BNF Chapter 2 - Cardiovascular System Flashcards
(94 cards)
1
Q
What do positive inotropic drugs do?
A
Increase force of contraction
2
Q
Cardiac Glycosides:
Digoxin - how does it work? what is it useful for? how long does it take to work?
A
- Increase force of myocardial contraction and reduces conductivity in atrio-ventricular node
- Controlling AF and flutter
Management of AF - dose of digoxin should be determined by the ventricular rate at rest, should not fall persistently below 60 BPM - Response to digoxin can take some time, even hours by IV route
3
Q
Cardiac Glycosides:
Digoxin toxicity - management and what happens?
A
- Hypokalaemia predisposes patient to digitalis toxicity - managed by giving K sparing diuretic or K supplements
- In toxicity - digoxin specific antibody fragments available to reverse life-threatening overdosage
4
Q
Diuretics: Thiazide and related diuretics
What are they used for?
How do moderately potent diuretics work?
How long for these to act and when do we give them?
A
- Relieve oedema from CHF and reduce BP in lower doses
- Inhibit Na reabsorption at beginning of DCT
- Act within 1-2 hours of oral administration with duration of action 12-24 hours
Given in morning so diuresis does not interfere with sleep
5
Q
Diuretics: Thiazide and related diuretics
In hypertension - low and high doses
Bendroflumethiazide - used for?
Chlortalidone - duration and when given?
A
- Low dose thiazide (bendro 2.5) will give maximal BP lowering effect, high doses cause more changes in plasma electrolytes and ions
- Mild or moderate HF and hypertension
- Thiazide related compound, longer duration than thiazides, given alternate days to control oedema
6
Q
Diuretics: Thiazide and related diuretics
Indapamide - what does it do and who is it best for?
Contra-indications of thiazide and related diuretics
A
- Chemically related to chlortalidone, can lower BP with less metabolic disturbance and less aggravation of diabetes mellitus
- Should be avoided in hypokalaemia, hyponatraemia, hypercalcaemia and Addison’s disease
Used in caution in patients with hepatic impairment and avoided in severe liver disease
7
Q
Loop Diuretics:
How do they work?
When are they used?
What can be added to them?
Examples and when they act
A
- Inhibit reabsorption from ascending limb of LoH
- Used in pulmonary oedema from left ventricular failure and in CHF
Diuretic resistant oedema can usually be treated with a loop - Can be added to anti-hypertensive to achieve better control of BP
- Furosemide and Bumetanide act within 1 hr of oral admin., similar in activity
8
Q
Loop Diuretics:
Contra-indications
A
Avoid in severe hypokalaemia, severe hyponatraemia and renal failure from nephrotoxic drugs
Hypokalaemia induced by loop diuretics can cause hepatic encephalopathy and coma - K sparing diuretics can be used to prevent this
9
Q
Potassium-sparing diuretics:
Weak diuretics
What can K-sparing cause?
K supplements
What can certain add ons cause?
A
- Amiloride and triamterene are weak on their own
- Cause retention of K and therefore given with thiazide or loop diuretics - more effective alternative to K supplements
- Must not be given when patient also taking K-sparing diuretics
- Use of K-sparing with an ACEi or ATII antagonist can also cause severe hyperkalaemia
Combo treatments available, if compliance is a problem - co-amilozide, co-amilofruse
10
Q
Aldosterone antagonists:
What does spironolactone do?
When is it used?
When is eplerenone used?
K supplements
A
- Potentiates thiazide or loop diuretics by antagonising aldosterone
- Treatmnt of oedema and ascites caused by cirrhosis of liver
- As adjunct in LV dysfunction and HF after myocardial infarction
- Must not be given with aldosterone antagonists
11
Q
Drugs for arrhythmias:
How do these act?
Verapamil
Amiodarone
Lidocaine
A
- Acts on supraventricular arrhythmias
- Acts on supraventricular and ventricular arrhythmias
- Acts on ventricular arrhythmias
12
Q
Drugs for arrhythmias:
Vaughn Williams classification
A
I - membrane stabilising: lidocaine
II - beta-blockers
III - amiodarone, sotalol (also class II)
IV - CCBs
13
Q
Beta-adrenoreceptor blocking drugs:
How do they work?
Intrinsic sympathomimetic activity
What drugs have intrinsic activity?
