Pharmacology Flashcards
what are alpha blockers used for? give 4 side effects? when should caution be exercised?
Alpha blockers are used in the management of benign prostatic hyperplasia and hypertension. Examples include doxazosin and tamsulosin.
Side-effects
postural hypotension drowsiness dyspnoea cough
Caution should be exercised in patients who are having cataract surgery due to the risk of intra-operative floppy iris syndrome
What is finasteride used for? give 4 adverse effects? what blood test does this have effect?
Finasteride is an inhibitor of 5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone.
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
What are PDE5 inhibitors? give 3 examples?
Phosphodiesterase type V (PDE5) inhibitors are used in the treatment of erectile dysfunction. They are also used in the management of pulmonary hypertension. PDE5 inhibitors cause vasodilation through an increase in cGMP leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum.
Examples
sildenafil (Viagra)
this was the first phosphodiesterase type V inhibitor
short-acting - usually taken 1 hour before sexual activity
tadalafil (Cialis)
longer acting than sildenafil, may be taken on a regular basis (e.g. once daily)
vardenafil (Levitra)
Give 3 contraindications to give PDE5 inhibitors
Contraindications
patients taking nitrates and related drugs such as nicorandil hypotension recent stroke or myocardial infarction (NICE recommend waiting 6 months)
Gvie 6 side effects of PDE5 inhibitors
Side-effects
visual disturbances
blue discolouration
non-arteritic anterior ischaemic neuropathy
nasal congestion
flushing
gastrointestinal side-effects
headache
priapism - esp. in sickle cell
Verapamil: what should this not be given with
Angina, hypertension, arrhythmias
Highly negatively inotropic
Should not be given with beta-blockers as may cause heart block
Give 5 side effects of verapamil
Heart failure, constipation, hypotension, bradycardia, flushing
Diltiazem - who should this be used in caution with?
Angina, hypertension
Less negatively inotropic than verapamil but caution should still be exercised when patients have heart failure or are taking beta-blockers
Give 4 side effects of diltiazem
Hypotension, bradycardia, heart failure, ankle swelling
Nifedipine/amlodipine/felodipine - how does this work and what can this commonly cuase?
Give 3 side effects
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
Shorter acting dihydropyridines (e.g. nifedipine) cause peripheral vasodilation which may result in reflex tachycardia
Flushing, headache, ankle swelling
Give 10 side effects of amiodarone? give 2 drug interactions
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
Amiodarone-induced hypothyroidism
-what is this due to?
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:
-What are the two types?
-Is a goitre present?
-what is the management of either?
AIT type 1:
-Excess iodine-induced thyroid hormone synthesis
-Goitre present
-Carbimazole or potassium perchlorate
AIT type 2:
-Amiodarone-related destructive thyroiditis
-Goitre absent
-Corticosteroids
What is the mechanism of actione of digoxin? what is the monitoring requirement?
Digoxin is a cardiac glycoside now mainly used for rate control in the management of atrial fibrillation. As it has positive inotropic properties it is sometimes used for improving symptoms (but not mortality) in patients with heart failure.
Mechanism of action
decreases conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter increases the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump. Also stimulates vagus nerve digoxin has a narrow therapeutic index
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
How do you diagnose digoxin toxicity? what are the 3 features?
Plasma concentration alone does not determine whether a patient has developed digoxin toxicity. Toxicity may occur even when the concentration is within the therapeutic range. The BNF advises that the likelihood of toxicity increases progressively from 1.5 to 3 mcg/l.
Features
generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision arrhythmias (e.g. AV block, bradycardia) gynaecomastia
What is the classical precipitating factors for digoxin toxicity? give a further 8
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
What are the 3 management points for digoxin toxicitiy
-Digiband
-Correct arrythmia
-Monitor potassium
Potassium-sparing diuretics: how may these be divided? who should these be used in caution with?
Potassium-sparing diuretics may be divided into the epithelial sodium channel blockers (amiloride and triamterene) and aldosterone antagonists (spironolactone and eplerenone).
