Clinical Pharmacology/ Toxicology Flashcards
(145 cards)
1
Q
what is ciclosporin
A
immunosuppressant which decreases clonal proliferation of T cells by reducing IL-2 release. It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphatase that activates various transcription factors in T cells
2
Q
Adverse effect of ciclosporin
A
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
3
Q
Indications for ciclosporin
A
following organ transplantation rheumatoid arthritis psoriasis (has a direct effect on keratinocytes as well as modulating T cell function) ulcerative colitis pure red cell aplasia
4
Q
effects of organophosphate insecticide poisoning
A
inhibition of acetylcholinesterase leading to upregulation of nicotinic and muscarinic cholinergic neurotransmission. In warfare, sarin gas is a highly toxic synthetic organophosphorus compound that has similar effects.
5
Q
Features of organophosphate insecticide poisoning
A
Salivation Lacrimation Urination Defecation/diarrhoea cardiovascular: hypotension, bradycardia also: small pupils, muscle fasciculation
6
Q
Management of organophophate insecticide poisoning
A
atropine
the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit
7
Q
P450 inhibitors
A
antibiotics: ciprofloxacin, erythromycin isoniazid cimetidine,omeprazole amiodarone allopurinol imidazoles: ketoconazole, fluconazole SSRIs: fluoxetine, sertraline ritonavir sodium valproate acute alcohol intake quinupristin
8
Q
p450 inducers
A
antiepileptics: phenytoin, carbamazepine
barbiturates: phenobarbitone
rifampicin
St John’s Wort
chronic alcohol intake
griseofulvin
smoking (affects CYP1A2, reason why smokers require more aminophylline)
9
Q
Management of paracetamol overdose
A
activated charcoal if ingested < 1 hour ago
N-acetylcysteine (NAC)
liver transplantation
10
Q
Management of salicylate overdose
A
urinary alkalinization with IV bicarbonate
haemodialysis
11
Q
Management of opioid overdose
A
Naloxone
12
Q
Management of benzodiazepines overdose
A
Flumazenil
The majority of overdoses are managed with supportive care only due to the risk of seizures with flumazenil. It is generally only used with severe or iatrogenic overdoses.
13
Q
Management of TCA overdose
A
IV bicarbonate may reduce the risk of seizures and arrhythmias in severe toxicity
arrhythmias: class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation. Class III drugs such as amiodarone should also be avoided as they prolong the QT interval. Response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias
dialysis is ineffective in removing tricyclics
14
Q
Management of lithium overdose
A
mild-moderate toxicity may respond to volume resuscitation with normal saline
haemodialysis may be needed in severe toxicity
sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion
15
Q
Management of warfarin overdose
A
vitamin K , prothrombin complex
16
Q
Management of heparin overdose
A
protamine complex
17
Q
Management of Beta Blocker overdose
A
if bradycardic then atropine
in resistant cases glucagon may be used
18
Q
Management of ethylene glycol overdose
A
ethanol has been used for many years
works by competing with ethylene glycol for the enzyme alcohol dehydrogenase
this limits the formation of toxic metabolites (e.g. Glycoaldehyde and glycolic acid) which are responsible for the haemodynamic/metabolic features of poisoning
fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol
haemodialysis also has a role in refractory cases
19
Q
Management of methanol overdose
A
fomepizole or ethanol
haemodialysis
20
Q
Management of digoxin overdose
