General Flashcards
1
Q
What is acute porphyria?
A
Autosomal dominant
defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem
Abdominal pain + neuropsychiatric
2
Q
What drugs precipitate a porphyria attack?
A
Alcohol
Barbiturate
BZD
Contraceptive pill
Halothane
Sulphonadmies
If you go to a BAR on a BENZ,say HALO to a guy,take a SULFi,have some ALCOHOL n dont forget the OCP.
3
Q
What is the dose for adrenaline in anaphylaxis?
A
anaphylaxis: 0.5ml 1:1,000 IM
4
Q
What is the dose of adrenaline for cardiac arrest?
A
cardiac arrest: 10ml 1:10,000 IV or 1ml of 1:1000 IV
5
Q
What is the action of adrenaline?
A
responsible for the fight or flight
vessels-causing vasodilation
increases cardiac output and total peripheral resistance
causes vasoconstriction in the skin and kidneys causing a narrow pulse pressure
6
Q
What receptors dose adrenaline work on ?
A
α 1, α 2, β 1, β 2 receptors
acts on β 2 receptors in skeletal muscle vessels-causing vasodilation
7
Q
Action of adrenaline on alpha adrenergic receptors?
A
inhibits insulin secretion by the pancreas
stimulates glycogenolysis in the liver and muscle
stimulates glycolysis in muscle
8
Q
What type of receptor is alpha adrenergic receptors?
A
G protein coupled receptor
9
Q
Action of adrenaline on beta adrenergic receptors?
A
stimulates glucagon secretion in the pancreas
stimulates ACTH
stimulates lipolysis by adipose tissue
10
Q
What is an agonist of alpha 1 adrenoceptors?
A
Phenylephrine
11
Q
What is an agonist of alpha 2 adrenoceptors?
A
Clonidine
12
Q
What is an agonist of beta 1 adrenoceptors?
A
Dobutamine
13
Q
What is an agonist of beta 2 adrenoceptors?
A
Salbutamol
14
Q
What is an antagonist of alpha 1 adrenoceptors?
A
alpha-1: doxazosin
alpha-1a: tamsulosin - acts mainly on urogenital tract
15
Q
What is a non-selective alpha 1 adrenceptor antagonist?
A
phenoxybenzamine (previously used in peripheral arterial disease)
16
Q
What is a non-selective beta adrenoceptor antagonist?
A
Carvedilol and labetalol are mixed alpha and beta antagonists
17
Q
What is a beta 1 adrenoceptor antagonist?
A
Atenolol
18
Q
What is activation of alpha 1 adrenoceptor cause?
A
vasoconstriction
relaxation of GI smooth muscle
salivary secretion
hepatic glycogenolysis
19
Q
What is activation of alpha 2 adrenoceptor cause?
A
mainly presynaptic: inhibition of transmitter release (inc NA, Ach from autonomic nerves)
inhibits insulin
platelet aggregation
20
Q
What does activation of Beta 1 adrenoceptors cause?
A
increase heart rate + force
21
Q
What does activation of beta 2 adrenoceptors cause?
A
vasodilation
bronchodilation
relaxation of GI smooth muscle
22
Q
What does activation of beta 3 receptors cause?
A
Lipolysis
23
Q
What is the secondary messenger system of alpha 1 receptors?
A
Phospholipase C
24
Q
What is the secondary messenger system of alpha 2 receptors?
A
Inhibit adenylate cyclase A
→ IP3 → DAG
25
What is the secondary messenger system of beta receptors?
Activation of adenolyte cyclase
26
What is management of acute alcohol withdrawal?
BZD
27
What drug can be used to promote abstinence?
Disulfram
28
What is the mechanism of action of disulfram?
acetaldehyde dehydrogenase.
29
What drug has been shown to promote abstinence?
Acamprost
30
What is the mechanism of action of acampost?
Weak NMDA antagonist
31
What is the mechanism of allopurinol?
Inhibits xanthine oxidase
32
How should gout be managed?
100 mg allopurinol
Reduce if renal function a problem
Start colchicine
If cannot tolerate colchicine consider ibuprofen
33
What are the indications for starting allopurinol?
Start in first flare of gout. Particularly if:
>= 2 attacks in 12 months
tophi
renal disease
uric acid renal stones
prophylaxis if on cytotoxics or diuretics
34
What sever adverse affects are seen in allopurinol?
Who is at increased risk of these reactions?
severe cutaneous adverse reaction (SCAR)
drug reaction with eosinophilia and systemic symptoms (DRESS)
Stevens-Johnson syndrome
Asian populations increased risk
35
If severe skin reaction occurs with allopurinol, what additional test should be completed?
HLA B 5801 panel
36
What drugs interact with allopurinol?
What are the drug interaction mechanisms?
Azathioprine
- metabolised to active compound 6-mercaptopurine
- xanthine oxidase is responsible for the oxidation of 6-mercaptopurine to 6-thiouric acid
- High levels of active metabolite - required dose reduction
Cyclophosphamide
- allopurinol reduces renal clearance, therefore may cause marrow toxicity
Theophylline
-allopurinol causes an increase in plasma concentration of theophylline by inhibiting its breakdown
37
What can amiodarone do to the thyroid?
Hypothyroidism
Hyperthyroidism
38
What is the mechanism of amiodarone hypothyroidism?
Wolff-Chaikoff effect
an autoregulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide
39
What are the types of hyperthyroidism caused by amiodarone?
Autoimmune thyroid type 1:
- Excess iodine-induced thyroid hormone synthesis
- Goitre
- Mnx: Carbimazole / potassium percholate
Autoimmune thyroid type 2:
- Amiodarone related destruction
- No goitre
- Mnx: corticosteroids
40
Mechanism of propofol?
