Drugs - CVS Flashcards
(141 cards)
1
Q
Give some examples of ACE inhibitors
A
Ramipril, lisinopril etc
2
Q
Indications of ACE inhibitors?
A
- Hypertension - 1st line in patients <55 and NOT of black african or african-caribbean origin OR all patients with type 2 diabetes
- LV failure
- Symptomatic heart failure
- Prophylaxis post MI in patients with evidence of heart failure
3
Q
Mechanism of ACE inhibitors?
A
- Blocks conversion of angiotensin I to II by ACE
- This blocks vasoconstrictive effects of angiotensin II, causing blood vessels to relax and widen which reduces O2 demand on heart
- Blocking of angiotensin II also prevents release of aldosterone - this increases excretion of salt and water which lowers BP further
4
Q
What are the most common side effects of ACE inhibitors?
A
- Dry cough (as ACE inhibitors prevent breakdown of bradykinin)
- Low blood pressure
- Headaches
5
Q
Contraindications for ACE inhibitors?
A
- Hypotension
- Hypersensitivity
- Angioedema
- Renal artery stenosis
6
Q
What class of drug are azilartan, candesartan and losartan?
A
Angiotensin receptor blockers (ARBs)
7
Q
Indications of ARBs?
A
- Hypertension (if ACEi contraindicated)
- Heart failure
- Post MI
- CKD
8
Q
Mechanism of ARBs?
A
Block the action of angiotensin II at the receptor
9
Q
Contraindications of ARBs?
A
- If patient is already taking ACE inhibitor
- Pregnancy
10
Q
How do ACEi and ARBs affect potassium levels?
A
ACE inhibitors and ARBs reduce proteinuria by lowering the intraglomerular pressure, reducing hyperfiltration. These drugs tend to raise the serum potassium level** and **reduce the glomerular filtration rate (GFR).
11
Q
Why can ACEi and ARBs not be taken together?
A
Risk of hyperkalaemia and AKI (as both drugs increase potassium levels)
12
Q
What other medications should ARBs NOT be taken with?
A
Any other medications that increase potassium levels e.g. ibuprofen, potassium-sparing diuretics
13
Q
Main side effects of ARBs?
A
Dizziness
Headache
Fainting
Fatigue
14
Q
What class of drugs are atenolol and bisoprolol?
A
Beta blockers (b2 antagonists)
15
Q
Indications for beta blockers?
A
- Tachycardia
- Angina
- Atrial fibrillation
- Hypertension
- Post MI
- Congestive heart failure
- CAD
- Arrhythmias
16
Q
Mechanism of beta blockers?
A
Block the effects of catecholamines at B1 adrenergic receptors which decreases the sympathetic activity of the heart (by decreasing conduction through the AV node).
Also reduces renin secretion which blocks the formation of angiotensin II.
17
Q
Contraindications of beta blockers?
A
- Bradycardia
- Hypotension
- Wolf-Parkinson-White syndrome
- Asthma → likely to exacerbate bronchoconstriction
- 2nd/3rd degree AV block
- Peripheral vascular disease (i.e. poor circulation)
- Diabetes
- Hypersensitivity
18
Q
Why is atenolol contraindicated in diabetes?
A
As atenolol may mask signs of hypoglycaemia e.g. increased HR
19
Q
Main side effects of beta blockers?
A
- GI disorder; diarrhoea, constipation, N&V
- Dizziness, syncope, confusion (bradycardia)
- Rash → concern
- Cold fingers and toes
20
Q
Why must beta blockers be prescribed with caution in the elderly?
A
Consider other medications, bradycardia, heart block, diabetes, asthma, obstructive respiratory diseases
21
Q
Why should you avoid abrupt withdrawal of beta blockers?
A
- Avoid abrupt withdrawal, especially in heart disease patients as may cause rebound worsening of myocardial ischaemia
- Encourage gradual reduction
22
Q
Why are patients encouraged to initially take beta blockers before bed?
A
May feel dizzy after first dose so take at bedtime, then can take in morning if you do not feel dizzy
23
Q
What are the 3 major classes of diuretics?
A
- thiazide
- loop
- potassium-sparing
24
Q
Give the site of action of each of the 3 classes of diuretics
A
- Thiazide → distal convoluted tubule & connecting segment
- Loop → ascending loop of Henle
- Potassium sparing → cortical collecting duct
25
Give one example of a thiazide diuretic
**Bendroflumethiazide**
26
Mechanism of bendroflumethiazide?
Inhibits the sodium/chloride transporter (Na+ Cl- carrier) in the **distal convoluted tubule** of the nephron.
