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Pharmacology > Blood > Flashcards

Blood Flashcards

1
Q

Name some examples of antiplatelet drugs (ADP receptor antagonists)

A

Clopidogrel, ticagrelor, prasugrel

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2
Q

What are the common indications for antiplatelet drugs? (ADP)

A
  1. For treatment of acute coronary syndrome (in combo with aspirin)
  2. To prevent occlusion of coronary artery stents (+ aspirin)
  3. For long term secondary prevention of thrombotic arterial events in patients with CV disease (with or without aspirin)
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3
Q

How do antiplatelet drugs work?

A

Prevent platelet aggregation and reduce the risk of arterial occlusion by binding irreversibly to ADP receptors on the surface of platelets

As this is independent of the COX pathway, it’s actions are synergistic with aspirin

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4
Q

What are the adverse effects of antiplatelet drugs?

A

Bleeding- inc GI or intracranial or following surgery

GI upset

Rare- thrombocytopenia

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5
Q

What are the contraindications to antiplatelet drugs?

A

They should not be prescribed to those with sign active bleeding and may need to be stopped 7 days b for elective surgery

Used with caution in patients with renal and hepatic impairment

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6
Q

What are the important interactions to antiplatelet drugs?

A

Clopidogrel is a pro-drug that requires metabolism by hepatic enzymes P450 (CYP) to become its active form

Therefore inhibitors of CYP can stop its activation e.g. Omeprazole, ciprafloxacin, erythromycin, some antifungals and some SSRIs
(Other antiplatelets have less interactions)

Co-prescription with other anti-platelet drugs, anticoagulation or NSAIDS increases risk of bleeding

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7
Q

How is clopidogrel prescribed?

A

Oral- given with or without food
Low doses take a week to reach full effect

Loading dose for rapid effec- 300mg for ACS once only
Maintenance dose- 75mg orally daily

TIP- clopidogrel binds irreversibly so takes the lifespan of a platelet (7-10 days) to wear off, so stop 7 days before elective surgery

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8
Q

How does aspirin work?

A

Irreversibly inhibits cyclooxygenase (COX) to reduce production of thromboxane to prevent platelet aggregation

The antiplatelet effects of aspirin work st low doses and last for the lifetime of the platelet

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9
Q

What are the common indications for aspirin?

A
  1. Treatment of ACS

2. For longer term secondary prevention of thrombotic arterial events in high risk patients

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10
Q

What are the important adverse effects of aspirin?

A

GI irritation most common

More serious effects include peptic ulceration and haemorrhage and hypersensitivity reactions including bronchospsm

In regular high dose usage it can cause tinnitus

It is life threatening in OD

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11
Q

Who shouldn’t aspirin be given to?

A

Children under the age of 16 due to the risk of Reye’s syndrome

Also shouldn’t be given to people with aspirin hypersensitivity e.g bronchospasm (however it is not routinely contraindicated in asthma)

It should be avoided in 3rd trimester where prostaglandin inhibition may lead to premature closing of the ductus arteriosus

Should be used in caution in people with gout or peptic ulceration

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12
Q

What are important interactions of aspirin?

A

Caution when given with other antiplatelet drugs and anticoagulants due to increased risk of bleeding

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13
Q

How is aspirin prescribed?

A

Oral and rectal doses

In ACS, it is prescribed firstly as a once-only loafing dose of 300mg, followed by a regular dose of 300mg daily for 2 weeks

For long term prevention, it is given 75mg daily

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14
Q

What else should be prescribed alongside aspirin?

A

PPI for gastric protection e.g omeprazole 20mg daily

People who are at risk of gastric complications are:
Age >65
Prev peptic ulcer disease
Comorbidities
Drug therapy such as NSAIDS or prednisolone

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15
Q

How should aspirin be administered?

A

Taken after food to minimise gastric irritation

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16
Q

What advice should be given about aspirin?

A

For SECONDARY prevention not PRIMARY

It’s purpose in this case is to prevent heart attacks and strokes and to prolong life

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17
Q

Name some examples of direct oral anticoagulants (DOACs)

A

Apixaban, dabigatran, edoxaban, rivaroxaban

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18
Q

How do DOACs work?

A

They act on the final common pathway of the coagulation cascade by directly inhibiting factor X, except dabigatran which directly inhibits thrombin

They all prevent fibrin formation and prevent clot formation in the veins and heart (work less well in arterial circulation which is more platelet driven)

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19
Q

What are the common indications for DOACS?