A
Digoxin-specific antibody fragments
21
Q
Management of iron overdose
A
Desferrioxamine, a chelating agent
22
Q
Management of lead overdose
A
Dimercaprol, calcium edetate
23
Q
Management of Carbon Monoxide overdose
A
100% oxygen
hyperbaric oxygen
24
Q
Management of cyanide overdose
A
Hydroxocobalamin; also combination of amyl nitrite, sodium nitrite, and sodium thiosulfate
25
Indications for verapamil
Angina, hypertension, arrhythmias
Highly negatively inotropic
Should not be given with beta-blockers as may cause heart block
26
Side effects of verapamil
Heart failure, constipation, hypotension, bradycardia, flushing
27
Side effects of diltazem
Hypotension, bradycardia, heart failure, ankle swelling
28
indications for diltazem
Angina, hypertension
Less negatively inotropic than verapamil but caution should still be exercised when patients have heart failure or are taking beta-blockers
29
Indications for nifedipine/amlodipine/felodipine (dihydropyridines)
Hypertension, angina, Raynaud's
Affects the peripheral vascular smooth muscle more than the myocardium and therefore do not result in worsening of heart failure but may therefore cause ankle swelling
30
Side effects of dihydropyridines
Flushing, headache, ankle swelling
31
Digoxin - mechanism of action
decreases conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter
increases the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump. Also stimulates vagus nerve
digoxin has a narrow therapeutic index
32
Monitoring of digoxin levels
digoxin level is not monitored routinely, except in suspected toxicity
if toxicity is suspected, digoxin concentrations should be measured within 8 to 12 hours of the last dose
33
Features of digoxin toxicity
generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
arrhythmias (e.g. AV block, bradycardia)
gynaecomastia
34
Precipitating features of digoxin toxicity
classically: hypokalaemia
digoxin normally binds to the ATPase pump on the same site as potassium. Hypokalaemia → digoxin more easily bind to the ATPase pump → increased inhibitory effects
increasing age
renal failure
myocardial ischaemia
hypomagnesaemia, hypercalcaemia, hypernatraemia, acidosis
hypoalbuminaemia
hypothermia
hypothyroidism
drugs: amiodarone, quinidine, verapamil, diltiazem, spironolactone (competes for secretion in distal convoluted tubule therefore reduce excretion), ciclosporin. Also drugs which cause hypokalaemia e.g. thiazides and loop diuretics
35
Management of Digoxin toxicity
Digibind
correct arrhythmias
monitor potassium
36
Rifampicin - MOA and SE
mechanism of action: inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
potent liver enzyme inducer
hepatitis, orange secretions
flu-like symptoms
37
Isoniazid - MOA and SE
mechanism of action: inhibits mycolic acid synthesis
peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor
38
Pyrazinamide - MOA and SE
mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis
39
Ethambutamol - MOA and SE
mechanism of action: inhibits the 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
40
Drugs that impair glucose tolerance
```
thiazides, furosemide (less common)
steroids
tacrolimus, ciclosporin
interferon-alpha
nicotinic acid
antipsychotics
```
41
what are phosphodiesterase type 5 inhibitors
Phosphodiesterase type V (PDE5) inhibitors are used in the treatment of erectile dysfunction. They are also used in the management of pulmonary hypertension. PDE5 inhibitors cause vasodilation through an increase in cGMP leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum.
