Quiz 3 Flashcards
Pain Transduction (Phase 1)
- Begins when nociceptor nerve endings in the peripheral nervous system are stimulated
- Local tissue injury causes the release of chemical mediators of inflammation, including prostaglandins, leukotrienes, histamine, bradykin and substance P
- Substances sensitize peripheral nociceptors making them easy to activate
Pain Transmission (Phase 2)
Nerve impulse signalling pain travel from the nociceptor to the spinal cord along 2 sensory neurons:
- A-delta fibres = transmit SHARP pain
- C-fibres = transmit DULL ache (unmyelinated and slow)
- Nerve block involves the injection of alcohol or other neurotoxic substances into neurons for irreversible blockage of impulse transmissions along nerves
GLUTAMATE IS THE MAIN EXCITATORY NEUROTRANSMITTER**
Pain Perception (Phase 3)
Perception = conscious experience of pain, occurs in the brain
- Numerous cortical structures and pathways are involved, including the reticular activating system, somatosensory system and limbic system
- Brain maps it out and says that you are feeling pain and tells where the pain is
Pain Modulation (Phase 4)
- Modulation involves descending nervous impulses travelling down the spinal cord that inhibit afferent pain transmission
- Neurotransmitters (eg serotonin, norepinephrine, endogenous opioids) inhibit pain transmission
- GABA inhibits
PQRST Pain Assessment
Provocation = Relieving/aggravating factors
Quality = What’s it feel like?
Region = Where?
Severity = How intense?
Timing = When does it hurt?
Pain Management (NON-PHARMACOLOGICAL)
COGNITIVE-BEHAVIORAL INTERVENTIONS:
Typically more effective if taught before pain is present
- Relaxation (eg slow rhythmic breathing)
- Distraction (activities requiring concentration like counting)
- Imagery (developing a mental picture)
- Meditation
PHYSICAL AGENTS:
Heat = stimulates thermoreceptors in the skin, interfering w/ pain signal transmission to the brain, reducing the perception of pain
- Increases local blood flow helping to deliver more O2 and nutrients to injured tissues promoting healing and reduces inflammation
- Relaxes muscle tension, decreasing mechanical pressure on nociceptors
Cold = Numbs the area, slowing down nerve signal transmission which reduces pain perception
- Constricts blood vessels which helps reduce inflammation and swelling limiting further irritation of pain receptors
- No more than 10-20min at a time
Pain Management (PHARMACOLOGICAL TREATMENT)
At CNS Level:
- Non-opioid centrally acting agents (Eg Acetaminophen)
**NO Anti-inflammatory properties
- Opioids = From ‘opium’, Narcotics
At Peripheral Level:
- Non-steroidal anti-inflammatory drugs (NSAIDS)
**High efficacy if inflammation also present
Opioid Analgesics (Narcotics)
Narcotics = morphine-like drugs that produce analgesia and CNS depression
-Opioids DO NOT lower the threshold for pain at nociceptor level or slow/block the transmission of the pain impulse
-Opioids DO influence perception and emotional response to pain
2 Main Opioids Involved in Pain Management
Mu:
- produce analgesia, euphoria, RESPIRATORY DEPRESSION** (slow down breathing), physical dependence, sedation and GI MOTILITY** (slow down)
Kappa:
- Primarily associated w/ analgesia, sedation, MIOSIS and GI Motility
BOTH include = euphoria, Res Depression, Physical dependence, miosis
OPIOIDS = SLOW DOWN**
Opioid Agonists
Bind receptors and inhibit release of substance P (& Glutamate)
FULL AGONIST:
- Fully activate the mu and/or kappa receptors, leading to maximum effects (eg pain relief, euphoria etc)
Eg) Morphine, Fentanyl, Hydromorph, Oxy, Hydrocodone, Methadone
PARTIAL AGONIST:
- Have a ceiling so you can still give pain relief but it doesn’t feed addiction
- Partially activate the mu receptor and have a weaker effect even at higher doses
- May act as antagonists at other receptors (kappa)
Eg) Buprenorphine (partial mu agonist and kappa antagonist) produces less euphoria
ANTAGONIST:
- Block the effects of other opioids by binding to mu and/or kappa receptors without activating them
- Used to reverse opioid overdose or prevent opioid effects
Eg) Naloxone acts on all opioid receptors
Narcan only lasts 1-2hrs in blood stream so always continue monitoring because it can reactivate after the 2hrs. Multiple doses may be required***
Besides Analgesic Effects, Opiates Also…
- Cause sedation
- Suppress cough reflex
- Slow GI motility/emptying (useful in diarrhea)
- Cause Euphoria and intense relaxation
Can cause immunosuppression w/ long-term use (decrease in pro-inflammatory cytokines, suppression of macrophages activity, T-cells dysfunction etc) - Cause histamine release by stimulating mast cells (Lead to itching, rashes, low BP AND Morphine is the opioid most likely to cause this**)
Key Facts for Opioids
- Morphine crosses placenta and Breast Milk
- Hydromorphone (dilaudid) is prepared from morphine BUT is 5X MORE POTENT
- Routes of Opioid Administration = PO, SL, IM, IV, SC, Inhalation, Transdermal, Rectal, Epidural
Combination Opioids
- Can be combined w/ acetaminophen to enhance pain-relief and reduce the amount of opioid needed for effective pain management
- Minimizes adverse effects assoc, w/ higher opioid doses (Eg constipation, sedation, Res Depression)
Eg)
Percocet = Oxy + Acetaminophen (Ace.)
