Pharmacology and toxicology Flashcards
pathophysiology amiodarone induced hypothyroidism
The pathophysiology of amiodarone-induced hypothyroidism (AIH) is thought to be due to the high iodine content of amiodarone causing a Wolff-Chaikoff effect, an autoregulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide
Amiodarone may be continued if this is desirable
Amiodarone induced thyrotoxicosis type 1
Excess iodine-induced thyroid hormone synthesis
present goitre
Mx
Carbimazole or potassium perchlorate
Amiodarone induced thyrotoxicosis type 2
Amiodarone-related destructive thyroiditis
no goitre
corticosteoids Mx
common causes of drug induced peripheral neuropathy
I AM Very Numbed
Isoniazid Amiodarone Metronidazole Vinicristine Nitrofurantoin
p450 inducers
PC BRAS- phenytoin,carbamazepine,barbiturates,rifampicin,alcohol (chronic),sulfonylurea
p450 inhibitors
SICKFACES.COM Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Alcohol...binge drinking Chloramphenicol Erythromycin Sulphonamides (.) Ciprofloxacin Omeprazole Metronidazole
heparin mechanism of action
Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
low molecular weight heparin mechanism of action
Activates antithrombin III. Forms a complex that inhibits factor Xa
heparin monitoring
Activated partial thromboplastin time (APTT)
LMWH monitoring
Anti-Factor Xa (although routine monitoring is not required)
pathophysiology 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
despite being associated with low platelets HIT is actually a prothrombotic condition
features include a greater than 50% reduction in platelets, thrombosis and skin allergy
address need for ongoing anticoagulation:
direct thrombin inhibitor e.g. argatroban
danaparoid
heparin reversal
protamine sulphate, although this only partially reverses the effect of LMWH.
pathophysiology paracetamol overdose
The liver normally conjugates paracetamol with glucuronic acid/sulphate. During an overdose the conjugation system becomes saturated leading to oxidation by P450 mixed function oxidases*. This produces a toxic metabolite (N-acetyl-B-benzoquinone imine)
Normally glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid. If glutathione stores run-out, the toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death. This occurs not only in hepatocytes but also in the renal tubules
why is NAC used in paracetamol overdose
N-acetyl cysteine is used in the management of paracetamol overdose as it is a precursor of glutathione and hence can increase hepatic glutathione production
ciclosporin side effects
(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
what should be checked before starting allopurinol
The most significant adverse effects are dermatological and patients should be warned to stop allopurinol immediately if they develop a rash:
severe cutaneous adverse reaction (SCAR)
drug reaction with eosinophilia and systemic symptoms (DRESS)
Stevens-Johnson syndrome
Certain ethnic groups such as the Chinese, Korean and Thai people seem to be at an increased risk of these dermatological reactions.
Patients at a high risk of severe cutaneous adverse reaction should be screened for the HLA-B *5801 allele.
allopurinol interactions
Azathioprine
metabolised to active compound 6-mercaptopurine
xanthine oxidase is responsible for the oxidation of 6-mercaptopurine to 6-thiouric acid
allopurinol can therefore lead to high levels of 6-mercaptopurine
a much reduced dose (e.g. 25%) must therefore be used if the combination cannot be avoided
Cyclophosphamide
allopurinol reduces renal clearance, therefore may cause marrow toxicity
Theophylline
allopurinol causes an increase in plasma concentration of theophylline by inhibiting its breakdown
avoid ciprofloxacin in whcih genetic disorder
G6PD
MDMA use features
neurological: agitation, anxiety, confusion, ataxia
cardiovascular: tachycardia, hypertension
hyponatraemia
hyperthermia
rhabdomyolysis
MDMA management
supportive
dantrolene may be used for hyperthermia if simple measures fail
aspirin overdose management
urinary alkalinization with IV bicarbonate
haemodialysis
benzodiazipine overdose management
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.
