Final clinical flashcards
1
Q
Classes of antiarrhythmic drugs (5)
A
- Na+ blocking, membrane stabilising
- Beta blockers
- K+ channel blocking
- Non dihydropyridine CCBS
- Others
2
Q
Class 1 antiarrhythmic drugs (3)
A
- Na+ blocking
- E.g lidocaine, propenafone, flecanide (split into further classifications)
- Contraindicated in asthma, copd, structural/IHD
3
Q
Class 2 antiarrhythmic drugs (2)
A
- Beta blockers
2. Cardiospecific beta blockers: acebutol, atenolol, bisoprolol metoprolol, nebevilol
4
Q
Class 3 antiarrhyhmic drugs (4)
A
- K+ channel blockers
- E.g. amiodarone, dronedarone, sotalol
- Amiodarone is 4 weeks before and 12 months after electrical cardioversion to increase success
- Dronedarone is associated with hepatotoxic and HF side effects
5
Q
Class 4 antiarrhythmic drugs (4)
A
- Rate limiting CCBS (non-dihydropyridine)
- E.g verapamil, diltiazem
- Avoid verapamil in beta blocker pts (increased risk of hypotension and asystole)
- Diltiazem is unlicesned for arrhythmia
6
Q
Class 5 antiarrhythmic drugs (3)
A
- Other
- E.g adenosine and digoxin
- Digoxin is only used if sedentary + AF+ congestive heart failure altogether
7
Q
Maintenance treatment AF (2)
A
- Rate control is 1st line, rhythm control is 2nd line
2. Anticoagulation needed for stroke prophylaxis?
8
Q
Rate control for AF (3)
A
- Beta blocker
- Rate limiting CCB
- Beta blocker+rate limiting CCB/ digoxin
9
Q
Rhythm control for AF (2)
A
- Beta blocker
2. Sotalol/ amiodarone/ flecainide, propafenone, dronedarone
10
Q
How to assess stroke and bleed risk in AF
A
- CHADsVASc and HASBLED
- Anticoagulate if chadvasc is 2 or more
- Consider further if HASBLED high risk of bleed 3 or more
11
Q
CHADsVASc risk factors
A
Congestive HF HTN Age (75+) -2 Diabetes Stroke - 2 Vascular disease Age (65-74) Sex
12
Q
HAS BLED risk factors
A
HTN Liver disease (bilirubin 2x normal and ALT etc 3x normla) Renal impairment Stroke history Bleeding history Labile INR Elderly Drugs (inc etoh)
13
Q
If anticoagulation indicated in AF (as per chadvasc and hasbled)
A
If new onset give parenteral
If diagnosed, warfarin or DOAC
14
Q
Amiodarone main indication
A
Treatment of arrhythmias, particularly when other drugs are ineffective or contraindicated
15
Q
Amiodarone mode of action
A
K+ channel blocker. Prolongs the repolarization of the heart during phase 3 of the cardiac action potential, prolonging the length of the action potential.
16
Q
Amiodarone side effects (8)
A
- Optic neuropathy (may cause blindness). Stop immediately if signs of impaired vision.
- Corneal microdeposits. May reverse on stopping. Cause night time glares when driving.
- Grey slated skin on exposure to sunlight (use wide spectrum, high SPF sunscreen for months after stopping)
- Phototoxicity.
- Peripheral neuropathy
- Pulmonary fibrosis, pneumonitis (SOB, cough)
- Hepatotoxicity. Watch out for nausea, vomiting, malaise, jaundice, itching, bruising, abdo pain.
- Thyroid issues (if hyper stop and give carbimazole, if hypo can continue and give levo)
Also commonly causes constpiatiom, movement disorders, sleep disorders, altered taste, vomiting
17
Q
Amiodarone monitoring (5)
A
- K+ beforehand as may cause hypokalemia
- Chest x ray before
- TFTs before and then 6 monthly
- LFTs before and 6 monthly
- Annual eye tests (not in BNF)
+HR and BP as can cause hypotension and bradycardia
18
Q
Amiodarone interactions (4)
A
Remember has a half life of around 50 days
- Enzyme inhibitors can increase the concentration of amiodarone e.g. grapefruit
- Amiodarone itself is an enyzme INHIBITOR and so increases the concentration of digoxin, warfarin and phenytoin (must half dose)
- Amiodarone increases the risk of myopathy and so avoid where possible. Manufacturer advises for simvastatin max 20mg OD with amiodarone/ amlodipine/ ranolazine/ verapamil/ diltiazem. (note max 40mg max for ticagrelor+simvastatin)
- Beta blockers and rate limiting CCBS can cause bradycardia, AV block and myocardial depression
- QT prolongation. Quinolone, macrolides, TCAs, SSRIs, lithium, quinine, hydroxychloroquinie, anti-malarials, antipsychotics
19
Q
Drugs which prolong QT and therefore interact with amiodarone (9)
A
- TCAs
- SSRIs
- Lithium
- Quinine
- Quinolones
- Macrolides
- Hydroxychloroquinine
- Antimalarials
- Antipsychotics
20
Q
Amiodarone: other
A
MHRA/CHM advice: Sofosbuvir with daclatasvir; sofosbuvir and ledipasvir (May 2015); simeprevir with sofosbuvir (August 2015): risk of severe bradycardia and heart block when taken with amiodarone (avoid but if necessary, counsel on signs of bradycardia and heart block)
21
Q
Indications for digoxin (2)
A
- Maintenance for AF/ flutter (125-250)
2. Worsening/ severe heart failure in sinus rhythm (62.5-125)
22
Q
Mode of action of digoxin
A
Digoxin induces an increase in intracellular sodium that will drive an influx of calcium in the heart and cause an increase in contractility. Cardiac output increases (positive inotrope) with a subsequent decrease in ventricular filling pressures. AV Node Inhibition: Digoxin has vagomimetic effects on the AV node. By stimulating the parasympathetic nervous system, it slows electrical conduction in the atrioventricular node, therefore, decreases the heart rate (negative chronotrope)
23
Q
Bioavailability of digoxin preparations
A
Elixir 65%
Tablet 90%
IV 100%
BNF: “when switching from IV to oral route may need to increase dose by 20-33% to maintain the same plasma digoxin concentration)
24
Q
Causes of digoxin toxiicty (4)
A
- Hypokalemia
- Hypomagnemesia
- Hypercalcemia
- Renal impairment
25
Signs of digoxin toxiicty
1. Bradycardia/ heart block
2. N+V, diarrhoea, abdo pain
3. Blurred/ yellow vision
4. Confusion/ delirium
5. Rash
26
Digoxin - interactions (4)
1. Increased Cp due to presence of enzyme inhibitors
2. Decreased Cp in response to enzyme inducers
3. Reduced renal excretio may lead to toxicity - watch out for NSAIDs, ACEI/ ARBs
4. Hypokalemia predisposes, so avoid diuretics, B2 agonists, steroids, K+sparing diuretics
27
Drugs which may cause hypokalemia and therefore precipitate digoixin toxicity (4)
1. Diuretics (loops eg furosemide and thiazides eg bendro)
2. B2 agonists
3. Steroids
4. Theophylline
28
Target K+ if patient is on digoixin
4.5mmol/L.
