Prolonged QT CI: pregnant, breast feeding, G6PD
Mech: inh topoisomerase 2 (DNA gyrase) + topoisomerase 4
Mech of res: mutations to DNA gyrase, efflux pumps > reduce quinolone conc
G6PD = heinz bodies
Drugs affected by acetylator status (5)
50% of the UK population are deficient in hepatic N-acetyltransferase
Drugs affected by acetylator status • isoniazid • procainamide • hydralazine • dapsone sulfasalazine
zero order kinetics - what is it, what 4 drugs see it
Zero-order kinetics
= metabolism which is indep of the concentration of the reactant.
- This is due to metabolic pathways becoming saturated resulting in a constant amount of drug being eliminated per unit time.
- This explains why people may fail a breathalyser test in the morning if they have been drinking the night before
Drugs exhibiting zero-order kinetics • phenytoin • salicylates (e.g. high-dose aspirin) • heparin • Ethanol
1st pass metabolism
what is it
eg drugs
= phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism.
- As a consequence much larger doses are need orally than if given by other routes
This effect is seen in many drugs, including: • aspirin • isosorbide dinitrate • glyceryl trinitrate • lignocaine • propranolol • verapamil • isoprenaline • testosterone hydrocortisone
what are phase 1 and 2 reactions in drug metabolism
where are they usually
Drug metabolism usually involves 2 types of biochem reactions - phase I and phase II
• phase I reactions: oxidation, reduction, hydrolysis.
○ Mainly done by P450 enzymes but some drugs are metabolised by specific enzymes, EG alcohol dehydrogenase and xanthine oxidase.
○ Products of phase I reactions are typically more active and potentially toxic
• phase II reactions: conjugation.
○ Products are typically inactive and excreted in urine or bile.
○ Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved
Most phase 1 & II reactions take place in the liver
statin
- mech of action
- SE (2)
if on a statin and hx of myalgia, what drug do you avoid adding?
HMG CoA reductase inhibitor
myositis, deranged LFTs
avoid adding fibrates - risk of muscle toxicity
digoxin
- mech of action
- fts of tox
- triggers of tox
- incl drugs that trigger it (8)
- when do you check the level if suspect tox
Mech of action
- decreases conduction through AVN > slows ventricular rate in AF and flutter
increases force of cardiac muscle contraction due inhibition of the Na+/K+ ATPase pump. Also stimulates vagus nerve
Suspect toxicity: measure conc within 8-12h of last dose
Features of tox:
- Confused, yellow-green vision (xanthopsia) - Unwell, tired, n/v, anorexia - Arrhythmias: AV block, bradycardia - Gynaecomastia
Triggers of toxicity
- Low K - Older age - Myocardial ischaemia - Low Mg, low albumin - Hypothermia - Hypothyroid - High calcium, high Na - Acidosis - Drugs: amiodarone, quinidine, verapamil, diltiazem, spironolactone, ciclosporin - Drugs that cause low K: thiazides, loop diuretics
Digoxin binds ATPase pump on same site as K. low K > digoxin can bind easier > increased ing effects
heparin
- 2 main types
- mech of action?
- SE (4)
- OD tx
- differences between the 2 types incl how to monitor
- what is HIT: fts, mech, when does it occur
Activate antithrombin 3
- Unfractionated: form a complex > inhibits thombin, factors Xa, Ixa, Xia, XIIa - LMWH increases action of antithrombin 3 >> inhibition of factor Xa
SE of heparin: Bleeding, low plts, osteoporosis, hyperkalaemia
Lmwh v unfractionated LMWH - SC, long action - Lower risk of HIT and osteoporosis - Monitor: anti-factor XA (but usually don’t need routine monitoring)
Standard/unfractionated heparin
- IV admin - Short action - Use in renal failure - Use in high risk of bleeding as can stop quickly - Monitor: APTT
Heparin overdose tx: protamine sulphate (only partly reverses LMWH)
Heparin induced thrombocytopenia
- Antibodies form against complexes of heparin + plt factor 4
- Develops 5-10ds after starting treatment
- Fts = >50% fall in plts, thrombosis, skin allergy
Low plts but prothrombotic
therapeutic drug monitoring
when do you take levels for
- lithium, ciclosporin, digoxin, phenytoin
Lithium: take 12 hrs post-dose
Ciclosporin: trough levels immediately before dose
Digoxin: at least 6 hrs post-dose
Phenytoin: trough levels, immediately before dose
should be checked if:
• adjustment of phenytoin dose
• suspected toxicity
• detection of non-adherence to the prescribed medication
(doesn’t need routine monitoring)
drugs acting on common receptors
- alpha: agonist & blocker
- beta 1, beta 2: agonists and blockers
- dopamine: ag & antag
- GABA: ag and antag
- histamine 1 and 2 antagonists
- muscarinic ag and antag
- nicotinic ag and antag
- serotonin ag and antag
Alpha
- Blocker: tamsulosin, doxazosin - Agonist: brimonidine, phenylephrine (1), clonidine (a-2)
Beta-blockers:
- B-1: atenolol, bisoprolol - B-2 propranolol, labetalol
Beta-agonists
- B-1: inotropes = dobutamine - B-2 bronchodilators = salbutamol
Dopamine
- Agonists: ropinirole - Antagonists: haloperidol, metoclopramide, domperidone
GABA
- Agonists: benzos, baclofen - Antagonists: flumazenil
Histamine antagonists
- Hist 1=antihistamines eg loratidine - Hist 2=antacids eg ranitidine
Muscarinic
- Agonist: pilocarpine - Antag: atropine, ipratropium, oxybutynin
Nicotinine
- Agonist: nicotine, vareniciline, suxamethonium - Anatag: atracurium
Serotonin
- Agonist: triptan
Antag: ondansetron
TB drugs (4)
which one/ones do you need to reduce dose of in renal impairment?