TCA overdose management
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
Lithium overdose management
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
beta blocker overdose management
if bradycardic then atropine
in resistant cases glucagon may be used
ethylene glycol overdose management
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
methanol poisoning management
fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
haemodialysis
organophosphate management
atropine
the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit
digoxin overdose management
Digoxin-specific antibody fragments
iron poisoning Mx
Desferrioxamine, a chelating agent
lead poisonin Mx
Dimercaprol, calcium edetate
cyanide Mx
Hydroxocobalamin; also combination of amyl nitrite, sodium nitrite, and sodium thiosulfate
DRESS syndrome
extensive skin rash, high fever, and organ involvement
sulfonylureas side effects
Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
drugs contraindicated in pregnancy
Antibiotics tetracyclines aminoglycosides sulphonamides and trimethoprim quinolones: the BNF advises to avoid due to arthropathy in some animal studies
Other drugs ACE inhibitors, angiotensin II receptor antagonists statins warfarin sulfonylureas retinoids (including topical) cytotoxic agents
MoA abciximab
Glycoprotein IIb/IIIa receptor antagonist such as abciximab used in primary angioplasty has shown a tendency towards reducing the incidence of adverse coronary events (e.g. death or myocardial infarction) within the first 30 days.
lithium toxicity precipitated by
dehydration
renal failure
drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
lithium toxicity features
coarse tremor (a fine tremor is seen in therapeutic levels) hyperreflexia acute confusion polyuria seizure coma
why does alcohol make you pee
Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal.
how does mathanol cause vision changes?
formic acid. The actual pathophysiology of methanol-associated visual loss is not fully understood but it is thought to be caused by a form of optic neuropathy
causes of hypomagnesimia
drugs: diuretics, proton pump inhibitors
total parenteral nutrition
diarrhoea
alcohol
hypokalaemia, hypocalcaemia
conditions causing diarrhoea: Crohn’s, ulcerative colitis
metabolic disorders: Gitleman’s and Bartter’s
features of hypomagnesaemia
paraesthesia tetany seizures arrhythmias decreased PTH secretion → hypocalcaemia ECG features similar to those of hypokalaemia exacerbates digoxin toxicity
cocaine mechanism
cocaine blocks the uptake of dopamine, noradrenaline and serotonin
cocaine side effects
Cardiovascular effects myocardial infarction both tachycardia and bradycardia may occur hypertension QRS widening and QT prolongation aortic dissection
Neurological effects seizures mydriasis hypertonia hyperreflexia
Psychiatric effects
agitation
psychosis
hallucinations
Others 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
cocaine toxicity management
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
how does cyanide work
Cyanide inhibits the enzyme cytochrome c oxidase, resulting in cessation of the mitochondrial electron transfer chain.
cyanide presentation
‘classical’ features: brick-red skin, smell of bitter almonds
acute: hypoxia, hypotension, headache, confusion
chronic: ataxia, peripheral neuropathy, dermatitis
lowers seizure threshold
ciprofloxacin
pilocarpine MoA
muscarinic agonist
It can be used to treat acute closed-angle glaucoma as it causes miosis, or to treat dry mouth following head and neck radiotherapy (or in sjogren’s disease).
drugs which impair glucose tolerance
TASTINg (SUGAR)
Thiazide Antipschotics Steroids T cell (tacrolimus/ciclosporin) Interferon Alpha Nicotinic Acid
metformin mechanism
acts by activation of the AMP-activated protein kinase (AMPK)
increases insulin sensitivity
decreases hepatic gluconeogenesis
may also reduce gastrointestinal absorption of carbohydrates
metformin adverse effects
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
starting metformin
metformin should be titrated up slowly to reduce the incidence of gastrointestinal side-effects
if patients develop unacceptable side-effects then modified-release metformin should be considered
aspirin mechanism
Aspirin, non-reversible cyclooxygenase (COX) 1 and 2 inhibitor so decreases the formation of thromboxane A2 resulting in decreased platelet aggregation
ciclosporin monitoring
trough
digoxin monitoring
atleast 6-hrs post dose
phenytoin monitoring
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:
adjustment of phenytoin dose
suspected toxicity
detection of non-adherence to the prescribed medication
phase 1 reaction
phase I reactions: oxidation, 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
phase 2 reaction
phase II reactions: conjugation. Products are typically inactive and excreted in urine or bile. Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved
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
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
WTF is an acetylator status?
50% of the UK population are deficient in hepatic N-acetyltransferase
Drugs affected by acetylator status isoniazid procainamide hydralazine dapsone sulfasalazine
flecanide mechanism
Vaughan Williams class 1c antiarrhythmic. It slows conduction of the action potential by acting as a potent sodium channel blocker (specifically the Nav1.5 sodium channels). This may be reflected by widening of the QRS complex and prolongation of the PR interval.
tamoxifen adverse effects
menstrual disturbance: vaginal bleeding, amenorrhoea
hot flushes - 3% of patients stop taking tamoxifen due to climacteric side-effects
venous thromboembolism
endometrial cancer
oligogyric crisis features
restlessness, agitation
involuntary upward deviation of the eyes
oligogyric crisis management
intravenous antimuscarinic: benztropine or procyclidine
prasugrel mechanism
ADP receptor antagonists such as clopidogrel and prasugrel antagonize the P2Y12 platelet receptors and prevent the binding of ADP to it. This leads to a decrease in platelet aggregation and prevents clot formation.