They should be used with caution in patients taking ACE inhibitors as they precipitate hyperkalaemia.
Amiloride:
-how does this work?
-who is this given to?
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)
Aldosterone antagonists:
-Where does this act?
-Give 4 indications
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
Give 2 common side effects of ACEI
Cough
Hyperkalaemia
Give 4 common side effects of bendroflumethiazide
Gout
Hypokalaemia
Hyponatraemia
Impaired glucose tolerance
Give 3 common side effects of calcium channel blockers
Headache
Flushing
Ankle oedema
Give 3 common side effects of beta blockers
Bronchospasm (especially in asthmatics)
Fatigue
Cold peripheries
Give 1 common side effect of doxazosin
postural hypotension
Give 4 medications that may exacerbate heart failure:
The following medications may 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)
Give 4 drugs to avoid in renal failure
Drugs to avoid in renal failure
antibiotics: tetracycline, nitrofurantoin NSAIDs lithium metformin
Give 8 drugs that need dose adjustment in renal failure
Drugs likely to accumulate in chronic kidney disease - need dose adjustment
-most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
-digoxin, atenolol
-methotrexate
-sulphonylureas
-furosemide
-opioids
Can you use:
-erythromycin/rifampicin
-diazepam
-warfarin
in renal failure?
yes
Give 6 drugs that may worsen seizure control
The following drugs may worsen seizure control in patients with epilepsy:
-alcohol, cocaine, amphetamines
-ciprofloxacin, levofloxacin
-aminophylline, theophylline
-bupropion
-methylphenidate (used in ADHD)
-mefenamic acid
Some medications such as benzodiazepines, baclofen and hydroxyzine may provoke seizures whilst they are being withdrawn.
Other medications may worsen seizure control by interfering with the metabolism of anti-epileptic drugs (i.e. P450 inducers/inhibitors)
What are 8 P450 exyme inducers
What are 12 P450 enxyme inhibitors?
Inducers: CRAP GPs - because crap GPs induce rage ;)
Carbamazepine, Rifampicin, Alcohol (chronic), Phenytoin, Griseofulvin, Phenobarbitone, Sulphonylureas (also St. John’s Wort and smoking)
Inhibitors: SICKFACES.COM - I remember the alcoholic binge part because a hangover = sick face!
Sodium valproate, Isoniazid, Cimetidine, Ketoconazole, Fluconazole, Alcohol (binge)/allopurinol/amiodarone, Chloramphenicol, Erythromycin, Sulphonamides, Ciprofloxacin, Omeprazole, Metronidazole
(copied)
INR will increase with inhibition
what is acute itermittent porphyria and give 6 drugs which may precipitate attack
Acute intermittent porphyria (AIP) is an autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40 year olds. AIP is more common in females (5:1)
Drugs which may precipitate attack
barbiturates halothane benzodiazepines alcohol oral contraceptive pill sulphonamides
Can you use the following drugs in acute intermittent porphyria
paracetamol aspirin codeine morphine chlorpromazine beta-blockers penicillin metformin
yes
Adrenaline:
-What is the adult does in anaphylaxis?
-What is the adult dose in cardiac arrest?
-What is the management of accidental injection?
Recommend Adult Life Support (ALS) 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 e.g. resulting in digital ischaemia: local infiltration of phentolamine
Adrenaline
-What is the action on alpha adrenergic receptors?
-What is the action on beta adrenergic receptors?
Background
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
Actions on α adrenergic receptors:
inhibits insulin secretion by the pancreas stimulates glycogenolysis in the liver and muscle stimulates glycolysis in muscle
Actions onβ adrenergic receptors:
stimulates glucagon secretion in the pancreas stimulates ACTH stimulates lipolysis by adipose tissue
What 3 things does aspirin potentiate? Who should aspirin not be used in?
Potentiates
oral hypoglycaemics warfarin steroids
Aspirin should not be used in children under 16 due to the risk of Reye’s syndrome. An exception is Kawasaki disease, where the benefits are thought to outweigh the risks.
