module 1

What is included under the general term "salicylate"?

Aspirin and related compounds.

(Acetylsalicylic acid)

Why might aspirin be manufactured as an enteric-coated tablet like Ecotrin?

To avoid stomach irritation and ulcers by dissolving in the duodenum instead of the stomach.

Aspirin analgesic effect

Relieves mild-to-moderate pain by inhibiting prostaglandin release from damaged tissue.

How does aspirin act as an anti-inflammatory drug?

decreasing inflammation through inhibition of prostaglandin release from damaged tissue.

What is the antipyretic action of aspirin?

Reduces fever via hypothalamic action and promotes vasodilation and sweating.

How does aspirin function as an anticoagulant?

It inhibits thromboxane, which normally promotes platelet aggregation, thus prolonging clotting time.

What cardiovascular events can aspirin help prevent due to its anticoagulant effect?

Myocardial infarction (MI) and cerebrovascular accident (CVA).

Reye’s Syndrome associated

Use of aspirin to treat aches and pains during viral illnesses (e.g., cold, flu, chickenpox).

Causes: Liver damage, increased serum ammonia levels, and encephalitis.

Aspirin no longer given to kids due to risk of Ryes

Therapeutic action of non salicylate (Tylenol)

Analgesic (mechanism unclear) and antipyretic (via hypothalamus and vasodilation).

No anti inflammatory or anticoagulant

What is acetaminophen considered first-line treatment for?

Osteoarthritis and low back pain

Risk of high dose acetaminophen

Liver toxicity (major risk)

Chronic kidney disease, hypertension, and peptic ulcer disease

Half life of acetaminophen

2-3 hrs

Reg strength – 325 mg, Extra strength – 500 mg, Arthritis strength – 650 mg.

COX -1 prostaglandins

Protects gastric lining and kidney

Cox 2 prostaglandins cause

Pain and inflammation

What are the side effects of NSAIDs?

Cardiac attack and stroke, upper respiratory infection, GI disturbances, fluid retention, increased blood pressure.

What is the risk associated with NSAIDs in patients with cardiovascular disease?

Increased risk of heart attack and stroke due to vasoconstriction and reduced prostaglandins leading to clot formation.

non-selective NSAIDs?

Ibuprofen (Advil, Motrin IB) and naproxen (Aleve).

Risk of ulcers

What is an example of a COX-1 inhibitor and what does it do?

Low-dose aspirin; decreases thromboxane A2, reducing platelet stimulation.

COX-2 inhibitor example and function

Celebrex; decreases prostacyclin, reducing platelet inhibition—requires monitoring.

Reduced risk of peptic ulcers while still relieving pain and inflammation.

Cox 2 inhibitor risk

Increased CVD

How do narcotics (opiates) relieve pain?

Binding to operate receptor site in brain, blocking pain signals from ascending pathways

NSAIDs do to prostaglandin production?

inhibit prostaglandin providing analgesic and anti inflammatory effects

Why might NSAIDs be preferred over salicylates in some patients?

They are less likely to cause GI ulcers and side effects

NSAIDs treat

Mild-to-moderate pain from arthritis, migraines, and other conditions.

What do non-selective NSAIDs inhibit?

Both COX-1 and COX-2 enzymes.

Adverse effects of NSAID long term use

GI toxicity, renal dysfunction, hypertension, and reduced effectiveness of antihypertensives and aspirin

Caution with older adults

Opiate receptor names

Mu, kappa, delta

Opiates used for

Moderate-to-severe pain, pre/post-op pain relief, sedation, and maintaining general anesthesia.

common narcotic drugs

Codeine, fentanyl (Duragesic-25), hydromorphone (Dilaudid), morphine sulfate.

side effects of narcotics

Respiratory depression, sedation, euphoria, constipation, pruritus, and decreased renal function.

opioid-induced constipation?

Decreased intestinal peristalsis via effects on opioid receptors in the enteric nervous system.

What is opioid-induced hyperalgesia?

condition where opioid use increases sensitivity to pain

serious interaction can occur between opioids and antidepressants or migraine medications?

