!!Exam 1 patho final review

bioavailability

extent of administration, some of drug will be eliminated

first pass effect

PO/NG route must go through liver, and part of drug may be converted to inactive metabolites

- leading to smaller bioavailability

half life

the time until 50% of the drug is removed from the body

steady state

rate of absorption equals the rate of elimination

trough

lowest concentration of meds, measured before the next dose

therapeutic index

the ratio between the toxic and therapeutic concentrations of a drug

- the smaller the number, the greater likelihood of an AE

additive interaction

1+1=2

Synergistic interaction

1+1=3

antagonistic interactions

1+1 = <2

ARAS

ascending reticular activating system
- promotes activity in cerebral cortex, excitatory neurotransmitters

what neuropeptide is released by ARAS

orexin (keeps us awake)

GABA neurotransmitters

sleep promoting neurons in the hypothalamus

what does the pineal gland secrete

melatonin; light exposure suppresses release

stages of sleep

• NREM 1 : internal, thoughts, light sleep, easily awakened

• NREM 2: deeper sleep, HR/temp decrease

• NREM3: deepest level of sleep

• REM: muscle paralysis, vivid dreams

OSA risk factors

• obesity— BMI 30+

• male, older than 65

• large neck circumference greater or equal to 17 inches

• post menopausal women

OSA manifestations

• frequent awakenings/ insomnia

• daytime sleepiness / morning headach

• irritability

• personality changes

• reports by others: witnessed apneic episodes, snoring

OSA complications

• Cardiac: HTN, arrythmias, HF, overactive SNS

• neurologic/psych: poor concentration/memory, depression

• sexual impotence

how is OSA diagnosed

medical/sleep history and a polysomnography

Narcolepsy

chronic neurological disorder

• uncontrollable urges to sleep, often go directly into REM stage

• destruction of neurons that produce orexin

• cataplexy (loss of msucle tone)

stress

• more common in women

• men are more likely to die from stress related ilness

Stress effects on the body

• glycogenesis

• increase BP, HR, sweating, breathing

Decreases nonessential functions

• peristalsis

• urine formation

• immune function

• inflammatory response

PNS/ SNS

• SNS: flight or fight

• PNS: rest and digest

cerebral cortex

• controls cognition, affect, movement

• evaluates stressor in light of past experiences, future consequences

limbic system

• emotional brain

• mediator between emotions and behavior

• goal: survival

Reticular formation

• contains RAS

  • sends impulses to alert the limbic system and cerebral cortex

  • stress increases frequency of impulses

  • icnreases degree of wakefullness

hypothalamus

• communicates between endocrine and nervous systems

Hypothalamic- Pituitary Response

• stressor signals hypothalamus to stimulate SNS

• SNS releases corticotropin stimulating hormone CRH

• anterior pituitary responds by releasing adrenocorticotropic hormone ACTH into blood stream

Adrenal Response (our bodys response to stress/cortisol)

• SNS stimulates adrenal medulla to release catecholamines (norepi and epi)

• ACTH stimulates adrenal cortex to secrete glucocorticoids (cortisol)

Stress and the immunosuppression

causes opposite effects of acute inflammatory response
- decreased number and function and NK cells, lymphocyte proliferation
- alters production of cytokines
- decreasing phagocytosis

cardinal signs of inflammation

• redness

• swelling

• heat

• pain

all lead to loss of function…

systemic manifestations of inflammation

• fever

• malaise

• nausea/anorexia

• shift to the left

• increased pulse, RR

Prostaglandin: Inflammation Mediator

vasodilation, increased set point in hypothalamus, increase pain sensitization

effects: redness and warmth, pain , fever

Thromboxane: Inflammation Mediator

• vasoconstriction and clotting

Leukotrienes: Inflammation Mediator

• airway narrowing (bronchoconstriction)