In what 4 situations is diclofenac contraindicated in?
Whilst it has long been known that NSAIDs may be linked to an increased risk of cardiovascular events the evidence base has now become much clearer. Diclofenac appears to be associated with a significantly increased risk of cardiovascular events compared with other NSAIDs.
It is therefore advised that diclofenac is contraindicated in patients with the following:
-ischaemic heart disease
-peripheral arterial disease
-cerebrovascular disease
-congestive heart failure (New York Heart Association classification II-IV)
Give 4 adverse effects of heparin
Adverse effects of heparins include:
-bleeding
-thrombocytopenia - see below
-osteoporosis and an increased risk of fractures
-hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion
Differences between standard and LMWH:
-administration
-duration of action
standard - IV and short duration
LMWH - SC and long duration
Differences between standard and LMWH:
-mechanism of action
Standard:
-Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
LMWH:
Activates antithrombin III. Forms a complex that inhibits factor Xa
Give the side effects of standard heparin vs LMWH
Standard:
Bleeding
Heparin-induced thrombocytopaenia (HIT)
Osteoporosis
LMWH:
Bleeding
Lower risk of HIT and osteoporosis with LMWH
What is HIT?
mmune 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
What is the monitoring of standard vs LMWH? When is either one used? how could heparin overdose be treated?
Standard:
-Activated partial thromboplastin time (APTT)
-Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly. Also useful in renal failure
LMWH:
-Anti-Factor Xa (although routine monitoring is not required)
-Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes
Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH.
What is lithium and what is the therapeutic range? when does lithium toxicity generally occur? How is lithium toxicity precipitated?
Lithium is a mood stabilising drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.
Toxicity may be precipitated by:
dehydration renal failure drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
Give 6 features of lithium toxicity?
Features of toxicity
coarse tremor (a fine tremor is seen in therapeutic levels) hyperreflexia acute confusion polyuria seizure coma
What is the management of lithium toxicity?
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
Metformin:
-What is the mechanism of action?
-Give 3 adverse effects
Mechanism of action
acts by activation of the AMP-activated protein kinase (AMPK) increases insulin sensitivity decreases hepatic gluconeogenesis may also reduce gastrointestinal absorption of carbohydrates
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
it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams
Give 4 contraindications to metformin
Contraindications
-chronic kidney disease: NICE recommend that the dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)
-metformin may cause lactic acidosis if taken during a period where there is tissue hypoxia. Examples include a recent myocardial infarction, sepsis, acute kidney injury and severe dehydration
-iodine-containing x-ray contrast media: examples include peripheral arterial angiography, coronary angiography, intravenous pyelography (IVP); there is an increasing risk of provoking renal impairment due to contrast nephropathy; metformin should be discontinued on the day of the procedure and for 48 hours thereafter
-alcohol abuse is a relative contraindication
Describe how metformin is started
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
Carbon monoxide poisoning:
-what is the pathophysiology?
Pathophysiology
carbon monoxide binds readily to haemoglobin, forming carboxyhaemoglobin → reduced oxygen-carrying capacity in carbon monoxide poisoning the oxygen saturation of haemoglobin decreases leading to an early plateau in the oxygen dissociation curve
Give 6 features of carbon monoxide poisoning
Features of carbon monoxide toxicity
-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
Give 2 investigations for carbon monoxide poisoning
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
What is the management of carbon monoxide poisoning
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
Oculogyric crisis:
-Give 3 features
-Give 3 causes
-What is the management
An oculogyric crisis is a dystonic reaction to certain drugs or medical conditions
Features
restlessness, agitation involuntary upward deviation of the eyes
Causes
antipsychotics metoclopramide postencephalitic Parkinson's disease
Management
cessation of causative medication if possible intravenous antimuscarinic: benztropine or procyclidine
Cardiac drug monitoring:
-Statins
-ACE inhibitors
-Amiodarone
Statins
LFTs at baseline, 3 months and 12 months
ACE inhibitors
U&E prior to treatment
U&E after increasing dose
U&E at least annually
Amiodarone
TFT, LFT, U&E, CXR prior to treatment
TFT, LFT every 6 months
Rheumatology drug monitoring:
-Methotrexate
-Azathioprine
Methotrexate
FBC, U+Es and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months
Azathioprine
FBC, LFT before treatment
FBC weekly for the first 4 weeks
FBC, LFT every 3 months
Neuropsychiatric drug monitoring:
-Lithium
-Sodium valproate
Lithium
TFT, U&E prior to treatment
Lithium levels weekly until stabilised then every 3 months
TFT, U&E every 6 months
Sodium valproate
LFT, FBC before treatment
LFT ‘periodically’ during first 6 months
Mefloquine
-What is this AKA
-How is this taken?
