Anticoagulant, Antithrombotic and Anti-Platelet Drugs

Anticoagulant, Antithrombotic and Anti-Platelet Drugs
By:Robert Taylor, MD, Ph.D.
Department of Pharmacology, Howard University

Clinical Thrombosis
Indications For Antithrombotic Therapy
* Venous thromboembolic disease
o Deep venous thrombosis (DVT)
o Pulmonary embolism (PE)
o Primary prophylaxis of DVT or PE
* Arterial thromboembolic disease
o Prosthetic heart valves
o Mitral valve disease, especially with atrial fibrillation
o Congestive cardiomyopathies, especially with atrial fibrillatio
o Atrial fibrillation
o Mural cardiac thrombi
o Transient ischemic attacks
o Stroke in evolution
* Disseminated intravascular coagulation
* Maintenance of patency of vascular grafts, shunts, bypasses

Recombinant Human Activated Protein C
* Drotrecogin alfa (activated)- Xigris
* Indicated for Severe Sepsis in Adults with Acute Organ Dysfunction with High Risk of Death
* Reduction in Death as Primary End Point
* Antithrombotic, Antiinfammatory, Profibrinolytic Properties
* Serious Bleeding is Major Side Effect

Antithrombin III Inhibits the Following Serine Proteases
* Coagulation
* Factor XIIa
* Factor XIa
* Factor IXa
* Factor Xa
* Thrombin
* Fibrinolysis
* Plasmin

Inhibitory activity against all these enzymes is substantially accelerated by heparin

Heparin
Anticoagulant Properties of Heparin
* Inhibits the thrombin-mediated conversion of fibrinogen to fibrin
* Inhibits the aggregation of platelets by thrombin
* Inhibits activation of fibrin stabilizing enzyme
* Inhibits activated factors XII, XI, IX, X and II
* Biologic Sources
* Bioavailability
* Metabolism
* Elimination
* Side Effects
* Overdose
* Contraindications
* Pregnancy- YES

Unfractionated Heparin
* High Dose
Monitoring of Anticoagulant Therapy
Heparin
Low Dose Unfractionated Heparin
Indications for and Contraindications to Parenteral Anticoagulant Agents
Regional anesthesia
Pregnancy
Prosthetic Heart Valves
Regional anesthesia
Antithrombin III inhibitor
Low-molecular-weight heparin
Unfractionated heparin
Enoxaparin(Lovenox)
Dalteparin(Fragmin)
Tinzaparin(Innohep)
Contraindication
Approved & Appropriate Indications
Class
Anticoagulant Agent
Thrombocytopenia other than heparin-induced thrombocytopenia
Direct thrombin inhibitor
Heparinoid
Hirudin derivative
Synthetic factor Xa inhibitor
Ardeparin
Lepirudin
Argatroban
Danaparoid
Bivalirudin
Fondaparinux(Arixtra)
Heparin-Antibiotic Interactions
Mechanisms of HIT
Therapy of HIT
Warfarin
* Bioavailability
* Metabolism
* Serum Protein Binding
* Vitamin K Status
* Protein C Effects
* Elimination
* Side Effects
* Overdose
* Contraindications
* Pregnancy- NO
Contraindications to Antithrombotic Therapy
Platelet Receptor Mediated Pathways: Drugs
GP IIB/IIIA Inhibitors
Abciximab (ReoPro)
Eptifibatide (Integrilin)
Tirofiban
Thrombin
-Final Common Pathway
-Promotes Platelet Adhesion (Fibrinogen, vWF)
Ticlopidine
Clopidogrel
ADP
ASA
NSAIDs
Arachidonic Acid
Anti Platelet Drugs
CAD
Stroke-TIAs
Permanently inhibits COX-1 and COX-2
Aspirin
TIAs;Stroke
CAD;PVD
Inhibits ADP PlatAg;active metabolite
Ticlopidine
Clopidrgrel
TIAs
Inhibits PDE; increases cAMP
Dipyridamole
Limited Reversibly inhibits COX-1
NSAIDs
Uses
Mechanism
Drug

Anticoagulant, Antithrombotic and Anti-Platelet Drugs.ppt

Read more...

Foot and Ankle Complaints

Foot and Ankle Complaints
By:Allyson Howe, MD
Major USAF MC
Capital Conference 2007


INTRODUCTION
* Anatomy and Function
o Foot
o Ankle
* Common complaints
* Common diagnoses

FOOT AND ANKLE ANATOMY
* 26 bones and 2 sesamoids
* Forefoot
o Metatarsals
o phalanges
* Midfoot
o 5 tarsals
* Rearfoot
o Talus and Calcaneus

FOOT AND ANKLE
* FUNCTIONS
o Absorb impact loading forces
o Adapt to uneven ground
o Allow efficient propulsion
FOOT AND ANKLE COMPLAINTS
HISTORICAL CLUES
* Previous injury?
* New shoes?
* New sport/activity?
* Sudden increase in mileage?
* Long term training without rest?
FOOT AND ANKLE COMMON COMPLAINTS
* Heel pain
* Forefoot pain
* Ankle pain
* Numbness/tingling/burning
* Ankle swelling
* Heel pain
* Forefoot pain
* Ankle pain
* Numbness/tingling/burning
* Ankle swelling

HEEL PAIN
* Determine location
o Plantar surface
+ Plantar fasciitis
+ Heel pad atrophy
+ Distal tarsal tunnel syndrome
+ Calcaneal stress fracture
o Posterior heel
+ Retrocalcaneal bursitis
+ Achilles tendinopathy
+ Sever’s disease
+ Stress fracture
+ Lateral Plantar Nerve entrapment