Vicodin = Hydrocodone + Ace.
Tramacet = Tramadol + Ace.
Tylenol 3 = Ace. + Codeine + caffeine
Opioid Adverse Effects
CNS Depression:
- Sedation
- Decreased RR, HR & BP
- Pupillary constriction
Nausea
Pruritus
Constipation
Urinary Retention
Euphoria
**If RR is less than 12 = HOLD OPIOIDS
Check for allergies (don’t give if asthmatic*)
Caution w/ Pregnancy
Opioids: Nursing Assessments
Vitals = RR, BP etc
CNS = dizziness, decreased LOC, seizures
Orthostatic hypotension (Check BP 3x - laying, sitting and standing)
Itching = histamine release (need antihistamine)
Nausea & Vomiting = may need anti-emetics
Constipation = consider laxatives
Urinary Retention = Assess Ins/Out if on high or frequency dosing (what are they drinking and whats coming out)
should be peeing 30ml/hr
Opioid Overdose & Dependence
Toxicity resulting from overly aggressive pain therapy or substance abuse
Symptoms:
- Res Depression (EMERGENCY), pinpoint pupils (miosis), unconsciousness, low BP
Treatment = Naloxone (Narcan)
- Opioid receptor antagonist
- Administered when RR < 12
- Onset 2-4min
- Duration 30-120min
-Constant monitoring is required
- More than 1 dose may be needed (0.4-2mg IV/IM/SC/Intranasal Q2-3min. max 10mg)
Effects = Opposite effects of opioids (may cause agitation)
Physical Dependence of Opioids
Physiological adaptation to the drug, requiring continued use to function or avoid withdrawal
Physical Dependence and Addiction are DIFFERENT
Addiction
Chronic condition characterized by a strong, compulsive need to use opioid drugs DESPITE HARMFUL CONSEQUENCES
adjusting lifestyle
Characteristics:
- Cravings, Compulsive use, continued use despite negative consequences
Compulsive use + tolerance + dependence (physical & psych) + loss of control + change in lifestyle etc
Withdrawal
- Experienced when opioid use is reduced or stopped in dependent users
- Typically occurs 6-72hrs after last use (can last 1-2 weeks)
Physical Discomfort = aches and pain, chills, muscle spasms, sweating, diarrhea, nausea and vomiting, insomnia
Psychological Distress = anxiety, irritability, intense cravings
Autonomic Symptoms = increased HR, elevated BP and dilated pupils
**use “COWS” aka Clinical Opiate Withdrawal Scale every hour to monitor
Treating Dependence, Addiction and Withdrawal
METHADONE:
- No intense euphoria
- Effects plateau at higher doses (reducing risk of misuse & OD)
- Activates mu receptors like other opioids BUT more slowly and steadily for longer-lasting effect
- LONG HALF-LIFE helps prevent withdrawal symptoms by stabilizing cravings
- DOES NOT cure dependence b/c pt must keep taking the medication to avoid withdrawal
SUBOXONE (BUPRENORPHINE + NALOXONE):
Buprenorphine = (partial opioid agonist) helps reduce cravings and manage withdrawal symptoms by partially activating the opioid receptors, easing the transition for people
Naloxone = blocks effects of opioids and can trigger precipitated withdrawal (unpleasant feeling discourages abuse)
Naltreoxone in alcohol and opioid withdrawal (if you take this and then take drugs or alcohol, instead of feeling the high, you feel terrible)
Patient-Controlled Analgesic (PCA)
-Self-administration
-Allows pt to participate in care
-Frequent, small doses of analgesia gives more consistent serum drug level than larger doses 3-4x a day
Non-Opioid Analgesics - NSAIDS
-Modulate pain from effect at peripheral site
- Inhibit cyclooxyrgenase = inhibiting prostaglandin production = analgesic, anti-inflammatory, anti-pyretic and anti-platelet effects
COX 1 Enzyme:
- Continuous produced by the body at baseline
- Maintain protection of gastric mucosa, renal perfusion, stimulate platelet aggregation
COX 2 Enzyme:
- Induced by tissue damage
- Responsible for inflammation, nociception, fever, inhibits platelet aggregation
Non-Opioid Medications
COX 1 INHIBITION:
Salicylate (aspirin) inhibits COX 1&2 (but 1 inhibition > 2)
- Side Effects = peptic ulcer, acid reflux, nephrotoxicity/renal failure, bleeding
COX 1 & 2 INHIBITION:
Ibuprofen, Naproxen, Ketorolac, Diclofenac, Indomethacin
- Little or no anti-platelet effects
COX 2 INHIBITION:
Celecoxib
- Effective for inflammation, pain, fever reduction
- Side Effects = increased risk for clotting (and cardiovascular events)
Nursing Considerations for Non-Opioid Analgesics
- Gastric upset is common = DO NOT TAKE ON EMPTY STOMACH
- NSAIDS may cause or worsen peptic ulcers or GI bleed (contraindicated in pts w/ peptic ulcers or GI bleed)
(Symptoms of GI Bleed = Bloody/coffee-ground emesis, black/tarry stool, abdominal cramps)
-Monitor Kidney Function: Creatinine (40-120umol/L) & Blood Urea Nitrogen (BUN) 3.0-9.0mmol/L
- Monitor Urine output
- Antacids may interfere w/ absorption (NSAIDS = weak acids = need acidic environment to dissolve aka don’t take with milk)
