time line for acute pain

less then 2 weeks

time line for chronic pain

more then 6 months

afferent pathway

starts at sensory receptors→ impulse needs to be strong enough to reach thrash hold (-50mlv) → travels through spinal cord→ thalamus → somatosensory cortex (where we become aware of stimulus

pain pathway

nociceptor→ 1st order neuron→ spinal ganglion → synaaps with second order neuron → ascend up spinal pathway → thalamus → synapse with 3rd order neuron → somatosensory cortex (aware of pain)

type a fibers

fast

myelinated fibres

sharp pain

often triggers reflexes

Type c nerve fibers

slow

unmylinated fibers

aching burning pain

cutaneous pain

outside of your body

visceral pain

organ related

interneurons

communicate information at CNS synapse (process, modify, relay info)

withdrawal reflex

reflex without cerebral control

activation of sensory neuron → interneuron → motor neuron → effector response

analgesia

treatment of pain

what are the different analgesists

CNS : acetaminophen, opioids

peripheral acting: anti inflammatory drugs (NSAIDS), steroidal drugs (Glucocorticoids)

Tylenol

• central acting analgesic

• PO Q4h

• most effective antipyretic

• central acting → stimulates hypothalamus → peripheral vasodilation → cooling

• NOT anti-inflammatory

opioids

• agonists for MU, kappa, and delta receptors

• mimic endogenous opioid peptides (inhibitory nuro transmitters) (ex: endorphins, enkephalins, dynorphins)

• inhibits substance P release→ inhibits pain

• receptor binding also stimulates histamine and dopamine release (what makes it addictive)

Mu receptors

opioid receptors responsible for analgesia effects

high efficacy opioids

• fentanyl

• hydromorphone

• meperidine

• morphine

• methadone

moderate efficacy

hydrocodone

oxycodone

oxycontin

tramadol

combo drug opioids

Percocet: oxycodone + acetaminophen

percodan: oxycodone + ASA

Vicodin: hydrocodone + acetaminophen

tramacet: tramadol + acetaminophen

codine

• prodrug

• gets activated into morphine

• bioavailability can be unpredictable

Tylenol ingredients

acetaminophen + codine + caffeine

side effects of opioids

• CNS depression: sedation, decreased RR,HR, BP, LOCS , pupillary constriction

• CNS Psycomimetic: euphoria, depression, nightmares

• N/V

• constipation

• pruitus (histamine relese )

• urinary retention

cautions around opioids

• decreased response rate: if below 12/min (stop/naloxone)

• allergies are common

• severe asthma patients: may trigger bc of histamine relapse

• pregnancy

what are NSAIDS

anti inflammatory pain meds

Non steroidal anti inflammatory drugs

• decrease pain

• decrese inflammation and swelling

• decrease fever

prostaglandins

cause pain and inflammation

arachnoid acid: turned into prostaglandins by COX enzymes

How do NSAIDS work?

Block COX → stops the conversion of prostaglandins → decrease pain/ inflammation

Non selective NSAIDS

block both Cox1 and COX2 enzymes

(cox 1 enzymes are used in some protective ways so blocking both can cause negative effects as well as positive)

examples:

• aspirin

• ibuphrophen

• naproxen

• diclofenac

• ketorolac

• indomethacin

COX2 selective NSAIDS

mainly block COX2 enzymes only

not 1st line treatment bc they have a history of cardiac problems

ex: celecoxib

cox 1 vs cox 2

cox 1: helps protect stomach and supports platelets(preventing blood clots) : blocking → stomach irritation and bleeding

cox 2: pain and inflammation: blocking decreases.

4 steps of inflammation

1. injury happens → skin damaged bacteria/ pathogens enter → macrophages and mast cells notice and release chemical signals (histamine) → histamine causes vessels to vasodialate and become more permeable→ redness, warmth, swelling

2. fluid + clotting proteins move to tissues → clotting starts (help heal) → extra fluid contributes to swelling

3. more immune cells called to area → damage cells release chemokines (release chemicals that alert white blood cells to come help.) neutrophils and other phagocytes leave bloodstream to tissue injury

4. immune cells clean up area (phagocytosis)

arachnoid acid

pre curser to prostaglandins that lives in the phospholipid bilayer of tissues.