A
- Block beta-adrenoreceptors in heart, peripheral vasculature, bronchi, pancreas and liver
- Capacity of beta blockers to stimulate as well as block adrenergic receptors
- Oxprenalol, Pindolol, Acebutolol and Celiprolol have and cause less bradycardia and less coldness of extremeties
14
Q
Beta-adrenoreceptor blocking drugs:
Water soluble beta blockers
Examples
How are they excreted?
Duration of action
A
- Less moves into the brain and therefore less sleep disturbance and less nightmares
- Atenolol, Celiprolol, Nadolol and Sotalol
- Excreted by kidneys, dosage reduction often needed in renal impairment
- Have short duration - need to given BD or TDs, but MR formulation available (OD)
Some have longer duration and are given OD -atenolol, bisoprolol, carvedilol, celiprolol and nadalol
15
Q
Beta-adrenoreceptor blocking drugs:
Beta blockers can precipitate?
What are beta blockers associated with?
What can they affect?
A
- Bronchospasm - usually avoided in asthma patients
If asthma is well controlled, a cardioselective beta blocker can be used at a low dose
Atenolo, bisoprolol, metopeolol and nebivolol are cardioselective but not cardiospecific - Associated with fatigue, coldness of extremities, sleep disturbances and nightmares
- Carbohydrate metabolism and affect metabolic responses to hypoglycaemia - can mask symptoms such as tachycardia
16
Q
Beta-adrenoreceptor blocking drugs in pregnancy
A
Should be avoided, may cause intra-uterine growth restriction, neonatal hypoglycaemia and bradycardia
- Latetalol not known to be harmful in maternal hypertension - except in 1st trimester
- Infants should be monitored if breastfed - possible toxicity due to beta-blockade
17
Q
Beta-adrenoreceptor blocking drugs - use in hypertension:
A
Reduce CO2 alter baroreceptor reflex sensitivity and block peripheral adrenoreceptors
Some B-blockers depress plasma renin secretion
18
Q
Beta-adrenoreceptor blocking drugs - use in angina:
A
Reduce cardiac work - improve exercise tolerance and relieve symptoms of angina
Sudden withdrawal can lead to angina exacerbation, gradual reduction in dose preferred
Risk of precipitating HF when B-blockers and Verapamil (CCB) used together
19
Q
Beta-adrenoreceptor blocking drugs - use in myocardial infarction:
A
Can sometimes reduce recurrence rate of MI
However not suitable in all conditions
Sudden cessation of B-blocker can cause rebound worsening of MI
20
Q
Beta-adrenoreceptor blocking drugs - use in arrhythmias:
A
Attenuate effects of sympathetic system on automacity and conductivity in the heart
Can be used in conjunction with digoxin to control ventricular response in AF
Also useful in management of supraventricular tachycardias
21
Q
Beta-adrenoreceptor blocking drugs - use in HF and other uses
A
- Can produce benefit in HF by blocking sympathetic activity
- Can also be used in anxiety, palpitation, tremor and tachycardia
Prophylaxis of migraine
Betaxolol, carteolol, levobunolol and timolol used topically in glaucoma (eyedrops)
22
Q
Beta-adrenoreceptor blocking drugs - side effects:
A
BBC Loses Viewers in Rochdale - Bradycardia, Bronchoconstriction, Claudication, Vivid dreams & nightmares, negative inotropic action, Reduced sensitivity to hypoglycaemia
23
Q
Beta-adrenoreceptor blocking drugs - contraindications:
A
ABCDE - Asthma, heart Block, Cardiac failure, Diabetes mellitus (hypoglycaemic shock), Extremities (occlusivearterial disease)
24
Q
Hypertension and HF:
What does lowering BP do?
What should be established?