| If less than this give either K+ supplements or K+ sparing diuretics (eg spironolactone, eplerenone)
29
Drugs which precipitate digoxin toxicity
Anything that causes hypokalemia (loop+thiazide diuretics, asthma drugs)
Enzyme inhibitors as they increase the level of digoxin (eg amiodarone)
Drugs which cause renal failure
Drugs which cause hypomagnemesia
Drugs which cause hypercalcemia
30
Types of VTE (2)
1. DVT
| 2. PE (detached blood clot travels to lungs and blocks pulmonary artery)
31
Risk factors for VTE (8)
```
Malignancy
History of VTE
Thrombophilic disorder
Pregnancy
COC/ HRT
Immobility
Age >60
BMI>60
```
32
Risk factors for bleed (5)
```
Systolic HTN
Anticoagulants
Bleeding disorders
Acute stroke
Thrombocytopenia
```
33
Prophylaxis of VTE: treatment options
```
Mechanical prophylaxis (TEDs, IVC)
LMWH+UFH preferred in renal impairment
Fondaparinux is another option in certain cases
Apixaban+ rivaroxaban+ dabigatran are for post knee/ hip replacement
Edoxaban is for recurrent VTE
```
34
Prophylaxis of VTE: duration of prophylaxis
5-7 days post surgery /sufficient mobility
extended if hip/ knee
28 day if cancer related abdo surgery/ pelvis surgery- major
35
Treatment of VTE (non pregnant)
Apixaban or rivaroxaban
LMWH or UFH (monitor APTT) in renal failure
Fondaparinux
LMWH for 5 days>> then edoxaban/ dabigatran
LMWH+ warfarin for 5 days or until INR 2.0 or more for 2 consecutive readings
36
Treatment of VTE in pregnancy
LMWH preferred
| Measure antixa activity routinely if extremes of body weight
37
Anticoagulants
Parenteral (UFH, LMWH, fondaparinux)
| Oral (DOAC, warfarin)
38
The heparins
UFH - activates antithrombin. short acting. good if high risk of bleed or renal impairment. Must monitor APTT.
LMWH - anti xa inhibitor. longer acting. used in pregnancy. lower risk of osteoporosis and HIT.
39
Heparins - side effects (4)
1. Haemorrhage (stop heparingive protamine)
2. Hyperkalemia (as inhibits aldosterone) - monitor before treatment+ if cont for >7 d. Higher risk if DM/ CKD.
3. Osteoporosis
4. HIT (usually starts 5-10 d after treatment). monitor platelets before+ if >4 d
40
DOACs
Dabigatran - direct thrombin inhibitor (note bottles have a 4 month expiry)
Others -anti xa
Rarely cause bleeds.
Patient alert card
Take at same time of day, with full glass of water
If dose missed do NOT double next day
Avoid if antiphospholipid syndrome (not as effective as warfarin as per MHRA warning)
41
DOAC reversal agents
Dabigatran - praxbind (idarucizumab)
| Apixaban+ rivaroxaban (ondexxya, andexanet alfa)
42
DOAC interactions (8)
https://hertsvalleysccg.nhs.uk/application
/files/1716/2340/3507/Drug_interactions_with
_NOACs_hmmc_june_2019_version_1.1.pdf
Strong inhibitors of p-gp or cyp3a4 increase the circulating levels of doacs
Many, so always check interactions
But the key key ones are:
1. Dronedarone
2. HIV protease inhibitors
3. Antifungals 4. Rifampicin
5. Antirejection agents (ciclosporin and tacrolimus)
6. AEDs (carbamazepine, phenytoin, phenobarbitone)
7. Antiplatelets (particulary prasugrel, ticagrelor)
8.St Johns wort
Also consider GI risk for NSAIDs, SSRIs, SNRIs
43
DOAC counselling
Patient alert card
Take at same time each day with a full glass of water
Do not double dose next day
44
Warfarin indications (3)
1. Prophylaxis of a clot (rheumatic heart disease, AF, insertion prosthetic heart valve)
2. Treatment of a VTE/ PE
3. TIAs
45
Warfarin mode of action
Inhibits VKORC1 - which activates vit K. This menas warfarin depletes levels of FUNCTIONAL vit k and so reduces production of clotting factors.
