Therapeutics & Toxic 9 Flashcards
(71 cards)
1
Q
Gentamicin = aminoglycoside, poorly lipid soluble so must be given parentally
Adverse effects?
C/I?
Dosing?
A
- irreversible ototoxicity
- nephrotoxic
- C/I in myasthenia gravis
- if trough level high then increase dosing interval
2
Q
Organophosphate insecticide poisoning = inhibition of acetylcholinesterase -> up regulation of nicotinic & muscarinic cholinergic neurotransmission
- features?
- Rx?
A
Salivation Lacrimation Urination Defecation/diarrhoea - also hypotension, bradycardia - small pupils, muscle fasciculation Rx = Atropine (pralidoxime role unclear)
3
Q
Overdoses that can be dialysed?
A
Barbiturates Lithium Alcohols Salicylates Theophyllines
4
Q
Quinolones inhibit DNA synthesis and are bactericidal
- MoA?
- MoResistance?
- adverse effects?
- C/I?
A
- inhibit DNA gyrase (topoisomerase II) & topoisomerase IV
- resistance by mutations to DNA gyros, efflux pumps which reduce intracellular quinolone conc
- lower seizure threshold
- tendon damage esp if taking steroids
- lengthens QT interval
- avoid in pregnancy, breastfeeding & G6PD
5
Q
Amiodarone-induced hypothyroidism
- pathphys?
- what to do?
A
- high iodine content causing an autorgeulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide
- can continue amiodarone if this is desirable
6
Q
Amiodarone-induced thyrotoxicosis type 1?
A
- XS iodine-induced thyroid hormone synthesis
- goitre
- Rx = Carbimazole/potassum perchlorate & stop amiodarone
7
Q
Amiodarone-induced thyrotoxicosis type 2?
A
- amiodarone-related destructive thyroiditis
- no goitre
- Rx = corticosteroids
8
Q
Poisonous snake in UK = adder/viper/viper berus
- can be extremely locally painful with systemic Sx, due to composition of venom (but also can have a bite without venom - still Sx)
A
- pain, swelling, erythema, paraesthesia, numbness, blood blistering
- tracking, compartment syndrome, tissue necrosis
- systemic Sx similar to anaphylaxis, can be delayed
- significant bruising
-> analgesia & supportive care
(tourniquet increases likelihood of localised necrosis & venous thrombosis, as well as arrhythmia)
- only for severe systemic envenomations in patients with resistant hypotension, new ECG changes, significant rise in white cell count, raised CK, metabolic acidosis or swelling involving more than half the affected limb or crossing a joint boundary - 20% have an anaphylactic reaction
9
Q
Rx of paracetamol OD?
A
- activated charcoal if <1h ago
- NAC
- liver Tx
10
Q
Rx of salicylate OD?
A
- haemodialysis if severe
11
Q
Rx of benzodiazepine OD?
A
Flumazenil if severe or iatrogenic (has risk of seizures)
- otherwise supportive
12
Q
Rx of tricyclic antidepressants OD?
A
- IV bicarbonate may reduce risk of seizures & arrhythmias in severe toxicity, to correct acidosis as 1st line of Rx
(1a 1c antiarrhythmics C/I, III avoid etc)
13
Q
Rx of lithium OD?
A
- volume resuscitation
- haemodialysis if severe
(sodium bicarb may promote lithium excretion through increasing alkalinity)
14
Q
Rx of heparin OD?
A
Protamine sulphate
15
Q
Rx of beta-blocker OD?
A
- atropine if bradycardia
- glucagon if resistant
16
Q
Rx of ethylene glycol OD or methanol poisoning?
A
- Fomepizole = inhibitor of ETOH dehydrogenase
- HD if refractory
17
Q
Rx of Digoxin OD?
A
Digoxin-specific Ab fragments
18
Q
Rx of iron OD?
A
Desferrioxamine, chelating agent
19
Q
Rx of lead OD?
A
Dimercaprol, calcium edetate
20
Q
Rx of cyanide OD?