A
- Lowering raised BP reduces risk of stroke and coronary events, HF and renal failure
- Possible causes of hypertension (renal, endocrine), contributory factors, risk factors and presence of complications
25
Hypertension and HF:
Lifestyle changes
- Smoking cessation
- Weight reduction
- Reduce excessive alcohol and caffeine
- Reduce dietary salt
- Reduce total and unsaturated fat
- Increase exercise
- Increase fruit and veg intake
26
Hypertension and HF - thresholds and targets for treatment
Target for patients U80 = 140/90 (clinic) or 135/85 (ambulatory or home)
Patients with 140/90mmHg or higher should be offered measurement in ambulatory position or home BP reading to confirm diagnosis and stage
27
Hypertension and HF - Stage 1 Hypertension
BP 140/90 or higher and ambulatory/home average 135/85 or higher
Treat patients U80 and target organ damage - LV hypertrophy, CKD, retinopathy, diabetes, CV disease
Give lifestyle changes for patients U40 with no target organ damage
28
Hypertension and HF - stage 2 hypertension:
Clinic BP 160/100 or higher and ambulatory/home average 150/95 or higher
Treat all patients with stage 2 hypertension regardless of age
29
Hypertension and HF - severe hypertension:
Clinic BP 180/110 or greater
Treat promptly - hypertensive crisis
30
31
Hypertension and HF - patients U55:
1. ACEi/AT2a - if both ACEi or AT2a are C/I or not tolerated, consider B-blocker
2. ACEi or AT2a in combo with CCB - if CCB not tolerated, give Thiazide related diuretic
If B-blocker given in step 1, add CCB instead of diuretic
3. ACEi or AT2a
Combined with CCB and thiazide related diuretic
4. Resistant hypertension - consider specialist advice, low dose spironolactone or high dose thiazide related diuretic, monitor renal function and electrolytes, consider alpha-blocker or B-blocker
32
Hypertension and HF - patients over 55 and patients any age of African/Caribbean origin
1. CCB or thiazide related diuretic
2. CCB or thiazide related diuretic
Add an ACEi or AT2a
Steps 3 and 4 same as patients U55 years
33
Hypertension in diabetes
Target of 140/80 or below 130/80 if kidney, eye or cerebrovascular disease present
Antihypertensive treatment prevents macrovascular and microvascular nephropathy
ACEi or AT2a can delay progression of microalbuminuria to nephropathy
In type 1 diabetes, hypertension usually indicates presence of nephropathy
34
Hypertension in renal disease
Target of 140/90 or 130/80 in CKD, diabetes, or if proteinuria exceeds 1g in 24h
35
Hypertension in pregnancy
Hazardous to mother and foetus
Labetolol and methyldopa are safe in pregnancy - stop methyldopa 2 days after birth and continue regular hypertension treatment
MR nifedipine [unlicensed] can also be used
Target of 150/100 in uncomplicated and 140/90 in chronic hypertension, or already given birth
36
Vasodilator antihypertensive drugs:
What effect do they have?
Common examples
1. Potent hypotensive effect, especially when used with B-blocker and thiazide
2. Diazoxide, hydralazine, sodium nitroprusside and minoxidil
37
Vasodilator antihypertensive drugs:
Hydralazine
Sitaxentan
1. Occurrence of s/e is lower if dose kept to <100mg daily, SLE should be suspected if unexplained weight loss, arthritis or other unexplained ill health
2. Withdrawn from market as benefit does not outweigh risk of severe hepatotoxicity
38
Centrally acting antihypertensive drugs:
Methyldopa
Clonidine
Moxonidine
1. Centrally acting, used for hypertension in pregnancy, s/e minimised if daily dose <1g
2. Can be used but disadvantage is sudden withdrawal can cause severe rebound hypertension
3. May have a role when normal antihypertensive therapy not appropriate or cannot control BP
39
Alpha-adrenoreceptor blocking drugs:
Prazosin
Which of the drugs have similar properties?
What drugs have another indication and what is it?
1. Post-synaptic alpha blocking and vasodilator properties, rarely causes tachycardia but may reduce BP rapidly after 1st dose - introduce with caution
2. Doxazosin, Indoramin and Terazosin
3. Alfuzosin, doxazosin, prazosin, tamsulosin, terazosin indicated for BPH
40
Drugs affecting the RAAS - ACEi:
How?