GABA receptor agonist
41
Side effect of propofol
Moderate cardiovascular depressant
Rapid onset anaesthesia
Painful IV injection
Metabolites with few accumulations / toxicity
42
What is the most appropriate anaesthetic for rapid sequence induction?
Sodium thiopentate
43
Side effects of sodium thiopentate?
Marked myocardial depression may occur
Metabolites build up quickly
Unsuitable for maintenance infusion
Little analgesic effects
44
Mechanism of ketamine is anaesthesia?
NMDA receptor antagonist
45
Side effects of ketamine?
- Has moderate to strong analgesic properties
- Produces little myocardial depression making it a suitable agent for anaesthesia in those who are haemodynamically unstable
- May induce state of dissociative anaesthesia resulting in nightmares
46
Features of etomdiate as anaesthetic?
Has favorable cardiac safety profile with very little haemodynamic instability
No analgesic properties
Unsuitable for maintaining sedation as prolonged (and even brief) use may result in adrenal suppression
Post operative vomiting is common
47
Actions of class 1a anti-arrhythmic? Examples?
Block sodium channels - Increases AP duration
Quinidine
Procainamide
Disopyramide
48
Actions of class 1b anti-arrhythmic? Examples?
Block sodium channel blockers - Decrease AP duration
Lidocaine
Mexiletine
Tocainide
49
Actions of class 1c anti-arrhythmic?Examples?
Block sodium channels No effect on AP duration
Flecainide
Encainide
Propafenone
50
Actions of class II anti-arrhythmic? Examples?
Beta-adrenoceptor antagonists
Propranolol
Atenolol
Bisoprolol
Metoprolol
51
Actions of class III anti-arrhythmic? Examples?
Block potassium channels
Amiodarone
Sotalol
Ibutilide
Bretylium
52
Actions of class IV anti-arrhythmic? Examples?
Verapamil
Diltiazem
Calcium channel blockers
53
What antibiotics work by inhibiting cell wall synthesis by preventing peptidoglycan cross-linking?
Penicillin
Cephalosporins
Carbopenems
54
What antibiotics work by inhibiting cell wall synthesis by preventing peptidoglycan synthesis?
Glycopeptides (e.g. vancomycin)
55
What antibiotics inhibits ribosomes, by disrupting the 50 S subunit?
Macrolides
chloramphenicol
clindamycin
linezolid,
56
What antibiotics inhibits ribosomes, by disrupting the 30 S subunit?
Aminoglycosides (Gentamicin)
Tetracyclines
57
What antibiotics inhibits DNA synthesis?
Quinolones
58
What antibiotics damages DNA?
Metronidazole
59
What antibiotics inhibits folic acid formation?
sulphonamides
trimethoprim
60
What antibiotics inhibits RNA synthesis?
Rifampicin
R = RNA
61
What is the mechanism of aspirin ?
Cyclooxygenase-1 and 2 inhibit
Prevents prostaglandin, prostacyclin and thromboxane synthesis
By blocking thromboxane A2 prevents platelet aggregation
62
Features of beta blocker overdose?
bradycardia
hypotension
heart failure
syncope
63
Mnx of beta blocker overdose?
Bradycardia --> Atropine
If resistant --> Glucagon
**Haemodialysis does not work in beta blocker overdose**
64
Mechanism of botulism toxin ?
Blocks presynaptic neurone from releasing in the synaptic cleft -
Neuromuscular blockade
65
What is the effect of verapamil?
Calcium channel blocker
Heavily inotropic
66
What is the effect of Diltiazem ?
Less inotropic than verapamil, but still inotropic
67
What is the effect and mechanism of dihydroperidine calcium channel blocker?
Peripheral vascular smooth muscle relaxation greater than myocardial. No inotropic effect
68
What is the order of antihypertensives?
69
What is the mechanism of carbon monoxide poisoning?
Carbon monoxide has a greater affinity for haemoglobin than O2
Left shift of the o2 dissociation curve
70
Features of carbon monoxide 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
71
What are the levels of severity of carboxyhaemoglobin ?
May give a high reading on O2 due to similarity of carboxyhemoglobin and oxyhemoglobin
< 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
72
How should carbon monoxide be managed?
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
73
What caustic substance is found in bleach? What type of agent is it?
Oxidising agent
Hydrogen peroxide
Sodium hypocholite
74
What caustic substance is found in cleaning substances
Strong alkali
sodium hydroxide
potassium hydroxide
75
What type of damage does a strong alkali cause?
liquefactive necrosis, more commonly resulting in oesophageal injury
76
What type of damage does a strong acid cause?
coagulative necrosis, more commonly resulting in gastric injury
77
What is the mechanism of action of cyclosporin?
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
78
What are the adverse affects of cyclosporin?
Everything is increases: K+, Hair, Lipid, Glucose, BP
nephrotoxicity
hepatotoxicity
fluid retention
hypertension
hyperkalaemia
hypertrichosis
gingival hyperplasia
tremor
impaired glucose tolerance
hyperlipidaemia
increased susceptibility to severe infection
79
What are the indications of ciclosporin?
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
80
What is the mechanism of cocaine?
blocks the uptake of dopamine, noradrenaline and serotonin
81
Effects of cocaine toxicity?