Serotonin syndrome

SHIVERS

• S: Shivering

• H: Hyperreflexia/myoclonus

• I: Increased temperature

• V: Vital sign abnormalities

• E: Encephalopathy

• R: Restlessness

• S: Sweating

rare condition can opioid use cause related to hormone production?

adrenal insufficiency (low cortisol levels)

To for adrenal insufficiency

Corticosteroids and weaning off opioids

signs of adrenal insufficiency

fatigue, weakness, dizziness, nausea, weight loss, low bp, and craving salty food

tolerance

Increase dosage to maintain same effect over time

Physical dependence

Onset withdrawal symptoms when drug abruptly stops

Addiction

Compulsive drug use and craving

Main function of Mu opioid receptor

Supraspinal and spinal analgesia, sedation, respiratory depression, slowed GI transit, and modulation of hormone and neurotransmitter release.

Deltoid opioid receptor

Supraspinal and spinal analgesia; modulation of hormone and neurotransmitter release

Kappa opioid receptor

Supraspinal and spinal analgesia; psychomimetic effects; slowed GI transit

What are strong agonist used for

MOA: High affinity for Mu receptors

Tx severe pain

Strong agonist side effects

sedation, respiratory depression, and constipation.

Strong agonist examples

Morphine sulfate, fentanyl (Duragesic-25), hydromorphone (Dilaudid), tramadol

Mild to moderate opioid MOA

Tx moderate pain

Bind to opioid receptors, but with lower affinity and efficacy than strong agonists.

Mild to moderate opioid agonist

Codeine

Mixed agonist-antagonist opioids

Provide analgesia with less respiratory depression risk

Used for opioid withdrawal

opioid antagonists u

treats overdose and opioid use disorder

Control side effect of constipation

opioid antagonists ex

Naloxone (Narcan): fast acting , reduces response depression, blocks receptor

Naltrexone (ReVia): slow acting

Naloxegol (Movantik)

Opioid agonist MOA

Knock agonists off opioid receptors, reversing their effects.

Side effects of agonist-antagonist

Greater psychotropic effects, hallucinations, vivid dreams.

Agonist-antagonist opioid example

Butorphanol: Binds and activates Kappa blocks or partially activates Mu

Buprenorphine: Partially activates Mu receptors and antagonizes Kappa receptors.

corticosteroids/glucocorticoids therapeutic effects

Anti inflammatory and immunosuppressive

Inhibit leukocytes and macrophages

Suppress immune response

Oral corticosteroids side effect

• Hyperglycemia (diabetes)

• Adrenal suppression

• Cushing syndrome

• Osteoporosis

• Aseptic necrosis of bone

• Myopathy

Toxicities of Corticosteroids

• Type 2 Diabetes Mellitus

• Muscle Wasting

• Osteoporosis

• Hypertension

• Hyperlipidemia

• Immunosuppression

• Adrenal Suppression (due to ↓ ACTH secretion from pituitary)

Adverse effects of glucocorticoid

• Psychiatric: sleep and mood disturbances, psychosis

• Skin/Hair/Face: Cushingoid appearance, acne, thin skin, hirsutism

• Endocrine: adrenal suppression, diabetes

• MSK: osteoporosis, myopathy

• Neuro: pseudotumor cerebri

• Cardio: hypertension

• Immune: immunosuppression, lymphocytopenia, decreased WBC function

• Ophthalmic: cataracts, glaucoma

• Developmental: growth retardation

Use of glucocorticoid steroid

• replacement therapy for adrenal insufficiency

• Anti inflammatory for

1)Allergy (e.g. hayfever),

2) Cancers(leukemia, cystic tumors)

3) CNSsurgeries(TBI,SCI)

4) Eyedisorders (conjunctivitis, optic neuritis)

5) GIdisorders (e.g., Ulcerative colitis)

6) Kidney (nephritic syndrome,glomerulitis)

7) Respiratorydisorders (TB,asthma, etc)

8) Skin disorders (e.g., psoriasis)

9) Osteoarthritis (OA)

Immunosuppression use of glucocorticoid

1) Blood disorders (e.g., anemia, thrombocytopenia)

2) Collagen disorders ( SLE,dermatomyositis, etc)

3) Organtransplant kidney,liver, heart, etc)

Anti inflammatory and immunosuppression action

Rheumaticdisorders (gout, RA)

Cushing syndrome related to corticosteroids

Delayed healing, blurred vision, fatigue, emotional instability, and high blood pressure.

