My macbook slows down after using external HDD

When I use an external drive via usb, my computer really slows down giving me no choice except reboot.
I watched memory usage with activity monitor. Free memory decreases  by time and inactive memory increases with the same amount and others  don't change much. If I continue using -esp. reading-, free memory comes  below to 100MB and then increases a bit -I think it starts paging  =other applications' memories= to system disk-, then continues to  decrease. Closing the application -that use the external- do not relese  memory from inactive to free but ejecting the external does. After  unplugging and trying to use the other applications, I face very  sluggish performance so that rebooting becomes a better-fast choice.  Both NTFS and FAT partitions produce the same result and I don't have  any other partition.
If I try to re-read the same file after the external drive stops  spinning (sleeps), it does not start spinning but trying to read another  file makes it start spining. This makes me think about some -overdone-  caching problem, but don't know what causes it and how to turn it off  (Tuxero's caching is already disabled in the preferences, although I  think it is only for writing only).
I made some research and found nothing specific; they tell to  reinstall the os or format the drive -to HFS+ -. What is causing this?
Note: All of my drives are in Spotlight's exclusion (privacy) list and using another usb slot did not change a thing.
My EtreCheck is:
EtreCheck version: 1.9.11 (43) - report generated June 15, 2014
Hardware Information:
    MacBook Pro (13-inch, Mid 2009)
    MacBook Pro - model: MacBookPro5,5
    1 2.26 GHz Intel Core 2 Duo CPU: 2 cores
    4 GB RAM
Video Information:
    NVIDIA GeForce 9400M - VRAM: 256 MB
System Software:
    OS X 10.8.3 (12D78) - Uptime: 0 days 1:4:54
Disk Information:
    Hitachi HTS5450 disk0 : (160.04 GB)
        disk0s1 (disk0s1) <not mounted>: 209.7 MB
        Macintosh HD (disk0s2) / [Startup]: 94.62 GB (48.81 GB free)
        Recovery HD (disk0s3) <not mounted>: 650 MB
        BOOTCAMP (disk0s4) /Volumes/BOOTCAMP: 64.57 GB (44.49 GB free)
    HL-DT-ST DVDRW  GS23N 
USB Information:
    Apple Inc. Built-in iSight
    JMicron Storage 500.11 GB
        BKPFAT (disk1s1) /Volumes/BKPFAT: 443.2 GB (25.08 GB free)
        BKPNTFS (disk1s2) <not mounted>: 56.9 GB
    Apple Internal Memory Card Reader
    Apple Inc. Apple Internal Keyboard / Trackpad
    Apple Computer, Inc. IR Receiver
    Apple Inc. BRCM2046 Hub
        Apple Inc. Bluetooth USB Host Controller
Configuration files:
    /etc/hosts - Count: 1
Gatekeeper:
    Anywhere
Startup Items:
    TuxeraNTFSUnmountHelper: Path: /Library/StartupItems/TuxeraNTFSUnmountHelper
Launch Daemons:
    [loaded]    com.adobe.fpsaud.plist Support
    [loaded]    com.barebones.authd.plist Support
    [loaded]    com.barebones.textwrangler.plist Support
    [loaded]    com.google.keystone.daemon.plist Support
    [loaded]    com.oracle.java.Helper-Tool.plist Support
    [not loaded]    de.jinx.SmartSleepDaemon.plist Support
    [loaded]    org.macosforge.xquartz.privileged_startx.plist Support
Launch Agents:
    [loaded]    com.google.keystone.agent.plist Support
    [loaded]    com.oracle.java.Java-Updater.plist Support
    [loaded]    org.macosforge.xquartz.startx.plist Support
User Login Items:
    GrowlHelperApp
    Google Drive
    witchdaemon
    BetterTouchTool
Internet Plug-ins:
    JavaAppletPlugin: Version: Java 8 Update 05 Check version
    FlashPlayer-10.6: Version: 12.0.0.38 - SDK 10.6 Support
    QuickTime Plugin: Version: 7.7.1
    Flash Player: Version: 12.0.0.38 - SDK 10.6 Outdated! Update
    o1dbrowserplugin: Version: 5.4.2.18903 Support
    googletalkbrowserplugin: Version: 5.4.2.18903 Support
    Silverlight: Version: 5.1.30317.0 - SDK 10.6 Support
    Unity Web Player: Version: UnityPlayer version 4.1.5f1 Support
    iPhotoPhotocast: Version: 7.0
Safari Extensions:
    Bing Highlights: Version: 1.0.20
    ClickToFlash: Version: 2.5.1
Audio Plug-ins:
    AirPlay: Version: 1.7 - SDK 10.8
    iSightAudio: Version: 7.7.1 - SDK 10.8
iTunes Plug-ins:
    Quartz Composer Visualizer: Version: 1.4 - SDK 10.8
3rd Party Preference Panes:
    Flash Player  Support
    FUSE for OS X (OSXFUSE)  Support
    GamePadCompanionPrefPanel  Support
    Growl  Support
    Java  Support
    MenuMeters  Support
    SmartSleep  Support
    Tuxera NTFS  Support
    Witch  Support
Time Machine:
    Time Machine not configured!
Top Processes by CPU:
        25% firefox
         4% activitymonitord
         4% WindowServer
         1% hidd
         1% BetterTouchTool
Top Processes by Memory:
    254 MB  firefox
    111 MB  Google Chrome
    66 MB   Sublime Text
    61 MB   mds
    59 MB   Google Chrome Helper
Virtual Memory Information:
    1.72 GB Free RAM
    1.21 GB Active RAM
    416 MB  Inactive RAM
    425 MB  Wired RAM
    378 MB  Page-ins
    0 B Page-outs

Thread continues as an OSX discussion here, please do not reply this.

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