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Pharmacology OTD > MUSCLE SPASTICITY AND INFECTIOUS DISEASE > Flashcards

MUSCLE SPASTICITY AND INFECTIOUS DISEASE Flashcards

1
Q

Muscle Spasticity:

A

A velocity-dependent increased resistance to passive stretch
Pathophysiology is poorly understood, but end result:
· Over activity of the alpha motor neuron
· Results from a lesion along the path of the corticospinal tracts
(Motor pathways of cortex, basal ganglia, thalamus, cerebellum, brainstem, central white matter, and spinal cord)

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2
Q

Symptoms of Spasticity:

A

· Hypertonia
· Hyperreflexia
· Spasms or involuntary movements
· Clonus
· Pain
· Difficulties with ADLs
· Contractures
· Bone and Joint deformities

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3
Q

Disorders associated with spasticity:

A

· MS (multiple sclerosis)
· Stroke
· SCI (spinal cord injury)
· TBI (traumatic brain injury)
· CP (cerebral palsy)

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4
Q

Treatment of Spasticity:

A

· PT/OT
· Orthotics
· Aids
· Medication
· Surgery

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5
Q

4 approved medications to treat chronic spasticity:

A

· Diazepam
· Dantrolene
· Tizanidine
· Baclofen
Other options include:
· Gabapentin
· Botox

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6
Q

Medication related facts for treatment of spasticity:

A
  • Only a few options can reduce disability
  • Many adverse effects associated with medications to reduce spasticity
  • Start with lowest dose and gradually increase dose to optimal effect
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7
Q

Diazepam
(Benzodiazepine)

A
  • Intermediate to long-acting half-life of 20-80 hours
  • Acts on the GABA channels in spinal pathways
    Dose: 2mg twice daily or 5mg at bedtime
    · May titrate up to 40-60mg/day in 3-4 doses
    ADRs:
    · Drowsiness
    · Ataxia
    · Fatigue
    · Cognitive slowing
  • Should not be stopped abruptly
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8
Q

Dantrolene

A
  • Acts peripherally at skeletal muscle
  • Interferes with calcium influx at skeletal muscle to reduce excitation of muscle
  • Dose increased gradually every 7 days to desired effect
    Starting dose: 25mg once daily
    Titrate to 100mg three times a day (max 100mg four times a day)

ADRs: (·Generally early in treatment and develop tolerance)
- drowsiness
- dizziness
- generalized weakness
- MINIMAL COGNITIVE EFFECTS

-Withdrawal of treatment could result in exacerbation of symptoms

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9
Q

Tizanidine

A
  • Central acting alpha 2 receptor agonist
  • Peak effect: 1-2 hours after dosing
  • Absorption increased by 20% when taken with food
    Dose: 2mg once daily at bedtime; max 36mg per day in 2-4 divided doses
  • Gradually taper when discontinuing (Rebound symptoms: hypertension, tachycardia, hypertonia)

ADRs:
- Sedation
- weakness
- hypotension
· Sedation seen 30 min after administration and peaks in 1.5 hours
· Hypotension can be seen 1 hour after administration and peak in 2-3 hours

  • BETTER TOLERATED THAN BACLOFEN AND DIAZEPAM
  • Less likely to weaken muscles
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10
Q

Baclofen

A
  • Binds to a GABA receptor (GABA-B)
    · Reduces neurotransmitter release → reduces neuron firing
  • Available orally or Intrathecal Baclofen Pump (ITB)
    · Oral is dosed three times daily
    · Max 80 mg daily orally
    · Intrathecal dose is about 1% of oral dose
    Requires titration until optimal effect achieved
    · May be increased every 3 days

ADRs: (CNS effects)
- SEDATION, ataxia (loss of control of bodily movement), cardiac and respiratory depression
- Should NOT be stopped abruptly

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11
Q

Intrathecal Baclofen Pump (ITB)

A

Treats spasticity of spinal cord origin
· Used in patients who do not respond well to oral therapy or whose CNS effects are intolerable
· Must demonstrate positive response to ITB screening trial
- Pump is placed subcutaneously in abdominal wall, tip of the catheter in subarachnoid space usually between T12 and L1
- Onset of action peaks at 4 hours and lasts 4-8 hours
- If dose suddenly needs increased → kink or catheter/pump malfunction
- Reservoir usually refilled every 3 months (takes about 30-45 min)
- Battery usually lasts 4-5 years

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12
Q

Therapeutic Concerns with ITB

A

Problems with pump:
· Infection, dislodgement, kinking or blocking of catheter, and pump failure