turned into prostaglandin by COX enzymes

treatment for pain less the 4/10

non opioid medications

PO

• ex: Nsaids, Tylenol

treatment for pain 4-6/10

opioid combo meds

PO, setting dependent

synergy is useful

treatment for pain more then 6/10

higher potency opioids

parenteral (IV, SC)

consider using a PCA (patient controlled anagelsia)

synergy also important and effective

Glucocorticoids

• endogenous hormone (cortisol)

• produced by the adrenal gland

• used during stress

• stimulates gluconeogenisis ( make more glucose readily available)

• stimulates protine degration

• facilitates lipolysis: breaking down fat for energy

• end in “sone”

why are glucocorticoids used to reduce inflammation

• decrease prostaglandin (through COX2 inhibition)

• suppressing WBC: phagocytes and lymphocytes

• decreasing histamine release: decrease swelling

downside of glucocorticoids

• increase infection risk

• weaker bones and muscles

• weight gain

• fluid retention

• stomach irritation

(never stop suddenly , always taper dose down slowly, bc adrenal glands may have reduced their own cortisol production)

asthma prevention treatments

anti inflammatory drugs: controllers

• Glucocorticoids

• ex: beclomethasone, budesonide, fluticasone

• as well as leukotriene modifiers and mast cell stabilizers

Rescue treatment of asthma

1st: Bronchodilators (B2 adronergic agonists) → B2 adrenergic receptor stimulation → bronchodiliation → increased lung perfusion → ventilation

• salbutamol (Ventolin)

• Anticholinergics (inhibit PNS) ex: Atrovent

• epinephrine

steps to allergy related inflammation

1. cell injury → mast cells in tissues degranulate (release histamine, leukotrienes, complements

2. chemicals cause many effect

• vasodilation: more blood reaches area → redness, heat

• increased vascular permeability: blood vessels become more “leaky” → fluid moves into the tissues → swelling/ edema

• cellular infiltration: WBC move out of blood into injured tissue→ phagocytosis, dead cells can form pus

• thrombosis: clot formation

• nerve endings are stimulated: pain

histamine release

stored within mast cells: released upon mast cell + allergen contact

binds to H1 receptors (g- protine receptor) : found in smooth muscle of vascular system, GI tract, CNS and bronchial tree

non desirable histamine effects

• capillary vasodilation + permeability

• itching

• urticaria

• pain

• increased HR

• Bronchoconstriction

Antihistimines

• H1 receptor antagonists

• 2 generations

- First generation: cross BBB (block histamine in brain: histamine in brain is normally excitatory → when blocked, causes drowsiness)

• drugs: diphenhydramine (Benadryl) chloropherinamine (benylin)

-second generation: dont cross BBB (non drowsy)

• drugs: fexofenadine (allegra) loratadine (Claritin) cetirizine (reactin) desloratadine (aerius)

antitussives

inhibit cough reflex

ex: codine, hydrocodone, dextromethorphan

decongestants

sympathetic stimulants → decrease secretions

ex: pseudoephedrine

interferons

immunogenicity proteins secreted by WBC (lymphocytes, macrophages) → stimulate immune response

pyrogens

substances that cause a sudden rise in temp/ fever

activating the hypothalamus

neutrophils

• up to 70% of WBC

• 1st to site of tissue damage

• lifespan: up to one week→ they self destruct during phagocytosis

• immature neutrophils : band cells (happens if they are not being made fast enough and there is an infection)

lymphocytes

• innate + adaptive immunity

• meomory cells

• NK cells, T, B cells

Monocytes

• in blood

• mature into macrophages in tissue

• specific to tissues → ex hepatic kupffer cells

Eoseniphils

• allergy response

• release enzymes and chemical mediators

• destroy allergies and parasites

basophils

• allergy response

• proinflammatory + anticoagulating

what are the 2 mechanisms of action causing infections

• strength in numbers

• toxin production (often more harmful then bacteria themselves)

microflora

micro-organisms present on or in human body

• commensilisum: host not negative effected but organism benefits

• mutualism: both host and organism benefit (eg: intestinal flora→ vitamin K formation)

