Miscellaneous Pharmacology Flashcards
Tricyclic Antidepressant Overdose eg. amitriptyline
Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision.
Features of severe poisoning include:
arrhythmias
seizures
metabolic acidosis
coma
ECG changes include:
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
Management;
Management
IV bicarbonate- first-line therapy for hypotension or arrhythmias/ indications include widening of the QRS interval >100 msec or a ventricular arrhythmia
other drugs for arrhythmias
NB- intravenous lipid emulsion is increasingly used to bind free drug and reduce toxicity/ dialysis is ineffective in removing tricyclics
Paracetamol Overdose
Increased risk of hepatotoxicity;
patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John’s Wort)
malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days
NB- acute alcohol intake is better than chronic alcohol excess (may be protective)
The minority of patients who present within 1 hour may benefit from activated charcoal to reduce absorption of the drug.
Acetylcysteine should be given if:
there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or patients who present 8-24 hours after ingestion of more than 150mg/kg of paracetamol (otherwise, wait for paracetamol levels to return)
Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.
When to give acetylcysteine 24 hours after ingestion;
The patent is clearly jaundiced
The patient has hepatic tenderness
The ALT is above the upper limit of normal
The INR is greater than 1.3
The paracetamol concentration is detectable
Liver transplant criteria;
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
Drug induced liver disease
The following drugs tend to cause a hepatocellular picture:
paracetamol
sodium valproate, phenytoin
MAOIs
halothane
anti-tuberculosis: isoniazid, rifampicin, pyrazinamide
statins
alcohol
amiodarone
methyldopa
nitrofurantoin
The following drugs tend to cause cholestasis (+/- hepatitis):
combined oral contraceptive pill
antibiotics: flucloxacillin, co-amoxiclav, erythromycin*
anabolic steroids, testosterones
phenothiazines: chlorpromazine, prochlorperazine
sulphonylureas
fibrates
rare reported causes: nifedipine
Liver cirrhosis
methotrexate
methyldopa
amiodarone
Diclofenac
Diclofenac is now contraindicated with any form of cardiovascular disease
Tetracycline SE
associated with sensitivity to light
Ciprofloxacin
Ciprofloxacin is contraindicated in G6PD deficiency
Heparin
Unfractionated, ‘standard’ heparin or low molecular weight heparin (LMWH) eg. fondaparinux/enoxaparin. Both activate antithrombin III
Adverse effects of heparins include:
-bleeding
-thrombocytopenia (HIT)
-osteoporosis and an increased risk of fractures
-hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion
Unfractionated/Standard heparin
-IV
-Short acting
-Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
-Requires monitoring: APTT
-Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly. Also useful in renal failure
LMWH
-S/C
-Long acting
-Activates antithrombin III. Forms a complex that inhibits factor Xa
-Routine monitoring not required (although Anti-Factor Xa can be used)
Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH.
Warfarin: management of high INR
INR 5.0-8.0
No bleeding
-Withhold 1 or 2 doses of warfarin
-Reduce subsequent maintenance dose
INR 5.0-8.0
Minor bleeding
-Stop warfarin
-Give intravenous vitamin K 1-3mg
-Restart when INR < 5.0
INR > 8.0
No bleeding
-Stop warfarin
-Give vitamin K 1-5mg by mouth, using the intravenous preparation orally
-Repeat dose of vitamin K if INR still too high after 24 hours
-Restart when INR < 5.0
INR > 8.0
Minor bleeding
-Stop warfarin
-Give intravenous vitamin K 1-3mg
-Repeat dose of vitamin K if INR still too high after 24 hours
Restart warfarin when INR < 5.0
Major bleeding (Any INR)
-Stop warfarin
-Give intravenous vitamin K 5mg
-Prothrombin complex concentrate - if not available then FFP*
SSRI and NSAID
Give a PPI
Beta blockers and acute heart failure
in acute heart failure with the presence of either a heart rate<50 beats/min, 2nd or 3rd-degree AV block, or shock, beta-blockers should be stopped.
Certain antiemetics to avoid in certain situations
Cyclizine is a H1-receptor antagonist that acts by blocking histamine receptors in the CTZ. It is safe to use in pregnancy. However, cyclizine can cause a drop in cardiac output and an increase in heart rate. For this reason, caution should be employed in patients with severe heart failure.
Dopamine antagonists, such as metoclopramide, are pro-kinetics and should therefore be avoided in intestinal obstruction. Dopamine antagonists should also be used with caution in patients with Parkinson’s disease.
DOAC’s/NOAC’s in Pregnancy
Contraindicated- use LMWH instead
IM Carboprost (uterine atony)
Avoid in asthmatics
Mirtazapine
Antidepressant that causes weight gain
Fluoxetine- antidepressant that causes weight loss
Adrenaline doses
anaphylaxis: 0.5ml 1:1,000 IM
cardiac arrest: 10ml 1:10,000 IV or 1ml of 1:1000 IV
Management of accidental injection- local infiltration of phentolamine
Problematic drinking management
disulfiram- unpleasant reaction. Don’t use in IHD/psychosis
acamprosate- reduces craving, known to be a weak antagonist of NMDA receptors
Allopurinol
works by inhibiting xanthine oxidase
Commencement of ULT is best delayed until inflammation has settled as ULT is better discussed when the patient is not in pain
urate-lowering therapy to all patients after their first attack of gout
adverse derm effects
interacts with- azathioprine, theophylline, cyclophosphamide
Alpha blockers and cataracts
Caution should be exercised in patients who are having cataract surgery due to the risk of intra-operative floppy iris syndrome
Amiodarone
Adverse effects of amiodarone use
thyroid dysfunction: both hypothyroidism and hyper-thyroidism
corneal deposits
pulmonary fibrosis/pneumonitis
liver fibrosis/hepatitis
peripheral neuropathy, myopathy
photosensitivity
‘slate-grey’ appearance
thrombophlebitis and injection site reactions
bradycardia
lengths QT interval
Important drug interactions of amiodarone include:
decreased metabolism of warfarin, therefore increased INR
increased digoxin levels
Aspirin
Aspirin works by blocking the action of both cyclooxygenase-1 and 2. (non reversible)
Cyclooxygenase is responsible for prostaglandin, prostacyclin and thromboxane 2 synthesis.