This **inhibits sodium uptake** and increases the **excretion of sodium and water.**
27
Indications for bendroflumethiazide
* Oedema due to chronic heart failure
* Hypertension (lower doses)
28
Contraindications of bendroflumethiazide?
* Addison's disease (adrenal insufficiency - decreased cortisol and aldosterone)
* Hyponatraemia
* Hypokalaemia
* Hypercalcaemia
* Symptomatic hyperuricaemia (gout)
* Hypersensitivity
* Liver failure
29
How do diuretics affect potassium levels?
Have potassium depleting effects - can cause hypokalaemia
30
Which drugs can **enhance** the potassium-depleting effects of diuretics?
Steroids
31
Side effects of bendroflumethiazide?
* Needing to urinate more often
* Dehydration (feeling thirsty with dry mouth)
* Electrolyte imbalances (e.g. hypokalaemia)
* Hyperuricaemia
* Constipation/diarrhoea
32
What class of diuretic are bumetanide and furosemide?
Loop diuretics
33
Indications for loop diuretics?
Pulmonary oedema due to LVF
Chronic heart failure
Hypertension
34
Mechanism of loop diuretics?
* Inhibits the **Na+/K+/2Cl co-transporter** in the loop of Henle (in the kidney) which reduces the Na & K reabsorption
* This leads to increase Na (& water) excretion
* Less fluid in bloodstream → eases symptoms of oedema
35
Contraindications of loop diuretics?
* Anuria
* Hypokalaemia/hyponatraemia
* Hypotension
* Hypersensitivity
* Liver disease
36
Side effects of loop diuretics?
* Urinating more frequently
* Symptoms of dehydration: feeling thirsty and dry mouth
* Weight loss (as body loses water)
* Headaches
* Confusion/dizziness
* Muscle cramps/weakness
* Electrolyte imbalance
* Hypotension
* Serious side effects (consult doctor):
* **Ringing in ears (_tinnitus_) or loss of hearing**
* **Unexplained bruising or bleeding**
37
Give an example of a potassium sparing diuretic
Spironolactone
38
Which diuretic is also an aldosterone antagonist?
Spironolactone
39
Which diuretic is also an anti-androgen?
Spironolactone
40
Why would spironolactone be given alongside thiazide/loop diuretics?
1. Only works as weak diuretic if used alone
2. Causes **retention of potassium** (thiazide/loops cause potassium loss) and are more effective alternative to potassium supplements
41
Indications for potassium sparing diuretics?
* Resistant hypertension
* Oedema & ascites (caused by liver cirrhosis)
* Oedema in CHF
* 1ary hyperaldosteronism (Conn's syndrome)
* Nephrotic syndrome
42
Mechanism of spironolactone?
* Resembles **_aldosterone_** (adrenocorticoid hormone) so **competitively inhibits** aldosterone which normally acts on the distal renal tubule
* This **_increases Na and H20 excretion**_ and _**reduces K excretion_** (potassium sparing) → urinate more often
43
Contraindications of spironolactone?
* Addison’s disease (adrenal insufficiency e.g. low aldosterone)
* Anuria
* Hyperkalaemia (due to K+ sparing)
* Hypersensitivity
* Hypercalcaemia, hypernatraemia
* Hypotension
44
Side effects of spironolactone?
* Hyperkalaemia (discontinue)
* Gynaecomastia
* GI upset
* Breast tenderness
* Irregular periods
* Low BP
* Increased urination
* Dizziness
45
What class of drug are amlodipine and felodipine?
Calcium channel blocker
46
What class of drug is diltiazem?
Calcium channel blocker
47
What class of drug is verapamil?
Calcium channel blocker
48
Indications for calcium channel blockers?
* **_Hypertension_** → 1st line in patients \>/= 55 y/o (without type 2 diabetes) or patients of **any age** of Black African or African-Caribbean origin (without type 2 diabetes)
* Angina
* Arrhythmias
49
Mechanism of calcium channel blockers?
1. Prevents calcium from entering the cells of the heart and arteries → this decreases conduction through the AV node
2. This causes the heart to contract less strongly (as SA and AV node AP upstroke is Ca2+ dependent)
50
Side effects of CCBs?
* Ankle swelling
* Constipation
* Headache
* Flushing
51
Contraindications of CCBs?
* Heart failure
* Severe bradycardia
* Hypotension
* Atrial flutter or fibrillation **due to accessory conducting pathways** (e.g. Wolff-Parkinson-White syndrome)
52
Give an example of a nitrate
Isosorbide mononitrate
53
Indications for nitrates?
**_Stable_** angina → relieve symptoms or used to prevent angina just before activities that may bring it on
54
Mechanism of nitrates?