46
Warfarin dosing: basics (dose, packet colors)
```
5mg starting dose. Test INR every 1-2 days. Maintenance 3-9mg. Same time every day.
0.5mg - white
1mg - brown
3mg - blue
5mg - pink
```
47
Warfarin dosing: duration of treatment (DVT, x2 VTE)
DVT in calf: 6 wks
VTE if provoked: 3 mths
VTE if unprovoked: 3mths + (long term considered)
48
Side effects of warfarin (2)
1. Bleeding (phytomenadione)
| 2. Calciphylaxis (MHRA - report if painful skin rash)
49
Monitoring of warfarin
```
Once stable, 3monthly INR
INR targets should be
<1.1 in normal people
2.5 for most indications, except
3.5 for valve replacement or recurrent DVT/ PE
```
50
Warfarin toxicity
Bleeding
| If major, stop warfarin give IV phytomenadione and dried prothrombin complex or fresh frozen plasma
51
Warfarin: food/ herbal/ drink interactions
```
Pomegranate, cranberry juice
Alcohol (decreases w effect)
Vitamin E
Vitamin K
St Johns Wort (decreases w effect)
```
52
Warfarin: drug interactions (serious) (6)
1. Antibiotics (trimethoprim, co-trimoxazole, sulfonamides, metronidazole, rifampicin )
2. Antifungals (miconazole - bleeding can take 15 days to develop. raised INR within 3 days., voriconazole)
3. Antidiabetic drugs (glucagon)
4. Antiepileptic drugs (carbamazepine, barbituates, primidone)
5. Heart drugs (amiodarone, fibrates)
6. Anticancer drugs/ hormones (anabolic steroids, tamoxifen, fluorouracil and prodrugs eg capcitabine, testosterone)
53
Warfarin: other key points (3)
1. Counselling - take at same time each day, yellow book, alert card
2.MHRA warnings - calciphylaxis, RISK INCREASED IF CKD.
Direct acting antivirals to treat chornic hepatitis C
3. Warfarin in surgery - special requirements as per BNF (differs depending on whether elective or emergency)
54
What increases the risk of calciphylaxis in patients on warfarin?
CKD
55
Warfarin and elective surgery
If elective - stop 5 days before.
Give PO phytomenadione if INR >1.5 the day before
Restart warfarin the evening of surgery or the next day if all g
If high risk of clot, bridge with a LMWH. Stop it at least 24h before surgery. Do not restart LMWH untli at least 48 hours after surgery.
56
Warfarin and emergency surgery
Delay for 6-12h and give IV phytomenadione
| If you can't delay, give dried prothrombin complex+ phytomenadione. Check INR before surgery.
57
Treatment of haemorrhagic stroke longer term (2)
Treat HTN, avoid hypoperfusion
| Avoid anticoag, aspirin, statins
58
Treatment of TIA
300mg aspirin for 14 days
Then onto clopidogrel 75mg OD long term (/ aspirin+ dipyridiamole/ aspirin)
+atorvastatin 80mg, HTN drug (But not a beta blocker)
HTN target <130/80
59
Treatment of ischaemic stroke
Alteplase within 4.5h
If no alteplase- aspirin within 48 hours
Then onto clopidogrel 75mg OD long term ( /aspirin+dipyridamole/ aspirin)
+atorvastatin 80mg, HTN drug (But not a beta blocker)
HTN target <130/80
60
What if the ischaemic stroke patient has AF?
Wait 2wks before anticoagulating - give aspirin before this.
61
Types of antiplatelets
1. Aspirin
2. Clopidogrel
3. Dipyridamole (take 30-60 mins before and discard after 6 weeks)
4. Glycoprotein IIa/IIb inhibitors
62
Stages of HTN
Normal: 120/80
Stage 1: 140/90 (135/85)
Stage 2: 160/100 (150/95)
Stage 3 (crisis): 180/110
63
What to do if at each stage of HTN
Stage 1 - only treat if meet 5 criteria
Stage 2 - always treat
Stage 3 - urgent IV (if target organ damage)/PO over 24-48h
64
5 criteria for treating stage 1 HTN (140/90 - 135/85) IF UNDER 80
If under 80...
1. QRISK 20 or more
2. Renal disease
3. Diabetes
4. CVD
5. Target organ damage
65
Treatment pathway for HTN
If <55 - ACEI/ARB/ diabetes
If 55 or older/ afro-carribean: CCB
If failure, both together
If failure again, add in thiazide like diuretic
If failure again, more diuretic, alpha blokcer, beta blocker (but not with thiazide diuretic due to risk of hyperglycaemia)
66
BP targets
>80: 150/90
Renal disease: 140/90 or 130/80 if CKD/ diabetes/ proteinuria >1g in 24h. consider ACEI or ARB if proteinuria present.