Lariam
-Start 2-3 weeks before travel
-End 4 weeks after travel
Give 5 side effects of mefloquine (lariam)
The following advice is therefore given:
certain side-effects such nightmares or anxiety may be 'prodromal' of a more serious neuropsychiatric event suicide and deliberate self harm have been reported in patients taking mefloquine adverse reactions may continue for several months due to the long half-life or mefloquine mefloquine should not be used in patients with a history of anxiety, depression schizophrenia or other psychiatric disorders patients who experience neuropsychiatric sife-effects should stop mefloquine and seek medical advice
Give 9 drugs which should be prescribed by brand
Drugs which should be prescribed by brand
modified release calcium channel blockers antiepileptics ciclosporin and tacrolimus mesalazine lithium aminophylline and theophylline methylphenidate CFC-free formulations of beclometasone dry powder inhaler devices
TB meds - Rifampicin
-What is the mechanism?
-Give 4 adverse effects
potent liver enzyme inducer
hepatitis, orange secretions
flu-like symptoms
TB meds - Isoniazid
-What is the mechanism of action?
-Give 4 adverse effects
Isoniazid
mechanism of action: inhibits mycolic acid synthesis peripheral neuropathy: prevent with pyridoxine (Vitamin B6) hepatitis, agranulocytosis liver enzyme inhibitor
TB meds - Pyrazinamide
-Give 4 side effects
Pyrazinamide
mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I hyperuricaemia causing gout arthralgia, myalgia hepatitis
TB meds - Ethambutol
-Mechanism of action
-What is 1 adverse effect and 1 set of patients who would need dose adjustment
Ethambutol
mechanism of action: inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan optic neuritis: check visual acuity before and during treatment dose needs adjusting in patients with renal impairment
What is the yellow card scheme? in what 3 situations should reactions be reported?
The Yellow Card scheme has become the standard way to report adverse reactions to medications. It is run by the Medicines and Healthcare products Regulatory Agency (MHRA).
The following should be reported (taken from the MHRA website)
all suspected adverse drug reactions for new medicines (identified by the black triangle symbol) should be reported
all suspected adverse drug reactions occurring in children, even if a medicine has been used off-label
all serious* suspected adverse drug reactions for established vaccines and
medicines, including unlicensed medicines, herbal remedies, and medicines used off-label
The yellow card scheme:
-Where can the yellow cards be found
-Who can report events?
-what happens to the yellow carD?