A
  1. VTE- for treatment and prevention of secondary recurrence
  2. Prevention in patients undergoing elective hip or knee surgery
  3. AF- to prevent stroke and systemic embolism in patients with non-valvular AF (based on CHADSVASc score)
    Warfarin is an alternative
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20
Q

What are the important adverse effects of DOACS?

A

Bleeding- epistaxis, GI and GU haemorrhage

Also anaemia, GI upset, dizziness, elevated liver enzymes

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21
Q

What are the contraindications to DOACs?

A

Should be avoided in people with active, clinically significant bleeding and those with RFs for major bleeding, such as peptic ulceration, cancer, and recent surgery or trauma

As they are excreted through P450 (CYP) enzyme, dose reduction or an alternative drug may be needed in hepatic or renal disease

They are CI’d in pregnancy and breastfeeding

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22
Q

What are important interactions to DOACs?

A

Risk of bleeding is increased with other antithrombotic agents e.g heparin, antiplatelet, NSAIDs

Other drug interactions arise with drugs that affect the metabolism of DOACs or their excretion e.g the anticoagulation effect can be increased by macro life’s, protease inhibitors, and fluconazole and decreased by rifampicin and phenytoin

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23
Q

How are DOACs prescribed?

A

Varies by indication
For example rivaroxaban is prescribed at 15mg 12-hourly for VTE treatment, 20mg daily for prevention of stroke in AF, and 10mg daily to prevent VTE following hip and knee replacement

DOACs are usually started without need for initial heparin Rx due to its fast onset of action. However, where dabigatran or edoxaban are used to test VTE, 5 days of prior anticoagulation with heparin are recommended

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24
Q

How are DOACs administered?

A

Orally once a day

Rivaroxaban, but not the other DOACs, must be taken with food as this affects its absorption

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25
Q

What should patients be advised on about DOACs?

A

They should be warned that the main side effect is bleeding

Should be provided with an alert card stating they are on anticoagulant medicine

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26
Q

Do DOACs need to be monitored?

A

No

Reversal agents are emerging, such as Idarucizumab and Andexanet

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27
Q

Name some examples of fibrinolytic drugs?

A

Alteplase, streptokinase

28
Q

How do fibrinolytic drugs work?

A

They catalyse the conversion of plasminogen to plasmin, which acts to dissolve fibrinous clots and re-canalise occluded vessels
This allows reperfusion of affected tissue

29
Q

What are the common indications for fibrinolytic drugs?

A
  1. In acute ischaemic stroke, alteplase increases the chance of living independently if given within 4.5 hours of the onset of a stroke
  2. In acute ST elevation MI, alteplase and streptokinase can reduce mortality when they are given within 12 hours of the onset of symptoms in combination with antiplatelet agents and anticoagulation However primary percutaneous coronary intervention has superseded fibrinolytics
  3. For massive PE with haemodynamic instability fibrinolytic drugs reduce clot size and pulmonary artery pressures
30
Q

What are the important adverse effects for fibrinolytic drugs?

A

N&V
bruising around the injection site
hypotension

Those that require intervention- serious bleeding, allergic reaction, cardiogenic shock, cardiac arrest.
Antifibrinolytics e.g. tranexamic acid can stop serious bleeding

Reperfusion of infarcted brain or heart can lead to cerebral oedema and arrhythmias

31
Q

What are the contraindications thrombolysis?

A

Factors that predispose to bleeding- recent haemorrhage, recent trauma or surgery, bleeding disorders, severe hypertension, peptic ulcers

Rule out intracranial haemorrhage with CT

Prev streptokinase is a contraindication to repeat dosing

32
Q

What are important interactions with fibrinolytics?

A

Anticoagulants, antiplatelet agents

ACEi appear to increase the risk of anaphylactoid reactions

33
Q

How are fibrinolytics prescribed?

A

Given in a high dependency area
A bolus dose is given first, followed by an IV infusion by diluting in 0.9% NaCl

Patients should be monitored in a high dependency unit, with vital signs checked every 15 mins for the first 2 hours

The faster it’s given, the better chance of recovery

Alteplase costs £300-600

34
Q

Name some drugs in the heparins and fondaparinux class

A

Enoxaparin, dalteparin, fondaparinux, unfractionated heparin

35
Q

What are the common indications for heparins and fondaparinux?