Dabigatran MoA
Direct thrombin inhibitors (DTIs) such as dabigatran prevent clotting by directly inhibiting the enzyme thrombin (factor IIa). Novel oral anticoagulants (NOACs) such as dabigatran are not routinely used in the management of acute coronary syndrome (ACS).
drugs that cause pulmonary fibrosis
amiodarone
cytotoxic agents: busulphan, bleomycin
anti-rheumatoid drugs: methotrexate, sulfasalazine
nitrofurantoin
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide)
sildenafil mechanism
phosphodiesterase type V inhibitor
PDE5 inhibitors cause vasodilation through an increase in cGMP leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum.
contraindications sildenafil
patients taking nitrates and related drugs such as nicorandil
hypotension
recent stroke or myocardial infarction (NICE recommend waiting 6 months)
sildenafil side-effects
visual disturbances e.g. blue discolouration, non-arteritic anterior ischaemic neuropathy nasal congestion flushing gastrointestinal side-effects headache
dopamine agonist effects
nausea/vomiting
postural hypotension
hallucinations
daytime somnolence
sarin mechanism
Sarin gas is a highly toxic synthetic organophosphorus compound which causes inhibition of the enzyme acetylcholinesterase. This results in high levels of acetylcholine (ACh).
sarin effects
DUMBELLS: Diarrhoea Urination Miosis/muscle weakness Bronchorrhea/Bradycardia Emesis Lacrimation Salivation/sweating
sarin is a
organophosphate
sarin management
atropine
the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit
motion sickness Mx
hyoscine > cyclizine > promethazine
TCA overdose presentation
arrhythmias
seizures
metabolic acidosis
coma
ECG TCA overdose
sinus tachycardia
widening of QRS
prolongation of QT interval
Widening of QRS > 100ms is associated with an increased risk of seizures whilst QRS > 160ms is associated with ventricular arrhythmias
how is unfractionated heparin metabolised
clearance of UFH occurs mainly via the reticuloendothelial system (with secondary clearance via the kidneys), as such is safer to use in renal impairment, however, may still need dose reduction.
What is trastuzumab
Trastuzumab (Herceptin) is a monoclonal antibody directed against the HER2/neu receptor. It is used mainly in metastatic breast cancer although some patients with early disease are now also given trastuzumab.
Adverse effects
flu-like symptoms and diarrhoea are common
cardiotoxicity: more common when anthracyclines have also been used. An echo is usually performed before starting treatment
carbon monoxide pathophysiology
in carbon monoxide poisoning the oxygen saturation of haemoglobin decreases leading to an early plateau in the oxygen dissociation curve
CO features
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
CO investigations
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
CO Management
patients with suspected carbon monoxide poisoning should be assessed in the emergency department
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
alpha antagonists
alpha-1: doxazosin
alpha-1a: tamsulosin - acts mainly on urogenital tract
alpha-2: yohimbine
non-selective: phenoxybenzamine (previously used in peripheral arterial disease)
beta antagonists
beta-1: atenolol
non-selective: propranolol
mixed alpha and beta agonists
Carvedilol and labetalol
ciclosporin mechanism
Ciclosporin + tacrolimus: inhibit calcineurin thus decreasing IL-2
Amiloride mechanism
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)
aldosetrone agonist mechanism
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
criteria for liver transplant in paracetamol OD
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
serotonin syndrome causes
monoamine oxidase inhibitors SSRIs St John's Wort, often taken over the counter for depression, can interact with SSRIs to cause serotonin syndrome ecstasy amphetaminesFE
features of serotonin syndrome
neuromuscular excitation (e.g. hyperreflexia, myoclonus, rigidity) autonomic nervous system excitation (e.g. hyperthermia) altered mental state
serotonin syndrome management
supportive including IV fluids
benzodiazepines
more severe cases are managed using serotonin antagonists such as cyproheptadine and chlorpromazine
Octreotide
Overview
long-acting analogue of somatostatin
somatostatin is released from D cells of pancreas and inhibits the release of growth hormone, glucagon and insulin