Pregnancy (chronic HTN): 150/90 or 140/90 if had birth or target organ damage
Diabetes: 140/80 or 130/80 if end target organ damage
Healthy: 140/90
Atherscleortic CVD: 130/80
67
Gestational diabetes
Target for chronic HTN: 150/90 or 140/90 if given birth/ target organ damage
Treatment options:
1. Labetalol is 1st line (hepatotoxic) but do NOT give in 1st trimester
2. Methyldopa (must stop 2 days after birth) - drowsiness and driving
3. M/R nifedipine (this is unlicensed)
68
Labetalol key points (3)
1. 1st line
2. Do NOT give in 1st trimester
3. Is hepatotoxic
69
Methyldopa key points (3)
1. Must stop 2 days after birth
2. Drowsiness and driving
3. 2nd line
70
Antihypertensives
1. ACEIs
2. ARBs
3. CCBs
4. Diuretics
5. Alpha blockers (prazosin)
6. Beta blockers
7. Centrally acting - methyldopa, clonidine (flushing)
71
ACEI key points (3)
1. Perindopril should be taken 30-60 minutes before food
2. Captopril is only BD
3. Take first dose at bedtime
+avoid in pregnancy
72
ACEI/ ARB side effects (6)
```
Dry cough due to build up of bradykinin (give ARB)
Hyperkalemia
Angiodema (anaphylaxis)
Nephrotoxic
Hepatic effects
Hypoglycaemia
```
73
ACEI/ARB interactions (3)
1. Hyperkalemia-k+ sparing diuretics
2. Nephrotoxicity and reduced eGFR-nsaids
3. Hypotension-diuretics
74
Intrinsic sympathomimetic activity beta blockers
```
PACO
Pinodolo
Acebutol
Celiprolol
Oxprenolol
Mean that less bradycardia and less coldness of extremities
```
75
Water soluble beta blockers
```
Water CANS
Celiprolol
Atenolol
Nadolol
Sotalol
Less likely to cross the BBB and so cause nightmares and sleep disturbance.
REDUCE DOSE IN RENAL IMPAIRMENT.
```
76
Cardioselective beta blockers
```
Atenolol
Acebutolol
BISOPROLOL
Nebivolol
Metoprolol
Cardioselective
Less bronchospasm and so well controlled asthma under a specialist if no other choice
```
77
Beta blockers with an intrinsically long duration of action
```
BACoN
Bisoprolol
Atenolol
Celiprolol
Nadolol
```
78
Side effects of beta blocker (4)
1. Bradycardia
2. Cold peripheries
3. Hypotension
4. Masks symptoms of hypoglycaemia
79
Contraindications of beta blockers (4)
1. Asthma (bronchospasm)
2. Unstable heart failure
3. 2nd/3rd degree heart block
4. Severe hypotension and bradycardia
++++++++++caution if enzyme inhibitors as these increase Cp of beta blockers
80
Beta blockers interactions (2)
1. Asystole+hypotension eg verapamil injection
| 2. Hyperglycaemia eg thiazide diuretics
81
Side effects of CCBs (3)
Ankle swelling
Flushing
Headaches
82
Rate limiting CCBs- key factors
Verapamil causes constipation
| Diltiazem must maintain same brand when doses >60mg
83
Heart failure symptoms
Oedema (pulmonary-SOB, peripheral - swollen ankles or legs)
Dyspnoea (during activity/ at rest)
Fatigue/ exercise intolerance
84
Treatment of HF as per NICE guidance
1. ACEI/ARB + beta blocker (alternatively hydralazine+isosorbide dinitrate for specialist use only)
2. Add in spironolactone/ epleronone (alternatively hydralazine and isosorbide dinitrate in Afro/carribean, or and ARB with an ACE if no other option)
3. Ivabrandine/ digoxin
+for fluid overload add on loop diuretics/ thiazide like diuretics
85
Diuretics in HF
Give epleronone as 2nd line for HF instead of spiro if the patient has had an acute MI with LVSD or mild HF
Loop diuretics for fluid overload are preferred in patients with poor renal function (<30ml/min) whereas thiazide like diuretics are of benefit in patients with mil HF and good renal function
86
Causes of hyperlipidemia
Drugs-antipsychotics, immunosuppressants, corticosteroids, HIV drugs
Conditions-r HYPOTHYROIDISM, renal disease, liver disease, diabetes, family hx, lifestyle
87
Cholesterol targets in healthy people
Total - <5mmol/L
LDL - <3mmol/L
HDL ->1mmol/L
88
Cholesterol targets in at risk people
Total- <4mmol/L
LDL - <2mmol/L
HDL ->1mmol/L
89
When to give primary prevention (atorvastatin 20mg OD)
QRISK >10% in 84 or younger
OR
No QRISK needed (or treatment to be considered) if T1DM/ over 85/ CKD/ familial hypercholesterolemia
https://cks.nice.org.uk/topics/lipid-modification-cvd-prevention/
90
Types of lipid modifying drugs (4)
```
Statins
Fibrates
Ezetimibe
Bile acid sequestrants
Nicotinic acid
```
91
Statin indications
```
Primary hypercholesterolaemia (high intensity)
Familial hypercholesterolaemia (high intensity)
Moderate hypertriglyceridemia
```
92
Statin MOA
Decreases LDL cholesterol by inhibition of HMG-CoA reductase
93
The 5 types of statin
```
Atorvastatin
Fluvastatin
Pravastatin
Rosuvastatin
Simvastatin
```
94
Statin side effects (3)
1. Myopathy
2. DM
3. Interstitial lung disease
95
Statin monitoring
LFTs (discontinue if transaminases 3x normal)
TFTs
Renal function
Lipid profile (baseline)
HbA1c - high risk of developing diabetes
Creatinine kinase if muscle pain (discontinue if 5x than usual)
96
Statins interactions
1. Antimicrobials - macrolides, fusidic acid, imidazole, triazoles
2. Heart drugs - CCBS, amiodarone, ezetimibe/ fibrates
3. Other- grapefruit juice, ciclosporin (atorva), clopidogrel (rosuva)
ALL INCREASE THE CP OF STATIN, INCREASING THE RISK OF MYOPATHY
97
What to do if macrolide+ statin
Stop statin until course complete
98
What to do if fusidic acid+ statin
Restart statin 7 days after last fusidic acid dose
99
What to do if fibrate+ simvastatin
Max 10mg simvastatin
100
What to do if amiodarone+simvastatin
Max 20mg simvastatin
101
What to do if amlodipine/ diltiazem/ verapamil+simvastatin
Max 20mg simvastatin
102
What to do if ciclosporin+ atorvastatin
Max 10mg atorvastatin
103
What to do if rosuvastatin + clopidogrel
Initially 5mg, max 20mg rosuvastatin
104
Statins in pregnancy
Teratogenic
Effective contraception during+ 1 month after stopping
Stop taking 3 months before conceiving and restart after breastfeeding finished
105
MHRA warning simvastatin
80mg high risk of myopthay
106
People who are high risk of myopathy
Family hx
High etoh intake
Renal impairment
Hypothyroidism
107
Things to check for before initiating statin (4)
Hypothyroidism
DM
Nephrotic syndrome
Liver disease
108
High intensity statins >40% reduction
Atorva 80, 40, 20
Rosuva 40, 20, 10
Simva 80
109
Medium intensity statins (31-40%)
Atorva 10
Fluva 80
Rosuva 5
Simva 40, 20
110
Low intensity statins (20-30%)
Fluva 40,20
Prava 10,20,40
Simva 10
111
Ezetimibe - key facts (2)
Alternative to statin in primary/ familial hypercholestermia
| Interacts with statins - myopathy
112
Fibrates - key facts (2)
Used for severe hypertriglyceridemia >10mmol or in those who cannot tolerate statins
Do not use with statin due to myopathy risk
Also risk of renal impairment7
113
Bile acid sequestrants - key facts
Decrease cholesterol, specialist use. Colesevam, colestipol and colestyramine.