Consider inflammatory conditions also:
Gout
Reiter’s
Psoriasis

PLANTAR FASCIITIS
* Pain at the most anterior portion of the heel pad
* Medial tubercle
* Worst with first step in the morning or after inactivity
* Pain increases with active dorsiflexion of first toe
* Treatment
o ICE
o Stretching
o NSAIDs
o Correction of arch abnormalities
o Improved shoe quality
o Training adjustment
o Night splints
o Injections

HEEL PAD ATROPHY
TARSAL TUNNEL SYNDROME
RETROCALCANEAL BURSITIS
ACHILLES TENDINOPATHY
SEVER’S DISEASE aka. Calcaneal Apophysitis
LATERAL PLANTAR NERVE ENTRAPMENT
FOREFOOT PAIN
* Acute
* Trauma
* Chronic
5th METATARSAL FRACTURE
METATARSAL FRACTURE
GOUT
LIS FRANC SPRAIN
METATARSALGIA
STRESS FRACTURE
ANKLE PAIN
OSTEOCHONDRAL DEFECT
ANKLE SPRAIN
OTTAWA ANKLE AND FOOT RULES
Ottawa Ankle Rules
Radiographs
A-P View of Ankle
Lateral View of Ankle
Mortise View of Ankle
Mortise View Normals
CLASSIFICATION OF LATERAL ANKLE SPRAINS
Instability testing
Grade II
Grade I
OTHER (THAN LATERAL) ANKLE SPRAINS
ANKLE SPRAIN TREATMENT
NON-HEALING ANKLE SPRAINS
NUMBNESS/TINGLING/BURNING
Peripheral Neuropathy
Diabetes
Nutritional deficiency
Alcoholism
Heavy metal exposure
Chemotherapy
Renal disease
INH therapy
HIV
JOGGER’S FOOT
MORTON’S NEUROMA
ATRAUMATIC ANKLE SWELLING
TAKE HOME POINTS
RHEUMATOID ARTHRITIS
* ANKLE
o Ankle sprains- medial and lateral and high
+ Ottawa ankle rules
o Achilles tendonitis
o Retrocalcaneal bursitis
o Posterior tibial tendonitis
o Sever’s disease (calcaneal apophysitis)
o Tarsal tunnel syndrome
o OCD
* FOOT
o Plantar fasciitis
o Metatarsalgia
o Morton’s neuroma
o Tarsal tunnel
o Toe fracture
o Navicular stress fracture
o Freiberg’s infarction

Foot and Ankle Complaints.ppt

Read more...

Hormone Replacement Therapy

Hormone Replacement Therapy… and other options
By:Marc Childress, MD


Risks vs. Benefits in a post-WHI world
* Cancer Risk
* Osteoporosis
* Dementia
* Vasomotor Symptoms
* Urogenital Symptoms
* Cardiovascular Disease

Breast Cancer
* Mixed Results
* Excess risk approx ½ of anticipated
* Question of prognosis, timeframe of concern

Gratuitous Perspective Slide
* Increased risk of breast CA with 10% weight gain (2 add’l cases per 1000 pt-years)
* Increased risk of breast CA with combined tx (0.8 add’l cases per 1000 pt-years)

Endometrial Cancer
* Known increase in risk with unopposed estrogen
* WHI showed no signif risk of CA with combined tx

Ovarian Cancer
* No overt correlation b/w combined HRT and ovarian CA risk
* There IS a signif risk reduction associated with OCPs

Colorectal Cancer
* Signif Risk Reduction of Colon CA with combined Est/Pro
* While less cases, trend toward worse prognosis (nodal spread)
* No risk reduction observed with estrogen alone

Osteoporosis
* Well established
* Risk reduced at hip, vertebrae, and wrist over placebo
* Similar numbers for estrogen alone vs combined tx.

Dementia
* Presumed correlation with long-term estrogen and cognitive fxn
* WHIMS (memory study)

Vasomotor Symptoms
* Signif Reduction in hot flashes
* Mod improvement in sleep
* Well-known and unchanged

Urogenital Symptoms
* Can preclude occurrence of atrophic vaginitis
* Thought to prevent urinary incontinence, contradicted by WHI and HERS

Cardiovascular Disease
* Counter to previous belief, very small increase in risk of CV events with combined tx
* Estrogen alone did not show increase in risk of CV events,
* Stroke
* Venous Thromboembolism

* Which one of the following would be accurate advice regarding these risks and benefits?
* The incidence of stroke is decreased
* The incidence of myocardial infarction is decreased
* The incidence of pulmonary embolism is decreased
* The risk of breast cancer is increased
* The incidence of colorectal cancer is increased

Overview
* Current indications (brief? Tx)
o Vasomotor sxs
o Sleep disturbance
o Urogenital changes
* Additional benefits
o Osteoporosis prevention
* Risks include
o Increase in ischemic stroke
o Increase in DVT, PE
o Mild increase in breast CA risk for combined tx
o Increase in inconclusive mammograms
o Increase in GB dz with combined tx

Osteoporosis
Vasomotor Symptoms
* Pharmacologic Therapies
Vasomotor Symptoms
* Pharmacologic Therapies
Herbal Options
Vasomotor Symptoms
* Herbal/Complementary Compounds
Vasomotor Symptoms
* Not Helpful
Urogenital Symptoms

Hormone Replacement Therapy.ppt

Read more...