Cardiovascular effects include:
coronary artery spasm → myocardial ischaemia/infarction (including ischaemic colitis)
both tachycardia and bradycardia may occur
hypertension
QRS widening and QT prolongation
aortic dissection
Neurological effects
- seizures
- mydriasis (dilation)
- hypertonia
- hyperreflexia
Psychiatric effects
- agitation
- psychosis
- hallucinations
Hyperthermia
rhabdomyolysis
Metabolic acidosis
82
What is a recognised complication post ischaemic colitis?
ischaemic colitis is recognised in patients following cocaine ingestion. This should be considered if patients complain of abdominal pain or rectal bleeding
83
Management of cocaine toxicity?
BZD!!
If chest pain:
BZD + GTN infusion
If primary MI:
PCI
If Hypertension :
BZD + Sodium nitropusside
84
What are disadvantages of taking the OCP?
Increased risk of venous thromboembolic disease
Increased risk of breast and cervical cancer
Increased risk of stroke and ischaemic heart disease (especially in smokers)
temporary side-effects such as headache, nausea, breast tenderness may be seen
85
What are advantages of taking the pill?
usually makes periods regular, lighter and less painful
reduced risk of ovarian, endometrial - this effect may last for several decades after cessation
reduced risk of colorectal cancer
may protect against pelvic inflammatory disease
may reduce ovarian cysts, benign breast disease, acne vulgaris
86
What are the levels of contraindication for OCP?
UKMEC 1: a condition for which there is no restriction for the use of the contraceptive method
UKMEC 2: advantages generally outweigh the disadvantages
UKMEC 3: disadvantages generally outweigh the advantages
UKMEC 4: represents an unacceptable health risk
87
What are UKMEC 3 for OCP?
More than 35 years old and smoking less than 15 cigarettes/day
BMI > 35 kg/m^2*
Family history of thromboembolic disease in first degree relatives < 45 years
Controlled hypertension
Immobility e.g. wheel chair use
Carrier of known gene mutations Associated with breast cancer (e.g. BRCA1/BRCA2)
Current gallbladder disease
Diabetes (depends on severity)
88
What are UKMEC 4?
More than 35 years old and smoking More than 15 cigarettes/day
Migraine with aura
History of thromboembolic disease or Thrombogenic mutation
History of stroke or ischaemic heart disease
Breast feeding < 6 weeks post-partum
Uncontrolled hypertension
Current breast cancer
Major surgery with prolonged immobilisation
Positive antiphospholipid antibodies (e.g. in SLE)
Diabetes - depends on severity
89
How should you start the pill?
If within 5 days of cycle do not need any additional protection
90
Do you need a pill free break?
No - can take pill back to back
91
Occasions efficacy of pill reduced?
- If vomiting within 2 hours of taking COC pill
- Medication that induce diarrhoea or vomiting may reduce effectiveness of oral contraception (for example orlistat)
- If taking liver enzyme-inducing drugs
Generally concurrent Abx do not have an effect. Unless liver enzyme inducing
92
What is the mechanism of cyanide?
Cyanide inhibits the enzyme cytochrome c oxidase, resulting in cessation of the mitochondrial electron transfer chain.
93
Features of cyanide poisoning?
- Classical' features: brick-red skin, smell of bitter almonds
- Acute: hypoxia, hypotension, headache, confusion
- Chronic: ataxia, peripheral neuropathy, dermatitis
Think of it with burning plastics
94
Management of cyanide poisoning?
1. supportive measures: 100% oxygen
2. definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)
95
What type of drug is digoxin and what does it do?
Cardiac glycoside
Used for rate control in AF
Positive inotropic effect
96
Mechanism of action of digoxin?
1. Decreases conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter
2. Increases the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump. Also stimulates vagus nerve
97
What are the features of digoxin toxicity?
generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
arrhythmias (e.g. AV block, bradycardia)
gynaecomastia
98
How does hypokalaemia precipitate digoxin toxicity?
1. Digoxin normally binds to the ATPase pump on the same site as potassium.
2.Hypokalaemia → digoxin more easily bind to the ATPase pump → increased inhibitory effects
99
Factors that cause digoxin toxicity?
HYPOKALAEMIA
increasing age
renal failure
myocardial ischaemia
hypomagnesaemia, hypercalcaemia, hypernatraemia, acidosis
hypoalbuminaemia
hypothermia
hypothyroidism
100
What drugs can cause digoxin toxicity? Why?
Compete for excretion in DCT
amiodarone, quinidine, verapamil, diltiazem, spironolactone ciclosporin.
Also drugs which cause hypokalaemia e.g. thiazides and loop diuretics
101
Management of digoxin toxicity?
Digibind
correct arrhythmias
monitor potassium
102
What are indications for dopamine agonist therapy?
Parkinson's disease
prolactinoma/galactorrhoea
cyclical breast disease
acromegaly
103
Side effects of dopamine receptor agonists?
pulmonary, retroperitoneal and cardiac fibrosis
104
Side effects of dopamine receptor agonists?
nausea/vomiting
postural hypotension
hallucinations
daytime somnolence
105
What are features of DRESS syndrome?
Hospitalisation
Reaction suspected to be drug related
Acute skin rash (Morbilliform --> erythroderma / something else)
Fever about 38ºC
Enlarged lymph nodes at two sites
Involvement of at least one internal organ
Blood count abnormalities such as low platelets, raised eosinophils or abnormal lymphocyte count.
106
What are common drug causes of DRESS?
Allopurinol anti-epileptics, antibiotics, immunosuppresants, HIV treatment and NSAIDS.
107
What are drug causes of agranulocytosis?
Antithyroid drugs - carbimazole, propylthiouracil
Antipsychotics - atypical antipsychotics (CLOZAPINE)
Antiepileptics - carbamazepine
Antibiotics - penicillin, chloramphenicol, co-trimoxazole
Antidepressant - mirtazapine
Cytotoxic drugs - methotrexate
108
Drug causes of urticaria?
aspirin
penicillins
NSAIDs
opiates
109
How often should statins be monitored?