1. Causes **_vasodilation of coronary vessels_** which increases the oxygen supply to the myocardium
2. Dilation of peripheral veins/arteries also reduces preload and afterload → this lowers myocardial oxygen consumption (and stress of heart)
55
Cause of angina?
narrowing/blockage/spasms of **coronary** **arteries** which reduces oxygenated blood reaching heart
56
In what form are nitrates typically taken?
GTN spray (sublingual)
57
Side effects of nitrates?
* Hypotension (don't use spray repeatedly!)
* **_Headaches_** (common)
* Dizziness, light-headed, flushing
58
What is the most commonly prescribed class of drug in the UK?
Statins
59
Give 2 examples of statins
Atorvastain, Simvastatin
60
What class of drugs are statins?
HMG co-reductase inhibitors
61
Indications for statins?
* Hypercholesterolaemia
* Coronary heart disease
* Stroke
* Prevent MI
62
Mechanism of statins?
1. Inhibit HMG CoA reductase which blocks the pathway synthesising **cholesterol in the liver** (most circulating cholesterol comes from internal synthesis NOT diet)
2. Liver senses reduced cholesterol → increased expression of LDL receptors → increased uptake of cholesterol from blood → less circulating LDLs
3. Also enhances **stability** of **atherosclerotic plaques** → reduces risk of blood clots
63
Most common side effect of statins?
Muscle aches
64
Link between statins and Alzheimer's?
Alzheimer’s prevalence 70% lower in people taking statins BUT does not slow development in **symptomatic** Alzheimer’s patients.
65
Statins should be stopped temporarily if patients are started on which **antibiotic**? Why?
Clarithromcyin → due to greater risk of muscle pain/damage
66
How does grapefruit affect statins?
Grapefruit is an **inhibitor** → slows liver metabolism of statins
67
Give 3 examples of antiplatelets
1. Aspirin
2. Clopidogrel
3. Ticagrelor
68
Indication for aspirin?
Post MI (dual antiplatelet therapy)
N.B. antiplatelets should not be prescribed for the **primary prevention** of CVS disease
69
What class of drug is aspirin?
NSAID
70
Mechanism of aspirin?
COX inhibitor → prevents formation of thromboxane A2 and prostaglandins from arachidonic acid (which is released from activated platelets)
Thromboxane is a **potent vasoconstrictor** and **platelet aggregant**
71
Reversal agent for aspirin?
No reversal agents – irreversible effect (lasts 4-5 days).
72
Contraindications for aspirin?
* Age \<16
* Hypersensitivity
* Peptic ulceration
* Haemophilia
* Reye's syndrome
* Thrombocytopenia
73
Side effects of aspirin?
* GI upset: N&V
* Heartburn
* Bleeding
* Bruising
* Ulcers
74
What class of drug are ticagrelor & clopidogrel?
P2Y12 receptor antagonist
75
Indications for clopidogrel/ticagrelor?
Post MI (dual antiplatelet therapy)
* Prevent **atherothrombotic** events in patients with acute coronary syndrome (in combination with aspirin)
* Prevention of atherothrombotic events in patients with history of MI and high risk of atherothrombotic event (in combination with aspirin)
76
Contraindications for ticagrelor/clopidogrel?
* Active bleeding
* Intracranial haemorrhage
* Liver failure
77
Mechanism of P2Y12 receptor antagonists (clopidogrel/ticagrelor)?
Prevents ADP-mediated **P2Y12 dependent platelet activation and aggregation** by irreversibly binding to P2Y12 class of _ADP receptor_ on platelets
78
Main side effect of clopdiogrel/ticagrelor?
Bleeding - nosebleeds, bruising, gum bleeding, heavy periods
79
What class of drug is warfarin?
Anticoagulant (vitamin K antagonist)
80
What is the most commonly prescribed anticoagulant?
Warfarin
81
Why is the preference for warfarin slowly decreasing?
* Extensive drug and diet interactions
* Higher incidence of major bleeding
* Need for laboratory monitoring compared to DOACs
82
Warfarin is the anticoagulant of choice in patients with which 3 conditions?
1. Mechanical heart valves
2. Valvular AF
3. End stage renal failure
83
Mechanism of warfarin?
Antagonises vitamin K which is responsible for synthesising vitamin K dependent clotting factors
84
What are the vitamin K dependent clotting factors?
10, 9, 7, 2 (and protein C and protein S)
85
DOACs inhibit a **single clotting factor**. Which clotting factor does Dabigatran inhibit?