• increased vascular permeability

Histamine: Inflammation Mediator

• released by degranulated mast cells

• vasodilation

• increased capillary permeability

Kinin System: Inflammation Mediator

• pain sensitization

• increased capillary permeability

• leukocyte recruitment

complement: Inflammation Mediator

increased inflamatory response and cell death

• vasodilation, increased cap permeability

• chemotaxis—> phagocytosis

• cell lysis

Types of pain

• neuropathic: burning, shooting, electric shock like

• somatic: skin, mucous membranes, muscle , bones, tendons

• visceral: organs

Pain transmission

conduction of pain impulses along the A delta and C fibers into the dorsal horn and the spinal cord

Transduction

• step 1 of pain transmission

• chemical mediators released and activate nociceptors and create action potential

Transmission

• step 2

• action potential carries signal to spinal cord by either

  • Myelinated A fibers (faster, sharp, sudden pain ) OR

  • unmyelinated C fibers (slower, throbbing pain, first order neurons)

• pain signals relayed to dorsal horn of spinal cord

• signal picked up by second order neurons and sent to third order in thalamus and cerebral cortex

Perception

• step 3

• conscious awareness of pain, recognized and defiend

• RAS, somatosensory, limbic system

Modulation

• step 4 in pain

• ho wbody interprets and responds to pain

• activation of descending pathway

• inhibitory or faciliatory

gate theory of pain transmission

Uses the analogy of a gate (dorsal horn) to describe how impulses from damaged tissues are sensed in the brain

types of immunity

• innate: inflammatory response

• acquired

  • active (body makes antibodies)

    • natural or vaccination

  • passive (passed on)

    • maternal or artificial

Eosinophils

• allergy symptoms: parasitic infections

Basophils

• asthma; release histamine

Lymphocytes

migrate from bone marrow to peripheral organs

• B cells= humoral immunity (mature in thymus gland)

• T cells= cell mediated immunity (mature in bone marrow)

Antigen Presenting Cells

activate immune response

• transports fragment of antigen until it meets a t cell with specificity for that antigen

  • dendritic cells : found on skin, lining of nose, lungs, stomach, intestine

  • macrophages: found in tissues

  • monocytes: found in blood

Humorla immunity process

• presented to B cell specific for antigen

• diferentiates into

  • plasma B cell (secretes antibodies)

  • memory cells

cell mediated immunity

T helper cells CD4

• stimulate and regulate cell mediated immunity and humoral antibody resposnes

• differentiates into subsets of cells that make cytokines

T cytotoxic cells CD8

• sensitized by exposure to antigen by T helpercells

• attack antigens on cell membrane of foreign pathogens

• release cytolytic substances that destroy the pathogen

Type 1 hypersensitivity reactions

IgE

• mild to life threatening allergic responses

• mediators: mast cells (histamine), leukotrienes, prostaglandins

• examples: angioedema,anaphylaxis, allergic rhinitis, atopic dermatitis

• genetic predisposition

Type 2 Hypersensitivity reation

cytotoxic

• takes minutes to hours

• cells are directly affected by antibodies

• mediated by complement system— result is lysis and phagocytosis

Type 3 Hypersensitivity Reactions

immune complexes

• cause tissue damage in immune-complex reactions

• take hours to days

• mediated by neutrophils, complement system, macrophages

• associated autimmune disorders: lupus, acute glomerulonephritis, RA

type 4 hypersensitivity reaction

delayed/cell mediated

• mediated by helper T cells, cytokines and cytotoxic killer (T cells) — results in tissue damage

• ex: contact dermatitis and transplant rejection

HIV

retorvirus that targets CD4 cells, spread in body fluids with the highest concentration in the blood

Perinatal HIV transmission

• during pregnancy, delivery or breastfeeding

• 25% risk of infection if mother has untreated HIV

• risk is reduced to less than 2% if mother treated with antiviral therapy

AIDs Criteria

CD4<200 and/or presence of an opportunistic infection or wasting syndrome

examples of opportunistic infections

pneumocystis jiroveci pneumonia, kaposi sarcoma, invasive cervical cancer, mycobacterium TB, lymphoma

normal CD4 count and viral load

• 800-1400

• viral load: the lover the viral load the less active the disease

Super Infections

normal flora reduced or eliminated

• vaginal yeast infections

• C diff