Pain relievers 2

Continuation of Pain relievers 1

Meloxicam

Non selective preferential COX 2 inhibitor (which is longer acting)

Etodolac

Preferential COX 2 inhibitor with less GIT tox

Nabumetone

Preferential COX 2 inhibitor that is non acidic, prodrug, and longer acting

COX-1

• Physiologic, normal

• present in most tissues

• synthesizes Prostaglandins regulating physiologic processes

COX-1

A cyclooxygenase important in:

• gastric mucosa

• kidneys

• platelets

• vascular endothelium

COX-2

• present if there is inflammation

• induced mainly at sites of inflammation by cytokinesis

• synthesizes Prostaglandin that mediate inflammation, pain, and fever

COX-2

A cyclooxygenase that is constituive expression primarily in:

• brain

• kidneys

Selective COX-2 inhibitors

• celecoxib

• etoricoxib

• rofecoxib

• valdecoxib

• Celecoxib

• Etoricoxib

• Rofecoxib

• Valdecoxib

Drugs that inhibit prostacyclin (COX2) in sites of inflammation; has antipyretic and analgesic and anti-inflammatory effect.

Celecoxib

COX-2 selective given to

• oseoarthritis (100-200mg BID)

• rheumatoid arthritis

• dysmenorrhea

• acute gouty attacks

• acute musculoskeletal pain

Rofecoxib (VIOXX) and Valdecoxib

• withdrawn from the market

• higher incidence of CV thrombotic events

• inhibits prostacyclin (PGI2) in vascular endothelium, letting TXA2 act free and promote platelet aggregation,

Glucocorticoids

• causes the increase of glucose

• increase in protein

• has effect in lipid metabolism

  e.g. steroids

Cortisol

this facilitates the breakdown of muscle into amino acids and lipids into free fatty acids, which can be transported to the liver to form glucose

Gluconeogenesis

Process wherein the cortisol facilitates the breakdown of muscle into amino acids and lipids into free fatty acids, which can be transported to the liver to form glucose

glucose

Synthesized in the liver that can be stored as glycogen and released back into the bloodstream to increase its level.

Muscle cell

Cortisol in this cell:

• decrease glucose uptake

• increase protein breakdown

• release amino acids

thus increase glucose in the blood

Fat cell

• decrease glucose uptake

• fat breakdown

• release fatty acids

thus increase lipids in the blood.

glucocorticoids

Effective and potent anti-inflammatory agents

Suppress transcription of genes involved in inflammation

Corticosteroid effect on inflammatory gene transcription

Phospholipase A2

Corticosteroids inhibit ________, preventing the release of Arachidonic acid (AA) from the cell membrane

Arachidonic acid

Glucocorticoids inhibits Phospholipase A2, preventing the release of _______ from the cell membrane

• stabilize the membranes

  • making less fragile and susceptible to rupture

Glucocorticoids effect on lysosomal membranes

Lysosomes

These organelles contain degradative enzymes

degradative enzymes

Lysosomes are organelles that contain _______

Inflammation

When lysosomes are ruptured, these enzymes begin to digest cellular components contributing to ______

edema (swelling) and erythema (redness)

Corticosteroids decrease vascular permeability that helps control:

• __________

• __________

Allergic disorders

Decreased inflammation to:

• anaphylactic reactions

• drug allergies

• hay fever

• serum

• sickness

Collagen Disorders

Immunosuppression to:

• rheumatic carditis

• dermatomyositis

• lupus

• erythematosus

Dermatologic disorders

Decreased inflammation to:

• alopecia areata

• dermatitis

• keloids

• lichens

• mycosis

• fungoides

• pemphigus

• psoriasis

Gastrointestinal disorders

Decreased inflammation to:

• Crohn disease

• ulcerative colitis

Hematologic Disorders

Immunosuppression to:

• anemia

• erythroblastopenia

• thrombocytopenia

Nonrheumatic inflammation

Decreased inflammation to:

• bursitis

• tenosynovitis

Neoplastic disease

Antilymphocytic effects

• leukemias

• lymphomas

• nasal polyps

• cystic tumors

Neurologic disease

Decrease inflammation to:

• tuberculous meningitis

• sclerosis

• myasthenia gravis

Neurotrauma

Immunosupression to:

• brain surgery

• closed head injury

• brain tumors

• spinal cord injury

Opthalmic disorders

Decrease edema; inhibit free radical to:

• chorioretinitis

• conjunctivitis

• herpes zoster ophthalmicus

• iridocyclitis

• keratitis

• optis neuritis

Organ transplant

Induced neuronal damage to:

• liver transplant

• kidney transplant

• heart transplant etc.