Use in HF
1. Inhibit conversion of angiotensin I to II
2. Used in all grades of HF
Usually combo with B-blocker
K supplements and K-sparing diuretics stopped before starting - risk of hyperkalaemia
1st dose hypotension can occur when patient already taking high dose diuretic (80mg furosemide daily or equivalent)
41
Drugs affecting RAAS - ACEi:
Hypertension
Renal effects
1. Usually initial therapy in young Caucasian patients, Afro-Caribbean, >55 etc. respond less well
2. Check renal function before starting and monitor throughout, hyperkalaemia can be s/e, impaired renal function are more prone to s/e
Concomitant treatment with NSAID increases risk of renal damage and K-sparing diuretics/K supplements increase hyperkalaemia risk
Can cause hypotension, especially in high dose diuretic patients, low Na diet, on dialysis, dehydrated
42
Drugs affecting RAAS - ACEi:
Concomitant diuretics
ACEi can cause rapid fall in BP in volume depleted patients - start treatment at low dose
Sometimes diuretic dose needs to be stopped at least 24hrs before ACEi
May not be possible in HF - risk of pulmonary oedema
If high dose cannot be stopped, close supervision needed for 1st dose or 2 hours
43
Drugs affecting RAAS - ACEi - pregnancy:
Avoid in pregnancy
Can adversely affect foetal and neonatal BP control
Skull defects and oligohydraminos reported
Neonatal hypotension risk if ACEi given when breastfeeding young child
44
Drugs affecting RAAS - ACEi - side effects:
- Profound hypotension
- Renal impairment
- Angioedema
- Persistent dry cough - onset may be delayed, higher incidence in afro-caribbean patients
45
Drugs affecting RAAS - ACEi - combination products:
- Incorporate ACEi plus thiazide diuretic or CCB
- Use reserved for patients whose BP does not respond to regular single treatment
- Patient must be stabilised on individual drugs in combo products in same proportions
46
Drugs affecting RAAS - Angiotensin II receptor antagonists:
Common examples
Why are they less likely to cause dry cough?
Cautions
1. Candesartan, eprosartan, irbesartan, losartan, valsartan - similar properties to ACEi
2. Do not inhibit breakdown of bradykinin and other kinins (like ACEi do)
3. In elderly and renal impairment and avoid in pregnancy
47
Drugs affecting RAAS - Angiotensin II receptor antagonists:
Side effects
Usually mild
- Symptomatic hypotension
- Dizziness - especially patients with intravascular volume depletion (taking high dose diuretics)
- Hypokalaemia occasionally
48
Drugs affecting RAAS - renin inhibitors:
How do they work?
What are they licensed for?
What are they not recommended to be taken with?
1. Inhibit renin directly - renin converts angiotensinogen to angiotensin I
2. Aliskiren licensed for hypertension treatment
3. ACEi and renin inhibitors not recommended together
49
Nitrates and CCBs:
What effects do they have?
How do they work?
What can they cause?
1. Vasodilating effects - can act in HF by arteriolar dilation (also K channel blockers can too)
2. Reduces peripheral and vascular resistance and left ventricular pressure during systole, improves cardiac output
3. Venous dilation - dilation of capacitance vessels, increase venous pooling and reduce venous return to heart
50
Nitrates:
Useful for?
Unwanted effects
Sublingual
Duration and onset
1. Angina - reduce venous return which reduces left ventricular work
2. Limit therapy - flushing, headache, postural hypotension
3. Rapid asymptomatic relief, only lasts 20-30 mins, isosorbide dinitrate is more stable for patients who need nitrates infrequently
4. Slower to act but longer duration and MR 12 hours duration
51
Nitrates - tolerance:
- Many develop tolerance - reduced therapeutic effects
- Reduction of blood nitrates conc. to low levels for 4-8 hrs maintains effectiveness
- Nitrate free period, for patches - patch left off for several consecutive hours every 24 hrs
52
Calcium channel blockers:
How do they work? (3 things)
When should verapamil and diltiazem be avoided?
1. Interfere with inward displacement of Ca ions through slow channels of active cell membranes
Influence myocardial cells of heart and vascular smooth muscle cells
Contractility can be reduced, formation and propagation of electrical impulses depressed or systemic vascular tone diminished
2. In HF - can further depress cardiac function and cause deterioration
53
Dihydropyridine CCBs:
How do they work?
Examples
1. Relaxes vascular smooth muscle - reduces systemic vascular resistance and arterial pressure
No anti-arrhythmic activity
2. Amlodipine, felodipine, lacidipine, nifedipine
54
Phenylalkylamine CCBs:
Selectivity
How do they work?
Used for?