• parasitic: host is negatively effected

“ITIS” suffix

inflammation/ infection

“EMIA” suffix

pathogen present in blood

eg: bacterimia

time line of an infection

1. incubation period

• pathogen present and replicating

• no symptoms

• most contagious

2. Prodomal stage

• initial symptoms: malaise, mild fever, headache, myalgia

• generic in nature (hard to diagnose)

3. Acute stage

• max presence of pathogen

• max response by host

• max impact of infection

• more specific symptoms

4. convalescent period

• pathogen decreasing in numbers

• progressive host repair of damages

5. resolution

steps of determining an illness

step 1: where is the illness? health history, focused assessment, signs and symptoms

step 2: identify what is causing the illness? bacterial vs viral, CBC and differential, culture from source (gram positive vs negative)

step 3: antibacterial treatment: empiric, focused treatment

CBC differential meanings

WBC

RBC

HGB

HCT

MCV

MCH

MCHC

RDW

PLT

MPV

WBC: white blood cells

RBC: red blood cells

HGB: hemoglobin

HCT: hematocrit

MCV: mean corpuscular volume

MCH: Mean corpuscular hemoglobin

MCHC: average concentration or density of hemoglobin inside your red blood cells.

RDW: red blood cell distribution width

PLT: platelet count

MPV: mean platelet volume: average size of platelets

Gram negative bacteria

• thin peptoglycan layer

• outer membrane

• stain pink/red

• eg: e-coli. klebsiella, pseudomonas, salmonella, HIB, cholera, syphillis, gonorreha, nisseria M

Gram positive bacteria

• thick peptoglycan layer

• no outer membrane

• stain purple

• eg: staphylococci, streptococchi, enterococci, listeria, C-dif

antibiotic empiric vs focal treatment

EMPERIC:

• based on “suspected bacteria”

• broad spectrum (not sure exactly what it is)

• started ASAP

FOCAL:

• after culture and sensitivity results → focused treatment

• started once results are known

• empiric may be switched to focal

• narrow spectrum antibiotic

4 main types of antibiotics

• cell wall synthesis inhibitors

• protein synthesis inhibitors

• nucleic acid inhibitors (DNA, RNA)

• antimetabolites (inhibition of essential metabolites)

three main beta lactam antibiotics

call wall synthesis inhibitors

antibiotics with a beta lactam ring: stop bacteria from building a cell wall → withoyught bacteria break open and die

• penicillins

• cephalosporins

• carbapenems

Penicillins

• “illins” → suffix

• inhibit cell wall synthesis

• work for gram + or gram -

• can be narrow or broad spectrum

• 10% of people with a penicillin allergy also have an allergy to cephalosporins

beta-lactamase inhibitors

drugs that block bacterial beta-lactamase enzymes (made by some bacteria to break open the betalactamase ring of antibiotics making them ineffective

drugs: clavunic acid , tazobactam

Beta lactase inhibitor combo drugs

augmentin ( amoxicillin + clavulanic acid)

Timentin( ticarcillin + clauvonic acid)

tazosin, zosyn (piperacillin + tazobactum)

Cephalosporins

“Cef” - prefix

largest antibiotic class

5 generations (higher generations cross the BBB , 3rd-5th) → good for treating meningitis

ex: ceftriaxone, ceftaziidime, ceftaroline

1st choice for skin infections: cefazolin, cephalexin etc.

MRSA

Carbapenems

“penem” → suffix

potent→ not first line

eg: imipenem, meropenem

treat broad spectrum

good for serious and mixed infections eg: meningitis, aspiration pneumonia

Bacitracin

a topical antibiotic: skin, eyes, ears

works against gram positive bacteria

often used in combination products (ex:polysporin→ bactricin + polymyxin B )

common resistance pathogens

• staphylococcus aureus : MRSA

• enterococci- VRE

• 
  

common side effects of antibiotics

diarrhea, abdominal pain, nausea

viruses

• non living

• protein or lipid coated

• enter healthy cells to survive (require host cell to replicate)

• frequent mutation: hard to treat

common viruses that cause common cold

rhinoviruses

coronavirus

parainfluenza

viruses that cause chickenpox and shingles

herpex simplex 1&2

varicella

virus that causes aids

HIV

Treatment of viruses

difficult to treat

target is inside the human cell

antiviral drugs: decrease severity of disease, dont eliminate it

immunizations: most effective: prevention focused