Thrombin
86
DOACs inhibit a **single clotting factor**. Which clotting factor does Rivoraxaban, apixaban and edoxaban inhibit?
Factor Xa
87
Give 6 indications for warfarin
1. Treatment of VTE (DVT/PE) → 2nd line after DOACs
2. Atrial fibrillation → 2nd line after DOACs
3. Rheumatic heart disease
4. Mitral valve disease
5. Mechanical valve disease
6. Inherited, symptomatic thrombophilia
It is used for a) treatment or b) prophylaxis of systemic embolisation
88
Contraindications for warfarin?
* Cancer/malignancy
* Hypersensitivity
* Low vitamin K levels
* Haemorrhagic stroke
* Active bleeding (e.g. peptic ulcer, oesophageal varices)
* Pregnancy
* Drugs with which there is **significantly increased risk of bleeding** (e.g. antiplatelet drugs, NSAIDs and enzyme inhibitors)
89
Why is warfarin contraindicated in pregnancy?
Teratogenic
90
In malignancy, what should be used instead of warfarin?
Heparin or DOAC
91
Treatment targets for warfarin are referred to in the terms of what?
**International normalised ratio (INR)**.
92
What is the INR? What does a high/low INR mean?
A standardised version of the **prothrombin time** (the time taken for blood to clot via the **extrinsic** pathway)
Higher INR → Blood clots more slowly (risk of bleeding)
Lower INR → Blood clots more quickly (risk of clotting)
93
INR target for treatment of VTE, atrial fibrillation, mitral valve disease and inherited symptomatic thrombophilia?
2-3
94
INR target for mechanical heart valves?
2.5-3.5
95
How long may warfarin take to achieve an INR within the therapeutic range?
5 days
96
Warfarin may initially induce a hypercoaguable state. Why?
Suppression of protein C (vit K dependent) occurs much more quickly than that of the coagulation factors (10, 9, 7, 2) due to protein C having a short half life → cannot degrade coagulation factors
97
What can be considered as concurrent treatment during this ‘hypercoaguable’ state induced by warfarin initially?
If patient develops an acute VTE and is at high risk of further thrombosis → consider **concurrent administration of heparin** for at least 5 days until INR is within therapeutic range
98
Side effects of warfarin?
* Haemorrhage (most common) → can be life threatening or not
* Coumarin induced skin necrosis
99
What is coumarin induced skin necrosis? Why does it occur?
Skin and subcutaneous tissue necrosis occur due to **acquired protein C deficiency** following treatment with vitamin K anticoagulant
100
What is administered concurrently for four to five days after warfarin initiation?
Heparin
101
Give some P450 enzyme inhibitors
Amiodarone, ciprofloxacin, clarithromycin, erythromycin, oral contraceptives, St John's Wort
102
Give some P450 enzyme inducers
Carbamazepine
Phenytoin
Alcohol
Allopurinol
Paracetamol
SSRIs
103
An advantage of warfarin over DOACs is its ability to be **rapidly reversed**. Give 2 scenarios where warfarin might need to be reversed?
1. Prior to surgery
2. INR is supratherapeutic (clots too quickly → bleeding)
104
Give 3 main options for reversing warfarin
1. Withholding warfarin
2. Vitamin K (oral or IV)
3. Prothrombin complex concentrate (PCC)
105
Why would PCC be given for reversing warfarin?
Contains vitamin K dependent clotting factors (10, 9, 2, 2)
106
If PCC is unavailable, what can be given instead to reverse warfarin?
Fresh frozen plasma → contains normal levels of all coagulation factors
107
How do **inducers** of the P450 system affect warfarin?
Induce enzymes → warfarin metabolised more quickly → efficiency of warfarin decreases → blood clots more slowly (decreased INR → tendency to clot)
108
How do **inhibitors** of the P450 system affect warfarin?
Inhibit enzymes → warfarin metabolised more slowly → blood warfarin levels rise → blood clots more quickly (higher INR → risk of bleeding)
109
How do cranberries affect warfarin?
Inhibitor → increases warfarin potency
110
What type of drug are Tinzaparin and Enoxaparin examples of?
Heparin (Enoxaparin is a LMWH)
111
What class of drug is heparin?
Anticoagulant
112
Why is heparin more often used in LMWH form?
as this has a lower risk of HIT (heparin induced thrombocytopenia)
113
What is HIT (heparin induced thrombocytopenia)?
Occurs when heparin dependent IgG antibodies bind to heparin/platelet factor 4 complexes to activate platelets and produce a **_hypercoagulable state_**
114
Indications for heparin?
* Used alongside warfarin to prevent hypercoaguable state
* PE
* Unstable angina
* Prophylaxis for thrombosis
115
Mechanism of heparin vs LMWH?
