year 3 drugs of the week Flashcards
what are ramipril, enalapril and lisinopril examples of?
Angiotensin-converting enzyme (ACE) inhibitors
ACE inhibitors MoA
block ACE — prevent it from converting angiotensin I to its active form angiotensin II; decrease aldosterone secretion
what are 3 indications for ACE inhibitors?
- hypertension
- heart failure
- secondary prevention CVD
ACE inhibitor dosing
dosing individual to each medication — start low and increase to maximum dose tolerated by the patient
what are 4 contraindications to ACE inhibitors?
- severe aortic stenosis
- severe hyperkalaemia
- symptomatic hypotension
- history of angioedema
ACE inhibitors cautions
- moderate renal impairment
- mild hyperkalaemia
- asymptomatic hypotension or at risk of hypotension
- ethnicity — higher rate of angioedema in black patients than in non black patients
- may be less effective in lowering BP in black peoples than in non black patients
cautions from passmed: avoid in pregnancy and breastfeeding, caution in renovascular disease (may result in renal impairment), aortic stenosis (may result in hypotension), hereditary of idiopathic angioedema
what is generally recommended before initiating ACE inhibitor treatment?
correct dehydration, hypovolaemia or salt depletion
what are side effects of ACE inhibitors?
common (not exhaustive):
dry cough, dizziness, dry mouth, electrolyte imbalance (hyperkalaemia), GI discomfort (diarrhoea/constipation), headache, hypotension, nausea
from passmed: cough, angioedema, hyperkalaemia, first dose hypertension (more common in patients taking diuretics)
what should be monitored during ACE inhibitor treatment and checked before starting/increasing dose?
renal function and electrolytes
ACE inhibitors in pregnancy?
recommended during 1st trimester and contraindicated during the 2nd and 3rd trimesters
what percentage of people on ACEi get a dry cough?
10% — if it occurs the only way to stop it is to discontinue the medication and start another class of drugs
what are bisoprolol, atenolol, and betaxolol?
beta blockers
how do beta blockers work?
block the B1 receptors of the autonomic nervous system — slows the heart rate and reduces contractility of the heart
cardioselective beta blockers are 20x more potent at blocking what?
beta 1 receptors than b2 (located in the bronchial smooth muscle of the airways, which has the potential to cause bronchoconstriction)
what are 4 indications for beta blockers?
- hypertension
- heart failure
- secondary prevention CVD
- atrial fibrillation
beta blocker dosing
dosing individual to each medication — start low and increase to max dose tolerated by the patient
what are some contraindications to beta blockers?
- asthma (risk of bronchospasm)
- hypotension
- marked bradycardia
- severe peripheral arterial disease
- uncontrolled heart failure
beta blocker cautions
- diabetes (symptoms of hypoglycaemia may be masked)
- history of obstructive airways disease (introduce cautiously)
- portal hypertension (risk of deterioration in liver function)
- symptoms of thyrotoxicosis may be masked
what are some side effects of beta blockers?
common (not exhaustive):
- coldness of the peripheries
- headaches
- syncope
- erectile dysfunction
- dizziness
- hypotension
- sleep disturbances
beta blocker monitoring?
monitor lung function in patients with a history of obstructive airway disease
what can sudden cessation of a beta blocker cause?
a rebound worsening of myocardial ischaemia — therefore gradual reduction of dose is preferable when beta blockers are to be stopped
what are losartan and valsartan examples of?
angiotensin receptor blockers (ARBs)
ARB MoA
- reduce the action of angiotensin II to prevent blood vessel constriction
- angiotensin II also stimulates salt and water retention in the body, so reducing this action also reduces BP
what are 3 indications for ARBs?
- hypertension
- congestive heart failure
- diabetic nephropathy
ARB dosing
dosing individual to each medication — start low and increase to max dose tolerated by the patient
what are cautions for ARBs?
- aortic or mitral valve stenosis
- elderly (lower initial dose may be appropriate)
- black african or african-caribbean origin
- history of angioedema
- renal artery stenosis
what are some side effects of ARBs?
common (not exhaustive):
- abdominal pain
- diarrhoea
- dizziness
- headache
- hyperkalaemia
- hypotension
- nausea
- postural hypotension
- renal impairment
- vertigo
- vomiting
monitoring with ARBs?
measure renal function (serum creatinine and estimated GFR) and serum electrolytes before starting treatment, 1-2 weeks after starting treatment and 1-2 weeks after each dose increase
when should ARBs be avoided unless essential?
pregnancy
what can ARBs not be used with?