These impzzair the absorption of fat soluble vitamins eg ADEK
+ other drugs should be taken 1 hour before it or 4 hours after it OR 4 hours before and 4 hours after in the case of coleveselam
114
Acute angina attack
GTN (spray/ tab) - a short acting vasodilator which improves blood supply
Works for 20-30 minutes
Give 1 dose (1 tab or 1-2 sprays), wait 5 mins and readminister if not worked. Give 3 doses (15 minutes waited). If not worked, call an ambulance.
115
Angina prophylaxis
Beta blocker or rate limiting CCB
Beta blocker+ normal CCB
If these contraindicated use vasodilators (long acting nitrates, ivabrandine or nicorandil if an adult)
Max 2 drugs
Note that abrupt withdrawal of nitrates (vasodilators) and CCBs WORSENS angina
116
GTN - key points
SL tabs/ spray
Effect lasts 20-30 mins
If >2 times a week, long term prophylaxis.
Tablets expire 8 week after opening.
117
Vasodilators used as 2nd line in angina prophylaxis
1. Long acting nitrates
2. Ivabrandine
3. Nicorandil in adults only (K channel activator)
118
Nicorandil MHRA warning
Risk of ulcer complications (mouth, skin, eye, GI)
| Do not drive until established perfomranc enot impaired
119
Long acting nitrates - examples
MR isosorbite dinitrate BD
MR isosorbide mononitrate BD
Isosorbide mononitrate OD
120
How to avoid tolerance with nitrates
If long acting/ transdermal leave patches off for 8-12 hours, take 2nd dose after 8 hours not 12 hours
NOTE THAT MR isosorbide mononitrate is once daily and so does not produce tolerance
121
Side effects of nitrates
Headache, dizziness, flushig, postural hypotension, tachycardia, dyspepsia, heartburn
With injection you can get severe hypotensions, restlessness, palpitations
Always avoid abrupt withdrawal as can worsen angina
122
NSTEMI/ STEMI initial management drugs (6)
1. GTN
2. Aspirin 300mg
3. Morphine
4. Metoclopramide
5. Oxygen
6. LMWH
123
NSTEMI/ STEMI long term management drugs
1. DAPT (12mths, then either aspirin or clopidogrel lifelong)
2. Beta blocker (review after 12mth)
3. ACEI
4. High intensity statin
124
Cardiac arrest
Resuscitation
IV adrenaline 1 in 1000 every 3-5 mins
IV amiodarone if Vfib present
125
Types of diuretics
1. Loop eg bumetanide, furosemide, torsonamide
2. Thiazide/ thiazide like eg chortalidone, bendro, indapamide
3. K+ sparing/ aldosterone antagonists
+mannitol (osmotic), acetazolamide (carbonic anhydrae inhibitors
126
Loop diuretics - uses, action, side effects, monitoring
HF (BD) + resistant HTN
1h onset + 6 h duration
Electrolyte loss+ ototoxicity (more common in renal impairment)+ urinary retention (caution in BPH)
Monitor electrolytes
127
Bumetanide - key facts
The most potent of the loop diuretics
128
Furosemide - key facts
Causes gout (hyperuricaemi(
129
Torsonamide - key facts
Musculoskeletal side effects
130
Thiazides+ thiazide like - uses, action, side effects, interactions, monitoring
HF, HTN
1-2 hour onset, 12-24 hour duration
Electrolyet loss, except for Ca which increases
Can cause diabetes (indapamide least likely to aggravate)
GI disturbance, impotence, high LDL
Not effective in poor renal function, monitor electrolytes
131
Loop diuretics - interactions
```
Amiodarone (hypo K+)
Citalopram (hypo K+, hypo Na+)
Clarithromycin (hypo K+)
Digoxin (increased risk of toxicity)
Fluconazole (hypo K+)
Lithium (toxicity)
Methadone (hypo K+)
+ others which cause hypotension, hypo K+, toxicity, hypo Na+
```
132
Thiazides+ thiazide like diuretics interactions
Things which cause hypokalemia, hyponatremia, hypotension, hyPERCalcemia
133
K+ sparing diuretics+ aldosterone antagonists - onset, duration, s/es, monitoring
Used in hypokalemia
Spironolactone is used in ascites in liver failure and may be useful in HF and when used in resistant HTN
Eplerenone is used for HF
Cause hyperkalemia (avoid in ACEI/ ARB/ K supplement)
Aldosterone antagonists cause gynaecomastia, hypertrichiosis, change in libido, hyperuricemia, HYPOnatremia. Spiro causes breast pain.
