PMCOL 343 Final Drugs/Therapies to Know

Oxytocin

- A neuropeptide that functions as a hormone in the peripheral circulation and as a neurotransmitter in the CNS

- Comes from magnocellular neurons that project into posterior pituitary

- Used for Labour induction, Augmentation of dysfunctional Child birth, and prevention of postpartum hemorrhage

- Investigated to also be used in social and psychiatric disorders

Vasopressin

- Comes from magnocellular neurons that project into posterior pituitary

- Vasoconstriction and prophylaxis against bleeding in haemophilia in vascular smooth muscle

- Treats diabetes insipidus and nocturnal enuresis in Kidney

- Investigated to have an effect in treating autism

Pegvistomant

GH antagonist that is used for acromegaly

Octreotide

GH antagonist that is used in acromegaly and gigantism

GH replacement

Therapy used in pituitary dwarfism, turners syndrome, and adult GH deficiency

Predinsolone

- Short acting synthetic derivative of cortisol

- Used in replacement therapy, anti-inflammatory therapy, immunosuppressive therapy, and antiproliferative stuff (cancer)

Hydrocortisone

- Cortisol, the endogenous glucocorticoid

- Used in replacement therapy, anti-inflammatory therapy, immunosuppressive therapy, and antiproliferative stuff (cancer)

- Aims to replicate circadian rhythm

Dexamethasone

- Long acting synthetic derivative of cortisol

- Used in replacement therapy, anti-inflammatory therapy, immunosuppressive therapy, and antiproliferative stuff (cancer)

Vamolorone

- A SGRM

- Opts for anti-inflammatory Transrepression effects rather than Transactivation effects

Ketoconazole

- Antiandrogen

- 17⍺-hydroxylase inhibitor

- prevents the creation of Cortisol and Androstenedione

- used for Cushing syndrome

- Side effect is it increases levels of progesterone and aldosterone

- Inhibits testosterone synthesis- BHP and prostate cancer

Metyrapone

- 11β-hydroxylase

- Prevents the creation of cortisol and aldosterone

- Used to treat Cushing syndrome

Anastrozole

- Antiestrogen

- Aromatase inhibitor

- Prevents the conversion of Androgens to estrogens

- used for treatment of breast cancer

Clomiphene Citrate

- SERM

- Inhibits the negative feedback sent to hypothalamus and pituitary

- This increases GnRH, FSH, LH, Estrogen and progesterone

- Used to induce ovulation, infertility,

- Can cause ovarian enlargement and cysts, blurred vision, hot flashes

Tamoxifen

- SERM

- Antagonistic (anti-proliferative) effects in breast tissue

- Agonist on Bones

- Agonistic effects in uterus

- Is a prodrug that gets converted to endoxifen via CYP2D6 and 3A4

- Used to treat breast cancer

- Can increase uterine cancer and increases blood clot risk

Raloxifene

- SERM

- Antagonistic (anti-proliferative) effects in breast tissue

- Agonist on Bones

- Neutral effects in uterus

- Used for breast cancer and osteoporosis

- No risk for endometrial cancer

- Increases blood clot risk and does not relieve hot flash

Fluvestrant

- SERD

- Binds to ER in monomeric form and prevents dimerization of ER, preventing activation

- Increases ER-degredation through ubiquitin-proteasome pathway

- Targets ER⍺ for treatment of metastatic breast cancer

PROTACS

- proteolysis targeting chimeras

- Bind to ER and E3 ligase and induce artificial ubiquitination leading to degradation of ER by the proteasome

- useful for cancers with resistant to estrogen deprivation therapies

Mifepristone

- SPRM

- Binds to PR with more affinity than P

- Selective antagonist to progesterone, this causes lining of the uterus to thin, making embryo babe to stay implanted in the uterine wall

- Used with misoprostol which triggers muscle contractions

- Abortion in first trimester

Ulipristal acetate (UPA)

- SPRM

- Used for symptoms of uterine fibroids (withdrew)

- Emergency contraception (not in Canada)

- Inhibits or delays ovulation

Levonorgestrel

- Plan B

- Emergency contraception pill that impairs luteal function and prevents/delays ovulation

- Only has progestin

Yuzpe method

- Emergency hormonal contraceptive

- combines estrogen and progestin

- Inhibits implantation of a fertilized egg

- delays/suppresses ovulation, interferes with corpus luteum, changes to endometrium

Abiraterone acetate

- Antiandorgen

- Inhibits 17⍺-hydroxylase and 17,20 lyase

- Effective in androgen dependent prostate cancer

- May cause cortisol deficiency

Finasteride

- Antiandrogen

- 5⍺-reductase inhibitor

- Inhibits the conversion of testosterone to DHT

- Used to treat BPH, minimally used in PC

- Lower chances to cause impotence, infertility, and loss of libido due to no testosterone interference

