28 May 2009

Antiviral Agents



Antiviral Agents
By:Jillian H. Davis
Department of Pharmacology, Howard University

Viruses
* Obligate intracellular parasites
* Consist of a core genome in a protein shell and some are surrounded by a lipoprotein
* lack a cell wall and cell membrane
* do not carry out metabolic processes
* Replication depends on the host cell machinery
* Steps for Viral Replication

Sites of Drug Action
Antiviral Agents
Antiherpes Agents
* Acyclovir- prototype
* Valacyclovir
* Famciclovir
* Penciclovir
* Trifluridine
* Vidarabine
Mechanism of Action Acyclovir
* an acyclic guanosine derivative
* Phosphorylated by viral thymidine kinase
* Di-and tri-phosphorylated by host cellular enzymes
* Inhibits viral DNA synthesis
* Alteration in viral thymidine kinase
* Alteration in viral DNA polymerase
* Cross-resistance with valacyclovir, famciclovir, and ganciclovir

Clinical Uses Acyclovir
* Oral, IV, and Topical formulations
* Cleared by glomerular filtration and tubular secretion
* Uses:
o Herpes Simplex Virus 1 and 2 (HSV)
o Varicella-zoster virus (VZV)
* Side Effects: nausea, diarrhea, headache, tremors, and delirium

Valacyclovir
* L-valyl ester of acyclovir
* Converted to acyclovir when ingested
* M.O.A.: same as acyclovir
* Uses:
o 1) recurrent genital herpes
o 2) herpes zoster infections
* Side Effects: nausea, diarrhea, and headache

Famciclovir
* Prodrug of penciclovir (a guanosine analog)
* M.O.A.: same as acyclovir
* does not cause chain termination
* Uses: HSV-1, HSV-2, VZV, EBV, and hepatitis B
* Side Effects: nausea, diarrhea, and headache

Trifluridine
* Trifluridine- fluorinated pyrimidine
o inhibits viral DNA synthesis same as acyclovir
o incorporates into viral and cellular DNA
o Uses: HSV-1 and HSV-2 (topically)
Vidarabine
* An adenosine analog
* inhibits viral DNA polymerase
* incorporated into viral and cellular DNA
* metabolized to hypoxanthine arabinoside
* Side Effects: GI intolerance and myelosuppression

Anti-Cytomegalovirus Agents
* Gancyclovir
* Valgancyclovir
* Cidofovir
* Foscarnet
* Fomivirsen

Ganciclovir
* An acyclic guanosine analog
* requires triphosphorylation for activation
* monophosphorylation is catalyzed by a phosphotransferase in CMV and by thymidine kinase in HSV cells
* M.O.A.: same as acyclovir
* Uses: CMV*, HSV, VZV,and EBV
* Side Effect: myelosuppression

Valgancyclovir
* Monovalyl ester prodrug of gancyclovir
* Metabolized by intestinal and hepatic esterases when administered orally
* M.O.A.: same as gancyclovir
* Uses: CMV*
* Side Effect: myelosuppression

Cidofovir
* A cytosine analog
* phosphorylation not dependent on viral enzymes
* Uses: CMV*, HSV-1, HSV-2, VZV, EBV, HHV-6, adenovirus, and human papillomavirus
* Side Effects: nephrotoxicity (prevented by admin. of probenecid)
* Resistance: mutation in DNA polymerase gene

Foscarnet
* An inorganic pyrophosphate
* inhibits viral DNA polymerase, RNA polymerase, and HIV reverse transcriptase
* does not have to be phosphorylated
* Uses: HSV, VZV, CMV, EBV, HHV-6, HBV, and HIV
* Resistance due to mutations in DNA polymerase gene
* Side Effects: hypo- or hypercalcemia and phosphotemia

Fomivirsen
* An oligonucleotide
* M.O.A.: binds to mRNA and inhibits protein synthesis and viral replication
* Uses: CMV retinitis
* Side effects: iritis and increased intraocular pressure

Antiretroviral Agents
1) Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
2) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
3)Protease inhibitors

Reverse Transcriptase Inhibitors
* Zidovudine (AZT)
* Didanosine- causes pancreatitis*
* Lamivudine- causes pancreatitis
* Zalcitabine- causes peripheral neuropathy*
* Stavudine- causes peripheral neuropathy*
* Abacavir

Mechanism of Action Zidovudine (AZT)
* A deoxythymidine analog
* enters the cell via passive diffusion
* must be converted to the triphosphate form by mammalian thymidine kinase
* competitively inhibits deoxythymidine triphosphate for the reverse transcriptase enzyme
* causes chain termination

Mechanism of Resistance Zidovudine
* Due to mutations in the reverse transcriptase gene
* more frequent after prolong therapy and in persons with HIV

Clinical Uses Zidovudine
* Available in IV and oral formulations
* activity against HIV-1, HIV-2, and human T cell lymphotropic viruses
* mainly used for treatment of HIV, decreases rate of progression and prolongs survival
* prevents mother to newborn transmission of HIV

Side Effects Zidovudine
* Myelosuppression, including anemia and neutropenia
* GI intolerance, headaches, and insomnia

Other NRTIs
* Didanosine- synthetic deoxy-adenosine analog; causes pancreatitis*
* Lamivudine- cytosine analog
* Zalcitabine- cytosine analog; causes peripheral neuropathy*
* Stavudine- thymidine analog;causes peripheral neuropathy*
* Abacavir- guanosine analog; more effective than the other agents; fatal hypersensitivity reactions can occur


Nucleotide Inhibitors
* Tenofovir
* Adefovir

Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
* Nevirapine
* Delavirdine
* Efavirenz
Mechanism of Action NNRTIs
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Protease Inhibitors
Indinavir and Ritonavir
Saquinavir
Nelfinavir and Amprenavir
Fusion Inhibitors
Anti-Hepatitis Agents
Interferons
Ribavirin
Anti-Influenza Agents
Amantadine and Rimantadine
Zanamivir and Oseltamivir
Antifungal Agents
Fungal Infections
Systemic Antifungals
Amphotericin B
Flucytosine
Azoles
Differences in Azoles
Mucocutaneous Antifungals
Topical Antifungals

Antiviral Agents.ppt

Read more...

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...

27 May 2009

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...
All links posted here are collected from various websites. No video or powerpoint files are uploaded on this blog. If you are the original author and do not wish to display your content on this blog please Email me anandkumarreddy at gmail dot com I will remove it. The contents of this blog are meant for educational purpose and not for commercial use. If you use any content give due credit to the original author.

This site uses cookies from Google to deliver its services, to personalise ads and to analyse traffic. Information about your use of this site is shared with Google. By using this site, you agree to its use of cookies.

  © Blogger templates Newspaper III by Ourblogtemplates.com 2008

Back to TOP