ACEi
what are the 2 types of calcium channel blockers? give examples
- dihydropyridines — nifedipine, amlodipine
- non-dihydropyridines — diltiazem, verapamil
CCB MoA
act on calcium channels and inhibits Ca influx in vascular smooth muscle — results in reduced cardiac contractility and vasodilation
non-dihydropyridines also block calcium going into the conducting cells in the heart, which has the effect of slowing down heart rate. therefore can help to control certain fast heart rhythms
what are the 2 indications for CCB?
hypertension and angina
CCB dosing?
dosing individual to each medication — start low and increase to max dose tolerated by the patient
what are 3 contraindications to CCB?
- cardiogenic shock
- significant aortic stenosis
- unstable angina
in who should you be cautious with CCB?
elderly
what are side effects of CCBs?
common (not exhaustive):
- dizziness
- flushing
- palpitations
- headaches
- peripheral oedema (usually leg swelling)
what should be monitored with CCBs?
BP
some CCBs are available as _____________ - be careful when prescribing these
modified release preparations
ankle oedema in CCBs?
this is often dose related so if troublesome to patient, try reducing dose. can also try switching CCBs (non-dihydropyridines potentially better). another alternative is switching drug class
name the 4 different types of diuretics and give examples
- LOOP — furosemide, bumetanide
- THIAZIDE — bendroflumethiazide, indapamide
- K SPARING — spironolactone
- OSMOTIC — mannitol
MoA of diuretics
increase Na excretion via digression ultimately reduced cardiac afterload
what are indications for diuretics?
- heart failure
- fluid overload
- oedema, including pulmonary oedema
- hypertension
what are the starting doses for diuretics?
- furosemide — PO 40-120mg daily, IV 20-50mg (max 1.5g total)
- bumetanide — PO 1-5mg OD
- bendroflumethiazide — PO 2.5-5mg OD
- spirinolactone — PO 25-100mg OD
what are contraindications for loop diuretics?
- renal failure due to nephro/hepatotoxic or hepatotoxic drugs
- severe hypokalaemia
- severe hyponatraemia
what are contraindications for thiazide diuretics?
- Addison’s disease
- hypercalcaemia
- hyponatraemia
- refractory hypokalaemia
- symptomatic hyperuricaemia
what are contraindications for K+ sparing diuretics?
- Addison’s disease
- anuria
- hyperkalaemia
cautions of loop diuretics
- can exacerbate diabetes (but hyperglycaemia less likely than with thiazides)
- can exacerbate gout
- hypotension and hypovolaemia should be corrected before initiation
cautions of thiazide diuretics
- diabetes
- gout
- risk of hypokalaemia
cautions of K+ sparing diuretics
elderly
common (not exhaustive) side effects of loop diuretics
- dizziness
- electrolyte imbalance
- fatigue
- muscle spasms
- nausea
common (not exhaustive) side effects of thiazide diuretics
- constipation
- diarrhoea
- dizziness
- electrolyte imbalance
- fatigue
- hyperglycaemia
- hyperuricaemia
- nausea
- postural hypotension
common (not exhaustive) side effects of K+ sparing diuretics
- dizziness
- electrolyte imbalance
- GI disorder
- hyperkalaemia (discontinue)
- leg cramps
- nausea
what should be monitored whilst taking diuretics?
electrolytes and renal function should be monitored during treatment. daily weights may be measured in certain indications to measure effect
acute kidney injury and diuretics?
diuretics should, in most cases, be held if a patient has an AKI. loop diuretics may be continued in certain circumstances eg. if a patient has heart failure and there is a risk of fluid overload
when should patients be advised to take diuretics and why?
morning/lunchtime to avoid needing to urinate overnight
aspirin MoA
irreversible COX1 inhibitor
clopidogrel/prasugrel/ticagrelor MoA
irreversibly bind to P2Y12 ADP receptors and prevent ADP binding to P2Y12 receptors
what are indications for antiplatelets?