A
Hydroxocobalamin, also combo of amyl nitrite, sodium nitrite, sodium thiosulfate
21
Q
Drugs known to cause impaired glucose tolerance?
A
- steroids
- tacrolimus, ciclosporin
- IFN-alpha
- nicotinic acid
- antipsychotics
- thiazides, furosemide
- beta-blockers
22
Q
Indications for dopamine receptor agonists?
Monitoring?
Adverse effects?
A
PD
prolactinoma/galactorrhoea
cyclical breast disease
acromegaly
- bloods & CXR before starting, and closely monitor with Echo due to risk of pulmonary, pericardial & retroperitoneal fibrosis
- nausea, vomiting, postural hypotension, hallucinations, somnolence
23
Q
Drugs causing lung fibrosis?
A
amiodarone cytotoxics: busulphan, bleomycin anti-rheum: MTX, sulfasalazine, gold nitrofurantoin ergot-derived dopamine receptor agonists: bromocriptine, cabergoline, pergolide
24
Q
Salicylate OD - acid-base picture?
features?
Rx?
indications for HD?
A
- mixed resp alkalosis & metabolic acidosis
- hyperventilation, tinnitus, lethargy, fever, sweating, nausea, vomit, hyperglycaemia & hypo, seizures, coma
- ABC, charcoal, sodium bicarb, haemodialysis
- serum conc >700
- metabolic acidosis resistant to Rx
- acute renal failure
- pulmonary oedema
- seizures
- coma
25
Tricyclic OD
- early features?
- if severe?
- ECG changes?
- Rx?
- dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision
- arrythmia, seizure, metabolic acidosis, coma
- sinus tachycardia, QRS widening, prolonged QT (>100 seizure >160 ventricular arrhythmia)
- IV bicarb
- IV lipid emulsion can help bind free drug and reduce toxicity
26
Novel psychoactive substances: Stimulants similar to MDMA, amphetamines, cocaine
examples?
- increased serotonin, dopamine, noradrenaline -> euphoria
- mephedrone = cathinone = bath salts, m-cat, meow meow
- benzylpiperazine = exodus, legal x, legal e
- pill/powder/snorted
- similar adverse effect profile to MDMA/cocaine, with risk of serotonin syndrome
27
Novel psychoactive substances: Cannabinoids which are synthetic agonists
- examples?
- 'spice'
| - sprayed onto herbal mixtures which are then smoked, also can be liquid
28
Novel psychoactive substances: Hallucinogenics examples?
dissociatives - similar effect to ketamine with a sense of not being connected to physical body/time = mexxy/methoxetamine - NMDA antagonist - tachycardia, HTN, mydriasis, confusion, agitation, nystagmus, dysarthria, ataxia
psychedelics - similar effect to LSD but may also be stimulant
29
Novel psychoactive substances: Depressants?
- pill/powder
- opioid/benzodiazepine-based
- structurally v similar to original drug class with similar adverse effects
- but much longer half-life
30
Novel psychoactive substances: GHB risks?
- G, Geebs, liquid ecstasy
- colourless, odourless, bitter-tasting
- CNS depressant
- euphoria, amnesia, hypnosis - date-rape drug
- resp depression, bradycardia, vomiting, coma
- short recovery time in 6hours, often spontaneously in ED
31
MoA of standard heparin
- IV
- short acting
- activated antithrombin III - forms complex that inhibits thrombin, factors Xa, IXa, Xia, XIIa
- bleeding, HIT, osteoporosis
- monitor with APTT
- useful in renal failure or when high risk bleeding
32
MoA of LMWH?
- SC
- long acting
- activated antithrombin III - forms complex that inhibits factor Xa
- bleeding; lower risk of HIT & osteoporosis
- can monitor anti-factor Xa levels
33
Adverse effects of hepatitis?
bleeding
thrombocytopenia
osteoporosis & inc risk fractures
hyperkalaemia (inhibition of aldosterone secretion)
34
MoA of HIT: heparin-induced thrombocytopenia?