SE of these drugs
(mechanisms if can)
2 have effects on liver enz - induce or inh?
NB renal impairment: need to reduce dose of ethambutol (others are fine)
RIPE
- R: hepatitis, orange secretions - I: peripheral neuropathy (tx with pyridoxine [vit B6] - Pyrazinamide: gout - Ethambutol: optic neuritis
Effect on liver enz
- Rifampicin: inducer - Isoniazid: inhibitor
NOTES Rifampicin • mech: inh bacterial DNA dependent RNA polymerase >> preventing transcription of DNA into mRNA • potent liver enzyme inducer • hepatitis, orange secretions • flu-like symptoms
Isoniazid • mech: inhibits mycolic acid synthesis • peripheral neuropathy: prevent with pyridoxine (Vitamin B6) • hepatitis, agranulocytosis • liver enzyme inhibitor
Pyrazinamide • mech: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) • hyperuricaemia causing gout • arthralgia, myalgia • hepatitis
Ethambutol
• Mech: inhibits enzyme arabinosyl transferase which polymerizes arabinose into arabinan
• optic neuritis: check visual acuity before and during treatment
• dose needs adjusting in patients with renal impairment
adrenoceptor antagonist
alpha antagonists for a1, a1a, a2, non-selective?
beta antagonists for beta 1 and non-selective?
mixed antagonists (2)
Alpha antagonists • alpha-1: doxazosin • alpha-1a: tamsulosin - acts mainly on urogenital tract • alpha-2: yohimbine • non-selective: phenoxybenzamine (previously used in peripheral arterial disease) Beta antagonists • beta-1: atenolol • non-selective: propranolol
Mixed a and b adrenoceptor antagonist: carvedilol, labetalol
trastuzumab
- targets?
- se (3)
herceptin
monoclonal Ab that acts on HER2/neu receptors
SE: cardiotoxicity (more common when with anthracyclines also eg doxorubicin)
- Mainly in metastatic breast cancer - SE common - flu, diarrhoea ECHO before tx
gentamicin - CI (1) - SE (2) - what levels do we measure & when? whats the action if one is high
Aminoglycoside nephrotox: due to acute tubular necrosis
NOTES
CI: myasthenia gravis
SE:
1. ototoxicity (due to auditory/vestibular nerve damage: irreversible) 2. Nephrotoxicity (due to ATN. Increased risk w furosemide.
Measure peak and trough levels
- Peak: 1h after admin - if high, decrease dose - Trough: just before next dose - if high, increase interval between doses
aspirin
- mech
- potentiates (3)
irreversible inh of cox 1 and 2 Potentiates - oral hypoglycaemics - warfarin steroids
alcohol
- what effect does it have on ADH?
- what drugs for acute withdrawal?
- what 2 drugs can promote abstinence?