Signs of overdose:
· Sedation, confusion, respiratory depression, coma

Signs of withdrawal:
· Spasticity, agitation, hallucinations, and death (rare)

Assess Balance as patient adjusts to new muscle tone

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13
Q

Botulinum Toxin

A
  • Neurotoxin produced by Clostridium botulinum, spore-forming anaerobic bacillus
  • Appears to affect only the presynaptic membrane of the neuromuscular junction in humans
  • Prevents calcium-dependent release of acetylcholine and produces a state of denervation
  • Muscle inactivation persists until new fibrils grow from the nerve and form junction plates on new areas of the muscle cell walls
  • Blocks the release of Acetylcholine from nerve terminals
  • Injections into affected muscles muscle weakness in area of injection – use caution if targeting therapy in injected area

ADRs:
* Swelling at the injection site: treat with cold compress and elastic wrap
* Weakness

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14
Q

Why do we use Botox (Botulinum Toxin)

A
  • Relax a muscle that is too tense (dystonic)
  • Contracting when it should be relaxed
  • Lower extremities
  • Relax calf muscle
  • Fit for brace
  • Upper extremities
  • Free up movements of arm
  • Improved function
  • Increase in independence and ADLs
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15
Q

Therapeutics Concerns with Botox

A
  • May have diminished function initially after injection
    (Weakness in antagonist muscles uncovered)
  • Ensure safety as patient adjusts to reduced muscle tone
  • Avoid therapy modalities over the injection site for at least 10 days
  • Patients may develop antibodies
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16
Q

Skeletal Muscle Relaxant

A

Cyclobenzaprine: used to treat spasms associated with musculoskeletal injury without interfering with muscle function (ineffective at treating spasms of CNS origin)

ADRs:
- drowsiness
- dizziness
- dry mouth

Indicated for short-term use of 2-3 weeks

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17
Q

Antimicrobials:
Bacterial Infections/Bacteria

A
  • Gram-positive, Gram-negative (commonly bacillus), or anaerobic (different stain effect)
  • Common misconception that antibiotics work on viral infection
    · They DO NOT kill viruses
  • Bacteria have a rigid cell walls – provides target for antibiotics
    (Antibiotic will have little effect on the host since human cells do not have rigid cell walls)
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18
Q

Antibiotics

A
  • Antibiotic Target bacteria NOT viruses
  • What they do:
    · Bacteriostatic → inhibit growth of bacteria but do not kill them – depend on our own immune system to kill them
    · Bactericidal→ kill the bacteria
    (Concentration dependent, Time dependent)
  • Type of antibiotic chosen depends on the organism you are trying to get rid of and the patient’s immune function
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19
Q

How to choose an antibiotic:

A

*Broad Spectrum vs. Narrow Spectrum
Choice based on organism you are treating
· Certain antibiotics work better on Gram-positive than Gram-negative
· Resources (Sanford’s Guide and Antibiograms) designed to guide antibiotic selection

*Patient factors:
· Allergies to antibiotics
· Liver and Kidney function of the patient
· Age of the patient (especially infant and young children)
· Pregnancy
· Site of the infection (brain/CSF harder to treat)

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20
Q

Bacterial Cell Wall Inhibitors:

A

Bactericidal, time-dependent killing
β-lactams
· Penicillins
· Cephalosporins
· Carbapenems
· Monobactams
Glycopeptides
Bacitracin

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21
Q

Bacterial Protein Synthesis Inhibitors

A

Protein synthesis takes place in the ribosome
· Bacterial ribosome is much different from mammalian ribosome, so this makes a good target

Aminoglycosides
· Nephrotoxic and ototoxic (kidneys and ears)
Macrolides
Tetracyclines
· Cause yellowing of teeth, bind to developing bones impairing growth
Streptogramins
Oxazolidinones
Glycylcyclines

22
Q

Inhibit Bacterial DNA Synthesis or Break DNA Strands

A

Fluroquinolones
· Inhibits DNA-gyrase required for replication, transcription, and repair of DNA
· Rare cases of tendon rupture

Nitroimidazoles (metronidazole)
· Interacts with bacterial DNA to cause of loss of helical structure and strand breakage
· Avoid with alcohol – causes severe reaction

Antifolates
· Interfere with the production of folate which is necessary to produce DNA
· Humans utilize folate from dietary sources
· Sulfonamides
· Very allergenic

23
Q

Major Antibiotics:

A

Penicillins
· Penicillin VK
· Amoxicillin
· Amoxicillin/Clavulanic acid
Cephalosporins
· Cephalexin
· Cefdinir
· Ceftriaxone
Macrolides
· Erythromycin
· Clarithromycin
· Azithromycin (Z-Pak)
Tetracyclines
· Tetracycline
· Doxycycline
· Minocycline
Fluoroquinolones
· Ciprofloxacin
· Levofloxacin
· Moxifloxacin
Metronidazole
Nitrofurantoin
Aminoglycosides
· Tobramycin
· Gentamicin
· Amikacin
Vancomycin
Linezolid
Daptomycin
Sulfamethoxazole/Trimethoprim

24
Q

Tuberculosis

A
  • Caused by Mycobacterium tuberculosis
  • Transmitted by airborne particles through coughs and sneezes
    Immunocompromised individuals most at risk
    Can be asymptomatic for years (latent TB)

Symptoms of active disease:
· Fever
· Night sweats
· Malaise
· Weight loss
Antimycobacterial Drugs:
· Isoniazid
· Rifampin
· Rifapentine
· Pyrazinamide
· Ethambutol
Non-compliance may lead to multi-drug resistant TB

25
Q

TB Medication: Adverse Effects

A

All TB Drugs
· Hepatotoxicity (liver)
· Dermatologic Reactions
· Drug Fever
Isoniazid
· Peripheral neuropathy
· Optic neuritis (rare)
Rifampin
· Thrombocytopenia
Ethambutol
· Optic neuritis

26
Q

C. diff
(Clostridium difficile)

A

· Gram-positive bacteria
· Produces inflammation of the colon; voluminous, infectious, and watery diarrhea
· Results in: dehydration, electrolyte depletion, and other complications (even death) can occur
· Typically occurs after a broad-spectrum antibiotic is given
· Normal gut bacteria is depleted, and C. diff growth occurs
· Health care workers who work with patients with C. diff – can spread person to person (hands, clothing, and stethoscopes)
· Can survive up to 5 months in environment

*Treatment is metronidazole or oral vancomycin

PREVENTION IS KEY: hand washing prevents the spread, not alcohol-based hand sanitizer
Must wash hands with actual soap and water (scrubbing)

26
Q

C. diff
(Clostridium difficile)

A

· Gram-positive bacteria
· Produces inflammation of the colon; voluminous, infectious, and watery diarrhea
· Results in: dehydration, electrolyte depletion, and other complications (even death) can occur
· Typically occurs after a broad-spectrum antibiotic is given
· Normal gut bacteria is depleted, and C. diff growth occurs
· Health care workers who work with patients with C. diff – can spread person to person (hands, clothing, and stethoscopes)
· Can survive up to 5 months in environment

*Treatment is metronidazole or oral vancomycin

PREVENTION IS KEY: hand washing prevents the spread, not alcohol-based hand sanitizer
Must wash hands with actual soap and water (scrubbing)

27
Q

MRSA
MRSA (methicillin-resistant Staphylococcus aureus)

A

· Staph is present on skin but can be a problem for elderly or immunocompromised (can cause a problem if given the opportunity
· Typical treatment of Staphylococcus aureus will not kill this (penicillin based)
· Hospitalized treatment of choice: Intravenous (IV) Vancomycin
· Alternative: Linezolid
· Outpatient treatment: Bactrim (TMP-SMZ), clindamycin, or doxycycline may work
· Hospitalized patients will remain in isolated rooms and contact precautions will be used
**isolation for both cases (C. diff and MRSA)

28
Q

Common Adverse Reactions of Antibiotics

A

Most common:
· GI effects
· Allergy
GI Effects:
· Nausea, diarrhea, vomiting, abdominal discomfort
· If it can be taken with food, take with food to minimize discomfort
· If yogurt is tolerated, it can help replace gut bacteria lost due to antibiotic
Allergy:
· Hives/difficulty breathing

29
Q

Overuse/Misuse of Antibiotics

A

Important for patients to take antibiotic exactly as prescribed
· Not to miss doses – bacteria can continue to grow during lapses in doses
· Some need to be taken with/without food or antacids
· Stopping the antibiotic early can allow bacteria to grow again can lead to resistance
Resistance is becoming more common due misuse/overuse of antibiotics
Overuse allows for drug resistant bacteria to grow as well and allows for greater chance of side effects

30
Q

Preventing Antibiotic Resistance and Spread of Infection
Preventing Antibiotic Resistance

A

· Appropriate prescribing – antibiotics may not be needed (viral infections)
· Choosing the right one – the more narrow the target the fewer chances of resistance
· Using proper medications to treat symptoms (cold and flu virus)