1. Relatively selective for myocardium cells - reduce myocardial oxygen demand
2. Negative inotropy is main MOA (weaken force of heart muscle contraction)
Slows heart rate (has some anti-arrhythmic activity)
3. Angina
55
Phenylalkylamine CCBs:
What minimal effects do they have?
Example
What should they not be used with?
1. Minimal vasodilatory compared to dihydropyridines - less reflex tachycardia, better for angina treatment
2. Verapamil
3. With B-blockers - can precipitate HF
56
Benzothiazepine:
What is it?
How do they work?
Example
Caution
1. Intermediate between phenylalkylamine and dihydropyridine CCB in selectivity for vascular Ca channels
2. Diltiazem
3. With B-blockers due to risk of bradycardia
57
Unstable angina:
CCBs
Using Diltiazem and Verapamil
Withdrawal
1. Do not reduce risk of MI in unstable angina
2. Should be reserved for patients resistant to B-blocker treatment
3. Sudden withdrawal may cause exacerbation of angina
58
Other anti-anginal drugs:
Nicorandil - how does it work? what properties does it have? what is it licensed for?
Ranolazine - when is this therapy used?
1. K channel activator with nitrate compound
2. Has both arterial and venous vasodilating properties
3. Long term treatment of angina
4. Adjunct therapy for patients inadequately controlled/intolerant of 1st line anti-anginals
59
Other anti-anginal drugs:
Ivabradine - how does it work? what is it licensed for? how can it be given?
1. Lowers HR by action on sinus node
2. Licensed for angina in patients with normal sinus rhythm and also stable chronic HF
3. Given either with B-blocker or without if B-blocker c/i
60
Anticoagulants and Protamine:
How do they work?
What should all hospital admissions undergo?
Patients scheduled for surgery
1. Prevent thrombus formation or extension of existing thrombus
2. Risk assessment of VTE – high risk:
pts with low mobility, obese, history, over 60
3. Mechanical prophylaxis (stockings) and
should continue until pt mobile
High risk pts should be offered pharmacological prophylaxis
61
Anticoagulants and Protamine:
What anticoagulant is used for general/orthopaedic surgery?
What anticoagulant is used for patients in renal failure?
What anticoagulant is used for hip/knee surgery or day surgery?
What anticoagulant is used for thromboprophylaxis after knee/hip surgery?
1. LMWH
2. UFH
3. Fondaparinux
4. Dabigatran/rivaroxaban
62
Anticoagulants and Protamine:
How long should pharmacoprophylaxis continue after surgery?
5-7 days or until mobility re-established (major surgery needs more time)
63
Heparin:
How does it work?
Duration of action
Pregnancy
1. Initiates anticoagulation rapidly but has short duration of action (unfractionated/normal)
2. LMWHs have longer duration of action than normal heparin
3. Can be used for VTE in pregnancy – does not cross placenta
- LMWH preferred – less risk of osteoporosis and heparin induced thrombocytopenia
- Eliminated more rapidly in preg – dosage adjustion for enoxaparin, dalteparin needed
64
Haemorrhage:
What should happen to heparin?
Protamine sulphate
1. Should normally be withdrawn
2. Antidote for rapid reversal of heparin effects
65
Hyperkalaemia:
How is hyperkalaemia caused by UFH or LMWH?
What patients are more susceptible?
When is risk increased?
1. Inhibition of aldosterone secretion
2. Patients with diabetes, chronic renal failure, acidosis, raised plasma K, or those taking K-sparing drugs
3. Increased with duration of therapy – plasma K conc should be measured before starting and during treatment
66
LMWH:
Examples
When is it preferred?
Duration of action
1. Dalteparin, Enoxaparin and Tinzaparin
2. Usually preferred over UFH as lower risk of heparin induced thrombocytopenia
3. Longer duration of action and OD dose – more convenient
67
LMWH:
When is it used?
When is dalteparin licensed?
1. Used in prophylaxis of DVT, treatment of DVT, PE and MI
2. Dalteparin licensed for extended treatment and prophylaxis of VT in patients with solid tumours
68
Oral anticoagulants - Coumarins and Phenidione:
Examples
How do they work?
How long for them to work?
Monitoring
1. Warfarin, acenocoumarol and phenidone
2. Antagonise effects of Vit K
3. 48-72 hours for full effect
4. INR regularly and patient should be given warfarin book
69
Oral anticoagulants - haemorrhage:
What is it an adverse effect of?