LFTs at baseline, 3 months and 12 months
110
How should amiodarone be monitored?
TFT, LFT, U&E, CXR prior to treatment
TFT, LFT every 6 months
111
How should methotrexate be monitored?
'FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months'
112
How should azathioprine be monitored?
FBC, LFT before treatment
FBC weekly for the first 4 weeks
FBC, LFT every 3 months
113
How often should lithium levels be monitored?
TFT, U&E prior to treatment
Lithium levels weekly until stabilised then every 3 months
TFT, U&E every 6 months
114
Drugs that impair glucose tolerance?
thiazides, furosemide (less common)
steroids
tacrolimus, ciclosporin
interferon-alpha
nicotinic acid
antipsychotics
115
Drugs that cause thrombocytopenia?
quinine
abciximab
NSAIDs
diuretics: furosemide
antibiotics: penicillins, sulphonamides, rifampicin
anticonvulsants: carbamazepine, valproate
heparin
116
Drugs that cause urinary retention ?
tricyclic antidepressants e.g. amitriptyline
anticholinergics e.g. antipsychotics, antihistamines
opioids
NSAIDs
disopyramide
117
What drug is an agonist of Alpha receptors?
Alpha-1: Decongestants (e.g. phenylephrine/oxymetazoline)
Alpha-2: Glaucoma (e.g. topical brimonidine)
118
What drug is an antagonist of Alpha receptors?
Benign prostatic hyperplasia (e.g. tamsulosin)
Hypertension (e.g. doxazosin)
119
What drug is an agonist of Beta 1 receptors?
Dobutamine
120
What drug is a antagonist of Beta 1 receptors?
Non-selective & selective beta-blockers (e.g. atenolol, bisoprolol)
121
What drug is agonist of Beta 2 receptors?
Bronchodilators (e.g. salbutamol)
122
What drug is an antagonist of Beta 2?
Non-selective beta-blockers (e.g. propranolol, labetalol)
123
What drug is an agonist of dopamine receptor?
Parkinson's disease (e.g. ropinirole)
Prolactinoma
124
What drug is a dopamine antagonist?
Schizophrenia (antipsychotics e.g. haloperidol)
Anti-emetics (e.g. metoclopramide/domperidone)
125
GABA agonist?
BZD
Baclofen
126
GABA antagonist?
Flumazenil
127
Muscaranic agonist?
Pilocarpine (Glaucoma)
128
Muscarinic antagonist?
Atropine (e.g. for bradycardia)
Bronchodilator (e.g. ipratropium bromide, tiotropium)
Urge incontinence (e.g. oxybutynin)
129
Nicotinic agonist?
Nicotine
Varenicline (used for smoking cessation)
Depolarising muscle relaxant (e.g. suxamethonium)
130
Nicotinic antagonist?
Non-depolarising muscle relaxants (e.g. atracurium)
131
Serotonin agonist?
Triptans
132
Serotonin antagonist?
pizotifen is a 5-HT2 receptor antagonist used in the prophylaxis of migraine attacks. Methysergide is another antagonist of the 5-HT2 receptor but is rarely used due to the risk of retroperitoneal fibrosis
cyproheptadine is a 5-HT2 receptor antagonist which is used to control diarrhoea in patients with carcinoid syndrome
ondansetron is a 5-HT3 receptor antagonist and is used as an antiemetic
133
Drugs that cause lung fibrosis?
Amiodarone
Cytotoxic agents: busulphan, bleomycin
Anti-rheumatoid drugs: methotrexate, Sulfasalazine
Nitrofurantoin
Ergot-derived dopamine receptor Agonists (bromocriptine, cabergoline, pergolide)
134
Drugs that cause cataracts?
Steroids
135
Drugs that cause corneal opacity?
amiodarone
indomethacin
136
Drugs that cause optic neuritis?
ethambutol
amiodarone
metronidazole
137
Drugs that cause retinopathy?
chloroquine, quinine
138
What is ecstasy?
MDMA, 3,4-Methylenedioxymethamphetamine)
139
What is the mechanism of MDMA?
MDMA is a potent releaser and/or reuptake inhibitor of presynaptic serotonin (5-HT), dopamine (DA), and norepinephrine (NE)
140
What are the clinical features of MDMA?
neurological: agitation, anxiety, confusion, ataxia
cardiovascular: tachycardia, hypertension
hyponatraemia
hyperthermia
rhabdomyolysis
141
Features of ethylene glycol poisoning?
Stage 1: symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness
Stage 2: metabolic acidosis with high anion gap and high osmolar gap. Also tachycardia, hypertension
Stage 3: acute kidney injury
142
Treatment ethylene glycol?
fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol
Haemodialysis in refractory cases
143
What is the mechanism of finasteride?
inhibitor of 5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone.
144
Side effects of finasteride?
Adverse effects
impotence
decrease libido
ejaculation disorders
gynaecomastia and breast tenderness
145
What is the mechanism of flecanide?
class 1c antiarrhythmic
sodium channel blocker (specifically the Nav1.5 sodium channels)
146
Indications for flecanide?
atrial fibrillation
SVT associated with accessory pathway e.g. Wolf-Parkinson-White syndrome
147
Contraindications of flecanide?
post myocardial infarction
structural heart disease: e.g. heart failure
sinus node dysfunction; second-degree or greater AV block
atrial flutter
148
Adverse effects of flecanide?
negatively inotropic
bradycardia
proarrhythmic
oral paraesthesia
visual disturbances
149
What is a contraindication for gentamicin?