Examples
sildenafil (Viagra) - this was the first phosphodiesterase type V inhibitor
tadalafil (Cialis)
vardenafil (Levitra)
42
Contraindications of phosphodiesterase type V inhibitors
patients taking nitrates and related drugs such as nicorandil
hypotension
recent stroke or myocardial infarction (NICE recommend waiting 6 months)
43
Side effects of phophodiesterase type V inhibitors
```
visual disturbances e.g. blue discolouration, non-arteritic anterior ischaemic neuropathy
nasal congestion
flushing
gastrointestinal side-effects
headache
```
44
cytochrome p450 inducers
reduce the concentration of drugs metabolised by P450
CRAPS out drugs
- Carbomazepine
- Rifampicin
- bArbituates
- Phenytoin
- St Johns' Wort
45
Cytochrome p450 inhibitors
increase the concentration of drugs metabolised by P450
Some Certain Silly Compounds Annoyingly Inhibit Enzymes, Grrrrrr
```
Sodium Valproate
Ciprofloxacin
Sulphonamides
Cimetidine/omeprazole
Antifungals/amiodarone
Isoniazid
Erythromycin/clarithromycin
Grapefruit
```
46
Features of CO poisoning
```
headache: 90% of cases
nausea and vomiting: 50%
vertigo: 50%
confusion: 30%
subjective weakness: 20%
severe toxicity: 'pink' skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death
```
47
Investigations CO poisoning
pulse oximetry may be falsely high due to similarities between oxyhaemoglobin and carboxyhaemoglobin
therefore a venous or arterial blood gas should be taken
typical carboxyhaemoglobin levels
< 3% non-smokers
< 10% smokers
10 - 30% symptomatic: headache, vomiting
> 30% severe toxicity
an ECG is a useful supplementary investgation to look for cardiac ischaemia
48
Management of CO poisoning
100% high-flow oxygen via a non-rebreather mask
from a physiological perspective, this decreases the half-life of carboxyhemoglobin (COHb)
should be administered as soon as possible, with treatment continuing for a minimum of six hours
target oxygen saturations are 100%
treatment is generally continued until all symptoms have resolved, rather than monitoring CO levels
hyperbaric oxygen
due to the small number of cases the evidence base is limited, but there is some evidence that long-term outcomes may be better than standard oxygen therapy for more severe cases
therefore, discussion with a specialist should be considered for more severe cases (e.g. levels > 25%)
in 2008, the Department of Health publication 'Recognising Carbon Monoxide Poisoning' also listed loss of consciousness at any point, neurological signs other than headache, myocardial ischaemia or arrhythmia and pregnancy as indications for hyperbaric oxygen
49
Mechanism of action for cocaine
cocaine blocks the uptake of dopamine, noradrenaline and serotonin
50
Adverse effects of cocaine
coronary artery spasm → myocardial ischaemia/infarction
both tachycardia and bradycardia may occur
hypertension
QRS widening and QT prolongation
aortic dissection
51
Neurological effects of cocaine
seizures
mydriasis
hypertonia
hyperreflexia
52
Psychiatric effects of cocaine
agitation
psychosis
hallucinations
53
other effects of cocaine
ischaemic colitis is recognised in patients following cocaine ingestion. This should be considered if patients complain of abdominal pain or rectal bleeding
hyperthermia
metabolic acidosis
rhabdomyolysis
54
Management of cocaine toxicity
in general, benzodiazepines are generally first-line for most cocaine-related problems
chest pain: benzodiazepines + glyceryl trinitrate. If myocardial infarction develops then primary percutaneous coronary intervention
hypertension: benzodiazepines + sodium nitroprusside
the use of beta-blockers in cocaine-induced cardiovascular problems is a controversial issue. The American Heart Association issued a statement in 2008 warning against the use of beta-blockers (due to the risk of unopposed alpha-mediated coronary vasospasm) but many cardiologists since have questioned whether this is valid. If a reasonable alternative is given in an exam it is probably wise to choose it
55
Phase 1 reactions: oxydation, reduction, hydrolysis
Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic
56