- primary and secondary prevention of CVD
- ACS
- prevention of atherothrombotic and thromoembolic events
what are the starting doses of aspirin, clopidogrel and ticagrelor?
aspirin - PO 75mg OD
clopidogrel - PO 75mg OD
ticagrelor - PI 90mg BD
aspirin contraindications
active peptic ulceration, bleeding disorders, under 16 years (risk of Reye’s syndrome), haemophilia
clopidogrel contraindications
active bleeding
ticagrelor contraindications
active bleeding, history of intracranial haemorrhage
aspirin cautions
- asthma
- elderly
- G6PD deficiency
- history of gout
- HTN
- may mask symptoms of infection
- previous peptic ulceration
- thyrotoxicosis
ticagrelor cautions
- asthma
- bradycardia
- COPD
how long before elective surgery should aspirin/clopidogrel/ticagrelor be stopped?
aspirin - 14 days before
clopidogrel - 7 days before
ticagrelor - 5 days before
what are some side effects of aspirin, clopidogrel, ticagrelor?
common (not exhaustive):
- aspirin — dyspepsia, haemorrhage
- clopidogrel — diarrhoea, GI discomfort, haemorrhage
- ticagrelor — constipation, diarrhoea, dyspepsia, dyspnoea, gout, gouty arthritis, haemorrhage, nausea
owing to an association with Reye’s syndrome, manufacturer advises aspirin-containing preparations should not be given to children under 16 years, unless specifically indicated eg. for ________ disease
Kawasaki
What does digoxin do?
Increases the force of contraction of the muscle of the heart by inhibiting the activity of ATPase
Inhibiting ATPase increases calcium in heart muscle and therefore increases the force of heart contractions
Also reduces conductivity within the AV node
What are 2 indications for digoxin?
Atrial fibrillation and heart failure
Digoxin dosing?
Starting doses: dependent on indication but should be in micrograms
What are contraindications to digoxin?
- Wolff-Parkinson-White syndrome
- intermittent complete heart block or atrioventricular heart block
- ventricular tachycardia or fibrillation
Digoxin cautions
- recent MI
- thyroid disease
- severe respiratory disease
- hypokalaemia
- hypomagnesaemia
- hypercalcaemia
- toxicity increased by electrolyte disturbances
- elderly people (reduce dose)
Side effects of digoxin
Common, not exhaustive:
- arrhythmias
- cardiac conduction disorder
- cerebral impairment
- diarrhoea
- dizziness
- eosinophilia
- nausea
- skin reactions
- vision disorders
- vomiting
Digoxin monitoring
- monitor serum electrolytes and renal function — toxicity increased by electrolyte disturbances
- routine monitoring of serum digoxin is not recommended
- consider checking serum digoxin levels if: — the person experiences adverse effects suggestive of toxicity (such as confusion, nausea, anorexia, or disturbance of colour vision)
When can digoxin toxicity occur?
Even when the serum digoxin conc is within the therapeutic range (0.7 nano grams/mL and 2.0 nano grams/mL). Take blood samples at least 6 hours after the previous dose, but ideally 8-12 hours afterwards
Name 4 DOACs
Apixaban, rivaroxaban, dabigatran and edoxaban
How do the DOACs work?
- apixaban, edoxaban and rivaroxaban — direct and reversible inhibitors of factor Xa
- dabigatran — a reversible inhibitor of free thrombin, fibrin-bound thrombin, and thrombin-induced platelet aggregation
Indications for DOACs?
- stroke prevention in AF
- DVT/PE treatment and prevention
DOAC dosing?
All have different doses
Be aware all need renal adjustment. Often body weight dependant
DOAC = antiplatelet or anticoagulant?
Anticoagulants
DOAC contraindications?
- Active, clinically significant bleeding
- prosthetic heart valve
- current/recent GI ulceration
- significant risk of major bleeding
- use with any other anticoagulant
DOAC cautions?