- Avoid or use NSAIDS cautiously in asthma pts (shift of arachidonic acid pathway towards leukotrienes which increase bronchoconstriction)
DO NOT TAKE 2 NSAIDS AT THE SAME TIME
- No ASA in kids** especially from viral infection (use tylenol NOT ibuprofen or aspirin)
ASA may cause Tinnitus
Acetaminophen
- Primarily inhibits COX-2 activity in CNS
- Reduces production of prostaglandins
- UNLIKE NSAIDS, has minimal peripheral COX-1 and COX-2 inhibition = has analgesic and anti-pyretic effects but NO ANTI-INFLAMMATORY properties
- Reduced risk of GI and platelet-related side effects
- Can cause hepatotoxicity at high doses
(<4g/day, monitor liver lab results, Avoid ETOH)
Antidote for OD = Acetylcysteine
DO NOT TAKE TYLENOL FOR A HANGOVER, USE IBUPROFEN**
Tension Headache
Occurs when muscles of the head and neck become very tight due to stress, causing steady and lingering pain
- Mild to moderate pain which can be utilized in one area of the head and generalized
- Can be effectively treated w/ OTC non-opioid analgesia
Migraine
- Headache w/ severe, recurrent pain
- Characterized by throbbing or pulsating pain on one side (but can be both sides)
- Often accompanied by nausea, vomiting, and sensitivity to light and sound
- May or may not be preceded by Aura
Aura = sensory cue that tells one a migraine is coming (eg flashing lights, special smell, taste etc)
Acute Migraine Treatment = OTC Non-opioid = Triptans (eg. Sumatriptan) which cause vasoconstriction (serotonin agonists)
Migraine Prophylaxis = Beta-Blockers (eg. Propranolol), Anti-epileptics, anti-depressants etc
Core Body Temp
Reflection of the balance between heat gain and heat loss by the body (36.0-37.5 degree C)
- Metabolic processes speed up or slow down depending on body temp
ACTUAL Core Temp
Rectal = most accurate
Esophagus
Pulmonary Artery
Urinary Cath
ESTIMATES of Core Temp
Oral = (0.2 lower than core)
Temporal
Axillary
Tympanic
Thermoregulation
Hypothalamus is the thermal control centre for the body
Receives info from the peripheral and central thermoreceptors, in the skin and other organs, and compares info w/ its temp set point (37 = ideal core temp)
- When temp falls under set point, hypothalamus signals for heat conservation (vasoconstriction and shivering = increase core temp)
- When core temp is higher than set point, hypothalamus signals for heat dissipation = vasodilation and sweating decreasing core temp
2 Adaptations of Temperature
Heat Production
Heat Loss
Heat Production
VASOCONSTRICTION = confines blood to inner core of body
SHIVERING = increases heat production by the muscles
PILOERECTIONS = contraction of pilomotor muscles of the skin raises skin hairs (goosebumps), reducing heat loss surface
INCREASED EPINEPHRINE PRODUCTION = shift body metabolism to heat production instead of energy production (might explain weakness/fatigue in fever)
INCREASE IN THYROID HORMONE = long-term mechanism to increase metabolism and heat production
Heat Loss
Most of the body’s heat losses occur at the skin surface as heat from the blood moves through the skin, then into the surrounding environment
VASODILATION = delivers blood to the periphery where heat is dissipated through radiation, conduction and convection
SWEATING = increases heat loss through evaporation (evaporation uses body heat to convert water on the skin to water vapor in cooling)
2 Types of Increased Body Temp
Fever
Hyperthermia
Fever aka Pyrexia
Change in Set point
Results from a cytokine induced increase in the temp set point in hypothalamus
- Phagocytotic cells digest bacteria, release cytokines (these induce prostaglandin production)
PGE-2 binds to receptors in the hypothalamus to induce increases in the thermostatic set point
Clinical manifestation:
Prodromal period = fatigue, malaise, aches & pains
Chills = result from body temp trying to catch up to the new set point. Causes shivering to generate heat and raise temp
Flush = vasodilation causing skin to become warm & flushed
Defervescence = reduction in temp, marked by sweating
TREATMENT:
-Increasing heat transfer from internal to external environment Eg) sponge bath w/ cool water, cold cloth
- Supporting hypermetabolic state that accompanies fever = adequate fluids and sufficient amount of simple carbs
- Protections of vulnerable organs & systems = treatment w/ anti-pyretic (re-set set point by blocking PGE-2 production)
- Treatment of original causes of fever (eg. infection)
Rigors
More intense chills that cause the muscles to shake uncontrollably when the body’s temp rises rapidly to a new set point (eg during a serious infection)
Hyperthermia
Increase in body temp WITHOUT A CHANGE IN HYPOTHALAMIC SET POINT
- Thermoregulatory centre struggles to control temp