Renal disease

Decrease inflammation to:

• nephrotic syndrome

• membranous glomerulonephritis

Respiratory disorders

Immunosuppression to:

• bronchial asthma

• berylliosis

• aspiration pneuomonitis

• sarcoidosis

• tuberculosis

Rheumatic disorders

Decreased inflammation to:

• ankylosing spondylitis

• psoriatic arthritis

• rhumatoid arthritis

• gouty arthritis

• osteoarthritis

Glaucoma

Side effects of glucocorticoids:

• on TOPICAL use

Limb muscle atrophy

Side effects of glucocorticoids:

• proximal myopathy

Ulcer peptic

Side effects of glucocorticoids:

• starts with the letter [U]

Cataract

Side effects of glucocorticoids:

• on SYSTEMATIC use

• posterior subscapular cataract kind

Osteoporosis

Side effects of glucocorticoids:

• dose/duration dependent

• ribs/vertebra

Cushing syndrome

Side effects of glucocorticoids:

• cushingoid features

• moon facies

Osteonecrosis

Side effects of glucocorticoids:

• aseptic necrosis

• femur head MC inv.

Retardation of growth

Side effects of glucocorticoids:

• also stands for retention of NA+ /H20

Thinning of skin

Side effects of glucocorticoids:

• easily bruising

Infections

Side effects of glucocorticoids:

• immunosuppression

Changes in moodpsyche

Side effects of glucocorticoids:

• behavioral disturbances

Oedema

Side effects of glucocorticoids:

• mineralcorticoid action

Impaired healing of wounds

Side effects of glucocorticoids:

• about wounds; starts with the letter [I]

Diabetes mellitus

Side effects of glucocorticoids:

• hyperglycemic action

Suppression of hypothalamus, pituitary gland, and adrenal gland

Side effects of glucocorticoids:

• serious; may cause acute adrenal insufficiency

Opioids

Most potent painkillers available in modern medicine

• used in perioperative care and pain management

Opioids

the term originates from Opos (Greek word for juice); the drug being derived from the juice of opium poppy PAPAVER SOMNIFERUM

PAPAVER SOMNIFERUM

where opium is derived from; the juice of the opium poppy

Opiates

Drugs derived from opium are reffered to as

Morphine

The development of synthetic drugs with ______-like properties has led to the use of the term opioid to refer to all exogenous substances, natural and synthetic

Naturally occuring, Semi synthetic, synthetic

Classification of opioids:

1. __

2. __

3. __

Naturally occuring

• morphine

• codeine

• papaverine

• thebaine

Phenanthrenes and Benzylisoquinolones

Classification of naturally occurring opioids:

1. ______

2. ______

Phenanthrenes

• morphine

• codeine

Benzylisoquinones

• papaverine

• noscapine

Antagonist and agonists antagonists

Opioids can be:

• agonists

• ________

• __________

Semi synthetic

• heroin

• dihydromophone, morphinone

• thebaine derivatives (etorphine, buprenorphine)

Synthetic

• morphinan derivatives

• diphenylpropylamine derivatives

• bensomorphan derivatives

• phenylpiperidine derivatives

Opioid receptors

They are classified as:

• μ

• d (delta)

• k (kappa)

morphine

μ (meu) receptor binds to

Ketocyclazocine

k (kappa) receptor binds to

isolated from mouse vas deferens

d (delta) receptor binds to

• periaqueductal gray

• locus ceruleus

• rostral ventral medulla

in the brain, this is where opioid receptor are primarily found

• interneurons

• primary afferent neurons in the dorsal horn

In the spinal cord, opioid receptors are found in:

intense analgesia

effect of direct application of opioid agonists to the SC that produces ____

• sensory neurons

• immune cells

Outside CNS, opioid receptors are found on

B-endorphin

Endogenous agonists for the μ receptor

Dynorphin

Endogenous agonists for k (kappa) receptors

Enkephalin

Endogenous agonists for the delta receptors

supraspinal and spinal analgesia

The mu receptors are responsibke for _____ and ______

inhibition of neurotransmitter

Result of activating k receptors via N-type calcium channels

k receptors

opioid agonist-antagonist often act principally on what receptor

enkephalins

Delta receptors respond to the endogenous ligands known as ___; these opioid receptors may serve to modulate the activity of the mu receptors.

OPIOIDS PHYSIO NA BUKAS MO NA ITULOY