Uses acute treatment of variceal haemorrhage acromegaly carcinoid syndrome prevent complications following pancreatic surgery VIPomas refractory diarrhoea
Adverse effects
gallstones (secondary to biliary stasis)
mercury poisoning features
paraesthesia visual field defects hearing loss irritability renal tubular acidosis
drugs causing thrombocytopenia
quinine
abciximab
NSAIDs
diuretics: furosemide
antibiotics: penicillins, sulphonamides, rifampicin
anticonvulsants: carbamazepine, valproate
heparin
COCP malignancy
increased risk of breast and cervical cancer
protective against ovarian and endometrial cancer
effects of ingesting caustic substances
Types of substance* - vital to obtain bottle/label if possible
Oxidising agents, e.g. hydrogen peroxide, sodium hypochlorite (found in household bleach)
Strong alkali, e.g. sodium hydroxide, potassium hydroxide (found in dishwasher cleaner, industrial cleaners) -> liquefactive necrosis, more commonly resulting in oesophageal injury
Strong acid, e.g. hydrochloric, nitric acid (found in car batteries, WC cleaner) -> coagulative necrosis, more commonly resulting in gastric injury
complications caustic substance ingestion
Acute Upper GI ulceration, perforation Upper airway injury and compromise Aspiration pneumonitis Infection Electrolyte disturbance (e.g. hypocalcaemia in hydrofluoric acid ingestion)
Chronic
Strictures, fistulae, gastric outlet obstruction
Upper GI carcinoma (estimated 1000-3000 fold increased risk)
alpha 1 stimulation results
vasoconstriction
relaxation of GI smooth muscle
salivary secretion
hepatic glycogenolysis
alpha 2 stimulation results
mainly presynaptic: inhibition of transmitter release (inc NA, Ach from autonomic nerves)
inhibits insulin
platelet aggregation
beta 1 stimulation results
mainly located in the heart
increase heart rate + force
beta 2 stimulation causes
vasodilation
bronchodilation
relaxation of GI smooth muscle
drugs causing photosensitivity
thiazides tetracyclines, sulphonamides, ciprofloxacin amiodarone NSAIDs e.g. piroxicam psoralens sulphonylureas
ethylene glycol poisoning features
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
features that put patients at risk during paracetamol overdose
patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John's Wort)- metabolised to NAPQI faster) malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days
Interestingly, acute alcohol intake, as opposed to chronic alcohol excess, is not associated with an increased risk of developing hepatotoxicity and may actually be protective.
finasteride mechanism
inhibitor of 5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone.
finasteride indications
benign prostatic hyperplasia
male-pattern baldness
finasteride adverse effects
impotence
decrease libido
ejaculation disorders
gynaecomastia and breast tenderness
Finasteride causes decreased levels of serum prostate-specific antigen
digoxin mechanism
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
digoxin toxicity features
generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
arrhythmias (e.g. AV block, bradycardia)
gynaecomastia
digoxin toxicity precipitating factors
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
verapamil indications and side-effects
Angina, hypertension, arrhythmias
Highly negatively inotropic
Should not be given with beta-blockers as may cause heart block Heart failure, constipation, hypotension, bradycardia, flushing
Diltiazem indaications and side effects
Angina, hypertension
Less negatively inotropic than verapamil but caution should still be exercised when patients have heart failure or are taking beta-blockers Hypotension, bradycardia, heart failure, ankle swelling
dihydropyridines examples
Nifedipine, amlodipine, felodipine
dihydropyridines side effects and indications
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 Flushing, headache, ankle swelling
drugs causing ocular problems
Cataracts
steroids
Corneal opacities
amiodarone
indomethacin
Optic neuritis
ethambutol
amiodarone
metronidazole
Retinopathy
chloroquine, quinine
Sildenafil can cause both blue discolouration and non-arteritic anterior ischaemic neuropathy
botulinum toxin uses
blepharospasm hemifacial spasm focal spasticity including cerebral palsy patients, hand and wrist disability associated with stroke spasmodic torticollis severe hyperhidrosis of the axillae achalasia
1a antiarrhythmics
Quinidine
Procainamide
