Back to Basics Practical Pharmacology – part 3 Dr. Roland Halil, BSc(Hon), BScPharm, ACPR, PharmD Assistant Professor, Dept of Family Medicine, University of Ottawa Clinical Pharmacist, Bruyere Academic Family Health Team April 2013 [email protected]
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Back to Basics Practical Pharmacology – part 3 Dr. Roland Halil, BSc(Hon), BScPharm, ACPR, PharmD Assistant Professor, Dept of Family Medicine, University.
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Back to BasicsPractical Pharmacology – part 3
Dr. Roland Halil, BSc(Hon), BScPharm, ACPR, PharmD
Assistant Professor, Dept of Family Medicine, University of Ottawa Clinical Pharmacist, Bruyere Academic Family Health Team
Clopidogrel Less GI bleed - clopidogrel < ASA (1.99% vs 2.66% p < 0.002) (Less severe GI bleed - 0.49 vs 0.71%; p < 0.05)Less GI events - clopidogrel < ASA (27.1 vs 29.8%; p < 0.001) More Diarrhea clopidogrel > ASA (4.46 vs 3.36%; p < 0.001)More Rash – clopidogrel > ASA (6.0% vs 4.6% p < 0.001)No difference in: Early D/C, Neutropenia, Thrombocytopenia & Intracranial bleed. (per CAPRIE)
Major bleeding – clop + ASA > ASA (3.7% vs. 2.7%; RR = 1.38; P=0.001), Life-threatening bleeding - no diff (2.1 percent vs. 1.8 percent, P=0.13) Hemorrhagic strokes – no diff (per CURE trial)
Prasugreluntested
More fatal and life-threatening bleeds vs clopid + ASA
Ticagreloruntested
More major and minor bleeds vs clopid + ASAMore dyspnea, & incr UA
• ASA or Clopidogrel or Aggrenox®– Any will do, until tie breaker trial between these
agents. – Aggrenox® might be more efficacious, but with
more side effects and less convenience.
Anticoagulants• Warfarin– Vitamin K antagonist – (clotting factors 2,7,9,10,
protein C & S)– For: Afib, VTE prophylaxis &
tx, valvular disease
• Dabigatran– Direct thrombin inhibitor
(factor 2)– For: Afib, VTE prophylaxis
post-op TKR/THA– (N.B. Ximelagatran – withdrawan
due to hepatotoxicity)
• Rivaroxaban– Factor Xa inhibitor– For: Afib, VTE
prophylaxis post-op TKR/THA, DVT tx
• Apixaban– Factor Xa inhibitor– For: Afib, VTE
prophylaxis post-op TKR/THA
Anticoagulants (VTE, Afib, Valve disease)
Agent Efficacy Toxicity
Warfarin Excellent vs placebo or ASA 1.3% - 3.5% -- major bleed< 0.25% - 0.5%/yr -- ICH
Dabigatran~ same
N.B. (~1% absolute difference)(RE-LY trial - industry funded)
Less intracranial & More GI bleeds; ?More MI?Untested > 79y.o. or CrCL < 30NO reversal agent
Rivaroxaban~ same
N.B. (<1% absolute difference)(ROCKET-AF trial – industry funded)
Less intracranial & More GI bleedsUntested > 79y.o. or CrCL < 30NO reversal agent
Apixaban~ same
N.B. (<1% absolute difference)(ARISTOTLE trial – industry
funded)
Less intracranial bleedsGI bleeding – no differenceUntested > 77y.o. or CrCL < 30NO reversal agent
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Anticoagulants (VTE, Afib, Valve disease)
Agent Cost Convenience
Warfarin ~ $40/mo (with INR monitoring)
QD poINR q3d – q1mo
(ODB covered)
Dabigatran $110/moBID po
(ODB w/ LU code 431 for AFib)
Rivaroxaban $100/moQD with food
(ODB w/ LU code post-op TRK/THA)
Apixaban $140/mo BID poNo coverage yet
Summary• Antiplatelets– Small differences in efficacy or toxicity, dictate that cost will
drive selection. – = ASA– Combination therapy where indicated
• Anticoagulants– Small differences in efficacy and important unknowns in newer
agents (age effects, renal dysfunction, lack of antidotes) dictate selection of warfarin except for carefully selected patients with significant compliance barriers due to the inconvenience of INR testing.
Anti-depressants & Anxiolytics
Dr. Roland Halil, BSc(Hon), BScPharm, ACPR, PharmD
Assistant Professor, Dept of Family Medicine, University of Ottawa Clinical Pharmacist, Bruyere Academic Family Health Team
• Cost– All ~ $25 - $35 / month– Newest agents, without
generics cost more.• Bupropion XL
– $45/mo• Escitalopram
– $65/mo• Paroxetine CR
– $60/mo– Not covered under ODB
• Desvenlafaxine– $85/mo– Not covered under ODB
• Convenience– Most once daily– Bupropion SR – BID
• Bupropion XL – QD
– Moclobemide - BID
The Evils of Benzodiazepines(Yes, this includes “z-drug, non-benzo alternatives” Eg. Zopiclone)
• Formerly one of the most commonly prescribed drug families of the 1960’s and 1970’s. – In 1975 – 100 million Rxs written in USA alone– Efficacy – excellent SHORT term efficacy
• Sedation & anxiolysis• Rapid tolerance is developed
– Toxicity – addictive! • D/C’ing after tolerance develops is VERY hard• Long term risk of dementia, falls, and memory impairment• Withdrawal can be fatal
Anti-psychotics• Efficacy– No clinically relevant differences (variable responses)• ?Olanzapine superiority?
– See CATIE trial
– Exception: Clozapine – clearly superior
• As ever, when efficacy is ~ equivalent, choose therapy based on potential toxicities
Anti-psychotics
• Toxicities:– Clozapine: • Agranulocytosis (10x higher risk vs other antipsychotics)• Hence, mandatory CBC q2-4weeks• Therefore, last line therapy, despite superior efficacy