MYASTHENIA GRAVIS
150
What drugs can be cleared through haemodialysis?
Barbiturate
Lithium
Alcohol (inc methanol, ethylene glycol)
Salicylates
Theophyllines (charcoal haemoperfusion is preferable)
151
What drugs cannot be cleared by haemodialysis?
tricyclics
benzodiazepines
dextropropoxyphene (Co-proxamol)
digoxin
beta-blockers
152
Mechanism of unfractionated heparin?
Forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa
153
Mechanism of LMWH?
increases the action of antithrombin III on factor Xa
154
Side effects of unfractionated heparin?
Osteoporosis
Bleeding
Heparin-induced thrombocytopaenia (HIT)
155
How should unfractionated heparin be monitored?
APTT
156
Side effects of LMWH heparin?
Lower risk of HIT and osteoporosis with LMWH
157
How is LMWH monitored?
Anti-Xa level
Not routinely measured
158
When should unfractionated heparin be considered?
Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly. Also useful in renal failure
159
What mediated heparin induced thrombocytopenia?
antibodies form against complexes of platelet factor 4 (PF4) and heparin
PF4-heparin complexes on the platelet surface and induce platelet activation by cross-linking FcγIIA receptors
Features:
DESPITE LOW PLATELETS IS PROTHROMBOTIC
- 50% reduction in platelets, thrombosis and skin allergy
160
How should patient be anti coagulated in HIT ?
direct thrombin inhibitor e.g. argatroban
danaparoid
161
How should heparin and LMWH be reversed?
Protamine
162
Mechanism of statins?
HMG CoA reductase inhibitors
163
Mechanism of ezetimibe?
Cholesterol absorption inhibitor
Decreases cholesterol absorption in the small intestine
164
Mechanism of nicotinic acid?
Decreases hepatic VLDL secretion
165
Mechanism of fibrates?
Agonist of PPAR-alpha therefore increases lipoprotein lipase expression
166
Mechanism of cholestryamine?
Decreases bile acid reabsorption in the small intestine, upregulating the amount of cholesterol that is converted to bile acid
167
Causes of hypomagnesaemia?
drugs
- diuretics
- proton pump inhibitors
-total parenteral nutrition
diarrhoea
alcohol
hypokalaemia
hypercalcaemia
- calcium and magnesium functionally compete for transport in the thick ascending limb of the loop of Henle
metabolic disorders
Gitleman's and Bartter's
168
What are features of hypomagnesaemia?
paraesthesia
tetany
seizures
arrhythmias
decreased PTH secretion → hypocalcaemia
ECG features similar to those of hypokalaemia
exacerbates digoxin toxicity
169
Management of magnesium < 0.4?
intravenous magnesium replacement is commonly given.
an example regime would be 40 mmol of magnesium sulphate over 24 hours
170
Indications to use immunoglobulin?
primary and secondary immunodeficiency
idiopathic thrombocytopenic purpura
myasthenia gravis
Guillain-Barre syndrome
Kawasaki disease
toxic epidermal necrolysis
pneumonitis induced by CMV following transplantation
low serum IgG levels following haematopoietic stem cell transplant for malignancy
dermatomyositis
chronic inflammatory demyelinating polyradiculopathy
171
What are the features of an IVIG infusion?
formed from large pool of donors (e.g. 5,000)
IgG molecules with a subclass distribution similar to that of normal blood
half-life of 3 weeks
172
What precipitates lithium toxicity?
dehydration
renal failure
drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
173
What are the features of lithium toxicity?
coarse tremor (a fine tremor is seen in therapeutic levels)
hyperreflexia
acute confusion
polyuria
seizure
coma
174
Mnx of lithium toxicity?
mild-moderate toxicity: Saline
Severe toxicity: Haemodialysis
175
How is lidocaine metabolised?
Hepatic
176
Mechanism of action of lidocaine?
Sodium channel blocker
177
How is local anaesthetic toxicity treated?
20% lipid emulsion
178
Features of lidocaine toxicity?
Initial CNS over activity then depression as lidocaine initially blocks inhibitory pathways then blocks both inhibitory and activating pathways. Cardiac arrhythmias.
179
What is the maximum dose of lignocaine ?
3mg/Kg plain
With adrenaline 7mg/Kg
180
Side effects of macrolides?
Prolongation of the QT interval
Gastrointestinal side-effects are common. Nausea is less common with clarithromycin than erythromycin
Cholestatic jaundice: risk may be reduced if erythromycin stearate is used
P450 inhibitor (see below)
azithromycin is associated with hearing loss and tinnitus
181
What are common interactions with macrolides?
statins should be stopped whilst taking a course of macrolides. Macrolides inhibit the cytochrome P450 isoenzyme CYP3A4 that metabolises statins.
increases the risk of myopathy and rhabdomyolysis.
182
What are the features of mercury poisoning?
visual field defects
hearing loss
irritability
renal tubular acidosis
183
What is the mechanism of inflixmab? What is it used in?
Anti-TNF
Rheumatoid
Crohn's disease
184
What is the mechanism of rituximab? What is it used in?
CD20
Non-hodgkin lymphoma
Rheumatoid arthritis
185
What is the mechanism of cetuximab?
What is it used in?
EGFR
Metastatic colorectal cancer
Head and neck cancer
186
What is the mechanism of trastuzumab?
What is it used in?
HER2
Metastatic breast cancer
187
What is the mechanism of almetuzumab?
What is it used in?