Flutamide

- Antiandrogen

- Binds to AR and prevents translocation to nucleus

- Used to treat prostate cancer

- Susceptible to AR mutations

Darolutamide

- Antiandrogen

- Inhibits wild type and mutated ARs

- More effective in blocking translocation

- Good for PC

PROTACS for androgen receptors

Effectively degrade ARs and eliminate active proteins of high hormone environment

SARMs

- Bind to AR and display tissue selective activation of androgenic signalling

- range from full agonists to antagonists in tissues

- Originally synthesized for muscle wasting conditions, osteoporosis, breast cancer and prostate cancer

- Highly attractive for doping

- Shit ton of side effects

Cocaine

- Local anesthetic Ester

- Blocks sodium channels and increases threshold of depolarization in specific tissue

- Unionized passes through membrane, then re-ionizes and enters sodium channel to block it

- Channel has to be open for drug to work

- Minimally bound to proteins in plasma, Alpha 1 acid glycoprotein

- Hydrolyzed by Plasma Cholinesterases to PABA

Lidocaine

- Local anesthetic Amide

- Blocks sodium channels and increases threshold of depolarization in specific tissue

- Unionized passes through membrane, then re-ionizes and enters sodium channel to block it

- Channel has to be open for drug to work

- Extensively bound to proteins in plasma, Albumin

- Metabolized in liver by aromatic hydroxylation, amide hydrolysis, N-delkylation (much slower than esters)

Propofol

- General Anesthetic

- Activates GABA receptors to cause hyperpolarization. Since it is inhibitory, leads to decreased neural activity. Potentiates Cl- ions through this channel

- Rapid onset and emergence

- No hangover

- Predictable context-sensitive half time

- Anti-emetic (no vomit or nausea)

- Anti-convulsant properties

- Most frequently used anesthetic

- Highly lipid-soluble with rapid clearance

Ketamine

- General Anesthetic

- NMDA receptor antagonist

- Analgesic and anesthetic effects

- Associated with delirium and hallucinations

- Increases HR and BP

- Mild respiratory depressions

Montelukast

- LTB4 antagonist used for prophylaxis in asthma

Misoprostol

- Synthetic PGE1

- Used for induction of labour and postpartum bleeding

- Used to treat NSAID-induced gastric ulcers via acting on EP1/2 on mucosal cells to increase bicarbonate and EP4 to increase mucous. Also acts on EP2/3 receptors on ECL cells to inhibit histamine production

Glucocorticoids and COX

- Induces lipocortin which inhibits phospholipase A2

- Only used for chronic inflammation due to lots of side effects

Non-steroidal inflammatory agents (NSAID)

- COX inhibitor

- Works on analgesic, anti-pyretic, and anti-inflammatory

- used to treat mild to moderate pain, fever, and inflammatory disorders

- Inhibiting COX reduces prostaglandins synthesis

- Antipyretic effects come from PGE2 synthesis inhibition in the hypothalamus

- Causes GI ulceration, inhibits platelet aggregation, Inhibits uterine motility, inhibition of PG-mediated renal blood flow

Acetylsalicyclic acid (ASA)

- NSAID

- Inhibits both COX isoforms

- Anti-inflammatory, anti-pyretic, analgesic effect, and anti-platelet effect

- Reduces myocardial infarction

- Irreversible binding

Ibuprofen

- NSAID

- Inhibits both COX isoforms

- Anti-inflammatory, anti-pyretic, analgesic effect, and anti-platelet effect

- Slightly more potent than ASA for producing analgesic effects at lower doses which limits GI bleeding

- Can cause hypertension by stopping PGE1 synthesis in kidney or altering TXA2/PGI2 synthesis

Naproxen

- NSAID

- Inhibits both COX isoforms

- Used in osteoarthritis

- Only NSAID that is a single isomer

Indomethacin

- NSAID

- Inhibits both COX isoforms

- Also inhibits Phospholipase A2

- Impedes migration and proliferation of immunocompetent cells

- Used in rheumatic conditions such as Gout and Ankylosing spondylitis

Celecoxib

- NSAID

- Selective for COX2

- Used for rheumatoid arthritis and osteoarthritis

- Less GI upset

- Has cardiovascular concern

Acetaminophen

- NOT AN NSAID

- Has analgesic, anti-pyretic but NOT anti-inflammatory or anti-platelet

- No GI bleeding

- May effect COX3 in brain which is involved with body temp (anti-pyretic)

- Used for mild pain

- Great toxicity with NAPQI metabolite (hepatic necrosis)