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BIVALIRUDIN
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Pathophysiology of STEMI

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v THE PRIMARY GOAL to establish

and maintain patency of the infarctrelated artery, in conjunction with reperfusion strategies

v SECONDARY GOAL prevent

further thrombus formation likelihood of mural thrombus formation or deep venous thrombosis pulmonary embolization
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BIVALIRUDIN

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PHARMACODYNAMIC S
q Inhibit both fibrin

bound and soluble thrombin of thrombin and prevent substrates from binding to the substrate recognition site thrombin slowly cleaves arginine-

q Block the active site

q After binding

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PHARMACOKINETICS
q Given by intravenous route q Volume of distribution- 0.1 L/kg q Not bind to plasma protein other than

thrombin & RBC

q Elimination 1. Proteolytic cleavage 2. Renal mechanism - 20% excreted

unchanged in urine
q Mean plasma clearance- 3.4 mL/min/kg
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Renal function Normal

Effect of renal impairmentElimination GFR(mL/min) Plasma

clearance 90 60-89 30-59 <=29 10 % 20 % 30 % 25 27 34 57

half life(min)

Mild impairment Moderate impairment Severe impairment

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THERAPEUTIC EFFICACY

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THERAPEUTIC EFFICACY

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TOLERABILITY

Thrombolysis In Myocardial Ischemia (TIMI)

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SIDE EFFECTS

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DOSE AND ADMINISTRATION

INITIAL DOSE 0.75 mg/kg bolus followed immediately by a 1.75mg/kg/hour for up to 4 hour after PCI 0.25 mg/kg/hour for 4-12 hour intravenous

SUBSEQUENT DOSAGE

ROUTE OF ADMINISTRATION

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CONTRAINDICATION

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BIVALIRUDIN M.O.A Act on both fibrin bound & soluble thrombin Not require

HEPARIN Act only on soluble thrombin Requires cofactor like anti thrombin III 40-90min more

ELIMINATION T1/2

25min

NACE(stroke, reless infarction, target vessel revascularization for ischemia, death, major bleeding)

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CONCLUSION

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REFERENCE
O Drugs2010;70(7)

O Harrisons internal medicine 17th

edition

O Robbins 8th edition

O www.medscape.com

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DAPOXETINE
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DAPOXETINE

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PREMATURE EJACULATION v MALE SEXUAL DYSFUNCTION

Ejaculatory dysfunction Erectile dysfunction Hypoactive sexual desire disorder

v Most prevalent male sexual

dysfunction (20-40%)
v Types
Primary (life long) - commences
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with onset of sexual activity

Neural control of ejaculation

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Neurophysiology
v The ejaculatory response is controlled by

higher centres in the brain

v Ejaculation is a reflex coordinated by a

group of cells in the spinal cord known as the SPINAL EJACULATION GENERATOR
v Serotonin and serotonergic pathways are

key in mediating signals regulating ejaculation from the brain

v Increased serotonin levels in the CNS

delay ejaculation

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PHARMACODYNAMIC S
SEROTONIN TRANSPORTER (5-HTT) REUPTAKE SYSTEM

INHIBI TS DAPOXETINE

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PHARMACOKINETICS
30mg Rapidly absorbed oraly 42% 98.5% 60mg Bio availability Plasma protein binding 42% 98.5%

Metabolism - Hepatic by cytochrome enzymes 162 L Volume of 162 L distribution Cmax Time to Cmax 297 ng/ml 1.01 hr 498 ng/ml 1.27 hr 21.9 hr 9/20/12

Terminal 18.7 hr elimination half life

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Comparison with other SSRI

Pl as m a co nc .

Time post dosing(hours)

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THERAPEUTIC EFFICACY

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SIDE EFFECTS

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DRUG INTERACTION
1. Co-administration with CYP3A4

inhibitor (ketoconazole, clarithromycin, erythromycin, fluconazole & verapamil) - dapoxetine level

1. Co-administration with CYP2D6

inhibitor(fluoxetine & other SSRI) higher incidence and severity of dose dependant adverse events
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1. Concomitant administration of

DOSE AND ADMINISTRATION

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CONTRAINDICATION

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Drawbacks of existing treatments

Behavioural therapy Clomipramine

Limited long-term efficacy Nausea Erectile dysfunction Generally require daily dosing Limited data on patient

Other anti depressant SSRI

reported outcomes SSRI discontinuation syndrome SSRI withdrawal Depressive mood changes, abnormally excited mood, syndrome irritability, anxiety, confusion, dizziness, headache, tiredness, 9/20/12 difficulty in falling asleep

CONCLUSION

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REFERENCES
O Drugs 2010; 70(11)

O Harrison 17th edition

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