Clinical Pharmacology Flashcards
what are the features of organophosphate insecticide poisoning?
One of the effects of organophosphate poisoning is inhibition of acetylcholinesterase leading to upregulation of nicotinic and muscarinic cholinergic neurotransmission
Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD)
Salivation
Lacrimation
Urination
Defecation/diarrhoea
cardiovascular: hypotension, bradycardia
also: small pupils, muscle fasciculation
In warfare, sarin gas is a highly toxic synthetic organophosphorus compound that has similar effects.
Management of Organophosphate insecticide posoning?
atropine
the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit
Inducers of the P450 enzyme system?
A man named (St. John’s) is a (smoker) and ( chronic alcohol drinker ) who has alcohol withdrawal seizures so he is on (Phenobarbital) (phenytoin ) and ( Carbamazepine ) and taking ( barbiturates ) for his depression. he has bad hygiene/lifestyle and being treated for fungal infections with (Griseofulvin) and TB with ( rifampin) and (Sulfonylureas) for his DM.
CYP450 inducers
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Barbituates
St. John’s wort
Carbamazepine
Rifampin
Alcohol (chronic)
Phenytoin
Griseofulvin
Phenobarbital
Sulfonylureas
CYP450 inhibitors
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Valproate
Isoniazid
Cimetidine
Ketoconazole
Sulfonamides
Fluconazole
Alcohol (acute)
Chloramphenicol
Erythromycin (macrolides)
Amiodarone
Omeprazole
Grapefruit juice
Quinidine
Metronidazole
What is the mechanism of action of cocaine?
cocaine blocks the uptake of dopamine, noradrenaline and serotonin
Adverse effects of cocaine?
Adverse effects
cardiovascular
coronary artery spasm → myocardial ischaemia/infarction
both tachycardia and bradycardia may occur
hypertension
QRS widening and QT prolongation
aortic dissection
neurological
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
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
Drug causes of photosensitivity ?
thiazides
tetracyclines, sulphonamides, ciprofloxacin
amiodarone
NSAIDs e.g. piroxicam
psoralens
sulphonylureas
What drugs can be cleared with dialysis?
Barbiturate
Lithium
Alcohol (inc methanol, ethylene glycol)
Salicylates
Theophyllines (charcoal haemoperfusion is preferable)
What drugs can not be cleared with haemodialysis?
tricyclics
benzodiazepines
dextropropoxyphene (Co-proxamol)
digoxin
beta-blockers
What may lead to lithium txicity?
dehydration
renal failure
drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
What are features of lithium toxicity?
coarse tremor (a fine tremor is seen in therapeutic levels)
hyperreflexia
acute confusion
polyuria
seizure
coma
Management of lithium toxicity?
mild-moderate toxicity may respond to volume resuscitation with normal saline
IV fluids with isotonic saline, until euvolemic, then typically twice maintenance rate
monitor serum sodium closely (every 4 hours with serial lithium concentrations) if there is a concern about lithium-induced nephrogenic diabetes insipidus
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
what drigs may cause lung fibrosis?
amiodarone
cytotoxic agents: busulphan, bleomycin
anti-rheumatoid drugs: methotrexate, sulfasalazine
nitrofurantoin
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide)
what doe P450 inducers/inhibitors do to patients taking warfarin?
Induces = lower INR
Inhibitors = higher INR
Adverse effects of Gentamicin?
ototoxicity
due to auditory or vestibular nerve damage
irreversible
nephrotoxicity
accumulates in renal failure
gentamicin is preferentially taken up by the proximal renal tubular cells. Once inside these cells, it can accumulate to toxic levels
the toxicity is secondary to acute tubular necrosis
concomitant use of furosemide increases the risk
lower doses and more frequent monitoring is required
what type of abx is Gentamicin?
Gentamicin is a type of aminoglycoside antibiotic. It is poorly lipid-soluble and is therefore given parentally (e.g. for infective endocarditis) or topically (e.g. for otitis externa).
Features of OPiod misuse?
rhinorrhoea
needle track marks
pinpoint pupils
drowsiness
watering eyes
yawning
Complications of Opiod misuse?
viral infection secondary to sharing needles: HIV, hepatitis B & C
bacterial infection secondary to injection: infective endocarditis, septic arthritis, septicaemia, necrotising fasciitis
venous thromboembolism
overdose may lead to respiratory depression and death
psychological problems: craving
social problems: crime, prostitution, homelessness
management of opiod misuse?