31
Q

Prevent the spread of infection

A

· Hand washing, especially before and after seeing patients
· Disinfecting equipment
Caution when treating patients who have serious infections (MRSA, C. diff, etc.)
· Use a mask, gloves, gown, etc. when necessary

32
Q

Therapeutic Concerns for Antibiotics

A

Most common adverse effects:
· GI problems and allergic reactions
Other adverse effects:
· Fluoroquinolones, sulfonamides, and tetracyclines all increase sensitivity to UV light → sunburn
· Nearly all antibiotics can cause C. diff
Take extreme caution when treating patients with the following:
· Metronidazole (reaction when mixed with alcohol can make patients very sick)
· Vancomycin
· Linezolid
· Quinupristin/Dalfopristin
· Patient has a resistant type of infection
· Use proper PPE (personal protective equipment) à gown, gloves, mask
Hand washing and disinfect any equipment used

33
Q

What is a Virus?

A
  • Viruses are one of the smallest classes of microorganisms
  • Can only replicate in the cells of their hosts
  • Replicate via RNA/DNA (gene transcription)
  • Enter the body via GI tract, respiratory tract, skin, mucous membranes, and can cross placenta
    **Very complex process
    · Extremely small parasites that consist of RNA and DNA in a protein shell or capsid.
    · DNA/RNA plus protein shell → nucleocapsid
    · For the most part they use the host’s enzymes to replicate
    · Whole structure of a virus (including lipoprotein envelope) → virion
34
Q

Common Viruses:

A

One of the most common viruses belongs to the Influenza Family
· Influenza A and B cause most human infections
· Influenza A viruses distinguished by a set of proteins (hemagglutinin – H and neuraminidase –N proteins)
· I.E.: H3N1, H1N1 (swine flu), H5N1 (avian flu)
· Mutations occur and cause new strains
- Why we have a NEW flu vaccine engineered every year – but it’s an educated guess

35
Q

Other Viruses:

A

· Respiratory Syncytial Virus (RSV)
· HIV
· HPV
· HSV-1 and HSV-2
· Chicken Pox
· Shingles
· Hepatitis A, B, and C,
· HIV

36
Q

How do Viruses Work?

A
  1. A virion reaches a host cell
  2. It attaches itself to the surface and prepares to deliver its capsid and enzymes
  3. The virion is extremely skilled at entering cell without detection
  4. Some receptors can be cytokines, neurotransmitters, hormones, ion channels, or membrane glycoproteins
  5. Many viruses depend on endocytosis to enter host cell
  6. After the virus penetrates the host cell and has shed the coat, the nucleic acids have to get to the nucleus
  7. Using the host’s supply of enzymes (polymerases), the DNA or RNA is replicated to create a new virion and then is released to go infect other host cells.
37
Q

How does our body fight viruses?

A

Innate immunity – skin, mucosal barriers, and the activation of:
· Leucocytes, Interferons (IFNs), and Natural Killer (NK) cells

Adaptive immunity – key cells are:
* Lymphocytes
- B Cells – produce antibodies
- T cells – inducing cell mediated immune reaction
- Cytotoxic T Cells

During the induction phase: the antigen is presented to the T lymphocytes and becomes activated. The T cell develops IL-2 receptors and produces IL-2 stimulates B cells to proliferate and mature into plasma cells that produce antibodies.

Antiviral antibodies are observed late in most infections and are thought to prevent cell to cell spreading

38
Q

Viral Infections are difficult to eradicate because:

A

· Replication of the virus typically reaches its peak BEFORE symptoms appear
· Antivirals are VIRUSTATIC (rely on body’s immune system to finish the job)
- A diseased host immune system prolonged and more serious illness
· Some viruses can retreat into areas where they are protected from immune system or escape detection of immune system
- Shingles (Chicken Pox virus that re-activates at a later time)
· Viruses can easily mutate into something that the body does not have defenses built up for

39
Q

Prevention of Viral Infections:

A

Vaccines are key:
· MMR (Measles, Mumps, Rubella)
· Tdap (Tetanus, diphtheria, pertussis)
· Polio
· Pneumococcal
· Influenza
· Rotavirus
· Meningococcal
· Shingles
· HPV
· Hepatitis A and B
· Hemophilus Influenza B (Hib)
· Varicella (Chicken Pox)

40
Q

What are vaccines?

A

Weakened or inactivated viruses given to help boost immunity
· Still possess specific antigenic sites

They don’t harm host but prepare body for future exposure

Beneficial when given BEFORE exposure

Limited side effects (occasional more serious ones)

41
Q

What is the flu?