Beta blocker overdose
Management
if bradycardic then atropine
in resistant cases glucagon may be used
Haemodialysis is not effective in beta-blocker overdose
Dihydropyridines
Nifedipine, amlodipine, felodipine
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
SE’s- Flushing, headache, ankle swelling
Non-dihydropyridines can cause heart failure/bradycardia/hypotension (and constipation-verapamil)
Ciclosporin
nephrotoxicity
hepatotoxicity
fluid retention
hypertension
hyperkalaemia
hypertrichosis
gingival hyperplasia
tremor
impaired glucose tolerance
hyperlipidaemia
increased susceptibility to severe infection
Cocaine
cocaine blocks the uptake of dopamine, noradrenaline and serotonin
Many SE’s during toxicity but some to remember;
both tachycardia and bradycardia may occur
hypertension
QRS widening and QT prolongation
aortic dissection
ischaemic colitis
hyperthermia
metabolic acidosis
rhabdomyolysis
Mx- benzodiazpines (GTN for chest pain, sodium nitroprusside for HTN), no beta blockers
Diclofenac contraindications
ischaemic heart disease
peripheral arterial disease
cerebrovascular disease
congestive heart failure (New York Heart Association classification II-IV)
Digoxin and toxicity
Monitoring
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
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, ciclosporin. Also drugs which cause hypokalaemia e.g. thiazides and loop diuretics
Urticaria
aspirin
penicillins
NSAIDs
opiates
Drug-induced impaired glucose tolerance
thiazides, furosemide (less common)
steroids
tacrolimus, ciclosporin
interferon-alpha
nicotinic acid
antipsychotics
Beta-blockers cause a slight impairment of glucose tolerance. They should also be used with caution in diabetics as they can interfere with the metabolic and autonomic responses to hypoglycaemia
Drug-induced thrombocytopenia
quinine
abciximab
NSAIDs
diuretics: furosemide
antibiotics: penicillins, sulphonamides, rifampicin
anticonvulsants: carbamazepine, valproate
heparin
Drug-induced urinary retention
tricyclic antidepressants e.g. amitriptyline
anticholinergics e.g. antipsychotics, antihistamines
opioids
NSAIDs
disopyramide
Drugs causing lung fibrosis
amiodarone
cytotoxic agents: busulphan, bleomycin
anti-rheumatoid drugs: methotrexate, sulfasalazine
nitrofurantoin
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide)
Drugs causing ocular problems
steroids
amiodarone
indomethacin
ethambutol
amiodarone
metronidazole
chloroquine, quinine
Sildenafil
Drugs causing photosensitivity
thiazides
tetracyclines, sulphonamides, ciprofloxacin
amiodarone
NSAIDs e.g. piroxicam
psoralens
sulphonylureas
Ecstasy overdose
supportive
dantrolene may be used for hyperthermia if simple measures fail
Ethylene glycol toxicity
metabolic acidosis with high anion gap and high osmolar gap.
fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol
haemodialysis also has a role in refractory cases
Finasteride
Indications
benign prostatic hyperplasia
male-pattern baldness
Adverse effects
impotence
decrease libido
ejaculation disorders
gynaecomastia and breast tenderness
Finasteride causes decreased levels of serum prostate-specific antigen
Flecanide
Contraindications
post myocardial infarction
structural heart disease: e.g. heart failure
sinus node dysfunction; second-degree or greater AV block
atrial flutter
Adverse effects
negatively inotropic
bradycardia
proarrhythmic
oral paraesthesia
visual disturbances
Gentamicin
both peak (1 hour after administration) and trough levels (just before the next dose) are measured
Myasthenia gravis is a contraindication
Hypomagnesia
drugs
diuretics
proton pump inhibitors
total parenteral nutrition
diarrhoea
may occur with acute or chronic diarrhoea
alcohol
hypokalaemia
hypercalcaemia
Features may be similar to hypocalcaemia:
paraesthesia
tetany
seizures
arrhythmias
decreased PTH secretion → hypocalcaemia
ECG features similar to those of hypokalaemia
exacerbates digoxin toxicity
<0.4 mmol/L or tetany, arrhythmias, or seizures
intravenous magnesium
> 0.4 mmol/l
oral magnesium salts
diarrhoea can occur
Lithium toxicity
Toxicity may be precipitated by:
dehydration
renal failure
drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
mild-moderate toxicity may respond to volume resuscitation with normal saline
haemodialysis may be needed in severe toxicity
Macrolides (erythromycin/clarithromycin/azithromycin)
Adverse effects
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
Common interactions
statins should be stopped whilst taking a course of macrolides. Macrolides inhibit the cytochrome P450 isoenzyme CYP3A4 that metabolises statins. Taking macrolides concurrently with statins significantly increases the risk of myopathy and rhabdomyolysis.