- Related to overproduction of heat, excessive environmental heat or impaired heat dissipation
3 Types of Hyperthermia
Heat Exhaustion
Heat Stroke
Malignant Hyperthermia
Heat Exhaustion
-Related to loss of salt and water after prolonged exertion in hot environment
- Temp >37.8 >40, tachy, thirst, fatigue, nausea, oliguria (low urine output), delirium
Heat Stroke
Core Temp >40
Severe, life-threatening**
Symptoms:
- Hot & dry skin
- Tachy
- Hyperventilation
- Weakness
- Delirium
- Blurred vision
- Convulsions
- Collapse
- Coma
Malignant Hyperthermia
- A genetic disorder where heat is generated from uncontrolled skeletal muscle contraction, resulting in severe and potentially fatal hyperthermia
- Typically triggered by GA agents and muscle relaxant used in surgery
- Mechanism r/t abnormally high release of calcium
- Treated w/ Dantrolene (muscle relaxant that blocks calcium release)
Hypothermia
Occurs when the body temp drops below 35 degrees, impairing normal physiological function
- Typically due to exposure to cold environments or immersion in cold water
Considerations:
- Malnutrition decreases fuel available for heat generation
- Loss of body fat decreases tissue insulation
- Alcohol and sedative drugs dull mental awareness to cold temps
- Certain diseases predispose pts to hypothermia (Eg diabetes, hypothyroidism, spinal cord injury)
Therapeutic Hypothermia
AKA induced or controlled hypothermia
- Medical treatment in which a pts body temp is deliberately lowered to around 32-34 degrees to help protect the brain and other organs after a cardiac arrest or severe brain injury
- Uses cooling blankets, ice packs, or circulation of cool fluids
- Slows down body’s metabolism, reducing demand for O2
3 Types of Hypothermia
Mild
Moderate
Severe
Mild Hypothermia
32-35 degrees
-Shivering
- Cold, pale skin
- Slurred speech or mild confusion
- Numbness in extremities
- Increased HR and RR
Moderate Hypothermia
28-32 degrees
- Shivering may stop
- Stumbling or difficulty walking
- Inability to think clearly or respond to questions
- Drowsiness or lethargy
- Slower HR, weak pulse
- Reduced or absent urine output
Severe Hypothermia
<28 degrees
- No shivering (body can’t produce heat anymore)
- Loss of consciousness
- Very slow, irregular or absent pulse
- Slow, irregular breath or apnea
- Fixed dilated pupils
- Risk of cardiac arrhythmias
Rewarming Shock
Rapid rewarming can cause hypotension, arrhythmias or cardiovascular collapse
gradual rewarming is crucial
Somatosensory Function
Designed to provide the CNS w/ info on: Touch, temp, body position and pain
3 Order Neurons of Somatosensory
1st Order Neuron:
- Transmit sensory info from PERIPHERY to CNS
2nd Order Neuron:
- Communicate w/ reflex networks and sensory pathways in the SPINAL CORD and transmit to THALAMUS
3rd Order Neuron:
- Relay info from THALAMUS to CEREBRAL CORTEX
Levels of Somatosensory System
Sensory Units
Ascending Pathways
Central Processing Unit
Sensory Units
Made up of sensory receptors and the neurons that carry signals from those receptors
3 Types of Nerve Fibres
Type A: FAST
- Myelinated = helps send messages quickly
- Carry info about SHARP PAIN, touch and pressure
- Help us react quickly to things like touching something hot (triggers reflexes)
Type B : REGULAR SPEED
-Myelinated
- Transmit signals related to sensations from internal organs and autonomic functions (like HR)
Type C: SLOW
- Unmyelinated
- Carry dull, aching, burning pain and sensations like warmth
- Responsible for longer-lasting, more diffuse pain after the initial sharp pain
Dorsal Root Ganglion (DRG)
Cluster of nerve cell bodies located near the dorsal (back) of spinal cord containing the cell bodies of sensory neurons
- When you feel something, the sensory nerve endings in the skin send that signal to the DRG, where the axon continues into the spinal cord to connect w/ second-order neurons
Ascending Pathways
Neural pathways that carry sensory information from the spinal cord up to the brain
- 2 Pathways
Discriminative Pathway
Anterolateral pathway
Both pathways work together to provide a complete picture of sensory experiences
Eg) if you touch something hot, the discriminative pathway helps you identify the exact spot and texture. The anterolateral pathway alerts you to the pain and temp
Discriminative Pathway
Helps you detect where and what kind of sensation is felt
- responsible for transmitting detail sensation (eg fine touch, 2-point discrimination, pressure, vibration and proprioception (aware of body position)
- Signals travel from the sensory receptors in skin though 1st order neurons to the spinal cord and then up to the brain without crossing over until they reach the brainstem
Anterolateral Pathways
Mainly carry info about pain, temp and crude (less precise) touch.