CD52
CLL
188
What is the mechanism of abciximab?
glycoprotein IIb/IIIa receptor antagonist
prevention of ischaemic events in patients undergoing percutaneous coronary interventions
189
what is the mechanism of OKT3
(anti-CD3)
used to prevent organ rejection
190
What type of drug is metformin?
Mechanism of action?
Biguanide
Acts by activation of the AMP-activated Protein kinase (AMPK)
Increases insulin sensitivity
Decreases hepatic gluconeogenesis
may also reduce gastrointestinal absorption of carbohydrates
191
Side effects of metformin?
Gastrointestinal upsets are common (nausea, anorexia, diarrhoea),
Reduced vitamin B12 absorption - rarely a clinical problem
Lactic acidosis with severe liver disease or renal failure
192
Contraindications to metformin?
Chronic kidney disease
- stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)
Recent MI, AKI, Sepsis - increased lactic acidosis
iodine-containing x-ray contrast media
alcohol abuse is a relative contraindication
192
Contraindications to metformin?
Chronic kidney disease
- stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)
Recent MI, AKI, Sepsis - increased lactic acidosis
iodine-containing x-ray contrast media
alcohol abuse is a relative contraindication
193
Features of methanol poisoning?
Mnx?
Alcohol intox
Blindness
High anion gap
Mnx:
fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
haemodialysis
cofactor therapy with folinic acid to reduce ophthalmological complications
194
What is an example of a depolarising neuromuscular blocker?
Suxamethonium
195
Examples of depolarising neuromuscular blockers?
Atracurium
Vecuronium
Pancuronium
196
What are the adverse effects of suxamethonium?
hyperkalaemia, malignant hyperthermia and lack of acetylcholinesterase
197
What can reuse some non-depolarising neuromuscular blockers?
Neostigamine
Atracurium - full reversal
Vecuronium - full reversal
Pancuronium - partial reversal
198
What is the mechanism of ocreotide?
long-acting analogue of somatostatin
somatostatin is released from D cells of pancreas and inhibits the release of growth hormone, glucagon and insulin
199
What is ocreotide used for?
acute treatment of variceal haemorrhage
acromegaly
carcinoid syndrome
prevent complications following pancreatic surgery
VIPomas
refractory diarrhoea
200
What is a side effect of ocreotide?
gallstones (secondary to biliary stasis)
201
What is an oculogyric crisis?
restlessness, agitation
involuntary upward deviation of the eyes
202
Causes of oculogyric crisis?
antipsychotics
metoclopramide
postencephalitic Parkinson's disease
203
What is the management of oculogyric crisis?
intravenous antimuscarinic: benztropine or procyclidine
204
What is the mechanism of organophosphate poisoning?
Organophosphate poisoning is inhibition of acetylcholinesterase leading to upregulation of nicotinic and muscarinic cholinergic neurotransmission
205
What are the features of organophosphate poisoning?
Accumulation of acetylcholine
SLUD
Salivation
Lacrimation
Urination
Defecation/diarrhoea
cardiovascular:
hypotension bradycardia
also: small pupils, muscle fasciculation
206
Management of organophosphate poisoning?
Atropine
207
Management of paracetamol overdose?
activated charcoal if ingested < 1 hour ago
N-acetylcysteine (NAC)
liver transplantation
208
Management of salicylate poisoning?
Within in 1 hour - activated charcoal
urinary alkalinization with IV bicarbonate
haemodialysis
209
BZD overdose reversal?
Flumazenil
210
Management of tricyclic antidepressant overdose?
IV bicarbonate may reduce seizure and arrhythmias
Priority to treat acidosis
Can consider lignocaine - other arrhythmias not used, due to QT prolongation
211
Heparin overdose reversal?
Protamine
212
Iron overdose mnx?
Desferrioxamine, a chelating agent
213
Lead poisoning mnx?
Dimercaprol, calcium edetate
214
Cyanide poisoning mnx?
Hydroxocobalamin; also combination of amyl nitrite, sodium nitrite, and sodium thiosulfate
215
Inducers of P450?
antiepileptics: phenytoin, carbamazepine
barbiturates: phenobarbitone
rifampicin
St John's Wort
chronic alcohol intake
griseofulvin
smoking (affects CYP1A2, reason why smokers require more aminophylline)
216
Inhibitors of P450?
antibiotics: ciprofloxacin, erythromycin
isoniazid
cimetidine,omeprazole
amiodarone
allopurinol
imidazoles: ketoconazole, fluconazole
SSRIs: fluoxetine, sertraline
ritonavir
sodium valproate
acute alcohol intake
quinupristin
p450 Inhibitor Mnemonic: CCOAAATS
217
When should N-acetylcystine for paracetamol overdose?
- Paracetamol level of 100mg at 4 hours
- Staggered overdose (taken over more than one hour)
- After 8-24 hours if > 150 mg
- > 24 hours if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of norma
218
Criteria for liver transplant in paracetamol?
Arterial pH < 7.3, 24 hours after ingestion
or all of the following:
prothrombin time > 100 seconds
creatinine > 300 µmol/l
grade III or IV encephalopathy
219
What is the normal metabolism of paracetamol?
conjugates paracetamol with glucuronic acid/sulphate
conjugation system becomes saturated leading to oxidation by P450 mixed function oxidases
Produces toxic metabolite N-acetyl-B-benzoquinone imine
glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid
Glutathione used up - toxin forms covalent bonds with cell proteins,
Affects kidney tubules and liver
220
What is n-acetylcycstine?
A precursor of glutathione
221
What percentage of people of penicillin allergic patients are cephalosporin allergic?