- when does it develop
- features?
- Rx?
- immune-mediated - Ab form against complexes of PF4 (platelet factor 4) & heparin -> they bind to PF4-heparin complexes on platelet surface -> induce platelet activation by X-linking FcgammaIIA receptors
- day 5-10
- prothrombotic, 50% reduction in platelets, thrombosis, skin allergy
- if less than high clinical probability and mod HIT Ab titre then can do serotonin release assay (high seas & spec) to help confirm/exclude Dx
- Rx options inc alternative anticoagulants: LEPIRUDIN & DANAPAROID - anticoag effect can be measured with anti-Xa assay
- or BIVALIRUDIN i.e. non-heparin anticoagulant
- (Rx fondaparinux also acceptable but unlicensed)
- continue Rx anticoag for 3months if thrombosis, 4 weeks if not
- When transitioning from argatroban to warfarin, the INR should be >4 for 2 days prior to discontinuing argatroban
- warfarin shouldn't be used until platelet count back to normal range
35
Lithium = mood stabiliser with v narrow therapeutic range 0.4-1.0 and long plasma half-life - excreted by kidneys
- toxicity usually occurs at conc >1.5
- precipitants?
- features?
- Rx?
- dehydration, renal failure, diuretics esp thiazide, ACE-I, NSAIDs, metronidazole
- coarse tremor, hyperreflexia, acute confusion, seizure, coma
- Rx = volume resuscitation with normal saline, HD if severe- cont until all new neuro Sx resolved, lithium conc stable at <1
- long-term rx can cause renal impairment, hypercalcaemia, hyperPTH, hypothyroidism
- ECG: flattened T waves, wide QRS
36
Paracetamol OD Rx?
When can NAC be stopped?
Criteria for liver Tx?
- NAC infused over 1h if staggered or doubt re: ingestion or on/above Rx line from 4-15h
- when INR <1.3 & ALT <2x ULN
- pH <7.3 24h after ingestion OR
- PT>100, Cr>300, grade III/IV encephalopathy
37
Rifampicin: MoA & side-effects?
- inhibits bacterial DNA-dependent RNA olymerase preventing transcription of DNA into mRNA
- potent liver enzyme INDUCER
- hepatitis, orange secretions, flu-like Sx
- increases metabolism of steroids
38
Isoniazid: MoA & side-effects?
- inhibits mycelia acid synthesis
- peripheral neuropathy prevented with it B6/pyridoxine
- hepatitis, agranulocytosis, liver enzyme inHIBitor
39
Pyrazinamide: MoA & side-effects?
- converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase I
- hyperuricaemia -> GOUT
- hepatitis
- arthralgia, myalgia
40
Ethambutol: MoA & side-effects?
- inhibits arabinosyl transferase which polymerises arabinose into arabinan
- optic neuritis (check acuity before & during Rx)
- adjust dose in renal impairment
41
Features of intrathecal baclofen withdrawal syndrome?
- severe spasticity, rhabdomyolysis, acute renal failure, multi system organ failure
- GABA agonist
- withdrawal resembles BZD & ETOH withdrawal
42
Drugs that may worsen seizure control in epilepsy?
- ETOH, cocaine, amphetamines
- ciprofloxacin, levofloxacin
- aminophylline, theophylline
- bupropion
- methylphenidate
- mefenamic acid, fentanyl, TRAMADOL
- aminophylline, amitriptyline, isotretinoin, haloperidol
- other drugs that interfere with metabolism of anti-epileptics
- some drugs on withdrawal
43
How are IV Igs formed?
| Uses?
- large pool of donors e.g. 5000
- IgG molecules with a subclass distribution similar to normal blood
- half-life 3 weeks
- 1ry & 2ry immunodeficiency, ITP, myasthenia, GBS, Kawasaki, TEN, CMY pneumonitis post-Tx, low IgG levels post-stem cell Tx for ca, dermatomyositis, CIDP
- Nb can cause a pseudohyponatraemia, as can high triglycerides, cholesterol, high serum protein e.g. myeloma
44
Adverse effects of Amiodarone?
