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Clinical Pharmacology > Stroke > Flashcards

Stroke Flashcards

1
Q

Thrombolysis, which drug and time window

A

Alteplase. Start within 4,5 hours from symptom onset. Best efficacy within 3 hours.

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2
Q

Alteplase - Dose and route

A

0,9 mg/kg (max 90mg) - 10% of total dose by bolus followed by remaining of total dose as infusion over 1 hour

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3
Q

Alteplase - MoA

A

Recombinant forms of human tissue plasminogen activator(t-PA) enzyme, converts plasminogen to plasmin and cause fibrinolysis

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4
Q

Alteplase - Adverse effects

A

Hemorrhage

Arrhythmias (Bradycardia, Tachycardia)

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5
Q

Alteplase - Contraindications

A
  • Unknown time of onset of symptoms or onset of symptoms after 4,5 hours
  • CT that shows intracranial bleeding
  • Previous intracranial bleeding
  • Known AV- malformation, aneurysm, or intracranial neoplasm
  • Blood glucose < 2,8 mmol/L or >22 mmol/L
  • Surgery or trauma within last 21 days
  • Aortic dissection
  • Risk of bleeding, anticoagulation therapy. Can give if INR<1,8
  • Systolic blood pressure > 185 mmHg, Diastolic blood pressure > 110 mmHg
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6
Q

Prehospital treatment

A
  • Observe vital function
  • Give oxygen 7-10 L/min with mask or 2-3 L/min with nasal catheterization if saturation is <95%
  • Slightly raised upper body (15-20 degrees), or position the pt sideways if unconscious
  • Give IV fluids (max 1000 mL) if dehydrated, Lower BP if it exceeds 220/120
  • Paracetamol 1 g PO if temp >37,5 °C. Don’t give PO if suspicion of swallowing problems.
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7
Q

Medical Treatment of Stroke

A

Prevent complications of bedridden pts: infections (pneumonia, UTI, skin), DVT with pulmonary embolism.
Heparin (subc), pneumatic compression stockings

BP: lower if it exceeds 220/120 (Esmolol- 500mcg/kg over 1 min IV), malignant HTN, myocardial ischemia, or if BP >185/110 and thrombolytic therapy is anticipated

Fever: antipyretic and surface cooling.

Serum glucose: keep <10,0 mmol/L (180 mg/dL), and above at least 3,3 mmol/L /60 mg/dL) Insulin infusion if necessary.

IV isotonic fluids: maintain intravascular V

Water restriction and IV mannitol: cerebral edema –> brain herniation. Raise the serum osmolarity, but avoid hypovolemia –> hypotension and worsening of infarction. May also perform hemicraniectomy.
Mannitol: 150 mg/ml 0,50-1g per kg

Cerebellar infarction: mimic labyrinthitis because of prominent vertigo and vomiting. Head or neck pain –> cerebellar stroke due to vertebral artery dissection. Small amounts of cerebellar edema can increase the ICP by obstructing CSF flow –> hydrocephalus or compress brainstem –> coma and respiratory arrest; surgical

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8
Q

Antithrombotic treatment

A

Platelet inhibition: all pts not receiving thrombolytic treatment should get Aspirin 250-300 mg initially in water-soluble form asap –> 75 mg daily

Anticoagulation: pts with acute stroke and atrial fibrillation –> aspirin + anticoagulation (heparin/LMWH) can be started after 4-7 days; more efficient as long-term prophylaxis.

Deep venous thrombosis prophylaxis: Dalteparin 5000 U or enoxaparin 40 mg subcutaneously is recommended

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9
Q

Enoxaparin - Dose and route

A

40mg x 1 subcutaneoulsy

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10
Q

Enoxaparin - MoA

A

Inactivate factor X

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11
Q

Enoxaparin - Adverse effects

A

Bleeding caused by excessive anticoagulation

Heparin induced thrombocytopenia(HIT)

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12
Q

Enoxaparin - Contraindications

A

Recent bleeding
Recent trauma or surgery
Bacterial endocarditis
Peptic ulcers

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13
Q

Secondary prophylaxis

A

Antiplatelet agents:
Aspirin (75mg x 1)/Dipyridamole (200mg x 2) and Clopidogrel (75mg x 1)

Anticoagulation agents:
Warfarin for patients with prosthetic heart valve and INR should be less than 2,5. Newer anticoagulation drugs such as Dabigatran, rivaroxaban and apixaban.