0.5% - 6.5%
222
What is first order kinetics?
the rate of drug elimination is proportional to drug concentration
223
What is zero orders kinetics?
rate of excretion is constant despite changes in plasma concentration, this is due to saturation of the metabolic process
e.g. salicylates, phenytoin
224
What are phases of metabolism?
phase I reactions: oxidation, reduction, hydrolysis.
Phase II conjugation
225
What is first pass metabolism? What drugs go through first pass metabolism?
phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism.
Consequences need larger doses orally
226
Mechanism of phosphodiesterase inhibitor?
PDE5 inhibitors cause vasodilation through an increase in cGMP leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum.
227
Side effect of sildenafil ?
The blue pill, Viagra (sildenafil), causes blue discolouration of vision
228
Contraindication to sildenafil?
patients taking nitrates and related drugs such as nicorandil
hypotension
recent stroke or myocardial infarction (NICE recommend waiting 6 months)
229
Side effects of sildenafil?
visual disturbances
blue discolouration
non-arteritic anterior ischaemic neuropathy
nasal congestion
flushing
gastrointestinal side-effects
headache
priapism
230
Types of potassium sparing diuretics?
Epithelial sodium channel blockers
- amiloride and triamterene
Aldosterone antagonists
231
What is the mechanism of amiloride?
blocks the epithelial sodium channel in the distal convoluted tubule
232
What drugs should be prescribed with caution in heart failure?
Thiazolidinediones - fluid retention
Verapamil - negative inotropic
NSAID / steroids - fluid
Class 1 antiarrhythmics - proarrythmic
233
Advantages of progesterone pill?
can be used whilst breast-feeding
can be used in situations where the combined oral contraceptive pill is contraindicated e.g. in smokers > 35 years of age and women with a history of venous thromboembolic disease
234
Disadvantages of progesterone pill?
irregular periods: some users may not have periods whilst others may have irregular or light periods. This is the most common adverse effect
increased incidence of functional ovarian cysts
common side-effects include breast tenderness, weight gain, acne and headaches. These symptoms generally subside after the first few months
235
What is cinchonism?
Quinine toxicity
Cardiac arrhythmia
Hypoglycaemia
Tinnitus
visual blurring, flushed and dry skin and abdominal pain.
236
What are features of salicylate overdose?
hyperventilation (centrally stimulates respiration)
tinnitus
lethargy
sweating, pyrexia*
nausea/vomiting
hyperglycaemia and hypoglycaemia
seizures
coma
237
Treatment of salicylate overdose?
general (ABC, charcoal)
urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine
haemodialysis
238
what are indications for haemodilaysis in salicylate overdose?
serum concentration > 700mg/L
metabolic acidosis resistant to treatment
acute renal failure
pulmonary oedema
seizures
coma
239
Mechanism of quinolones?
inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
240
What are adverse effects of quinolones?
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
241
Causes of serotonin syndrome?
monoamine oxidase inhibitors
SSRIs
St John's Wort, often taken over the counter for depression, can interact with SSRIs to cause serotonin syndrome
tramadol may also interact with SSRIs
ecstasy
amphetamines
242
Features of serotonin syndrome?
neuromuscular excitation
hyperreflexia
myoclonus
rigidity
autonomic nervous system excitation
hyperthermia
sweating
altered mental state
confusion
243
Mnx of serotonin syndrome?
supportive including IV fluids
benzodiazepines
more severe cases are managed using serotonin antagonists such as cyproheptadine and chlorpromazine
244
Difference between serotonin syndrome and neuroleptic malignant syndrome?
245
Side effects of CCB?
Headache
Flushing
Ankle oedema
Verapamil also commonly causes constipation
246
Side effect of beta blockers?
Bronchospasm (especially in asthmatics)
Fatigue
Cold peripheries
Sleep disturbances
247
Side effect of nitrates?
Headache
Postural hypotension
Tachycardia
248
Side effect of nicorandil?
Headache
Flushing
Anal ulceration
249
Side effects of metformin?
Gastrointestinal side-effects
Lactic acidosis
250
Side effects of sulphurylurea?
Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
251
Side effect of glitazones?
Weight gain
Fluid retention
Liver dysfunction
Fractures
252
Side effect of gliptans?
Pancreatitis
253
Mechanism of tacrolimus?
decreases clonal proliferation of T cells by reducing IL-2 release
binds to FKBP forming a complex which inhibits calcineurin, a phosphotase that activates various transcription factors in T cells
this contrasts with ciclosporin, which binds to cyclophilin rather than FKBP
254
Side effect tacrolimus
nephrotoxicity and impaired glucose tolerance
Tacrolimus more potent than cyclosporin
255
How long should tamoxifen be used post tumour removal?
Side effects?
5 years
menstrual disturbance: vaginal bleeding, amenorrhoea
hot flushes - 3% of patients stop taking tamoxifen due to climacteric side-effects
venous thromboembolism
endometrial cancer
256
Mechanism of tamoxifen?
Selective oEstrogen Receptor Modulator (SERM) which acts as an oestrogen receptor antagonist and partial agonist.
257
teratogenic effect of ACEI?
Renal dysgenesis
Craniofacial abnormalities
258
teratogenic effect of alcohol?
Craniofacial abnormalities
259
teratogenic effect of ahminoglycosides?
Ototoxicity
260
teratogenic effect of a carbamazepine?
Neural tube defects
Craniofacial abnormalities
261
teratogenic effect chloramphenicol?
grey baby syndrome
262
teratogenic effect o f cocaine?
Intrauterine growth retardation
Preterm labour
263
teratogenic effect of lithium
Ebstein's anomaly (atrialized right ventricle)
264
effect of maternal diabetes on baby?