- elderly
- low body weight
- risk of bleeding
Side effects of DOACs
Common, not exhaustive:
- anaemia
- haemorrhage
- nausea
- skin reactions
- menorrhagia
- vomiting
- diarrhoea
DOAC monitoring
Patients should be monitored for signs of bleeding or anaemia. Treatment should be stopped if severe bleeding occurs
No routine anticoagulant monitoring required (INR tests are unreliable)
Warfarin MoA
Vitamin K antagonist — inhibits vitamin K dependent clotting factors (II, VII, IX, X) in addition to the anticoagulant proteins C and S
Warfarin indications
Although no longer first line for many indications, it is first choice in patients with mechanical heart valves and valvular AF and in patients with end-stage renal failure
Warfarin dosing
Variable starting dose. Dose may be variable day to day depending on INR
Warfarin contraindications
Haemorrhagic stroke, clinically significant bleeding, pregnancy, within 48 hours postpartum, high risk of falls
Warfarin interactions
- metabolised by CYP450 in the liver — extensive list of interactions including phenytoin, metronidazole, and clarithromycin. Also many other antibiotics
- also many food interactions — need to keep consistent levels of vitamins K containing products eg. Green leafy veg. Patients should be advised not to eat cranberries/drink cranberry juice also
Warfarin side effects
Common (not exhaustive):
Bruising, epistaxis and bleeding for longer than expected for simple wounds
Monitoring warfarin
INR is monitored. Firstly daily or on alternate days in early days of treatment, then at longer intervals (depending on response), then up to every 12 weeks. May take up to 5 days to achieve an INR within the therapeutic range. The treatment targets are usually INR 2-3: treatment of venous thromboembolism, AF, mitral valve disease and inherited symptomatic thrombophilia and INR 2.5-3.5: for mechanical heart valves
Statins MoA
Competitively inhibit HMG CoA reductase, an enzyme involved in cholesterol synthesis, esp in the liver
What are 3 indications for statins
- hypercholesterolaemia
- primary prevention of CVD
- secondary prevention of CVD
Statins dosing
Usually once daily. Certain statins (simvastatin and pravastatin) need to be taken at night, the others don’t
Statins cautions
Patients at higher risk of muscle toxicity eg. The elderly, liver disease or high alcohol intake
Statins interactions
Metabolised by CYP450 in the liver — therefore potentially a number of interactions. Key examples are clarithromycin (hold the statin for the antibiotic course length) and grapefruit juice (patients cannot drink this)
Statins side effects
Common (not exhaustive)
- myalgia, nausea, constipation diarrhoea, flatulence and headache
- need to inform patients to seek medical attention if signs of muscle toxicity
Statins monitoring
Pre-treatment cholesterol levels and liver function, repeated at 3 months and then 12 months. After this annually
QRISK assessment and statins
The QRISK assessment tool should be used to estimate a patient’s 10 year risk of developing CVD — this can be used to guide if a statin should be prescribed
What are the 4 types of laxatives?
- Bulk-forming. Eg. Ispaghula husk
- Stimulant. Eg. Bisacodyl, senna, sodium picosulfate
- Faecal softener. Eg. Docusate (also a stimulant), glycerol
- Osmotic. Eg. Lactulose, macrogol
Bulk-forming laxative MoA
Increase bulk of stool by helping to retain fluid, encourages peristalsis
Stimulant laxative MoA
Stimulate peristalsis and increases mobility of large intestine
Faecal softener laxative MoA
Increase fluid content of stool making them easier to pass
Osmotic laxative MoA
Increase amount of water in bowel, making stool easier to pass
Indication for laxatives
Constipation
Laxative dosing
Generally bulk-forming should be tried first. If unsuccessful add in/switch to osmotic. Next option would be stimulant
Dosing different for each medication, some best taken at night/in the morning
Laxative cautions
Risk of electrolyte imbalance with prolonged use, need to maintain adequate fluid intake
Laxative interactions
Nil of note
Laxative side effects
Common (not exhaustive):
GI discomfort, nausea
Laxatives pharmacokinetics
- bulk-forming — a number of days for onset of action
- stimulant — 8-12 hours onset of action
- faecal softener — 1-2 days onset of action
- osmotic — up to 48 hours onset of action
What class of drugs do these belong to?
Alendronate, zoledronate, risedronate, ibandronate
Bisphosphonates
How do Bisphosphonates work?
Slow down the process of bone breakdown by osteoclasts, whilst allowing osteoblasts to continue to enhance bone density
What are 3 indications for bisphosphonates?
- osteoporosis
- Paget’s disease
- patients with bone metastases
Dosing for Alendronate, zoledronate, risedronate, and ibandronate
Alendronate = 70mg once weekly PO
Zolendronate = 5mg yearly IV
Risedronate = 35mg once weekly PO
Ibandronate = 150mg once monthly PO
What are cautions for bisphosphonates?
- elderly
- active GI bleeding
- recent Hx of GI ulcers
- dysphagia
Bisphosphonates: directions for administration
Doses should be taken with plenty of water whilst sitting or standing, on an empty stomach at least 30 minutes before breakfast (or another oral medicine); patient should stand or sit upright for at least 30 mins after administration
What are some common (not exhaustive) side effects of bisphosphonates?
- Nausea
- oesophageal ulcer — discontinue
- oesophagitis — discontinue
- gastritis
- abdominal pain
Bisphosphonates monitoring
- correct calcium/vitamin D levels before commencing
- monitor serum calcium throughout
- monitor renal function. Should not be sued with CrCl<30-35ml/min (check each medication)
Bisphosphonates safety information