- Signals CROSS over the opposite side and thenascend to the brain
Decussation
Neuron crossover
- Helps in coordinating complex movement allowing for smoother and more integrated actions between both sides of the body
- Also affects how info is processed
Eg) Signals crossing over at brainstem (discriminative) allow brain to pinpoint locations and signal crossing over spinal cord (antero.) enable quicker response
Central Processing Unit
Specific areas of the brain that process and interpret sensory information coming from the ascending pathway
- Thalamus and somatosensory cortex
- Helps recognize what is being felt and where it’s coming from
- Afferent pathway relays sensory info from PNS to CNS
- Sensory impulse must be strong enough to reach threshold and general action potential
NO MESSAGE SENT IF STIMULI NOT STRONG ENOUGH
Mechanoreceptors
Detect changes in environment caused by mechanical forces (Eg pressure on the skin, stretching muscles and feelings vibrations)
Tactile Receptors:
- Found in skin
- Help us feel light touch, pressure and texture
- Free nerve endings, Meissner corpuscles, Merkel disks, Pacinian corpuscles, hair follicles and Ruffini end organs
Proprioceptors:
- Located in muscles and joints
- Sense body position and movement
Baroreceptors:
- Found in blood vessels
- Detect changes in BP
Thermoreceptors
Detect changes in temp
- Respond rapidly to sudden changes in temp and then adapt to over the next few min although they do not adapt completely
Nociceptors
Free nerve endings that are activated in response to actual or impending tissue injury
- Respond to mechanical, thermal and chemical stimuli
Mechanical:
- Intense pressure applied to skin from extreme stretch or contraction of muscles
Thermal:
- Extreme hot or cold
Chemical:
- Tissue trauma, ischemia, and inflammation that cause release of chemical mediators from injured or inflamed tissue
- Bradykinin, Histamine, serotonin, and potassium activate and also sensitize nociceptors
Prostaglandins sensitizes nociceptors by lowering mechanical and thermal activation thresholds in nociceptive nerve endings thus reducing stimulus intensity required to elicit action potential
PNS to CNS Nociceptor
A or C fibres (1st order) of the PNS contracts 2nd order pain-transmission neurons (interneuron) in the spinal cord
- 2nd order neurons ascend the spinal cord to the thalamus (relay centre)
- 2nd order neurons synapse w/ 3rd order neurons leading to the somatosensory cortex where perception and localization of pain takes place = awareness
Sensory Homunculus
Body part map in cortx
3 Pain Mediators
Chemical neurotransmitters released from nociceptive neurons
Glutamate = main excitatory neurotransmitter for pain (binds NMDA receptor)
Substance P = elicit slow, excitatory action potentials. Prolongs and enhances the action of glutamate (mostly C-fibres)
Endorphins = Inhibitory neurotransmitters aka “neuromodulators”
2 Pain Pathways
Neospinothalamic Tract:
- FAST-conducting fibres (sharp, fast pain) transmit info to thalamus which relays to somatosensory area to provide precise location of pain
Paleospinothalamic Tract:
- SLOW-conducting fibres terminate in several thalamic regions including parts that project to the limbic system
- Assoc. w/ emotional motivational aspects of pain
- Projects into the reticular nuclei, contributing to alertness which indirectly influences hypothalamus to increase BP, HR etc
Flexor Reflex
AKA Withdrawal Reflex
No cerebral control
-Activation of sensory neuron (afferent) = interneuron = automatic activation of motor neuron (efferent) = response by the effector
Pain Gate Control Theory
Postulates the presence of neural gating mechanisms at the segmental spinal cord level to account for interaction between pain and other sensory modalities
- Nociceptors inhibit inhibitory neurons but when other receptors are activated they block this
- Simultaneous firing of large diameter touch fibres (A-beta) can block transmission of impulses from small diameter myelinated and unmyelinated pain fibres
- Pain intensity can be reduced during active tactile stimulation
Endogenous Analgesic Mechanism - Efferent
Endogenous Opioid Peptides - Inhibitory neurotransmitters aka Neuromodulators: endorphins, enkephalins, dynorphins
Act on mu, delta and kappa receptors
Release from hypothalamus, limbic, reticular formation
DESCENDING pathway
Inhibit Substance P
Induced secretion of Serotonin and Norepinephrine
Virulence
Disease-producing potential of a microorganism
High Virulence = causes diseases even when present in small numbers
Main Types of Pathogens
Bacteria
Fungi
Virus
Parasites
Prions
Standard Precautions for Infection
Precautions with pts at all times to protect us and the pt
Hand Hygiene**
Contact Precautions
Transmitted from direct or indirect contact from pt or their environment
