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.
