CNSSSSSS - Avtoc0ids

Misoprostol

cytoprotective

Epoprosterol

hypertension

Dinoprostone

termination of pregnancy

Alprostadil

Erectile dysfunction

• Mu receptor

• Kappa receptor

Both Mu and Kappa receptors are Gi/Go couple receptors.

Opioid receptors mediating analgesia:

furan ring

Opioid Analgesics / Narcotic Analgesics

- Removal of this part of structure increase its lipophilicity

Fatal respiratory depression

common ADR from opiods PHENANTHRENE TYPE ABCDE

Buprenorphine (Phenan. type)

○ partial mu agonist

○ does not produce

dependence-promoting euphoria

○ may use to slowing down

addiction on morphine

Nalbuphine (Phenan. type)

○ kappa agonist/mu antagonist

○ mainly used for post-operative/obstetrical anesthesia

Levorphanol

Butorphanol

Morphinan-Types:

Levorphanol

○ Mu agonist

○ 4-8x more potent than morphine

Butorphanol

○ Kappa agonist/mu antagonist

○ 5x more potent than morphine

Fentanyl

○ 80x more potent than morphine

○ Commonly used for cancer pain

Meperidine - Phenylpiperidine

○ 0.1x more potent than morphine

○ may cause serious hypotension and neurotoxicity

normeperidine

Meperidine Toxic metabolite:

Tramadol

Methadone

Non-phenylpiperidine agents

Methadone

used for addiction recovery

Manages withdrawal symptoms

best (More addictive, more withdrawal symptoms)

COX-1

a PG responsible for housekeeping and maintenance functions like activating platelets and acts as a gastroprotective

opioid derived antidiarrheals

amide/cyanide modification eliminates CNS effects

Opioid antagonist

acts as a competitive inhibitor at the μ receptor

Naloxone

adjunct for opioid addiction recovery

Naltrexone

reverses life-threatening opioid

overdose

isoleucin

cox 1 sidechain

valine

cox 2 sidechain

COX-2

- kasi yung gusto lang natin si COX-1 (good sister). Kapag ininhibit ng NSAID yung COX, the arachidonic acid goes to the LOX na nagccause ng bronchodilation

what does NSAID inhibit

COX-1 and COX-2

pain and fever responses (they signal the body that there is an inflammation, pain and fever

liver

Most COX targets __

Acetylsalicylic acid

that's why aspirin can result to bleeding and ulcers since it irreversibly binds COX-1 (usual | high dosing - including COX-2)

Only irreversible COX-1 inhibitor

Diflunisal

Non-selective NSAID

Meclofenamic acid

○ Fenamate NSAID

○ 25x more potent

TIDES:

Tolmetin

Indomethacin

Diclofenac

Etodolac

Sulindac

Arylacetic acid:

TIDES

binds the -SH moiety and inhibits lysosomal enzymes responsible for inflammatory responses

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

MOA:

active gold (Au+)

DMARDS contains __ essential for binding

monosodium urate monohydrate crystals

Gout is a joint inflammation due to accumulation of uric acid or ___ in the synovial fluid

xanthine oxidase inhibitors

uricosurics

recombinant uricases

- attacks the causative agent (uric

acid) by the reducing its amounts

Chronic Gout - you need __ inhibitor

false.

Chronic - attacks the causative agent (uric

acid) by the reducing its amounts

Acute - colchicine; prevents microtubule polymerization

= reduce microtubule-based inflammation

TOF. Chronic Gout drugs prevents microtubule polymerization

xanthine oxidase inhibitors

inhibits the production of uric

uricosurics

areterm-80 agents that promote the

urination of uric acids (tutunaw sa namuong crystals(

Recombinant uricase

enzymes that can

breakdown uric acid

colchicine

to remove deposit (nagsstart na magcrystal in acute gout) give:

purines

Uric acids comes from _

Alluoporinol

xanthine oxidase inhibitor

non purine XO inhihibit

non purine XO inhihibit

Allopurinol

Famous drug for chronic gout

Probenecid

uricosuric agent

Colchicine

○ Anti-tubular

○ Acute gout

Febuxostat

Non-purine XO inhibitor

chronic bronchitis

emphysema

Common COPD

○ Beta-2 adrenergic agonists

○ Antimuscarinic agents

○ Methylxanthines

If you want relievers to relieve the symptoms you're experiencing, use:

○ Mast Cell Degranulation Inhibitors

○ Adrenocorticoids

○ Leukotriene Modifiers

○ Monoclonal Anti-IgE Antibody

○ Phosphodiesterase-4 Inhibitors

If you want to control the possibility of such conditions, use controllers such as:

Beta-2 agonists (phenylethylamines - PEAs)

terbutaline, salbutamol, pirbuterol

SABA (relief drugs:)

control of inflammation

main goal of therapy in CHRONIC ASTHMA:

● Mast cell stabilizers ("crom-")

● PDE Inhibitors (methylxanthines, roflumilast)

● Steroids/glucocorticoids

● Leukotriene antagonists (-lukasts, zileuton)

● Monoclonal anti-IgE antibody therapy

(omalizumab)

Drugs for Chronic Asthma

TRUE

Asthma can be reversed. TOF

spasmogens

Mast Cell inhibits the release of bronchial ___ (histidine, LTs, PGs) from sensitized mast cells (bound to IgE).

furan (khelin)

piperidone ring (nedocromil)

what maintains the activity in chromone

Methylxanthines (theophylline)

Roflumilast

Phosphodiesters (PDE) Inhibitors

dialkoxyphenyl ring

Roflumilast has what ring?

xanthine oxidase

theophylline metabolism

Theophylline

naturally occurring○ No clear SAR but it is scientifically

proven that it also targets PDE

lipocortin

Adrenocortids (Glucocorticoids) stimulates synthesis of __

pregnane ring skeleton must be trans-conformation

Adrenocortids (Glucocorticoids) drugs should have __conformation

- Antagonize LT receptor (Montelukast, Zafirlukast)

- inhibits the 5- lipoxygenase (Zileuton) resulting in decreased synthesis of LTs.

Leukotriene Modifiers MOA

Montelukast

● __ Quinoline derivative

mimics triene moiety of LTs = essential for activity

Zileuton

● Classified as N-hydroxyurea

N-OH

Zileuton - what is essential for its activity

Benzothienyl ring

It increases lipophilicity in Zileuton

5-HT1B and 5-HT1D receptors

"-TRIPTANS" stimulates ___ and __ receptors

- Leads to vasoconstriction = inhibition of

pain stimuli in vessels and nerve

endings in the brain.

migraines and cluster headaches

"-TRIPTANS" used for

High blood pressure

SIDE EFFECT of "-Triptans"

"-SETRONS"

Gold standard for chemotherapy and radiation-induced nausea and vomiting.

"-setrons"

They mimic serotonin

Sumatriptan

Prototype -triptan agent

Rizatriptan

Special because it is prescribed for pediatric migraine

Granisetron

Antiemetic that is commonly prescribed to chemotherapy patients

Alosetron

Anti-diarrheal IBS (irritable bowel syndrome)

Ergotamine

For migraine headache

Ergonovine

Aids in controlling bleeding from

labor

Lysergic Acid Diethylamide (LSD)

○ Commonly derived from mushrooms

○ Never been used

○ Literally addictive hallucinogen

Histaminergic Agents

those that works on histamine receptors and results in different pharmacologic uses (depending on which histamine receptor is being targeted)

mast cells and basophils

Histamine is commonly found in __ and __ in the body

- H1-blockers (1st and 2nd generation)

- H2-blocker

Histaminergic Agents

Classes:

Cationic amine

responsible for receptor binding at the anionic site

2-3c

The spacer that divides the aromatic moieties and amino group should be __ carbons in length

remember

bulkier ring = cis- aromatic moiety (can be substituted)

less bulky = trans- aromatic moiety (must be unsubstituted)

LOX or COX

Eicosanoids is metabolized by __

PG

affects inflammation, renal function, provides gastroprotection, and increase aqueous humor

LT

affects bronchoconstriction

Misoprostol= cytoprotective

Epoprosterol= hypertension

Dinoprostone= termination of pregnancy

Alprostadil= Erectile dysfunction

Latanaprost= glaucoma

MEDAL

Latanaprost

prostaglandin used for glaucoma

Analgesic

drugs which provides a relief from pain.

Opioid Analgesics

naturally occurring opium alkaloid from the latex of opium plants (Papaver somniferum).

false. no euphoria = less addictive stimulation

TOF. Kappa receptor stimulation results to decreased cAMP and Ca+2 → euphoria — may result to addiction and dependence.

Pure Antagonist

blocks all activity at both receptor sites with highest affinity to mu receptors

Agonist/Antagonist

produce potent analgesia at kappa receptor but has strong antagonist activity at mu

Pure Agonist (full/partial)

acts on the mu receptor; produce potent analgesia with ADRs similar to morphine use

Opioid Analgesics / Narcotic Analgesics

Substances that possess "morphine-like" effects

4-phenylpiperidine max of 5 rings

Opioid Analgesics / Narcotic Analgesics

SAR: __ phenylpiperidine

Codeine and Oxycodone

Opioid known to cause fatal cardiotoxicity in prolonged use

4-phenylpiperidine

morphine has ___ structure that must contain mx 5 rings