Lipidreducing agents:
Statins is recommended for every patient with ischemic stroke if LDL > 2,0 mmol/l.

  • Surgery: Carotid endarterectomy (Carotid stenosis), Encovascular stening (carotid disease)
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14
Q

Dipyridamole - MoA

A

Inhibiting platelet adhesion to the vessel wall.

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15
Q

Dipyridamole - Adverse effects

A

Headache
Dizziness
Nausea
Thrombocytopenia

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16
Q

Dipyridamole - Contraindications

A

Caution in patients with hypotension, coronary artery disease.

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17
Q

Clopidogrel - MoA

A

Adenosine diphosphate inhibitor

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18
Q

Clopidogrel - Adverse effects

A

Bleeding

Neutropenia

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19
Q

Clopidogrel - Contraindications

A

Previous intracranial bleeding
Thrombocytopenia
Neutropenia
Lever damage

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20
Q

Warfarin - Dose and route

A

7,5 mg orally

21
Q

Warfarin - MoA

A

Vitamin K antagonist

22
Q

Warfarin - Adverse effects

A

Bleeding (mild nose bleed to life threatening hemorrhage)

Fetal warfarin syndrome (bone deformities and bleeding.

23
Q

Warfarin - Contraindications

A

Pregnancy (Crosses the placenta and can cause fetal hemorrhage + fetal warfarin syndrome)

24
Q

Warfarin - Interactions

A

Interacts with drugs that induce or inhibit cyt P450.

Most serious interactions are with drugs that increase the anticoagulant effect and place the patients at risk of hemorrhage, ex: Salicylates (by reducing prothrombin), cephalosporins

Decrease anticoagulant effect by inducing CYP enzymes that metabolize warfarin: rifampin, barbiturates

Cholestyramine inhibit absorption of warfarin from gut.

Amiodarone, cimetidine, erythromycin, fluconazole, gemifibrozil, isoniazid, metronidazole, sulfinpyrazone inhibit metabolism of warfarin –> increase the risk of bleeding.

25
Q

Dabigatran - Dose and route

A

150 mg x 2 orally

26
Q

Dabigatran - MoA

A

Direct thrombin inhibitor

27
Q

Dabigatran - Adverse effects

A

Increased risk of bleeding

GI complains, dyspepsia, gastritis like symptoms

28
Q

Dabigatran - Contraindications

A

Decreased kidney function
Active bleeding
Decreased liver function
Pregnancy and breast feeding

29
Q

Dabigatran - Interactions

A

Pgp inhibitors such as amiodarone and verapamil increase the levels of dabigatran

Increased risk of bleeding with use of SSRI or SNRI

30
Q

Atorvastatin - Dose and route

A

Normal start dose is 10 mg x 1 orally. Maximal dose is 80 mg x 1.

31
Q

Atorvastatin - MoA

A

HMG-CoA Reductase Inhibitor

32
Q

Atorvastatin - Adverse effects

A

GI problems; abdominal cramps, constipation, diarrhea, heartburn.