Macrosomia
Neural tube defects
Polyhydramnios
Preterm labour
Caudal regression syndrome
265
teratogenic effect of tetracyclines?
discoloured teeth
266
teratogenic effect of thalidomide?
Limb reduction defects
267
teratogenic effect of valproate?
Neural tube defects
Craniofacial abnormalities
268
teratogenic effect of warfarin?
craniofacial abnormalities
269
Mechanism of action of rifampicin?
mechanism of action: inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
270
Side effects of rifampicin?
potent liver enzyme inducer
hepatitis, orange secretions
flu-like symptoms
271
Side effects of isoniazid?
peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor
272
Side effects of pyrazinamide?
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis
273
Side effects of ethambutol?
optic neuritis: check visual acuity before and during treatment
dose needs adjusting in patients with renal impairment
274
What type of receptor does thyroxine work on?
Nuclear receptor
275
what type of antibiotic is teicoplanin?
Glycopeptide
276
What drugs need to be avoided in G6PD?
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
277
What is the mechanism of nephrotoxicity in gentamicin?
Tubule necrosis
278
Choice of antiemetics in motion sickness?
hyoscine > cyclizine > promethazine
279
How are monoclonal antibodies made?
1. Somatic hybridisation
2. Fusion of mouse spleen with myeloma
3. Forms hybridoma
4. Mouse cells are antigenic - requires humanising
-involves combining the variable region from the mouse body with the constant region from a human antibody.
280
What drugs affect acetylator status?
isoniazid
procainamide
hydralazine
dapsone
sulfasalazine
interacts with hepatic N-acetyltransferase
Important for Phase II of drug metabolism - conjugation
281
Timing of lithium dose level?
12 hour post dose
282
Timing of ciclosporin dose level?
Trough level immediately before dose?
283
Timing of digoxin post dose?
6 hour post dose
284
What is the most useful prognostic marker for paracetamol overdose?
Prothrombin time
285
What are the outcomes of phase I and phase II metabolism?
Products of phase I reactions are typically more active and potentially toxic
Products are typically inactive and excreted in urine or bile.
286
If patient cannot tolerate metformin, what should you do?
Try modified release metformin
287
What should be completed prior to starting trastuzumab?
Echo
288
How high can carboxyhaemglobin be in smokers?
Up to 15%
289
What diabetic drugs can cause SIADH?
Sulphonylureas (particularly long-acting ones such as chlorpropamide) are well-established causes of the syndrome of inappropriate ADH1.
290
What is the mechanism in HIT?
immune mediated - antibodies form against complexes of platelet factor 4 (PF4) and heparin
these antibodies 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
291
What drugs undergo first pass metabolism?
aspirin
isosorbide dinitrate
glyceryl trinitrate
lignocaine
propranolol
verapamil
isoprenaline
testosterone
hydrocortisone
292
Antibiotics not safe in pregnancy?
tetracyclines
aminoglycosides
sulphonamides and trimethoprim
quinolones: the BNF advises to avoid due to arthropathy in some animal studies
293
Drugs not safe in pregnancy?
ACE inhibitors, angiotensin II receptor antagonists
statins
warfarin
sulfonylureas
retinoids (including topical)
cytotoxic agents
294
Features of tricyclic overdose?
Block alpha 1
dilated pupils, dry skin, confusion, urinary retention and tachycardia. Divergent pupils are a common finding in tricyclic overdose. TCAs are also cardiotoxic by inactivating sodium channels in the heart leading to, as seen here, a potential prolongation of the QTc interval and a widened QRS complex.
Seizures
Metabolic acidosis
295
What are side effects of trastuzumab?
flu-like symptoms and diarrhoea are common
cardiotoxicity
more common when anthracyclines have also been used
an echo is usually performed before starting treatment
296
Max of bleach ingestion?
NBM
IV PPI
Oesophageal dudenoscopy
297
What is the effect of digoxin on QT?
shortens QT
298
What are the features of hypomagnesaemia on ECG?
QT prolongation
299
Why can adrenaline cause increased lactate?
increase in hepatic glycogenolysis and an increase in gluconeogenesis.
300
Abnormally pink mucosa?
Carbon monoxide poisoning ?
301
Mechanism of action of nivolumab?
PD-1
Lung cancer
side effect: hypothyroidism
302
Drugs that cause photosensitivity ?
thiazides
tetracyclines, sulphonamides, ciprofloxacin
amiodarone
NSAIDs e.g. piroxicam
psoralens
sulphonylureas
303
What should be monitored with hydroxychloquine?
Retinopathy
304
What side effects of cyclosporin?
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
305
Features of excess Ach?
Diarrhoea
Urination
Miosis/muscle weakness
Bronchorrhea/Bradycardia
Emesis
Lacrimation
Salivation/sweating
306
Features of quinine toxicity?
ECG changes, hypotension, metabolic acidosis, hypoglycaemia and classically tinnitus, flushing and visual disturbances. Flash pulmonary oedema may occur
307
When is flecanide contraindicated?
structural heart disease or ischaemic heart disease
308
What can paracetamol overdose do to the kidneys?
Delayed nephrotoxicity
309
Effect of alcohol of hypothalamus?
Inhibits ADH secretion
310
phosphodiesterase inhibitor side effects?
visual disturbances
blue discolouration
non-arteritic anterior ischaemic neuropathy
nasal congestion
flushing
gastrointestinal side-effects
headache
priapism
311
Why marcolides in gastroparesis?
Promotes gastric emptying
312
Adrenaline induced ischaemia treatment ?
phentolamine
313
Side effect of doselupin?
Cause of pulmonary fibrosis