NICE recommend methadone or buprenorphine as the first-line treatment in opioid detoxification
What is the mechanism of action of methadone?
methadone is a full agonist of the mu-opioid receptor - binds to these receptors in the brain and fully activates them. This action can relieve withdrawal symptoms and cravings. Has a long half-life
What is the mechanism of action of buprenorphine?
buprenorphine is a partial agonist of the mu-opioid receptor and an antagonist of the kappa-opioid. It binds to the mu-opioid receptors in the brain but only partially activates them. This partial activation is enough to alleviate cravings and withdrawal symptoms in individuals with opioid dependence. Furthermore, the binding of buprenorphine to the mu-opioid receptor is very strong, or ‘high affinity,’ meaning it can displace other opioids from these receptors and prevent them from exerting their effects. As a kappa-opioid receptor antagonist, buprenorphine may contribute to its ability to reduce symptoms of opioid withdrawal and potentially reduce depressive and dysphoric states.
What are the different 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).
What is the mechanism of action of 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)
where do aldosterone antagnoists act?
acts in the cortical collecting duct
what class of antiarrhythmia is Flecanide?
Flecainide is a Vaughan Williams class 1c antiarrhythmic.
What is the mechanism of action of flecanide?
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.
Indiactions for Flecanide?
atrial fibrillation
SVT associated with accessory pathway e.g. Wolf-Parkinson-White syndrome
Contraindications to Flecanide?
post myocardial infarction
structural heart disease: e.g. heart failure
sinus node dysfunction; second-degree or greater AV block
atrial flutter
Adverse effects of Flecanide?
negatively inotropic
bradycardia
proarrhythmic
oral paraesthesia
visual disturbances
Class 1 antiarrhythmics?
Mnemonic - Class 1 antiarrhythmics (Na channel blockers);
‘Double Quarter Pounder, Lettuce Mayo, Fries Please’
1a - Disopyramide, Quinidine, and Procainamide
1b - Lidocaine and Mexiletine
1c - Flecainide and Propafenone
Mechanism of action of Quinolones?
Examples of Quinolones?
Quinolones are a group of antibiotics which work by inhibiting DNA synthesis and are bactericidal in nature. Examples include:
ciprofloxacin
levofloxacin
Mechanism of action
inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
Adverse effects of 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
Contraindications
Quinolones should generally be avoided in women who are pregnant or breastfeeding
avoid in G6PD
mechanism of action os Aspirin?
Aspirin works by blocking the action of both cyclooxygenase-1 and 2. Cyclooxygenase is responsible for prostaglandin, prostacyclin and thromboxane synthesis. The blocking of thromboxane A2 formation in platelets reduces the ability of platelets to aggregate which has lead to the widespread use of low-dose aspirin in cardiovascular disease
Mechanism of action of Ciclosporin?
Ciclosporin is an 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
Adverse effecrts of ciclosporin?
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
Indications for 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
Management of accidental injection e.g. resulting in digital ischaemia?
local infiltration of phentolamine
What is adrenaline responsible for?
where is it released?
where does it act?
responsible for the fight or flight response
released by the adrenal glands
acts on α 1 and 2, β 1 and 2 receptors
acts on β 2 receptors in skeletal muscle vessels-causing vasodilation
increases cardiac output and total peripheral resistance
causes vasoconstriction in the skin and kidneys causing a narrow pulse pressure
Adrenaline actions of alpha adrenergic receptors?
inhibits insulin secretion by the pancreas
stimulates glycogenolysis in the liver and muscle
stimulates glycolysis in muscle
Adrenaline action on beta adrenergic receptors?
stimulates glucagon secretion in the pancreas
stimulates ACTH
stimulates lipolysis by adipose tissue
What is Phentolamine?
Phentolamine, a short acting alpha blocker, may be used in this situation. It is normally used mainly to control blood pressure during surgical resection of phaeochromocytoma
Beta blocker overdose features and management?
Features
bradycardia
hypotension
heart failure
syncope
Management
if bradycardic then atropine
in resistant cases glucagon may be used
Haemodialysis is not effective in beta-blocker overdose
What are Immunoglobulins used for?
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
What are monoclonal antibodies?
Monoclonal antibodies have an increasing role in medicine. They are manufactured by a technique called somatic cell hybridization. This involves the fusion of myeloma cells with spleen cells from a mouse that has been immunized with the desired antigen. The resulting fused cells are termed a hybridoma and act as a ‘factory’ for producing monoclonal antibodies.
Clinical example of monoclonal antibodies?
infliximab (anti-TNF): used in rheumatoid arthritis and Crohn’s
rituximab (anti-CD20): used in non-Hodgkin’s lymphoma and rheumatoid arthritis
cetuximab (epidermal growth factor receptor antagonist): used in metastatic colorectal cancer and head and neck cancer
**trastuzumab (HER2/neu receptor antagonist): used in metastatic breast cancer
alemtuzumab (anti-CD52): used in chronic lymphocytic leukaemia
abciximab (glycoprotein IIb/IIIa receptor antagonist): **prevention of ischaemic events in patients undergoing percutaneous coronary interventions
**OKT3 (anti-CD3): used to prevent organ rejection**
What abx causes haemolysis in G6PD deficiency?
Ciprofloxacin
What criteria is used for liver transplant following paracetamol overdose?
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