Hepatitis and elevated liver enzymes
Rhabdomyolysis
Muscle myopathy(earliest stage is myalgia, which consists of muscle ache or weakness without creatine kinase levels)

Myalgia can be followed by myositis or muscle inflammation accompanied by muscle pain, leakage of muscle creatine kinase into the plasma, and elevated creatine kinase levels

33
Q

Atorvastatin - Contraindications

A

Because statins , fibric acid derivatives, and niacin may cause myopathies, the combined use of drugs should be undertaken with greater caution using lower doses of each agent employed

34
Q

Atorvastatin - Interactions

A

Metabolized by CYP3A4, plasma levels increases strong by inhibitors of this isozyme; erythromycin, itraconazole, ritonavir

35
Q

Stroke - Diagnosis

A

Facial drooping, Arm weakness, Speech difficulties, Time to call the ambulance
Check Vitals.
Clinical exam:
-Neurologic exam: localize anatomic site of stroke
- Carotid auscultation, Heart (murmur, dysrhythmia), Extremities (PE), Retina (effect of HTN and cholesterol emboli)
Imaging: immediately
- CT, MRI: Differentiate between hemorrhagic or ischemic stroke + exclude other causes
- CT- MRI angiography: vasculature of neck and intracranial vessels
- ECG: arrhythmia
- CXR
- Transthorasic/Esophageal Echo: Patent F.O, ASD
- Lab: CBC, glucose, CRP, ESR, electrolytes, BUN, INR, PT, PTT, Renal function tests, lipid profile
Holter Monitoring

36
Q

Stroke pt at hospital >4,5 h <6h - Treatment

Stroke pt at hospital <4,5 h - Treatment

A

Mechanical thrombectomy
Aspirin

Thrombolysis

37
Q

Intracerebral hemorrhage - Treatment

A

Correct coagulopathy:
- Pos takin VKAs: Prothrombin complex concentrated with vit K
- Dabigatra: Idarucizumab
- Xa inhibitors: PCC
- Thrombocytopenia: fresh plasma transfusion
Control HTN- Esmolol if high BP
Increased ICP, hydrocephalus: Osmotic agents
Cerebellar hematoma: Neurosurgery

38
Q

SAH - Diagnosis

A

Thunderclap headache
Noncontrast CT within 72 h
LP:
- Blood in CSF –> rupture of aneurysm
- Yellow color of CSF within 6-12 h
X-Ray angiography: anatomic details of anerysm
Electrolyte monitoring: hyponatremia can occur
ECG: ST-segment and T wave changes, Prolonged QRS complex, peaked or deeply innervated T was
Echo: regional wall motion abnormalities
Troponin elevated
Coagulation and platelet count

39
Q

SAH- Treatment

A

Aneurysm repair: clipped or coiled, placement of stent
Craniotomy: removing hematoma
Tranexamic acid
Hyponatremia: Oral salt + IV saline
Anticonvulsants as prophylactic therapy
BP should be lowered to 140 in pts with spontaneous ICH: Esmolol
Enoxaparin
Hydrocephalus: CSF drainage, permanent shunt placement
Vasospasm: Nimodipine

40
Q

Tranexamic acid - MoA

A

Fibrinolytic (Thrombolytic) drug

41
Q

Tranexamic acid - Adverse effects

A

Hemorrhage, Arrhythmia

42
Q

Tranexamic acid - Interactions

A

Contraceptive pills –> increased risk of thrombosis

43
Q

Tranexamic acid - Contraindication

A

Bleeding, recent surgery/trauma.

44
Q

Tranexamic acid - Dose

A

1g IV immediately and 1g after 2 h and then every 6 h until the aneurysm is stabilized

45
Q

Nimodipine - dose

A

60 mg PO every 4 h

46
Q

Nimodipine - Adverse effects

A

Headache, flushing, hypotension

47
Q

Nimodipine- Interaction

A

Excessive hypotensive effect with other hypotensive agents
Itraconazole increases conc
Carbamazepine decreases conc

48
Q

Nimodipine - Contraindication

A

Allergic reaction to nimodipine, hypotension

49
Q

Differential Diagnosis

A 
Todds paralysis 
Abscess with seizure
Tumor with bleed or seizure 
Toxic-metabolic insult with old cerebral lesion
Hypoglycemia
Subdural hematoma (acute)
Multiple sclerosis
cerebritis

Clinical Pharmacology (14 decks)

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