Heparin → Enhances action of **_antithrombin_** by binding to it; has equal effect in inhibiting both **thrombin** and **FXa** BUT will not be effective in inhibiting effects of thrombin bound to clot that already exists.
LMWH → Binds to antithrombin but has much greater effect on **FXa** than thrombin (FIIa) so functions more as inhibitor of FXa than as inhibitor of thrombin
116
Administration of heparin?
Subcutaneous injection (not orally)
117
How is dosage of heparin adjusted?
Body weight
118
Are DOACs used for prevention of thrombus formation or extension in the venous or arterial circulation? Why?
venous → fibrin rich (and affects clotting cascade which ends with a fibrin mesh)
119
Do venous or arterial thrombi contain lots of fibrin?
Venous
120
Indications for DOACs?
* AF
* VTE treatment (DVT/PE)
121
Which DOAC inhibits FIIa (thrombin)?
Dabigatran
122
Which DOACs inhibit FXa?
Rivaroxaban, apixaban, edoxaban
123
What class of drug is digoxin?
Digitalis glycoside
124
Indications for digoxin?
1) **For the treatment of mild to moderate heart failure in adult patients**
2) To increase myocardial contraction in children diagnosed with heart failure
3) To maintain control ventricular rate in adult patients diagnosed with chronic atrial fibrillation.
125
Contraindications of digoxin?
* Acute myocardial infarction.
* Severe renal failure
* Hypersensitivity.
* Ventricular fibrillation.
* Myocarditis.
* Hypomagnesemia.
* Hypokalemia.
* Wolf-Parkinson-White syndrome.
* Patient on other HR lowering drugs → bradycardia
126
Mechanism of digoxin?
Digoxin lowers the heart rate **by enhancing vagal tone**, which leads to slowing of SA and AV nodal conduction and thereby a reduction in heart rate.
(Inhibits Na+/K+ ATPase)
127
Side effects of digoxin?
* D&V
* Diarrhoea
* Fatigue
* Fainting
* Palpitations
* Visual disturbances
* **Digoxin toxicity** → delirium
128
Why is digoxin contraindicated in severe renal failure?
Digoxin is excreted by the kidneys without metabolism by the liver → In kidney failure, the body is unable to eliminate digoxin, causing levels to accumulate (digoxin toxicity)
129
What class of drug is amiodarone?
Class III Anti-arrhythmic
130
Indications for amiodarone?
1. Recurrent ventricular fibrillation (VF)
2. Recurrent hemodynamically unstable ventricular tachycardia (VT).
131
Mechanism of amiodarone?
1. **Blocks potassium** currents that cause repolarisation of heart during 3rd phase of action potential → increases duration of action potential
2. **Cardiac muscle cell excitability** is reduced → preventing and treating abnormal heart rhythms
132
Why is a loading dose of amiodarone often required?
58 days half life
133
Contraindications of amiodarone?
* Thyroid dysfunction → hyper/hypo, thyrotoxicosis
* Hypokalaemia
* Hypomagnesaemia
* Severe conduction disturbances (unless pacemaker fitted)
* Sinus node disease (unless pacemaker fitted)
134
Side effects of amiodarone?
* Arrythmias
* Hyper/hypothyroidism
* N&V
* Constipation
135
Why is amiodarone contraindicated in thyroid disorders?
As amiodarone contains **iodine** so can cause disorders of thyroid function
136
What class of drug is adenosine?
Class V Anti-arrhythmic
137
Indications for adenosine?
**emergent treatment of supraventricular tachycardia**
138
Calcium channel blockers should be avoided in heart failure as **they can further depress cardiac function and exacerbate symptoms**. Which CCB is the one exception to this?
Amlodipine
139
Why are CCBs contraindicated in Wolff-Parkinson-White syndrome?
In patients with WPW and atrial fibrillation, the erratic atrial action potentials can conduct through the accessory pathway very quickly (faster than through the AV node). Therefore, WPW patients who develop atrial fibrillation have higher ventricular rates than those without WPW.
If an AV blocking agent is given, fewer atrial action potentials will pass through the AV node and more will pass through the accessory pathway, paradoxically **increasing the ventricular rate** potentially causing **ventricular** **fibrillation** (fatal).
140
Which 3 classes of drugs block the AV node?
1. Beta blockers
2. Calcium channel blockers
3. Digoxin
141
Name 3 classes of drugs contraindicated in Wolff-Parkinson-White syndrome. Why?
1. Beta blockers
2. Calcium channel blockers
3. Digoxin
As block AV node, causing ventricular tachycardia