Medication resistant diseases (MRSA, C. diff)
PPE: Gloves, Gown, and standard
Droplet Precautions
Transmitted by talking, sneezing, coughing etc
- Can travel 3-6ft from the source before falling to the ground due to gravity
Eg) flu, pneumonia, Pertussis
PPE: Simple mask, eye protection, and standard precautions
Airborne Precautions
Transmitted by cough, sneezes etc
- Pathogens can remain suspended in the air and travel far
Eg) Varicella, Shingles, Measles, Tuberculosis
PPE: N95, goggles, standard precautions. Negative pressureroom
Invasiveness
- Ability of a pathogen to grow extremely rapidly and damage surrounding tissues
- Might take a week or more to mount an immune response against the organism, so this exponential growth can rapidly overwhelm body defenses and disrupt cellular function
Toxicity
Pathogens production of toxins
Exotoxin = proteins released by bacteria into surrounding tissues, that inactivate or kill host cells
Eg) Staphylococcus aureus produces a toxin that leads to food poisoning
Endotoxin = harmful non-protein chemicals released from the cell wall of GRAM NEGATIVE bacteria, elicit immune response
- Released when the bacteria dies, causing macrophages to release cytokines
- Initial dose of antibiotic may worsen symptoms by lysing bacteria and releasing larger amounts of endotoxins
Ability to Invade Host Defense
Capsules can prevent phagocytosis
- Antigenic shift of drift to avoid detections by immune system
- Inducing endocytosis to hide certain bacteria in host cells
Resistance to Anti-infective Medications
Pathogens can modify drug target site
- Pathogens can modify uptake of a drug by altering its capsule, cell wall membrane
- Pathogen can directly inactivate the drug
Bacteria
- Single-celled organisms that lack a nucleus
Classification of Bacteria
Shape:
- Bacilli = rod shape
- Cocci = spherical
- Spirilla = spiral
Organization:
- Di = pairs
- Strep = chains
- Staphy = clusters
Oxygen:
Aerobic
Anaerobic
Gram Positive:
- Contain thick cell wall made of peptidoclycan (helps retain VIOLET colour after staining)
Eg) Staphylococcus, streptococcus, enterococcus
Gram Negative:
- Have thinner cell walls causing them to lose gram stain
Eg) Escherichia, Klebsiella, Pseudomonas, Salmonella
Anti-Infectives
Drug that is effective against pathogens
Bactericidal = kills bacteria
Bacteriostatic = Prevents growth and reproduction
Anti-Infectives Classification
Susceptible Organsim = antibiotic, antiviral, anti-fungal, antiprotozoal
Chemical Structure of the Drug = group of drugs w/ similar properties and adverse effects
Eg) aminoglycosides, sulfonamides
Mechanism of Action = Inhibition of cell wall synthesis vs disruption of plasma membrane etc
Mechanisms of Anti-bacterial Agents
1) Inhibition of Cell Wall Synthesis:
- All bacteria have cell walls, so some antibiotics bind to specific proteins (penicilin-binding protein- PBP) that are essential to building that wall
Eg) Beta-lactam antibiotics inhibit cell wall synthesis and tend to be bactericidal
2) Inhibitions of protein Synthesis:
- Some antibiotics impede the synthesis of proteins at the ribosome (bacteriostatic)
3) Disruption of the Plasma Cell Membrane:
- Anti-bacterial and anti-fungal medications interfere w/ pathogens plasma membrane, affecting permeability
4) Inhibition of Nucleic Acid Synthesis:
- Antibiotics can disrupt the synthesis of DNA/RNA and bacterial cell division
5) Inhibition of Metabolic Pathways:
- Bacteria often need a steady supply of nutrients and metabolites as they divide very rapidly
- Some drugs are made to structurally resemble these building blocks so they can “fool” the cell into using them for growth
- When used, these drugs block growth and synthesis
Examples of Mechanism of Antibacterial Agents
1) RNA Synthesis inhibitors:
- Rifampin
2) Protein Synthesis inhibitors
- Aminoglycosides
- Ketolides
- Macroslides
- Streptogamins
- Tatracyclines
3) Anti-metabolites:
- Sulfonamides
4) DNA Synthesis Inhibitors:
- Fluoroquinolones
5) Cell wall synthesis Inhibitors:
- Carbapenems
- Cephalosporins
- Ioniazid
- Penicilins
- Vanco
Acquired Resistance
Ability of organism to become unresponsive to the effects of an anti-infective over time
Resistance is a major clinical problem, worsened by improper use of anti-infectives:
-Mechanisms = pathogen destroys drug, pathogen prevents drug entry or pumps drug out of itself, pathogen alters target site of drug or undergoes mutation or adapts to drug
Bacteria can change physiology to become resistant by:
- Replicating rapidly
- Mutating spontaneously and randomly
- Acquiring resistance and promoting resistance to other bacteria via CONJUGATION = Transfer of small pieces of DNA called PLASMIDS that contain resistance promoting gene
Healthcare-associated infections (HAIs)