What should happen?
1. All oral anticoags
2. Anticoag should be stopped and INR measured to ensure it is dropping
70
Oral anticoagulants - combined antiplatelet and anticoag therapy:
Risks
Plan of action to minimise risks
1. Increased bleeding risk
Risk of bleeding with aspirin and warfarin is lower than risk with clopidogrel and warfarin
2. If possible – withhold antiplatelet therapy until warfarin therapy complete or vice versa
71
Oral anticoagulants - cautions:
Avoid
1. Avoid in severe hepatic impairment especially if prothrombin time already prolonged
Avoid in severe renal impairment
72
Oral anticoagulants - pregnancy:
Teratogenic drugs
Haemorrhage risk
1. Warfarin, acenocoumarol and phenidone are teratogenic – should not be given in first trimester
- Stopping these drugs before sixth week of gestation can avoid most of the risk of foetal abnormality
- Cross placenta with risk of congenital malformations, placental, foetal and neonatal haemorrhage
- Especially during last few weeks of pregnancy and delivery
- Avoid in pregnancy especially in first and third trimesters
2. Risk of haemorrhage – increased by Vit K deficiency
73
Oral anticoagulants - dabigatran:
What is it?
Used for?
Onset and monitoring
Common s/e - how do avoid
Apixaban and rivaroxaban
1. Direct thrombin inhibitor
2. Prophylaxis for VTE in adults after hip or knee replacement surgery and prophylaxis of stroke and SE
3. Rapid onset and doesn’t need therapeutic monitoring
4. Haemorrhage – monitor for signs of bleeding or anaemia, stop treatment if bleeding occurs
5. Direct inhibitor of activated factor Xa
74
Oral anticoagulant - Protamine Sulphate:
Used for?
LMWH half life
Duration
Excessive doses can have what effect?
1. Overdosage of UFH or LMWH
2. Long 1/2 life of LMWH should be taken into account when determining PS dose
3. Can last up to 24 hours after admin.
4. Can have anticoagulant effect
75
Antiplatelet drugs:
How do they work?
Aspirin is used for?
What to do for patients at high bleeding risk?
What are the main antiplatelets?
What drugs can increase risk of bleeding?
1. Decrease platelet aggregation and inhibit thrombus formation
2. Primary prevention
3. PPI can be added
4. Aspirin, clopidogrel, dipyridamole
5. Aspirin + Clopidogrel
76
Fibrinolytic drugs:
How do they act and work?
Used for?
Main examples
What drugs should be given in short onset?
1. Act as thrombolytics – activate plasminogen, which degrades fibrin and breaks up thrombi
2. MI treatment
3. Streptokinase and Alteplase
4. Alteplase, reteplase and streptokinase given within 12 hours of symptom onset (ideally within 1 hour)
77
Fibrinolytic drugs - cautions:
Contraindications
Streptokinase antibodies
Avoid
Pregnancy
1. Used in caution if risk of bleeding, drugs that can cause bleeding
2. Recent haemorrhage, trauma, surgery, coag defects
3. Prolonged persistence of antibodies to streptokinase can reduce effectiveness of subsequent treatment
- Streptokinase shouldn’t be used again beyond 4 days of first administration
78
Fibrinolytic drugs - cautions:
Avoid
Pregnancy
1. Avoid in hepatic impairment as risk of bleeding
2. Pregnancy – thrombolytic drugs can lead to premature separation of placenta in first 18 weeks
- Also risk of maternal haemorrhage throughout pregnancy and post partum and foetal haemorrhage throughout pregnancy
79
Fibrinolytic drugs - s/e:
- N&V
- Bleeding
- Hypotension – usually controlled by elevating patient’s legs or reduce rate of infusion
- Pain, back fever, convulsions also reported
80
Antifibrinolytic drugs:
How do they work?
Used for?
What is also used?
1. Fibrin dissolution can be impaired by tranexamic acid – inhibits fibrinolysis
2. Prevent bleeding or treat bleeding due to excessive fibrinolysis and menorrhoea
3. Desmopressin also used
81
Lipid regulating drugs:
Preventative measures
High risk patients
1. Should be taken in patients with high risk of
developing CV disease (primary prevention) and to prevent recurrence of events in those who already have CV disease (secondary prevention)
2. Atherosclerotic disease, diabetes + over 40, familial hypercholesterolaemia, older age, smoker, hypertension
82
Lipid regulating drugs:
Hyperthyroid patients
How do these help?