134
K+ sparing diuretics + aldosterone antagonists - interactions
(For spiro) = things which cause hypotension, hyPOnatremia, hyPERkalemia
135
Occlusive vascular disease drugs (2)
1. Aspirin 75mg OD
2. Statin
For 2' prevention of CVD
136
Raynauds (vasospastic)
Stop smoking
Avoid exposure to cold
Nifedipine can be used
137
Drugs which prolong the QT interval (non-exhaustive)
1. CV - amiodarone, sotalol
2. CNS - apomorphine, methadone, lithium, SSRIs, risperidone, amisulpride (2nd gen) , chlorpromazine, levomepromazine, haloperidol, zuclopenthixol (1st gen),
3. Infections - macrolides, moxifloxacin, antifungals
4. Other - ondansetron, toltoredine
138
What is heart block?
Heart beats more slowly or with an abnormal rhythm. 1st degree, 2nd degree, 3rd degree (most severe). Only treat if causing symptoms. May need a pacemaker.
139
Dementia treatment for cognitive symptoms if disease mild-moderate
Acetylcholinesterase inhibitors eg donepezil, galantamine, rivastigmine (in PD only)
140
Dementia treatment for cognitive symptoms if disease moderate-severe (only if severe in Alzheimes)
NMDA glutamate receptor antagonist - memantine
141
Types of acetylcholinesterase inhibitors + what they are associated with
Donepezil- neuroleptic maligannt syndrome (increased risk with antipsychotics)
Galantamine - SJS. Stop if rash.
Rivastigmine - give if lewy bodies. Causes GI disturbance.
142
Memantine - key points
Give if moderate-severe dementia
ONLY give if SEVERE alzheimes
Cautioned in epilepsy/ convulsions
143
Side effects of anticholinesterase inhibitors eg donepezil, rivastigmine, galamantine (which are CHOLINGERGIC and so PARASYMPATHETIC)
```
Diarrhoea
Urination
Musculoskeletal cramps
Bradycardia
BRONCHOSPASM
Emesis
Lacrimation
Saliva
```
144
Treatment of non-cognitive symptoms in dementia
Antipsychotics.
Only treat if SEVERE symptoms. MHRA warning = increased risk of stroke+ death.
If extreme violence/ aggression/ agitation give PO benzos/ antipsychotic
But if IM give haloperidol, olanzapine, lorazepam
145
1st line for each type of seizure (5)
1. Focal - carbamazepine, lamotrigine (can also give levetiracetam, valproate, oxcarbazepine)
2. Tonic-clonic - valproate, carbamazepine (can also give lamotrigine)
3. Absence - valproate, ethosuximide (can also give lamotrigine)
4. Myoclonic - valproate (then levetiracetam, topiramate)
5. Atonic tonic - valproate
146
```
Terminology seizures:
Absence
Myoclonic
Clonic
Atonic
Tonic
Tonic-clonc
Focal
```
Absence- lose awareness of surroundings (15s)
Myoclonic - arms, legs upper body twitch
Clonic - longer twitching (up to 2 mins), may get LOC
Atonic - muscles suddenly relax
Tonic - sudden stiffened muscles
Tonic - clonic - 2 stages - stiffness and then twitching
Focal - small part of the brain affected (may be simple or complex depending on whether you remain consciousness or not)
147
Brand specific prescribing in CVD (2)
1. Diltiazem MR>60mg
| 2. Nifedipine MR
148
Antiepileptics - class 1 (4)
Carbamazepine
Phenytoin
Primodone
Phenobarbitol (once daily dosing)
149
Antiepileptics - class 2 (7+ 3 unusual)
```
Clobazam
Clonazepam
Oxcarbazepine
Lamotrigine (once daily dosing)
Valproate
Topiramate
Zonisamide
(Eslicarbazapine
Perampanel (once daily dosing)
Rufinamide)
```
150
Antiepileptics - class 3 (5+3 unusal)
```
Ethosuximide
Gabapentin
Pregabalin
Lacosamide
Levetiracetam
Tiagabaine
Vigabatrin
Brivaracetam
```
151
Epilepsy and driving
Typical driving licence
If a seizure while awake and LOC - will take licence away. When you get it back depends on a number of facors.
If your seizures are ONLY while you have been asleep, you may get to keep your licence.
If seizures don't affect consciousness or driving you may get to keep your licence, but this is dependent on lots of things.
Bus/ coach/ lorry
Will lose licence even if just a one off seizure
https://www.gov.uk/epilepsy-and-driving
152
Teratogenic AEDs
1. Valproate
2. Carbamazepine, primidone, phenobarbitol, phenytoin
3. Lamotrigine
+ topiramate> 1st trimester risk of cleft palate
Must use effective contraception, note that inducers reduce efficacy of contraceptives.
153
Which AEDs need dose adjustments based on plasma drug concentration during pregnancy?
1. Phenytoin (albumin is decreased in pregnancy)
2. Carbamazepine
3. Lamotrigine
154
Which AEDs require monitoring of fetal growth during preganncy?