Alcohol inhibits secretion of ADH
Nutritional support: oral thiamine if their ‘diet may be deficient’
Drugs
• benzodiazepines for acute withdrawal
• disulfram: promotes abstinence
○ alcohol intake causes severe reaction due to inhibition of acetaldehyde dehydrogenase
○ even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms
○ CI: IHD and psychosis
acamprosate: reduces craving, weak antagonist of NMDA receptors
Ciclosporin
- mech
- SE
Adverse effects of ciclosporin (note how everything is increased - fluid, BP, K+, hair, gums, glucose)
- nephrotoxicity - hepatotoxicity - fluid retention - hypertension - hyperkalaemia - hypertrichosis - gingival hyperplasia - tremor - impaired glucose tolerance - hyperlipidaemia - increased susceptibility to severe infection - decreases clonal proliferation of T cells by reducing IL-2 release - Acts by binding to cyclophilin > forming a complex which inhibits calcineurin (a phosphatase that activates various transcription factors in T cells)
what type of receptor do steroids and levothyroxine bind
nuclear receptors
TCA OD tx? (indications for it) does dialysis work? what 3 drugs to avoid which 2 are most dangerous in OD
more:
early fts
severe poisoning
ECG changes
Tx = IV bicarb (give if hypotension, arrhythmia, widening of QRS >100)
Dialysis is INEFFECTIVE at removing tricyclics
Class 1a (quinidine) and 1c anti-arrhythmics (flecainide) are CI - Because they prolong depolarisation
Amiodarone should be avoided as prolongs QT
Amitriptyline and dosulepin (dothiepin) are most dangerous in OD
Early fts: anticholinergic (dry mouth, dilated pupils, agitation, sinus tachy, blurred vision)
Severe poisoning: arrhythmias, seizures, metabolic acidosis, coma
ECG changes - Sinus tachy - Widening QRS ○ >100 = seizure risk ○ >160 = ventricular arrhythmias - Prolonged QT
octreotide
- uses (6)
- what is it
- SE 1
Overview
• long-acting analogue of somatostatin
• somatostatin is released from D cells of pancreas and inhibits the release of GH glucagon and insulin
Uses
• acute treatment of variceal haemorrhage
• acromegaly
• carcinoid syndrome
• prevent complications following pancreatic surgery
• VIPomas
• refractory diarrhoea
Adverse effects
gallstones (secondary to biliary stasis)
SE of sulphonylureas (4), glitazones (4), gliptins (1)
Sulphonylureas
EG chlorpropamide
SE: hypoglycaemia, increased appetite/wt, SIADH, liver dysfunction (cholestatic)
glitazones SE: wt gain, fluid retention, liver dysfunction, fractures
gliptins SE: pancreatitis
Oculogyric crisis
- causes (3)
- mx options (2)
Causes • antipsychotics • metoclopramide • postencephalitic Parkinson's disease Management intravenous antimuscarinic: benztropine or procyclidine
lidocaine
- fts of toxicity
- increased risk of tox (2)
- tx of tox
• Toxicity: due to IV or excess administration.
○ Increased risk if liver dysfunction or low protein states.
○ Acidosis causes lidocaine to detach from protein binding.
• Drug interactions: Beta blockers, ciprofloxacin, phenytoin
Features of toxicity:
• Initial CNS over activity then depression
○ lidocaine initially blocks inhib pathways then blocks both inh + activating pathways
• Cardiac arrhythmias.
tx: IV 20% lipid emulsion
tacrolimus mech of action
and what other cytotoxic also works this way
Ciclosporin + tacrolimus: inh calcineurin > decreased IL2
what abx affects epilepsy
ciprofloxacin reduces seizure threshold
abciximab mech of action
Glycoprotein IIb/IIIa receptor antagonist
methanol poisoning
- mx options
- abg pic
- specific effects
Management
• fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
• haemodialysis
• cofactor therapy with folinic acid to reduce ophthalmological complications
Methanol fts
• effects ass w alcohol (intoxication, nausea etc)
• + specific visual problems, incl blindness.
Methanol v ethylene glycol
raised anion-gap metabolic acidosis: differential = methanol or ethylene glycol
- Similar biochem + clinical pic
- But eye signs (macular oedema, poor pupillary response) in drowsy pt = methanol
DETAILS
- Visual effects are thought to be secondary to the accumulation of formic acid - thought to be caused by a form of optic neuropathy
More
cases involving methanol toxicity often involve patients not meeting your gaze or asking for the lights to be switched on, as well as the more traditional visual acuity results.
which abx inhibit protein synthesis and which part of the ribosome do they act on
- 50s subunit (5)
- 30s subunit (2)
Inhibits protein synthesis (by acting on the ribosome)
50S subunit: macrolides, chloramphenicol, clindamycin, linezolid, streptogrammins
30S subunit: aminoglycosides, tetracyclines
amiodarone hypothyroidism: mx?
amiodarone induced thyrotox:
- 2 types?
- mx?
Amiodarone induced hypothyroidism: can continue amiodarone
Amiodarone induced thyrotoxicosis
1. Excess iodine-induced thyroid hormone synth. Goitre. Mx: carbimaozle or K perchlorate
2. Amiodarone-rel destructive thyroiditis. No goitre. Mx: steroids
Stop the amiodarone in both types
when do you get central pontine myelinolysis
when you correct low Na too quick
organophosphate insecticide poisoning
- mx?