Phase 2 reactions: conjugation
Products are typically inactive and excreted in urine or bile. Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved
57
First pass metabolism
```
This is a 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
```
58
Zero order kinetics
Zero-order kinetics describes metabolism which is independent 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
```
59
Acetylator status
50% of the UK population are deficient in hepatic N-acetyltransferase
```
Drugs affected by acetylator status
isoniazid
procainamide
hydralazine
dapsone
sulfasalazine
```
60
Abx - inhibit cell wall formation
peptidoglycan cross-linking: penicillins, cephalosporins, carbopenems
peptidoglycan synthesis: glycopeptides (e.g. vancomycin)
61
peptidoglycan cross linking - inhibits cell wall formation
penicillins, cephalosporins, carbopenems
62
Peptidoglycan synthesis - inhibit cell wall formation
glycopeptides e.g. vancomycin
63
ABx MOA Inhibits protein synthesis (by acting on the ribosome)
50S subunit:
macrolides, chloramphenicol, clindamycin, linezolid, streptogrammins
64
ABx MOA Inhibits protein synthesis (by acting on the ribosome) 30S subunit:
aminoglycosides, tetracyclines
65
Abx MOA Inhibits DNA synthesis
quinolones e.g. ciprofloxacin
66
Abx MOA Damages DNA
metronidazole
67
Abx MOA inhibit folic acid formation
sulphonamides
| trimethoprim
68
Abx MOA inhibits RNA synthesis
rifampicin
69
drug induced hypotension
```
diltiazem
levodopa
isosorbide mononitrate
bromocriptine
verapamil
```
70
Drug induced ankle swelling
diltiazem
| amlodipine
71
Drug induced bronchospasm
adenosine
| beta-blockers
72
Management of hyperlipidaemia
Statins
HMG CoA reductase inhibitors
Adverse effects: Myositis, deranged LFTs
73
Management of hyperlipidaemia
Ezetimibe
Decreases cholesterol absorption in the small intestine
Adverse effects: Headache
74
Management of hyperlipidaemia
Nicotinic acid
Decreases hepatic VLDL secretion
Adverse effects: Flushing, myositis
75
Management of hyperlipidaemia
Fibrates
Agonist of PPAR-alpha therefore increases lipoprotein lipase expression
Adverse effects: Myositis, pruritus, cholestasis
76
Management of hyperlipidaemia
Cholestyramine
Decreases bile acid reabsorption in the small intestine, upregulating the amount of cholesterol that is converted to bile acid
Adverse effects: GI side effects
77
What is octreotide
long-acting analogue of somatostatin
| somatostatin is released from D cells of pancreas and inhibits the release of growth hormone, glucagon and insulin
78
Uses of octreotide
```
acute treatment of variceal haemorrhage
acromegaly
carcinoid syndrome
prevent complications following pancreatic surgery
VIPomas
refractory diarrhoea
```
Adverse effects: galls stones secondary to biliary stasis
79
Antibiotics that inhibit cell wall formation
glycopeptides
cephalosporins
carbopenems
penicillins
80
Antibiotics that inhibit protein synthesis by acting on the 30S subunit of ribosomes
tetracyclines
| aminoglycosides
81
infliximab
(anti-TNF): used in rheumatoid arthritis and Crohn's
82
rituximab
(anti-CD20): used in non-Hodgkin's lymphoma and rheumatoid arthritis
83
cetuximab
(epidermal growth factor receptor antagonist): used in metastatic colorectal cancer and head and neck cancer
84
trastuzumab
(HER2/neu receptor antagonist): used in metastatic breast cancer
85
alemtuzumab
(anti-CD52): used in chronic lymphocytic leukaemia
86
abciximab
(glycoprotein IIb/IIIa receptor antagonist): prevention of ischaemic events in patients undergoing percutaneous coronary interventions
87
OKT3
(anti-CD3): used to prevent organ rejection
88
Zero order kinetics
Drugs
phenytoin
salicylates (e.g. high-dose aspirin)
heparin
ethanol
89
Acetylator status
50% of the UK population are deficient in hepatic N-acetyltransferase
```
isoniazid
procainamide
hydralazine
dapsone
sulfasalazine
```
90
First pass metabolism
```
aspirin
isosorbide dinitrate
glyceryl trinitrate
lignocaine
propranolol
verapamil
isoprenaline
testosterone
hydrocortisone
```
91
Drugs causing lung fibrosis
amiodarone
cytotoxic agents: busulphan, bleomycin