Aka Nosocomial infections
Main sources:
Patient flora
Invasive devices
Medical personnel
Medical Equipment
MRSA
- Usually occurs in pts with weakened immune systems
- Resistant to certain antibiotics
- 60% or so of MRSA resistant to Penicilin
Vancomycin-resistant enterococci (VRE)
Found in wounds and pressure ulcers in hospitals and nursing homes
- pts w/ weakened immune systems most at risk
Super Infections
“secondary Infections”
- Develop when host flora is damaged by antibiotic, leaving nutrients and space for pathogens to grow
-Broad spectrum antibiotics can cause these
Eg) C. diff associated Colitis (caused by alteration of the normal bowel flora, which allows multiplication of C. diff) = Symptoms include abdominal pain, diarrhea containing blood and mucus = D/C antibiotics and consider fluid and electrolyte replacement, no anti-diarrheal
Candidiasis = Candida albicans is naturally occurring fungus that lives on the body
- Antibiotics can cause thrush or vaginal yeast infections when they disrupt the balance of healthy bacteria and candida
Guidelines for ABX
Use Culture and Sensitivity (C&S) testing to identify the organism and then the appropriate antibiotic
- If not, begin w/ broad spectrum antibiotic then use a narrow-spectrum antibiotic
- Antibiotics should NOT be used for viral infections or for coughs
- If infection caused by one microbe, treatment w/ single drug is usually best (combining antibiotics can decrease their effectiveness and promote resistant strains
Antibiotics are sometimes given:
- To prevent secondary infections
- Prophylactically for surgeries
Host Factors that Affect Anti-Infective selection
1) Host defenses and Immune System Status
2) Local tissue conditions
3) Allergy history and drug hypersensitivity
4) Pregnancy, age, genetics
Antibiotics by MOA
1) Inhibition of Cell Wall Synthesis:
- Penicillin, Cephalosporin, Carbapenems, Vanco
2) Inhibitions of DNA Synthesis:
- Fluoroquinolones, Sulfonamide
3) Inhibition of Protein Synthesis:
- Tetracyclines, Macrolides, Aminoglycosides
4) Disruption of Call Membrane:
- Polymyxins
Inhibition of Cell Wall Synthesis
Bacterial cell walls are made of peptidoglycan molecules that form a set of chains called Penicillin-binding proteins (PBPs)
Penicillin (Beta-lactam):
- Beta lactum rings structure of penicillin binds to PBPs causing lysis of growing bacteria by damaging walls
*Mainly active against gram+ bacteria**
Resistance to Penicillin = secreting an enzyme that splits penicillin’s beta lactam riing
Developed B-Lactamase Inhibitors = Clavulanate, Tazobactum
Narrow Spectrum (Penicillin V&G) = Broad Spectrum (amoxicillin, Ampicillin) = Extended Spectrum (Piperacillin - one of the broadest)
Generalizations r/t Penicillins
- Mainly active against gram+ bacteria
- Most have narrow spectrum
- Widely distributed to tissues
- Nearly all are rapidly excreted by kidneys (mindful w/ dosage could = renal impairment)
- Short Half-lives (monitor 30min after infusion)
- C. diff or other superinfections
Peptidoglycan
Strong, repeating network of carbohydrate and protein chains, CONSTRUCTED BY ENZYMES CALLED PENICILLIN_BINDING PROTEINS (PBP)
Cephalosporin
- Contain beta-lactam rings that interfere w/ cell wall synthesis (like penicillin)
- Over 20 cephalosporins in 5 generations
- Begin w/ ‘cef’ or ‘ceph’
5%-10% of pts allergic to penicillin are hypersensitive to cephalosporins
Contraindicated for clients who have experienced anaphylaxis following penicillin exposure
Cephalosporin Considerations
- Effective against GRAM - bacteria (except 1st gen)
- Risk of pseudomembranous colitis
- Because it eliminates through kidneys, need to monitor intake and output, BUN, and serum creatine
- If client is taking NSAIDs, MONITOR BLOOD COAGULATION STUDIES because ceph increases the effect of platelet inhibition
Carbapenems
- Contain beta-lactam rings that interfere w/ cell wall synthesis (like penicillin)
- Broad-spectrum abx w/ similar properties to other beta-lactams
- Slightly different beta-lactam ring making it resistant to beta-lactamase
*Better activity against serious Gram Negative and multidrug-resistant infections than ceph and penicillin
Sometimes “last resort” for treating multidrug-resistant infections
Medications:
- Meropenem, Imipenem-cilastatin (cilastatin blocks renal dipeptides, an enzyme responsible for the excretion of imipenem)
Look at Bug and Drugs For…
- Imipenem-cilastatin
- Cefotaxime or ceftriaxone
- Penicillin G potassium or Amoxicillin
- Gentamicin
Bacterial Growth
DNA = recipe book
RNA = chefs assistant (makes proteins by carrying out info/instructions on DNA
Protein synthesis in bacterial replication:
- Process by which bacteria produce proteins required for their growth and reproduction