- features
- mechanism behind fts
Features – ACh accumulates (SLUD) • Salivation • Lacrimation • Urination • Defecation/diarrhoea • CV: hypotension, bradycardia • Small pupils, muscle fasciculation • Sweating ++
Mx: Atropine
DETAILS
Overview
• Inhibits acheylcholinesterase»_space; upregulation of nicotinic + muscarinic cholinergic neurotransmission
• Ach is the main neurotransmitter for parasympathetic system so it presents as upregulation of this
• Sweat glands use cholinergic transmission so get sweaty too
cyanide
- fts
- mx
- action of cyanide
Presentation
• ‘classical’ fts: brick-red skin, smell of bitter almonds
• acute: hypoxia, hypotension, headache, confusion
• chronic: ataxia, peripheral neuropathy, dermatitis
Management
• supportive: 100% oxygen
• definitive: hydroxocobalamin (IV) + combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)
DETAILS
- may be used in insecticides, photograph development and the production of certain metals - Inhibits cytochrome c oxidase > cessation of mitochondrial electron transfer chain.
most common cause: smoke inhalation
mechs of aspirin, clopidogrel, ticagrelor, abciximab, tirofiban
Clotting drugs
- Aspirin: non reversible COX 1 and 2 inhibitor
- Clopidogrel/ticagrelor: P2Y12-ADP rec antag
- GP IIb/IIIa receptor inhibitors (such as abciximab, eptifibatide, tirofiban
causes of raised anion gap metabolic acidosis (6)
- lactic acidosis
- ketoacidosis
- renal failure (high urate)
- toxins such as methanol, ethylene glycol, salicylates
ethylene glycol
- 3 stages of presentation
- mx options
- ABG pic
1st line tx: fomepizole (inh of alcohol dehydrogenase)
- Used to give ethanol - competes for alcohol dehydrogenase - Refractory: dialysis
NOTES
EG after drinking antifreeze/coolant
Stage 1: symptoms of alcohol intox (confused, dizzy, slurred speech)
Stage 2:
- metabolic acidosis w high anion gap and high osmolar gap
- Tachycardia, hypotension
Stage 3: AKI
DETAILS
ethanol - it competes with ethylene glycol for alcohol dehydrogenase
- This limits formation of toxic metabolites (e.g. glycoaldehyde and glycolic acid) which are responsible for the haemodynamic/metabolic features of poisoning
More
blood gas shows metabolic acidosis with respiratory compensation.
- normal glucose level: excl DKA.
CO poisoning indications for hyperbaric oxygen (5)
Indications for hyperbaric oxygen: loss of consciousness, neuro signs, myocardial ischaemia, arrhythmia, pregnancy
vit C deficiency fts
Eg 64y old woman w multiple non-healing leg ulcers. Generally unwell for many months. Pale conjunctiva. Poor dentition w bleeding gums
NOTES
Vitamin C deficiency (scurvy)
» defective synthesis of collagen»_space; capillary fragility (bleeding tendency) and poor wound healing
Features • gingivitis, loose teeth • poor wound healing • bleeding from gums, haematuria, epistaxis • general malaise
amiloride action
• blocks the epithelial sodium channel in DCT
• weak diuretic
usually given with thiazides or loop diuretics as an alternative to potassium supplementation (remember that thiazides and loop diuretics often cause hypokalaemia)
k sparing diuretics (4)
use w caution w?
- epithelial sodium channel blockers (amiloride and triamterene)
- aldosterone antagonists (spironolactone and eplerenone).
Use w ACEi w caution: can cause hyperkalaemia
Amiloride
• blocks the epithelial sodium channel in DCT
• weak diuretic
• usually given with thiazides or loop diuretics as an alternative to potassium supplementation (remember that thiazides and loop diuretics often cause hypokalaemia)
Aldosterone antagonists e.g. spironolactone
• acts in the cortical collecting duct
• indications
○ ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used
○ heart failure
○ nephrotic syndrome
○ Conn’s syndrome
allopurinol what do you need to screen for before starting in pts at risk
Adverse effects
Most sig: derm - warm to stop allopurinol immediately if they develop a rash:
• severe cutaneous adverse reaction (SCAR)
• drug reaction with eosinophilia and systemic symptoms (DRESS)
• SJS
Certain ethnic groups (Chinese, Korean and Thai): increased risk of these reactions
- Pts at a high risk of severe cutaneous adverse reaction should be screened for HLA-B *5801 allele.