anti-rheumatoid drugs: methotrexate, sulfasalazine
nitrofurantoin
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide)
92
Phosphodiesterase type V (PDE5) inhibitors
side effects
```
visual disturbances e.g. blue discolouration, non-arteritic anterior ischaemic neuropathy
nasal congestion
flushing
gastrointestinal side-effects
headache
```
93
Drug contra-indications
recent MI
hydralazine
metformin
sildenafil
94
Mechanism of action
Metformin
acts by activation of the AMP-activated protein kinase (AMPK)
increases insulin sensitivity
decreases hepatic gluconeogenesis
may also reduce gastrointestinal absorption of carbohydrates
95
Adverse effects of metformin
gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
reduced vitamin B12 absorption - rarely a clinical problem
lactic acidosis with severe liver disease or renal failure
96
Contra-indications for metformin
chronic kidney disease:
tissue hypoxia e.g. recent MI, sepsis, AKI, severe dehydration
iodine-containing x-ray contrast media
intravenous pyelography (IVP)
97
Abx that inhibit folic acid formation
sulphonamides
| trimethoprim
98
Methanol poisoning - effects
causes both the effects associated with alcohol (intoxication, nausea etc) and also specific visual problems, including blindness. These effects are thought to be secondary to the accumulation of formic acid - optic neuropathy
99
Management of methanol poisoning
fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
haemodialysis
cofactor therapy with folinic acid to reduce ophthalmological complications
100
Quinolones - examples
ciprofloxacin, levofloxacin
101
Quinolones- Mechanism of action
work by inhibiting DNA synthesis and are bactericidal in nature
inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
102
Quinolones- mechanisms of resistance
mutations to DNA gyrase, efflux pumps which reduce intracellular quinolone concentration
103
Quinolones- adverse effects
```
lower seizure threshold in patients with epilepsy
tendon damage (including rupture) - the risk is increased in patients also taking steroids
cartilage damage has been demonstrated in animal models and for this reason quinolones are generally avoided (but not necessarily contraindicated) in children
lengthens QT interval
```
104
Quinolones- contra-indications
Quinolones should generally be avoided in women who are pregnant or breastfeeding
avoid in G6PD
105
types of potassium sparing diuretics
Potassium-sparing diuretics may be divided into the epithelial sodium channel blockers (amiloride and triamterene) and aldosterone antagonists (spironolactone and eplerenone).
They should be used with caution in patients taking ACE inhibitors as they precipitate hyperkalaemia.
106
Amiloride
blocks the epithelial sodium channel in the distal convoluted tubule
weak diuretic, usually given with thiazides or loop diuretics as an alternative to potassium supplementation (remember that thiazides and loop diuretics often cause hypokalaemia)
107
Aldosterone agonists
```
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
```
108
Adverse effects of heparin
bleeding
thrombocytopenia - see below
osteoporosis and an increased risk of fractures
hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion
109
Standard heparin - mechanism of action
Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
110
Standard heparin - mechanism of action
Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
111
LMWH- mechanism of action
Activates antithrombin III. Forms a complex that inhibits factor Xa
112
Heparin- induced thrombocytopenia
| Pathophysiology
immune mediated - antibodies form against complexes of platelet factor 4 (PF4) and heparin
bind to the PF4-heparin complexes on the platelet surface and induce platelet activation by cross-linking FcγIIA receptors
usually does not develop until after 5-10 days of treatment
113
Heparin induced thrombocytopenia
| Features
greater than 50% reduction in platelets, thrombosis and skin allergy
address need for ongoing anticoagulation:
direct thrombin inhibitor e.g. argatroban
danaparoid
Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH.