- Involves 2 main stages: Transcription (copying info from DNA) and Tramslation (decoding info to make protein) in 30S and 50S subunit of ribosome
Inhibition of DNA Replication
Fluoroquinolones:
- Ciprofloxacin**, Moxifloxacin etc
- Act on DNA gyrase and topoisomerase IV, preventing relaxation of supercoil and separation of new strands into daughter cells
- Mostly GRAM NEGATIVE bacteria
- Used for urinary tract infections, GI, respiratory, and skin infections
Many Adverse Effects:
- GI toxicity, cardiotoxicity, nerve damage, phototoxicity, cartilage toxicity leading to tendon abnormalities
Inhibition of DNA
Sulfonamides:
- Suppress DNA replication by inhibiting synthesis of folic acid (folate)
- Adverse effects include hypersensitivity reactions, blood abnormalities, nausea, vomiting, anorexia
- INCREASE FLUID INTAKE TO 1500-3000mL per day (r/t side effect of crystalluria = dehydration = crystal formation = kidney stones)
- Medication = Trimethoprim-Sulfamethoxazole (bactrim)
Inhibition of Protein Synthesis - Tetracyclines
Tetracyclines:
- Inhibit Protein synthesis at the 30S subunit by preventing tRNA from binding mRNA
- Active against GRAM + AND Gram - bacteria
- PO meds SHOULD BE TAKEN ON EMPTY STOMACH
- Bind metal ions so should NOT be taken w/ milk, antacids or iron supplements
- Can be hepatotoxic and cause photosensitivity
- Women on the Pill may be susceptible to vaginal candidiasis
- Tetracycline DECREASES the effectiveness of the pill
Inhibition of Protein Synthesis - Macrolides
Eg) Thromycin
- Inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit
- Most effective against Gram + bacteria
- Alternative drugs for pts allergic to penicillin
- Decrease hepatic metabolism of other drugs thus drug interaction are possible
- Macrolides are contraindicated in clients w/ hepatic disease
- Single dose of azithromycin is EFFECTIVE AGAINST NEISSERIA GONORRHOEAE
Inhibition of Protein Synthesis - Aminoglycosides
Genamicin, Tobramycin, Streptomycin
- Bind to 30S causing misreads of mRNA
- Has serious adverse effects including nephrotoxicity, ototoxicity (hearing loss and tinnitus), neurotoxicity, neuromuscular blockade
- Assoc w/ post-antibiotic effect
- Must be given parentally
- Effective against Gram - bacteria
- May cause muscle cramping* which is NOT an adverse affect
Vancomycin
Severe Gram + infections resistant to safer antibiotics
- Use to treat C. diff**
Effective against MRSA
Mechanism of action:
- Inhibits synthesis of bacterial cell wall
- Increases permeability of bacterial cell membrane
- Alters RNA synthesis
Narrow Therapeutic Range:
- Peak = highest concentration in bloodstream, measured 1-2hrs after a vanco infusion
- Troughs = Lowest concentration in bloodstream, usually measured 30min before next dose
BETWEEN 10-20 mcg/mL IS NORMAL
Adverse Effects:
- “red man” syndrome = CAUSED BY RAPID INFUSION, flushing, tachy, rash on upper body (hypotension*)
- Nausea, rash, fever, chills
- Burns during administration** can slow it down more or get a bigger vein/pic line
Serious Adverse Effects:
- Confusion, seizures and hallucinations
- Extravasation leading to tissue necrosis
- **Ototoxicity (cause balance issues, vertigo)
- **Nephrotoxicity
- Anaphylaxis
Give Vanco over 1hr
Urinary Tract Infections
Kidneys (pyelonephritis), Bladder (cystitis), Urethra
Caused by:
- Escherichia coli (E. coli)
- Klebsiella, Proteus, Staphylococcus saprophyticus (sexually active women), enterococcus species
Treatment:
- Sulfonamides
- Fluoroquinolones
OR
- Nitrofurantoin (macrobid) = used in uncomplicated acute cysritis and usually for prophylaxis of recurrent UTI)
MOA:
- Intermediates attack bacterial ribosomal proteins
- Prevents DNA and RNA synthesis
- Prevent protein synthesis**
- Inhibits Cell Wall synthesis**
Adverse Effects:
- Hypersensitivity responses
- Nausea & Vomiting
- Anorexia
- Headache
- Rash
Serious Adverse Effects:
- Hepatotoxicity
- Acute and chronic pulmonary toxicity
Tuberculosis
Pathophysiology:
- Caused by Mycobacterium tuberculosis
- Spread via AIRBORNE DROPLETS
- Immune system response leads to formation of tubercles in lungs that surround mycobacteria (visible on x-ray)
- In healthy person, mycobacteria remains dormant, person is asymptomatic
- If immunocompromised, infection becomes active
Pharmacotherapy:
- Initial phase = Active cells are killed
- Continuation Phase = Dormant mycobacteria are killed (may last 6-12months)
- Directly observed therapy (DOT) = necessary for high-risk pats that are non-compliant
Nurse must see patient swallow pills
Eg) Isoniazid = FIRST LINE
Ciprofloxacin = SECOND LINE
MOA = Inhibits synthesis of mycollic acid, a critical component of mycobacterial cell wall
Adverse Effects:
- Rash
- Fever
- Numbness of hands and feet
Serious Adverse Effects:
- **Neurotoxicity (no EtOH, related to decrease in Vit B6)
- Hepatotoxicity