A
  1. Heparin, LMWH, is used for primary prevention of DVT and PE in hospital inpatients
  2. ACS- heparin or fondaparinux is used with antiplatelet agents to reduce clot progression or maintain revascularisation
36
Q

How do heparins and fondaparinux work?

A

They work by enhancing the anticoagulation effect of antithrombin, which inactivates clotting factors, particularly factors IIa (thrombin) and Xa

37
Q

What are the adverse effects of heparins and fondaparinux?

A

Haemorrhage- risk is lower with fondaparinux than with LMWH or UFH
Hyperkalaemia occurs occasionally due to an effect on adrenal aldosterone secretion

Rarely, patients can experience HIT (heparin-induced thrombocytopenia)- characterised by a low platelet count and thrombosis

38
Q

Which patients should heparins be used in caution with?

A

Patients with clotting disorders, severe uncontrolled hypertension, and recent surgery or trauma

They should be stopped before and after invasive procedures, esp LP and spinal analgesia

In renal impairment, LMWH and fondaparinux accumulate, so a lower dose of UFH should be used instead

39
Q

What are the important interactions for heparins and fondaparinux?

A

Combining heparins with other antithrombotic drugs e.g. antiplatelet (warfarin) has an additive effect
This is sometimes desirable e.g. in treating ACS, but it is associated with an increased risk of bleeding, so should otherwise be avoided

In major bleeding, protamine is an option to reverse heparin anticoagulation

40
Q

How is LMWH prescribed?

A

Given SC into SC tissue of abdo wall
A typical VTE prophylaxis regimen is dalteparin 5000 units SC daily
UFH may be preferred in renal impairment

41
Q

How often is LMWH given for VTE prophylaxis?

A

OD

42
Q

Does LMWH need to be monitored?

A

No, expect in cases of renal impairment and pregnancy, when plasma antifactory Xa acivity is measured

43
Q

Does UFH need to be monitored?

A

It has a less predictable effect, so when used at the full therapeutic effect, usual dose is titrated against the activated partial thromboplastin ratio (APTR) (usual target 1.5-2.5)

FBC, baseline clotting and renal profiles should be checked before starting treatment

In prolonged therapy (>4 days), platelet count and serum potassium concentration should be monitored, as the risk of thrombocytopenia and hyperkalaemia increases with duration of therapy

44
Q

What is iron prescribed for and name some examples?

A

Ferrous fumarate, ferrous sulphate

  1. Treatment of iron-deficiency anaemia
  2. Prophylaxis of iron-deficiency anaemia in patients with RFs such as poor diet, malabsorption, menorrhagia, gastrectomy, haemodialysis and infants with low birth weight
45
Q

What is iron important for in the body?

A

Iron is essential for erythropoiesis (the formation of new RBCs). It is required for the haem component of haemoglobin

It is absorbed in the duodenum and jejunum, and its absorption is increased by stomach acid and dietary acids e.g. Vit C

46
Q

What are the side effects of iron therapy?

A

GI upset- inc nausea, epigastric pain, constipation and diarrhoea, black stools

47
Q

What are the warnings and interactions for iron medication?

A

Warnings- intestinal disease inc IBD, diverticular disease, intestinal strictures

Interactions- it can reduce the absorption of other drugs e.g. levothyroxine and bisphosphonates. These medicines should be taken at least 2 hours before iron

48
Q

How can iron be prescribed?

A

Oral or IV administration

For treatment of iron-deficiency anaemia, prescribe 100-200mg of elemental iron per day. Different oral iron preparations contain different amounts of elemental iron e.g. ferrous sulphate 200mg contains 65mg elemental iron (therefore prescribe 2-3 times a day)

Once the Hb has returned to normal, continue the prescription for a further 3 months to replenish iron stores fully

For prophylaxis of iron-deficiency of anaemia, ferrous sulphate 200mg daily should be sufficient

49
Q

When should iron tablets be taken?

A

Absorbed best on an empty stomach, but can be taken with food to reduce GI upset

IV iron is given as an injection over 10 mons or as an infusion

It should be stopped 7 days before a colonoscopy

50
Q

How is treatment with iron monitored?

A

Monitor FBC until the haemoglobin has returned to normal

You should expect the hb to rise by around 20g/L per month

51
Q

Name some indications for prescribing vitamins?