- thyroid dysfunction
- corneal deposits
- pulmonary fibrosis/pneumonitis
- liver fibrosis/hepatitis
- peripheral neuropathy, myopathy
- photosensivity
- slate-grey
thrombophlebitis & injection site reactions
- bradycardia
- LQTS
- decreases metabolism of warfarin -> increased INR
- increased digoxin levels
45
P450 enzyme INDUCERS?
- phenytoin, carbamazepine
- phenobarbitone
- rifampicin
- chronic ETOH
- griseofulvin
- st johns wort
- smoking
46
P450 enzyme INHIBITORS?
- ciprofloxacin, erythromycin
- isoniazid
- cimetidine, omeprazole
- amiodarone
- allopurinol
- ketoconazole, fluconazole
- fluoxetine, sertraline
- ritonavir
- sodium valproate
- acute ETOH
- quinupristin
47
Cathinon toxicity: NRG-1 - derivative of phenylpropanone (naturally occurring psychotrope in khat)
- how does it work?
- toxicity?
- Rx?
- increases synaptic conc of noradrenaline, dopamine, serotonin -> euphoria, detachment & wellbeing, up regulation of sympathetic system
- tachycardia, HTN, hyponatraemia due to XS water intake to reduce body temp, serotonin syndrome, ischaemia
- rapid correction of Na with 3% saline at max rate of 1ml/kg/hr if neuro compromise with hyponatraemia
(0. 9% NaCl worsens it)
48
Major complications of iron OD?
Rx?
decontamination procedure of choice?
when is desferrioxamine indicated?
```
metabolic acidosis
erosion of gastric mucosa
GI bleed
shock
hepatotoxicity & coagulopathy
```
- if ingestion <40mg/kg elemental iron & aSx -> can observe at home
- if ingestion >40mg/kg elemental iron/Sx then medical assessment + serum iron levels 2-4h post-dose + AXR
- whole bowel irrigation = decontamination procedure of choice - do on all presenting within 4h who have ingested >60mg/kgOR have undissolved tablets on AXR
Desferrioxamine:
- serum iron >90
- iron 60-90 + Sx/persistent iron on AXR despite whole bowel irrigation
- anyone with shock, coma or metabolic acidosis
49
CO has high affinity for Hb & myoglobin -> Left-shift of oxygen dissociation curve & tissue hypoxia
- features?
- typical carboxyHb levels?
- Rx?
- indications for hyperbaric oxygen?
- headache 90%, nausea/vomit 50%, vertigo 50%, confusion 30%, subjective weakness 20%
- severe: pink skin & mucosa, hyperpyrexia, arrhythmias, EPSE, coma, death
- >30% carboxyHb in severe toxicity, 10-30% Sx, <10% smokers, <3% non-smokers
- 100% O2 target sats 100%
Hyperbaric O2 if:
- LOC at any point
- neuro signs other than headache
- myocardial ischaemia/arrhythmia
- pregnancy
50
Cyanide is in insectivides, photograph development, metal production
- MoA?
- presentation of poisoning?
- Rx?
- inhibits cytochronc c oxidase -> cessation of mitochondrial electron transfer chain
- classically: brick-red skin, smell of bitter almonds
- acute: hypoxia, hypotension, headache, confusion
- chronic: ataxia, peripheral neuropathy, dermatitis
- v high lactic acidosis
Rx = supportive
definitive:
- IV Hydroxocobalamin or combo of:
- Inh amyl nitrite + IV sodium nitrite + IV sodium thiosulfate
- IV dicobalt edetate
51
Paraquat exposure - how to confirm?
Urine dithionite testing - colour change - +ve within 6h of ingestion for many days
- do not wait for results before giving oral Fuller's earth
52
Most important enzyme system for the P450 system?