Other information
Yellow Cards are found at the back of the BNF or reports can be completed online (www.yellowcard.gov.uk) any suspected reactions (not just confirmed) should be reported patients can report adverse events Yellow Cards are sent to the MHRA who in collate and assess the information. In turn the MHRA may consult with the Commission on Human Medicines (CHM), an independent scientific advisory body on medicines safety
Ecstasy:
-Give 5 clinical features
-What is the management
Clinical features
-neurological: agitation, anxiety, confusion, ataxia
-cardiovascular: tachycardia, hypertension
-hyponatraemia
this may result from either syndrome of inappropriate ADH secretion or excessive water consumption whilst taking MDMA
-hyperthermia
-rhabdomyolysis
Management
supportive dantrolene may be used for hyperthermia if simple measures fail
Give 4 antibiotics that are harmful in pregnancy
Antibiotics
tetracyclines aminoglycosides sulphonamides and trimethoprim quinolones: the BNF advises to avoid due to arthropathy in some animal studies
Give 6 non-antibiotic drugs that are harmful in pregnancy
Other drugs
ACE inhibitors, angiotensin II receptor antagonists statins warfarin sulfonylureas retinoids (including topical) cytotoxic agents
What is the treatment of hypomagnesaemia
<0.4 mmol/L or tetany, arrhythmias, or seizures
intravenous magnesium replacement is commonly given. an example regime would be 40 mmol of magnesium sulphate over 24 hours
> 0.4 mmol/l
oral magnesium salts (10-20 mmol orally per day in divided doses) diarrhoea can occur with oral magnesium salts
Give 4 causes of 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
tramadol may also interact with SSRIs
-ecstasy
-amphetamines
Give 6 features of serotonin syndrome
Features
neuromuscular excitation
hyperreflexia
myoclonus
rigidity
autonomic nervous system excitation
hyperthermia
sweating
altered mental state
confusion
What is the management of serotonin syndrome?
Management
supportive including IV fluids benzodiazepines more severe cases are managed using serotonin antagonists such as cyproheptadine and chlorpromazine
Give 7 drug causes of thrombocytopenia
Drug-induced thrombocytopenia (probable immune-mediated)
quinine abciximab NSAIDs diuretics: furosemide antibiotics: penicillins, sulphonamides, rifampicin anticonvulsants: carbamazepine, valproate heparin
Give 6 features of opioid misuse
Opioids are substances which bind to opioid receptors. This includes both naturally occurring opiates such as morphine and synthetic opioids such as buprenorphine and methadone.
Features of opioid misuse
rhinorrhoea needle track marks pinpoint pupils drowsiness watering eyes yawning
Give 6 complications of opioid misuse
Complications of opioid 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
What is the emergency management of opioid misuse? what are 2 harm reductions interventions
Emergency management of opioid overdose
IV or IM naloxone: has a rapid onset and relatively short duration of action
Harm reduction interventions may include
needle exchange offering testing for HIV, hepatitis B & C
What is the management of opioid dependence
Management of opioid dependence
patients are usually managed by specialist drug dependence clinics although some GPs with a specialist interest offer similar services
patients may be offered maintenance therapy or detoxification
NICE recommend methadone or buprenorphine as the first-line treatment in opioid detoxification
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
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.
compliance is monitored using urinalysis
detoxification should normally last up to 4 weeks in an inpatient/residential setting and up to 12 weeks in the community
Give 4 medications that may exacerbate heart failure
The following medications may 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)
Give 2 indications for HRT
Indications
vasomotor symptoms such as flushing, insomnia and headaches
this is considered the most important factor in choosing whether to start HRT, rather than other possible health benefits such as increased bone mineral density
other indications such as reversal of vaginal atrophy should be treated with other agents as first-line therapies
premature menopause
should be continued until the age of 50 years
the most important reason in giving HRT to younger women is preventing the development of osteoporosis
Quinolones:
-give the mechanism of action
-Give the mechanism of resistance
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
Mechanism of resistance
mutations to DNA gyrase, efflux pumps which reduce intracellular quinolone concentration
Gvie 4 adverse effects of quinolones
Give 2 contraindications
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
Give 4 common causes of urticaria
The following drugs commonly cause urticaria:
aspirin penicillins NSAIDs opiates
Drugs causing ocular problems
-Which drug causes cataracts
Steroid
Drugs causing ocular problems
-Which drug causes corneal opacities
amiodarone
indomethacin
Drugs causing ocular problems
-Which drug causes optic neuritis
Optic neuritis
ethambutol amiodarone metronidazole
Drugs causing ocular problems
-Which drug causes retinopathy
Retinopathy
chloroquine, quinine
Macrolides:
-What is the mechanism of action?
-What is the mechanism of resistance?
Erythromycin was the first macrolide used clinically. Newer examples include clarithromycin and azithromycin.