Topiramate and levetiracetam
155
Folic acid with epilepsy
Before conception + until week 12 of pregnancy
156
AEDs which are present in high amounts of breast milk
ZELP
| Zonisamide, ethosuximide, lamotrigine, primodone
157
AEDs which accumulate in BF due to slow metabolism by infant
Phenobarbital
| Lamotrigine
158
AEDs which inhibit sucking reflex in BF
Phenobarbital
| Primodine
159
AEDs which have an established risk of drowisness in babies
Benzos, phenobarb + primodone
| Avoid abrupt withdrawal of BF in all, but especially these
160
MHRA warning for all AEDs
Small increased risk with all AEDs
| Symptoms can occur within 1 week of startings
161
AED side effects (7) inc mhra warnings
1. Suicidial thoughts+ depression (within 1 week, all AEDs)
2. Respiratory depression with some - gabapentin, benzos (especoally), barbiturates, notes say AEDs
3. Blood dyscrasias -CVET PLZ
4. Skin rashes -lamotrigine, SJS
5. Encepalopathy
6. Eyes - vigabatrin, toprimate with 2' angle closure glaucoma
7.AED hypersensitivity (1-8wks after started) DISCONTINUE IMMEDIATELY. This means rash, fever, lymphadenopathy, systemic involvemnt. Most associated with CPPP+ lamotrigine
+mhra warning about switching+ classification+ pregnancy
162
AEDs which cause blood dyscrasias (7)
```
CVETPLZ
Carbamazepine
Valproate
Ethosuximide
Topiramate
Phenytoin
Lamotrigine
Zonisamide
```
163
AED interactions (2)
1. Inhibitors increase the conc of other drugs eg valproate
| 2. Inducers decrease the conc of other drugs eg contraception + warfarin
164
Phenytoin indications
Seizures. Focal and generalised tonic clonic seizures
| Avoid if absence/ myoclonic seizures
165
Phenytoin mode of action
Blocks Na+ channels
166
Phenytoin side effects (7) + iv specific s/es
TB
Change in appearance (acne, coarsening of facial features, gingivial hypertrophy)
Blood dyscrasias (FBC needed)
Liver (discontineu and report signs of liver toxicity eg n+v, dark urine, abdo pain, itching, jaundice)
Rash (discontinue and report. HLA0B 1502 allele, chinese and thai higher risk of SJS)
Hypersensitivity (watch out for fever, rash, swollen lymph nodes)
LOW VITAMIN D
Suicidal ideation
If IV - cardiac scary effects
IV fosphenytin is a phenytoin prodrg - iv less site reaction and can be given more rapidly (1.5mg-1mg)
167
Phenytoin therapeutic drug monitoring
10-20mg/L or 40-80mmol/L
Non linear relationship between dose and Cp
Highly protein bound
168
Signs of phenytoin toxicity
```
SNACHD
Slurred speech
Nystagmus
Ataxia
Confusion
Hyperglycaemia
DOUBLE VISION/ BLURRED VISION
```
169
Phenytoin interactions
1. Enzyme inhibitors + trimethoprim increase the concentration and so risk of toxicity
2. Enzyme inducers - st johsn wort+ rifampicin cause therapeutic failure
3. Quinolones, tramadol, mefloquine, SSRIs, antipsychotics, TCAs, antidepressants all antagonise the anticonvulsant effect
4. Methotrexate and trimethoprim increase the ANTIFOLATE EFFECT AND SO THE RISK OF BLOOD DYSCRASIAS
Is an enzyme inducer -reduces the concentration of warfarin, COC, levothyroxine, liohyronine
170
Phenytoin - other key points (2)
```
100mg phenytoin sodium = 92mg phenytoin base
MHRA warnings (4)- suicidal thoughts, risk of severe harm and death with injected phenytoin, dont switch between brands, pregnancy (increased risk of adverse effects on neurodelevlopemnt+congenital malformations)
```
171
Carbamazepine indications
Seizures -focal and generalised tonic clonic
| Avoid in atonic, clonic and myoclonic
172
Carbamazepine MOA
Inhibits Na+ channels
173
Carbamazepine s/es
```
Blood dyscrasias
Hepatotoxicity
Hypersensitivity syndrome
SJS (rashes)
Hyponatremia
M/R preparations reduce the risk of side effects
```
174
Carbamazepine monitoring
4-12mg/ L or 20-50mmol/L
Monitor 1-2 weeks after initiation
Manufacturer also advises blood counts, renal and hepatic tests but no evidence of practical benefit
MUST ALSO PRETREATMENT SCREEN FOR ALLELE FOR INCREASED RISK OF SJS
175
Carbamazepine toxicity
```
HANDIBAG
Hyponatremia
Ataxia
Nystagmus
Drowsienss
Incoordiantion
Blurred vision and double
ARRHYTHMIAS
GI disturbance
```
176
Carbamazepine interactions
1. Enzyme inhibitors increase Cp
2. Enzyme inducers decrease Cp
3. Anticonvulsant effect antagonised - SSRIs, antipsychotics, TCA, related antidepressants
4. Increased risk of hyponatremia (nsaids, diuretics, ssris, tcas, desmporessin)
5. increased risk of hepatotxicity (tetracyclines, sulfasalazine, na valproate, mtx, isoniazid, statins, fluconazole, etoh)
177
Carbamazepine - other
AED suicidal thoughts+ behaviour
Do not switch between brands
Suppositories not bioequivalent to tabs (125mg:100)
Preganncy (increased risk of major congenital malformations)
178
Sodium valproate indications
Seizures (1st line for everything except focal seizures)
179
Sodium valproate MOA
Weak Na+ channel inhibitor
180
Valproate s/es (3)
1. Hepatotoxicity
2. Blood dyscrasias
3. Pancreatitis
181
Valproate monitoring
```
No therapeutic (not an indicator of efficacy)
Monitor liver function before treament+ during 1st 6 months
Measure FBC
```
182
Valproate interactions
1. Hepatotoxicity - tetracycylines, sulfazalaisne, metx, isoniazid, statins, fluconazole
2. Is an inhibitor (increases cp of lamotrigine and phenobarb)
3. Antagonised by tramadol, quinolones, tcas, mefloquine
183
Valproate other
Suicidal thoughts and behaviorus, PPP, contraindicated in acute porphyrias, consider vit D supplementation, liver dysfucntion - usually in first 6mth - disocntinue if abnormally prolonged prothrombin. withdraw tretament immediatley if persistent vomiting+ abdomonal pain, anorexia, jaudnidce. discontinue if symptoms of pancretatis.