Disopyramide Block sodium channels
Increases AP duration Quinidine toxicity causes cinchonism (headache, tinnitus, thrombocytopaenia)
Procainamide may cause drug-induced lupus
1b antiarrhythmics
Lidocaine
Mexiletine
Tocainide Block sodium channels
Decreases AP duration
1c antiarrhythmics
Flecainide
Encainide
Propafenone Block sodium channels
No effect on AP duration
2 antiarrhythmics
Propranolol
Atenolol
Bisoprolol
Metoprolol Beta-adrenoceptor antagonists
3 antiarrhythmics
Amiodarone
Sotalol
Ibutilide
Bretylium Block potassium channels
4 antiarrhythmics
Verapamil
Diltiazem Calcium channel blockers
drugs cleared by haemodialysis
BLAST Barbiturate Lithium Alcohol (inc methanol, ethylene glycol) Salicylates Theophyllines (charcoal haemoperfusion is preferable)
drugs not cleared by haemodialysis
tricyclics benzodiazepines dextropropoxyphene (Co-proxamol) digoxin beta-blockers
medications that exacerbate heart failure
thiazolidinediones
pioglitazone is contraindicated as it causes fluid retention
verapamil
negative inotropic effect
NSAIDs/glucocorticoids
should be used with caution as they cause fluid retention
low-dose aspirin is an exception - many patients will have coexistent cardiovascular disease and the benefits of taking aspirin easily outweigh the risks
class I antiarrhythmics
flecainide (negative inotropic and proarrhythmic effect)
indications for ahemodialysis in salicylate overdose
serum concentration > 700mg/L metabolic acidosis resistant to treatment acute renal failure pulmonary oedema seizures coma
statin MoA and side effects
HMG CoA reductase inhibitors Myositis, deranged LFTs
Ezetimibe MoA and SE
Decreases cholesterol absorption in the small intestine Headache
Nicotinic acid MoA and SE
Decreases hepatic VLDL secretion Flushing, myositis
Fibrates MoA and SE
Agonist of PPAR-alpha therefore increases lipoprotein lipase expression Myositis, pruritus, cholestasis
Cholestyramine MoA and SE
Decreases bile acid reabsorption in the small intestine, upregulating the amount of cholesterol that is converted to bile acid GI side-effects
common drugs causing agranulocytosis
Antithyroid drugs - carbimazole, propylthiouracil
Antipsychotics - atypical antipsychotics (CLOZAPINE)
Antiepileptics - carbamazepine
Antibiotics - penicillin, chloramphenicol, co-trimoxazole
Antidepressant - mirtazapine
Cytotoxic drugs - methotrexate
drugs that precipitate acute intermittent porphyria
barbiturates halothane benzodiazepines alcohol oral contraceptive pill sulphonamides
drugs causing urinary retention
tricyclic antidepressants e.g. amitriptyline anticholinergics opioids NSAIDs disopyramide
sulfonylurea side effects
Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
gliclazones side effects
Weight gain
Fluid retention
Liver dysfunction
Fractures
gliptin side effects
pancreatitis
adverse effects gentamycin
ototoxicity
due to auditory or vestibular nerve damage
irreversible
nephrotoxicity
accumulates in renal failure
the toxicity is secondary to acute tubular necrosis
concomitant use of furosemide increases the risk
lower doses and more frequent monitoring is required
anion gap calculation
Anion Gap = Na+ – (Cl- + HCO3-)
casues of raised anion gap metabolic acidosis
(CATMUDPILES)
CO, CN Alcoholic ketoacidosis and starvation ketoacidosis Toluene Metformin, Methanol Uremia DKA Pyroglutamic acidosis, paracetamol, phenformin, propylene glycol, paraladehyde Iron, Isoniazid Lactic acidosis Ethylene glycol Salicylates
normal anion gap metabolic acidosis
(CAGE)
Chloride excess
Acetazolamide/Addisons
GI causes – diarrhea/vomiting, fistulae (pancreatic, ureters, billary, small bowel, ileostomy)
Extra – RTA
how to differentiate between GI and renal normal anion gap metabolic acidosis
urinary anion gap = (Na+ + K+) – Cl-
The remaining significant unmeasured ions are NH4+ and HCO3-
renal causes increased urinary HCO3- excretion thus increased urinary AG
GI causes increased NH4+ excretion thus decreased urinary AG
management of adrenaline ischaemia
local infiltration of phentolamine
medication cause sleep disturbances
beta-blocker
CCB side effects
Headache
Flushing
Ankle oedema
Verapamil also commonly causes constipation
beta blockers side effects
Bronchospasm (especially in asthmatics)
Fatigue
Cold peripheries
Sleep disturbances
nitrates side effects
Headache
Postural hypotension
Tachycardia
nicorandil side effects
Headache
Flushing
Anal ulceration