Macrolides act by inhibiting bacterial protein synthesis by blocking translocation. If pushed to give an answer they are bacteriostatic in nature, but in reality this depends on the dose and type of organism being treated.
Mechanism of resistance
post-transcriptional methylation of the 23S bacterial ribosomal RNA
Give 5 adverse effects of macrolides
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
What is a common interaction with macrolides?
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.
Give features of organophosphate poisoning? what is the management
Organophosphate poisoning is characterised by the acronym ‘DUMBBELLS’, which stands for Defecation, Urination, Miosis, Bronchorrhea, Bradycardia, Emesis, Lacrimation, Lethargy and Salivation.
Management
atropine the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit
Side effects of abx:
-Amoxicillin
Rash with infectious mononucleosis
Side effects of abx:
-co-amox
cholestasis
Side effects of abx:
-fluclox
cholestasis
Side effects of abx:
-erythromycin
QT prolongation
gastro upset
Side effects of abx:
-cipro
lowers seizure threshold
tendonitis
side effects of abx
-metronidazole
reaction following alcohol use
Side effects of abx:
-doxy
photosensitivity
Side effects of abx:
-trimethoprim
rashes and photosensitivity
pruritus
suppression of haematopoeisis
Does delayed prescribing effect antibiotic use
Delayed prescribing reduces antibiotic use by two-thirds
How is motion sickness managed?
Motion sickness describes the nausea and vomiting which occurs when an apparent discrepancy exists between visually perceived movement and the vestibular systems sense of movement
Management
the BNF recommends hyoscine (e.g. transdermal patch) as being the most effective treatment. Use is limited due to side-effects non-sedating antihistamines such as cyclizine or cinnarizine are recommended in preference to sedating preparation such as promethazine
When should a level be taken:
Lithium
Ciclosporin
Digoxin
Phenytoin
Lithium
range = 0.4 - 1.0 mmol/l take 12 hrs post-dose
Ciclosporin
trough levels immediately before dose
Digoxin
at least 6 hrs post-dose
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
What 5 drugs can cause lung fibrosis?
Causes
amiodarone cytotoxic agents: busulphan, bleomycin anti-rheumatoid drugs: methotrexate, sulfasalazine nitrofurantoin ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide)
Textbooks
Give 4 adverse effects of 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
Tamoxifen is typically used for 5 years following removal of the tumour.
Raloxifene is a pure oestrogen receptor antagonist, and carries a lower risk of endometrial cancer
Side effects of common diabetes drugs:
Metformin
Sulfonylureas
Glitazones
Gliptins
Metformin Gastrointestinal side-effects
Lactic acidosis
Sulfonylureas Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
Glitazones
Weight gain
Fluid retention
Liver dysfunction
Fractures
Gliptins: Pancreatitis
Give 11 adverse effects 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 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
What is cocaine and what is the mechanism of action?
Cocaine is an alkaloid derived from the coca plant. It is widely used as a recreational stimulant. The price of cocaine has fallen sharply in the past decade resulting in cocaine toxicity becoming a much more frequent clinical problem. This increase has made cocaine a favourite topic of question writers.
Mechanism of action
cocaine blocks the uptake of dopamine, noradrenaline and serotonin
What are the cardiovascular side 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
what are the neurological side effects of cocaine?
neurological
seizures mydriasis hypertonia hyperreflexia
What are the psychiatric side effects of cocaine? Give 4 non-cardiovascular/non-neurological/non-psychiatreic
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
What is the management of cocaine toxicity
Management of cocaine toxicity
in general, benzodiazepines are generally first-line for most cocaine-related problems
chest pain:
benzodiazepines + glyceryl trinitrate
if myocardial infarction develops then primary percutaneous coronary intervention
hypertension: benzodiazepines + sodium nitroprusside
the use of beta-blockers in cocaine-induced cardiovascular problems is a controversial issue
the American Heart Association issued a statement in 2008 warning against the use of beta-blockers (due to the risk of unopposed alpha-mediated coronary vasospasm) but many cardiologists since have questioned whether this is valid
if a reasonable alternative is given in an exam it is probably wise to choose it