A

The flu is caused by a virus, either Influenza A or B – a respiratory flu
· Fever, chills, cough, aches, can turn into pneumonia
· NOT the “stomach flu”
· Young, elderly and those with comorbid conditions → most at risk of complications

Treatment:
Only helps to shorten the duration of the illness and to prevent further shedding of the virus
· Oseltamivir (Tamiflu) – prophylaxis or treatment
· Zanamivir - prophylaxis or treatment

42
Q

Human Immunodeficiency Virus (HIV)

A

Retrovirus that targets the immune system, specifically CD4+ T Lymphocytes
Compromises ability to prevent infection or certain types of cancer
Drugs the reduce the viral load, can allow the immune system a chance to recover function
HAART – Highly active antiretroviral therapy
Combination treatment required
· Previously high pill burden (up to 18 pills/day)
· Now many once daily fixed combinations
Standard is at least a 3-drug regimen to minimize drug resistance

43
Q

HIV Treatment
Five types of antiretrovirals for HIV:

A

Nucleoside reverse transcriptase inhibitors
· Zidovudine, emtricitabine, lamivudine, tenofovir, didanosine, stavudine

Non-Nucleoside reverse transcriptase inhibitors
· Etravirine, nevirapine, delavirdine, efavirenz

Protease inhibitors
· Saquinavir, tipranavir, ritonavir, darunavir, indinavir, nelfinavir, amprenavir

Fusion inhibitors
· Enfuvirtide, maraviroc

Integrase inhibitors
· Raltegravir

44
Q

Therapeutic Concerns for HAART(Highly active antiretroviral therapy)

A

Medications may cause peripheral neuropathy and neurogenic pain leading to functional limitations and need for therapy
Metabolic effects from medications:
· Lipodystrophy (truncal obesity)
· Hyperlipidemia
· Hyperglycemia
· Insulin resistance
Cardiovascular risk recommend exercise and monitoring of vitals

45
Q

Hepatitis C

A

Blood borne transmission
85% infected develop chronic infection
Chronic infection leads to liver cirrhosis and hepatocellular cancer
Symptoms typically present 7-8 weeks after infection

Prior to 2014, treatment with:
· Interferon alpha + ribavirin
- High relapse rate

ADRs:
flu-like symptoms, depression, anemia

Now many oral options with much improved cure rates

46
Q

Hepatitis C Treatments

A

Treatment depends on genotype
Typically treated for 8-24 weeks
· Elbasvir and grazoprevir (Zepatier)
· Glecaprevir and pibrentasvir (Mavyret)
· Ledipasvir and sofosbuvir (Harvoni)
· Simeprevir (Olysio) and sofosbuvir (Sovaldi)
· Sofosbuvir and velpatasvir (Epclusa)
· Sofosbuvir, velpatasvir, and voxilaprevir (Vosevi)

47
Q

Hepatitis C Treatments

A

Treatment depends on genotype
Typically treated for 8-24 weeks
· Elbasvir and grazoprevir (Zepatier)
· Glecaprevir and pibrentasvir (Mavyret)
· Ledipasvir and sofosbuvir (Harvoni)
· Simeprevir (Olysio) and sofosbuvir (Sovaldi)
· Sofosbuvir and velpatasvir (Epclusa)
· Sofosbuvir, velpatasvir, and voxilaprevir (Vosevi)

48
Q

Therapeutic Concerns with Antivirals:

A

Most patients on routine antivirals may have serious illness (immunocompromised)
· Fatigue and malaise may be common
Take appropriate precautions when handling patients on antivirals
· Hand washing
· Gloves
· Disinfecting surfaces
Help prevent the spread of viruses to your patients
**Best way to prevent the flu → get vaccinated

49
Q

Fungal Infections:

A

Most fungi affect plants and do not cause serious harm in humans
· More serious infections can occur in those with weakened immune system or those that have had recent broad-spectrum antibiotics that allow for fungi growth
Minor infections common in humans:
· Athlete’s foot
· Vaginal yeast infection
Serious fungal infections occur in the immunocompromised (HIV) or by medications or chemotherapy that cause immunosuppression

50
Q

Antifungals

A

Amphotericin B
· Broad spectrum, considered drug of choice for systemic fungal infections

Antifungal Azoles:
· Miconazole
· Clotrimazole
· Fluconazole
· Itraconazole
· Ketoconazole

51
Q

Therapeutic Concerns for Antifungals

A

Length of treatment
· Many antifungals must be taken for weeks up to months depending on type of infection and/or immune system
· May need continued motivation

Pharmacology OTD (5 decks)

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