CYP3A4 system
- common reason for drug interactions
- substrates: macrolides, antiretrovirals, calcium channel blockers
- inhibitors: macrolides, PEs inc ritonavir, imidazoles
- inducers: carbamazepine, phenytoin, phenobarbitone, rifampicin, st johns wort
53
Methanol poisoning
Sx?
Rx?
- nausea, intoxication
- visual problems inc blindness - optic neurpathy
- 2ry to accumulation of formic acid
- Fomepizole
- HD
- Can give foiling acid to reduce ophthalmological complications
54
Serotonin syndrome:
- causes?
features?
Rx?
- MAO-Is, SSRIs, ecstasy, amphetamines
- neuromuscular excitation: hyperreflexia, myoclonus, rigidity
- ANS excitation eg hyperthermia
- altered mental state
- dilated pupils
Rx = IV fluids, supportive, benzodiazepines
- more severe: serotonin antagonists eg Cyproheptadine & chlorpromazine
55
Serotonin syndrome:
- causes?
features?
Rx?
- MAO-Is, SSRIs, ecstasy, amphetamines, linezolid
- neuromuscular excitation: hyperreflexia, myoclonus, rigidity
- ANS excitation eg hyperthermia
- altered mental state
- dilated pupils
Rx = IV fluids, supportive, benzodiazepines
- more severe: serotonin antagonists eg Cyproheptadine & chlorpromazine
56
What analgesia co-Px with SSRIs is a common cause of serotonin syndrome?
TRAMADOL
57
Flecainide = 1c antiarryhthmic - slows conduction of AP by acting as a potent na channel blocker -> wide QRS & prolonged PR
Indications?
C/I?
Adverse effects?
- AF
- SVT ass with accessory pathway e.g. WPW syndrome
C/I in: post-MI, structural heart disease e.g. heart failure, sinus node dysfunction e.g. 2nd degree/greater AV block, atrial flutter
- negative inotrope, bradycardia, pro arrhythmic, oral paraesthesia, visual disturbances
58
Disulfram reaction?
| C/I of disulfram?
- with ETOH -> acetaldehyde -> flushing, nausea, vomiting, arrhythmias, death
- IHD & psychosis
- promotes abstinence with ETOH
59
ETOH problem drinking Rx
- what promotes abstinence?
- what reduces craving?
Disulfram for abstinence
Acamprosate reduces craving: weak NMDA antagonist
60
Quinine = antimalarial & leg cramp prophylaxis
- toxicity = Cinchonism
- Sx?
- findings?
- Rx?
- tinnitus, blurred vision, flushed & dry skin, abdo pain
- prolonged QRS & QT arrhythmia, hypoglycaemia, pulm oedema, renal failure
- clinically similar to aspirin poisoning
- permanent neural damage unlike aspirin
- supportive Rx with fluids, interpose, bicarbonate, NIV
61
Malignant hyperthermia: hyperpyrexia & muscle rigidity due to XS release of Ca2+ from sarcoplasmic reticulum
- ass with defects on chr 19 encoding ryanodine receptor which controls Ca2+ release from SR
- causes?
- Ix?
- Rx?
halothane, suxamethonium, antipsychotics
- raised CK
- contracture tests with halothane & caffeine
- Dantrolene
62
Features of ethylene glycol toxicity?
1. confusion, slurred speech, dizziness (think etOH)
2. metabolic acidosis with high anion gap & high osmolar gap, tachycardia, HTN
3. acute renal failure
63
Features of ethylene glycol toxicity?
| = antifreeze
1. confusion, slurred speech, dizziness (think etOH)
2. metabolic acidosis with high anion gap & high osmolar gap, tachycardia, HTN
3. acute renal failure
64
Nexus (2CB) are drugs similar to MDMA
| features?
- agitation, aggression, hallucinations
- serotonergic/sympathomimetic toxidromes
- can be dangerously potent
- oral/snorting - v painful
- can stimulate at low dose with increased visual/auditory/tactile sensations
- high dose: HTN, tachycardia, hyperthermia, seizures, excited delirium
- unexpected cardiac arrest due to XS dopamine
65
Drugs to avoid in renal failure?
tetracycline, nitrofurantoin
NSAIDs
lithium
metformin
66
Drugs that are likely to accumulate in CKD - need dose adjustment?
