HTHSCI 2H03 - 8.2 Drugs for Inflammation

What is inflammation

a non-specific response to tissue injury

what are the types of inflammation

acute and chronic

what is acute inflammation

associated with minor physical injury, chemical damage, infection, antigens

usually self-limiting and non-pharmacological methods are used in addition to topicals or anti-inflammatory drugs

how long does acute inflammation last for

8 - 10 days

what is chronic inflammation

inflammation causes more inflammation (inflammatory response becomes maladaptive and can lead to tissue injury and inflammation meaning more tissue injury and inflammation... a maladaptive loop triggers more damage or autoimmune disease)

when does chronic inflammation occur

occurs if body cannot neutralize trigger of initial inflammation; associated with many chronic conditions (body still damaging)

how do chemical mediators play a role in inflammation

they act as nociceptors and contributes to pain response

what do the chemical mediators cause

vasodilation

vascular permeability

cellular infiltration

thrombosis

stimulation of nerve endings

pain (histamine + bradykinin + prostaglandins)

arachidonic acid pathway

produced when there is a tissue injury and the cell membrane ruptures

arachidonic acid is metabolized to produce inflammatory mediators (protaglandins and leukotrienes).

what are arachidonly esters and where are they found

precursor for arachidonic acids in plasma

conversion occurs with help of phospholipase A2

explain the arachidonic pathway

1. cell membrane ruptures due to injury

2. rupturing exposes arachidonyl esters and gets converted into AA

3. phospholipase A2 binds to exposed arachidonyl esters and immediately converts them to AA

5. AA circulats and COX converts it into prostaglandins or lipoxygenase is an enzyme that converts AA into leukotreinnes

COX 1

produces prostaglandins involved in platelet aggregation (due to thromboxane A2)

COX 2

creates prostaglandins in line with pain and inflammation and other organs (kidneys, guts, liver)

pros of prostaglandin

vasodilation

gastric cytoprotection (decreases stomach acid in stomach)

actions of leukotrienes

immune cell recruitment ( (brings phagocyte + activation, neutrophil chemotaxis, very bronchoconstirction

NSAIDS

non-selective CoX inhibitors that will block both cyclooxygenase 1 and 2 due to the side effects of having a drug that only targets one

There is one CoX 2 only inhibitor but that is only used in patients with a really low cardiovascular system (has high risks of MI, stroke, asymptomatic hypertension)

Anti-Inflammtory Drugs

to block inflammation, use

NSAIDs

glucocorticoid drugs

NSAIDs

used for management of mild to moderate pain, inflammation and fever

glucocorticoid drugs

used for short-term management of severe or disabling inflammation

used for autoimmune disorders such as lupus, rheumatoid arthritis

NSAIDs

reduces pain and inflammation by inhibiting the enzymatic activity of cyclooxyrgenase

Aspirin (NSAID) leading to worsening asthma?

NSAID inhibits COX to convert AA therefore, lipoxygenase converts AA into leukotriennes (bronchoconstriction)

functions of COX-1 and where is it found?

found in all cells

- protects gastric mucosa

- supports kidney function

- platelet aggregation

functions of COX-2 and where is it found?

found only at site of injury

- pro-inflammatory

- pain

- fever

inhibits of COX-1 vs COX-2

COX-1 → is undesirable as it increases risk for gastric bleeding and kidney failure

COX-2 → desirable as it results in suppression of inflammation

con of NSAID being non-selective

increases risk of gastric bleeding + kidney dysfunction → increases risk of peptic ulcer

as NSAIDs break down the gastric mucosa, the secretions increase, preventing clot formation → bleeding ulcers

enteric-coated vs regular vs buffered aspirin

enteric-coated: absorbed in small intestines (alkaline environment)

regular: dissolves and begins to absorb in stomach (for headache + once a day)

buffered product: contains ions that decrease gastric acidity and slow absorption

mechanism of glucocorticoid therapy

PHIC

blocks phospholipase A2 (no prostaglandins or leukotrienes)

inhibits histamine release (potent inflammatory mediator)

immunosuppresive: suppresses lymphocytes, platelet activating factor, IL 2 & 3

blocks COX-2 = no prostaglandins = no inflammation

administration of glucocorticoid therapy

topical (inhaled / creams) / intranasal

adverse effects of glucocorticoid therapy

increased BG levels

adrenal insufficiency

hyperglycaemia

mood changes

osteoporosis

immunosuppression

antipyretic + its drug classes

treating fever (prolonged fever can cause tissue damage / reduced mental acuity / delirium / coma)

can use NSAIDS or acetaminophen

Reye's Syndrome

occurs to kids 4 - 14 years old

disorder caused by using aspirin to treat viral illnesses (flu, chicken pox)

leads to:

inflammation in brain

fatty deposits in liver

death in days

acetaminophen

direct action on hypothalamus and dilation of peripheral blood vessels (enables sweating)

provides analgesic effect

antihistamines

does nothing for pain but helps with mild to moderate inflammation and allergies

inhibit allergic reactions of inflammation, redness, and itching caused by the release of histamine

blocks the action of histamine at H1 receptors to treat allergic rhinitis (runny nose + sneezing + itchy eyes/throat)

can also be used for motion sickness and vertigo

types of histamines

1st gen → sedative effects

2nd gen → prescribed for allergies

anaphylaxis (what is it + process)

massive allergic response where antihistamines do nothing at all

a hyperimmune & hyperinflammatory response to antigens

body responds within minutes to the antigen, releasing massive amounts of histamine and other chemical mediators of inflammation

what does anaphylaxis cause?

hives

itching

chest tightness

reflex tachycardia

bronchoconstriction

hypotension

can antihistamines be used for the treatment of anaphylaxis?

no because they are not potent / strong enough

anaphylaxis pharmacologicial management

1. Epinephrine adrenergic agonist drug (IM) which will stimulate sympathetic divisions (increased BP, bronchodilation, increased cardiac output)

2. oxygen

3. saline (if hypotensive to increase blood volume)

pharmacological treatment for continued upper airway obstruction (in anaphylaxis)

nebulized epinephrine

what is the pharmacological treatment for persistent wheeze (in anaphylaxis)

B2 agonist (bronchodialation)

glucocorticoid (inhibits inflammatory/immune response to antigen