A
  1. Thiamine (vit B1) is used in the treatment and prevention of Wernicke’s encephalopathy and Korsakoff’s psychosis, which is a manifestation of severe thiamine deficiency
  2. Folic acid (synthetic form of folate or vit B9) is used in megaloblastic anaemia as a result of folate deficiency, and in the first trimester of pregnancy to reduce the risk of neural tube defects
  3. Hydroxycobalamin (vit B12) is used in the treatment of megaloblastic anaemia and subacute degeneration of the cord as a result of vit B12 deficiency
  4. Phytomenadione (vit K) is recommended for all newborn babies to prevent vit K deficiency bleeding, and used to reverse the anticoagulation effect of warfarin
52
Q

What are the warnings for patients with vit B12 deficiency and folate deficiency?

A

Both vitamins should be replaced simultaneously because replacing folate alone may be associated with progression of neurological manifestations of vit B12 deficiency (subacute degenration of the cord)

Phytomenadione reverses warfarin but is less effective in patients with severe disease

53
Q

How is thiamine prescribed?

A

In hospital, it is prescribed with a compound preparation of vits B and C called Pabrinex

  • given as an injection
  • it is prescribed in ‘pairs’- for prophylaxis in high risk patients, the dose is 1 pair 12-hourly IV for 3 days; treatment doses are higher. The contents of both ampules are added to a small bag of 0.9% saline or 5% glucose, mixed, and infused over 30 mins

Oral thiamine (200mg daily) is used in the longer term

54
Q

When should folic acid be taken in pregnancy?

A

400mcg daily should ideally be started before conception, or otherwise at diagnosis in pregnancy, and continued until week 12
(can be purchased without prescription)

Where there is a higher risk of neural tube defects e.g. in epilepsy, a higher dose of 5mg daily is used. This is also used in folate deficiency anaemia

55
Q

How is hydroxycobalamin prescribed?

A

IM injection

56
Q

How is phytomenadione prescribed in neonates?

A

1mg IM is given once only to prevent vit K deficiency bleeding

57
Q

How are vitamin prescriptions monitored?

A

Thiamine- clinically
Folate and B12- clinically with FBCs
Phytomenadione- INR 12-24 hours after administration

58
Q

What is warfarin indicated for?

A
  1. VTE treatment and prevention of recurrence

2. To prevent arterial embolism in patients with AF or prosthetic heart valves

59
Q

How does warfarin work?

A

Inhibits hepatic production of vit-K dependent clotting factors II, VII, IX and X, and proteins C & S

60
Q

What is an important adverse effect of warfarin?

A

Bleeding

Severe over-warfarisation can trigger spontaneous bleeding such as epistaxis or retroperitoneal haemorrhage

61
Q

What drug reverses warfarin?

A

Phytomenadione (vit K)

62
Q

Which patients is warfarin contraindicated?

A

Those at risk of severe bleeding, including patients after trauma or requiring surgery
Patients with liver disease are less able to metabolise the drug and are at risk of overdose

Warfarin should not be used in the 1st trimester of pregnancy due to a risk of teratogenicity (cardiac and cranial abnormalities)

63
Q

Why does warfarin have a low therapeutic index?

A

The plasma concentration that is required to prevent clotting is close to the conc that cause bleeding

This means small changes in warfarin hepatic metabolism by P450 can cause significant changes in anticoagulation

64
Q

What are important interactions with warfarin?

A

CYP inducers (phenytoin, carbamazepine, rifampicin) increase warfarin metabolism and risk of clots

CYP inhibitors (fluconazole, macrolides) decrease warfarin metabolism and increase bleeding risk

Other antibiotics can increase the effect of warfarin by killing gut flora that synthesise vit K

65
Q

How is warfarin prescribed?

A

Taken orally OD
The dose is 5-10mg on day 1, with the lower dose used for patients who are elderly, lighter or at increased bleeding risk

Subsequent doses are guided by INR

Patients needing immediate anticoagulation usually start both heparin and warfarin. Heparin is stopped once the INR is in target range

A single episode of VTE is treated with warfarin for 3-6 months

66
Q

When is warfarin administered?

A

Taken around 6pm each day for consistent effects on the INR taken the following morning

Patients receive a ‘yellow book’ which contains info on their doses, blood test results, treatment indication and duration

67
Q

What is INR?

A

It is the prothrombin time of a person on warfarin divided by that of a control
The target INR varies by indication (2-3 in AF and VTE, higher in prosthetic cardiac valves)

It is measured daily in inpatients and every few days in outpatients

Pharmacology (9 decks)

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