114
Drugs affected by acelyator status
```
isoniazid
procainamide
hydralazine
dapsone
sulfasalazine
```
115
Zero order metabolism drugs
phenytoin
salicylates (e.g. high-dose aspirin)
heparin
ethanol
116
First pass metabolism drugs
```
aspirin
isosorbide dinitrate
glyceryl trinitrate
lignocaine
propranolol
verapamil
isoprenaline
testosterone
hydrocortisone
```
117
mechanism of action of rifampicin
Inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
118
Ethambutol mechanism of action
Inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
119
mechanism of action: Aspirin
Inhibits the formation of thromboxane A2
120
Ethanol and ADH
Inhibits ADH production, so increases thirst and urination
reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal
121
Interferon alpha and glucose tolerance
Impairs glucose tolerance
122
Paracetamol overdose: worsening factors
Concurrent carbamazepine
| Concurrent alcohol may be protective
123
Lithium toxicity
```
Acute - coarse tremor
Chronic - fine tremor
hyperreflexia
acute confusion
polyuria
seizure
coma
```
124
Quinolones and GP6D
Avoid quinolones - ciprofloxacin and levofloxacin
125
Cyanide poisoning- features
Classical' features: brick-red skin, smell of bitter almonds
acute: hypoxia, hypotension, headache, confusion
chronic: ataxia, peripheral neuropathy, dermatitis
126
Management of cyanide poisoning
supportive measures: 100% oxygen
definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)
127
Drugs that can be cleared with haemodialysis - mnemonic: BLAST
```
Barbiturate
Lithium
Alcohol (inc methanol, ethylene glycol)
Salicylates
Theophyllines (charcoal haemoperfusion is preferable)
```
128
Drugs that can't be cleared with haemofiltration
```
tricyclics
benzodiazepines
dextropropoxyphene (Co-proxamol)
digoxin
beta-blockers
```
129
Mechanism of action: levothyroxine
Acts on nuclear receptors to lead to an effect on gene transcription
130
Ciprofloxacin and G6PD
Contra-indicated, causes increased haemolysis
| Young, mediterranean/middle eastern, recent infection, jaundice
131
cefalexin and IgE mediated penicillin allergy
Avoid, small proportion of patients have cross-reactivity
132
Thiazides reactions
Photosensitivity - rash on sun exposed skin
133
Organophosphates
Found in pesticides
Treat with atropine
Headache, disorientation, weakness (due to over-stimulation at the neuromuscular junction), vomiting, and muscarinic effects such as miosis, bradycardia and increased urination
134
Verapamil can cause constipation
also heart failure, hypotension,
135
Aspirin skin side effects
Can cause urticarial rashes
136
Features of methanol poisoning
same as alcohol - nausea, intoxication
Visual problems, including blindness
Secondary to increased production of formic acid
137
Management of ethanol poisoning
Fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
haemodialysis
cofactor therapy with folinic acid to reduce ophthalmological complications
138
Management of serotonin syndrome
Supportive including IV fluids
benzodiazepines
more severe cases are managed using serotonin antagonists such as cyproheptadine and chlorpromazine
139
Adverse effects of Herceptin (trastuzumab)
Cardiomyopathy - pre-treatment ECHO
Flu like symptoms
Diarrhoea
140
Rituximab - target receptor
CD20
141
Mechanism of action: Nivolumab - used in lung cancer and melanoma
D-1 (programmed cell death) inhibitor. PD-1 receptors are found on the surface of T cells. When a T cell is alerted to a cancer cell the cancer cell can express the PD-L1 protein. This is a ligand which binds to the T cell receptor and deactivates it. It is therefore a mechanism cancer cells use to evade the immune system and disable T cells. The PD-1 inhibitors are antibodies which block this receptor, leaving the T cells to remain active and alert other immune cells for example macrophages to the cancer cells
142
DRESS syndrome
morbilliform skin rash in 80% cases which often leads to an exfoliative dermatitis, high fever, and inflammation of one or more organs. Vesicles and bullae may be seen
Haematological abnormalities
143
Amiodarone induced thyrotoxicosis Type 1
Excess iodine induced thyroid hormone synthesis
Goitre present
Managed with carbemazepine or potassium perchlorate
144
Amiodarone induced thyrotoxicosis Type 2
Amiodarone related destructive thyroiditis
No goitre
managed with corticosteroids
145
Ciclosporin and tacrolimus mechanism of action
Inhibit calcineurin --> reduction in IL2--> inhibits T cell proliferation