```
Most Abx eg penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
digoxin, atenolol
methotrextae
sulphonylureas
furosemide
opioids
```
67
DRESS syndrome = unexpected severe reaction to medication with multi-organ involvement
Sx?
2-8wks after starting offending drug
Drug causes?
Criteria for Dx?
- morbilliform skin rash 80% - exfoliative dermatitis, fever, inflammation, vesicles, bullar
- erythroderma 10%, mucosal involvement 25%, facial swelling 30%
- haem abnormalities
- LN involvement
- AKI/interstitial nephritis
- myocarditis, pericarditis, liver enlargement, hepatitis, lung disease, neuro involvement, GI Sx, colitis, pancreatitis, thyroiditis, diabetes
Dx v difficult
- common drug causes = Allopurinol, anti-epileptics, Abx, immunosuppressants, HIV Rx, NSAIDs
1. extensive skin rash
2. high fever
3. abnormal LFTs
3 of the following:
- hospitalisation
- reaction suspected drug-related
- acute skin rash
fever >38C
- enlarged LNs at 2 sites
- involvement of at least 1 internal organ
- blood count abnormalities e.g. low platelets, raised eosinophils or abnormal lymphocyte count
Skin Bx can help confirm Dx - can show inflammatory infiltrate esp eosinophils, extravasated erythrocytes, oedema
- reg BT
- ECG, CXR, echo, urinalysis etc
Rx = supportive, antihistamines, topical steroids, emollients, careful fluid balance, nutritional monitoring +/- systemic steroids
- occ immunosuprressants/IV Ig & plasmapherese started
mortality 8%
68
Octreotide = long-acting analogue of somatostatin - released from pancreatic D cells and inhibits release of GH, glucagon & insulin
Uses?
Adverse effects?
- acute rx variceal bleed
- acromegaly
- carcinoid syndrome
- prevent post-pancreatic surgery complications
- VIPomas
- refractory diarrhoea
- causes gallstones 2ry to biliary stasis
***can reduce high output diarrhoea following ileostomy/colectomy - can be given as continuous SC infusion***
69
Octreotide = long-acting analogue of somatostatin - released from pancreatic D cells and inhibits release of GH, glucagon & insulin
Uses?
Adverse effects?
- acute rx variceal bleed
- acromegaly
- carcinoid syndrome
- prevent post-pancreatic surgery complications
- VIPomas
- refractory diarrhoea
- causes gallstones 2ry to biliary stasis
***can reduce high output diarrhoea following ileostomy/colectomy - can be given as continuous SC infusion***
70
What recreational party drug can precipitate severe vitamin B12 deficiency with pronounced neurological & haematological signs??
NITROUS OXIDE - hippie crack
- brief euphoria, relaxation, anxiolytic, detachment, sensory changes
- when used medically is mixed with oxygen
- can cause rapid depletion in vitamin B12 esp in susceptible individuals e.g. vegan, anorexic, coeliac, malabsorption
71
Anabolic steroids
- Adverse effects
- Rx
- Reversible & irreversible unwanted effects
- increase in cardiac morbidity & mortality
- hepatic 2ry to chronic vascular injury: HCC, hepatic adenoma, cholestasis
- psych illness
- inc risk of blood-borne viruses in those who inject
- stop steroids; don't need x-tapering
- then bloods often normalised
- lifelong monitoring for potential complications
Reversible:
- inc appetite, GI dysfunction, mood swings, anxiety, acne, oedema, libido change, scrotal pain, ED, menstrual irregularities
IRREVERSIBLE:
- hirsutism, voice pitch change, male pattern baldness, skin striae/keloid scar, chest pain, clitoral hypertrophy, short stature
- unclear about testicular atrophy etc