Unlicensed in women of child bearing age for bipolar and migraine prophylaxis.
If needst o be given for epilepsy, divided dose/ MR. >1g associated iwth more tetarogenicity.
May give a false urine test for ketones
PAYIENTS MUST HAVE A PATIENT CARD
184
Status epilepticus -how to manage in hospital and community
Hospital: IV lorazepam (diaz would cause thrombophlebitis)
Community: >5 mins diaz rectal/ buccal midazolam. Can readminister after 10-15 mins.
185
Anxiety - drugs used
```
Long acting benzo
Short acting benzo (only lorazepam+ oxazepam)
Benzos - only for 2-4 wk release
Buspirone (takes 2 weeks to work)
Beta blocker
Antidepressants
Antipsychotics
Gabapentin
```
186
When to use short acting benzos (lorazepam and oxazepam)
1. Elderly
| 2. Liver impairment
187
When does benzo withdrawal happen?
1 day after a short acting
| 3 weeks after a long acting
188
How to help w benzo w/drawal
Convert over 1 wk to equivalent diazepam ON dose
| Reduce by 1-2mg dose every 2-4 wk
189
Interactions of benzos
1. Respiratory depression (antihistamines, antidepressants, barbituates, antipsychotics, z drugs)
2. Increased Cp due to enzyme inhibitors
190
ADHD treatment if <5
1. Methylphenidate
2. Lisdexamphetamine
or atomoxetine or guanfacine
191
ADHD treatment if adult
```
1. Methylphenidate or lisdexamphetamine
or atomoxetine (noradrenaline reuptake inhibitor)
Both methyphenidate and lisdexamphetamine work by increasing noradrenaline and dopamine in the brain
```
192
Methylphenidate key points
Prescribe modified release preps by brands
Side effects - skinny (ie you would lose weight, appetite reduced, insomnia, increased HR+ BP, tics and tourettes, growth restriction in chdilren)
Monitor- HR, BP, appetite, weight, height, psychiatric symptoms
Contraidnicated if CVD, hyperthyroidism, hypertension, bipolar, severe drpession
193
Atomoxetine key points
For ADHD but not first line
| Can cause suicidal ideation, hepatotoixicty and QT prolongation
194
Bipolar disorder treatment - episodes of mania and hypomania
For acute episodes give benzos short term or antipsychotics
For long term prophylaxis (>2y) give lithium, valproate, carbamazepine, olanzapine
Do not give antidepressants
195
Antipsychotics used in bipolar disorder
```
Quetiapine
Olanzapine
Risperidone
Lithium/ valproic acid if unpresponsive
Asenapine
```
196
Lithium indications
Treatment and prophylaxis of mania, bipolar disorder, recurrent depression and aggressive/ self harming behaviour
197
Lithium moa
Stimulates nmda receptor
198
Lithium side effects (5)
```
Thyroid disorders
Renal impairment
QT interval prolongation
Benign intracranial HTN
Lowers seizure threshold
```
199
Lithium monitoring
Before treatment: renal, cardiac (ECG), thyroid, BMI, serum electrolytes, FBC
Duirng treatmnet: BMI, serum electroyltes, egfr, renal every 6 months (more often if increased Ca++)
200
Lithium therapeutic monitoring
12 hours post dose, every 3 months
| 0.4-1 or 0.8-1 in acute
201
Lithium toxicity
```
Renal disturbance
Extrapyramidal
Visual disturbance
Nervous system - confusion
GI symptoms
```
202
Lithium interactions
Body systems
QT prolongation (antipsychotics, amiodarone, ssris, macrolides, tcas, things which cause hypokalemia)
Seizure threshold lowered (quinolones, ssris)
Renal impairment - ACEIs, ARBs, NSAIDs (increased risk of toxicity)
Neurotoxicity - with aeds, antipsychotics, amitryptylline
Electrolytes
Hyponatremia causes toxicity (diuretics, antidepressants)
Alginates and soluble analgesics affect salt balance
Enzyme inhibitors
Others
EPSE - antipsychotics, PD, metoclopramide
serotonin syndrome
203
Lithium - other
```
teratogenic
counselling on salt and water
purple book
otc nsaids, soluble analgesia,
same brand
hyponatremia-toxicity
avoid etoh
drowsiness
```
204
Antidepressants - types
TCAs, SSRIs, MOAIs
205
SSRIs side effects
GI
A
Suicidal
Hyponatremia
206
SSRIs- key points
Washout of 1 wk
Sertraline if MI
Fluoxetine if child
Paroxetine if risk of overdose
207
TCAs - key points
Washout of 1-2 wks
Drowsy vs non drowsy depending on anxiety
Trazadone is a tetracycline
208
MOAIs - key points
Washout of 2 wks unless moclobenamide (short acting and reversibel)
eg phenelzine, isoxicarbozi
Tyramine reaction - hypertensive crisis -