Lifestyle modifications
1. Correct thyroid insufficiency before starting lipid regulating drugs
- Correcting thyroid problems can resolve lipid problems too
- Untreated hypothyroidism increased risk of myositis with lipid regulating drugs
2. Lowering conc of LDL and raising HDL will slow progression of atherosclerosis and can cause regression
3. Change diet, exercise, weight management, alcohol, smoking cessation, lowering of raised BP, low dose aspirin, diabetes management
83
Lipid regulating drugs - treatment overview:
Reducing risk - 1st line
2nd line
Nicotinic acid
What should not be used in combo?
1. CV disease events – drug of first choice [primary + secondary prevention]
2. Fibrate or bile acid sequestrant – second line [primary + secondary prevention]
3. Nicotinic acid – option for secondary prevention
4. Fibrates, bile sequestrants or nicotinic acid shouldn’t be used in combination with statin for primary prevention
84
Lipid regulating drugs - treatment overview:
In secondary prevention
If not controlled
1. If total cholesterol less than 4mmol/L or LDL less than 2mmol/L not achieved with initial treatment – consider ‘high intensity’ statin
- A statin that produces a greater LDL cholesterol reduction than simvastatin 40
- High intensity statins associated with higher risk of muscle effects
2. If hyperlipidaemia not controlled with maximal statin dose – consider adding Ezetimbe or Colestyramine
85
Statins:
How do they work?
What are they more effective at?
1. Competitively inhibit HMG CoA reductase – enzyme involved with cholesterol synthesis
2. Statins more effective than other lipid regulating drugs at lowering LDL cholesterol
- But less effective than Fibrates at reducing triglyceride conc.
86
Statins:
Diabetic patients
When to consider statins
1. Risk of CV disease depends on duration and complications of diabetes, age
- Statin therapy for all pts over 40 with T1 and T2 diabetes
- In younger pts – statin only considered if there is target organ damage, poor glycaemic control (HbA1c greater than 9%), low HDL levels, and raised triglyceride conc, hypertension or familial history of premature CV disease
2. Generally statin treatment considered if total cholesterol conc to HDL cholesterol exceeds 6
87
Statins:
Cautions
Hx of liver disease or high alcohol intake
NICE – liver en zyme measurement before treatment and at 3 and 12 months as well if signs of hepatotoxicity
- Pts with serum transaminases more than 3 times upper limit – stop statins
- Atorvastatin and rosuvastatin – can be taken at any time as long acting, other statins normally taken at night
- Avoid use with fucidic acid, macrolide abx, imidazole, triazole – stop statin and restart after 7 days
88
Statins - pregnancy:
- Avoid in pregnancy – congenital anomalies and decreased synthesis of cholesterol can affect foetal development
- Adequate contraception required during treatment and 1 month afterwards
- Avoid in breastfeeding
89
Statins - s/e:
- Myalgia, myopathy, myositis and rhabdomylosis
- Liver function can be altered – hepatitis, jaundice
- Muscle toxicity
- Patient should report any unexplained muscle pain, weakness or tenderness
90
Statins - Ezetimbe:
How does it work?
Increased risk of what?
1. Inhibits absorption of cholesterol
2. Increased risk of rhabdomylosis when used with a statin
91
Statins - fibrates:
Examples
How do they work?
1st line for what?
1. Bezafibrate, ciprofibrate, fenofibrate and gemfibrozil
2. Decrease serum triglycerides
3. First line therapy ONLY in patients with serum triglyceride conc greater then 10mmol/L or those who cant tolerate a statin
92
Statins - fibrates:
What can they cause?
Combination with statins increase what?
Simvastatin and fibrates
1. Can cause myositis like syndrome – esp if poor renal function
2. Combination of statin with fibrate increases risk of muscle effects
3. Max strength of simvastatin 10mg with fibrates can be used – otherwise increased risk of rhabdomylosis
93
Statins - Omega-3 fatty acids:
Used to?
Triglycerides
1. Can be used to reduce triglycerides as alternative to fibrate and additional to statin
2. Triglyceride conc exceeding 10mmol/L associated with acute pancreatitis, lowering conc reduces risk
94