Natural corticosteroids in body

Adrenal cortex: hydrocortisone and cortisone

Decadron

Topical corticosteroids

Systemic corticosteroids

Medrol

MOA corticosteroids

• Alter protein synthesis

• Bind to glucocorticoid receptors in the cytosol to form a hormone-receptor complex that modifies DNA transcription in the nucleus.

• The activated hormone-receptor complex moves inside the nucleus:

• modulates transcription of DNA into mRNA which Inhibits other transcription factors that normally activate inflammatory genes.

Skeletal muscle relaxants

Tx Muscle spasm and stiffness either local issue or neuro spasticity

Antispasm agent (localized)

centrally acting but Tx local spasm

• Diazepam (Valium)

• Cyclobenzaprine (Flexeril)

• Carisoprodol (Soma)

• Metaxalone (Skelaxin)

Polysynaptic Inhibitors

CNS Depressants to Tx locally

• Soma

• Flexiril

• Skelaxin

side effects of polysynaptic inhibitors

• Drowsiness, dizziness

• Headache, nausea, vomiting

• Sedation

• Tolerance, physical dependence

• Withdrawal symptoms

• Rare: Rhabdomyolysis (esp. with Flexeril)

• Risk of fatal overdose

Drugs for Spasticity UMN

• Baclofen (Lioresal)

• Dantrolene (Dantrium)

• Tizanidine (Zanaflex)

• Diazepam (Valium)

Direct acting spasmolytic drug

• Botulinum toxin: inhibits Ach

• Dantrolene: inhibits calcium leading to muscle weakness

Centrally acting spasmolytic drugs that increase GABA activity?

• Baclofen: fatigue

• Gabapentin

• Diazepam (benzodiazepine)m dizzy

Zanaflex

Centrally acting spasmolytic drugs—alpha-2 adrenergic agonist

Q: What is the role of NSAIDs in RA treatment?

NSAIDs control inflammation but do not modify disease progression

first-line tx or combined with DMARDs.

What is the role of corticosteroids (e.g., prednisone) in RA?

used short term during acute exacerbations RA

DMARDS function

Modify the immune system by inhibiting monocytes and t and b cells to control RA

reduce joint inflammation and prevent damage

goal of DMARDS in RA

Control synovitis and erosion of affected joints.

Antimalarial Drug

Plaquenil

Anti-malarials drug MOA

Raise pH disrupt macrophages decreasing T cell stimulation

suppressing immune response

key side effect of anti-malarial?

Irreversible retinal damage—requires periodic eye exams.

Imuran

traditional DMARD

• used for organ transplant rejection preventions and RA unresponsive to other drugs

MOA of Imuran

Inhibits DNA/RNA synthesis, suppressing B and T cell function.

Common side effects of Imuran

Fever, chills, sore throat, fatigue, GI upset.

Gold therapy for RA

• traditional DMARD

• Inhibits T-cell and mononuclear phagocyte function

• used with liver disease pt or cant tolerate Hepatotoxic DMARDS

Gold therapy DMARD side effect

GI upset, skin rash, proteinuria, leukopenia, thrombocytopenia

Gold therapy drug ex

Ridaura

Arava MOA

Blocks RNA synthesis, preventing lymphocyte proliferation

used when patients cant respond other DMARDS

Q: Side effects of Arava?

GI issues, skin rash.

Q: What is the mechanism of Methotrexate/folex?

Inhibits folic acid conversion, blocks DNA synthesis; suppresses cytokines & boosts adenosine

use of Methotrexate

Cancer (high dose)

RA (low dose).

Methotrexate Side effects

GI upset, liver/pulmonary dysfunction, hair loss, hematologic disorders

TNF inhibitor

• Biological DMARDS

• Inhibit TNF a to delay RA progression, not for initial used

TNF-a role

cytokine promotes inflammatory action joint erosion in RA

Enbrel. Humira, and Remicade

TNF inhibitors

Side effects of TNF inhibitors

• Infections (upper respiratory, sepsis)

• Toxic effect easy to be infected, immune system is suppressed