Pharmacology Flashcards
1
Q
Surgical excision
A
Estrogen Receptor Positive Tumors
• Still the definitive treatment, best for primary, non-metastasized tumors
2
Q
o Goserelin
A
Estrogen Receptor Positive
– GnRH agonist, used for “chemical castration” in premenopause
• Causes downregulation of FSH/LH receptors to ultimately mute estrogen production
• SQ injection in upper abdominal wall lasting for 28 days
• Will cause an initial “flare” of symptoms for a few days (bone pain/breast tenderness and enlargement); should be treated with analgesics
• Adverse effects:
• Menopausal symptoms (hot flashes, vaginal dryness, mood swings, etc)
• Osteoporosis/osteopenia that may be irreversible
3
Q
o Raloxifen
A
Estrogen Receptor Positive
– SERM used to block action of estrogen at the breast (pre/postmenopause)
• Mixed agonist that has both anti/pro-estrogenic effects depending on the tissue
• Monthy IM injection
• Anti-estrogen on mammary tissue = stop breast cancer proliferation
• Pro-estrogen on bone = prevents osteoporosis
• Adverse effects:
• Teratogenic
• Thromboembolic disease (DVT, PE, stroke)
4
Q
o Tamoxifen
A
Estrogen Receptor Positive
– SERM used to block action of estrogen at the breast (pre/postmenopause)
• Mixed agonist that has both anti/pro-estrogenic effects depending on the tissue
• Daily PO pill
• Anti-estrogen on mammary tissue = stop breast cancer proliferation
• Pro-estrogen on bone = prevents osteoporosis
• Adverse effects:
• Teratogenic
• Endometrial hypertrophy/cancer with bleeding
• Thromboembolic disease (DVT, PE, stroke)
5
Q
o Toremifene/Bazodoxiene
A
Estrogen Receptor Positive
– SERM used to block action of estrogen at the breast (pre/postmenopause)
• 2nd generation SERM (derivative of Tamoxifen)
• Daily PO pill
• Anti-estrogen on mammary tissue = stop breast cancer proliferation
• Pro-estrogen on bone = prevents osteoporosis
• Adverse effects:
• Teratogenic
• Endometrial hypertrophy/cancer with bleeding
• Thromboembolic disease (DVT, PE, stroke)
• Prolongation of QT interval (risk of heart attack/arrhythmia)
6
Q
o Fulvestrant
A
Estrogen Receptor Positive
– SERD used to block action of estrogen at the breast (pre/postmenopause)
• Pure estrogen receptor antagonist that stops dimerization and nuclear translocation, thus signaling of the estrogen receptor; also downregulates ERs
• Monthly injection allows for sustained plasma levels
• Adverse effects: Menopausal symptoms (hot flashes, vaginal dryness, mood swings, etc)
7
Q
o Anastrozole
A
Estrogen Receptor Positive
– aromatase inhibitor to block adipocyte estrogen production in postmenopause
• Binds to the heme center of CYP19A1 (aromatase) to block it’s action
• Because ovaries no longer are the major source of estrogens, blocking peripheral aromatization of androgens into estrogens mutes estrogen production
• Daily oral pill
• Adverse Effects:
• Menopausal symptoms; but not as bad as tamoxifen
• Teratogenic
8
Q
o Exemestane
A
Estrogen Receptor Positive
– aromatase inhibitor to block adipocyte estrogen production in postmenopause
• Binds to the heme center of CYP19A1 (aromatase) to block it’s action
• Because ovaries no longer are the major source of estrogens, blocking peripheral aromatization of androgens into estrogens mutes estrogen production
• Daily oral pill
• Adverse Effects:
• Menopausal symptoms; but not as bad as tamoxifen
• Teratogenic
9
Q
o Letrozole
A
Estrogen Receptor Positive
– aromatase inhibitor to block adipocyte estrogen production in postmenopause
• Binds to the heme center of CYP19A1 (aromatase) to block it’s action
• Because ovaries no longer are the major source of estrogens, blocking peripheral aromatization of androgens into estrogens mutes estrogen production
• Daily oral pill
• Adverse Effects:
• Menopausal symptoms; but not as bad as tamoxifen
• Teratogenic
10
Q
o Pertuzumab
A
Human Epidermal Growth factor (HER-2) positive tumors
– IgG-kappa humanized antibody blocking HER-2 activity
• Binds to the extracellular juxtraglomerular region of HER2
• Adverse effects
• Hypersensitivity/Alopecia/loss of appetite
• Teratogenic
11
Q
o Trastuzumab
A
Human Epidermal Growth factor (HER-2) positive tumors
– IgG-kappa humanized antibody blocking HER-2 activity
• Binds to the extracellular dimerization domain of HER2 (Subdomain II)
• Adverse effects
• Pneumonia/respiratory failure/respiratory distress syndrome (infusion reaction)
• Cardiomyopathy/heart failure
• Teratogenic
12
Q
o Ado-Trastuzumab Emtasine
A
Human Epidermal Growth factor (HER-2) positive tumors
– IgG-kappa humanized antibody blocking HER-2 activity
• Bind to the HER2 receptor and is internalized, bringing in a linked microtubule active chemotherapeutic drug to halt cell cycling
• Adverse effects
• Cardiomyopathy/heart failure
• Teratogenic
13
Q
o Lapatinib
A
Human Epidermal Growth factor (HER-2) positive tumors
– small molecule Tyrosine kinase inhibitor that inhibits HER-1 and HER-2
• Binds to intracellular domain of ErbB1/ErbB2 to complete with ATP; preventing phosphorylation, thus action of the HER-2 receptor
• Adverse effects
• Liver disease/failure (increased drug levels); LFTs required
14
Q
o Progesterone receptor positive tumors
A
o Breast cancers expressing mutated autocrine signaling PR receptors (PR+) can be a potential target for therapy
o Not sure if there’s any drugs here, but apparently PR signals can repress ER+ activity
15
Q
o Surgical excision – effective in early, non-metastatic disease
o Radiation of solid tumors can help shrink the tumor
A
Triple negative tumors
16
Q
o Everolimus
A
Triple negative tumors
– mTOR inhibitor that stops cell proliferation/angiogenesis/cell metabolism
• Can be used with any type of breast cancer
• Adverse effects
• Immunosuppression – increased infection/neoplastic risk
• Risks related to grafts/transplants
17
Q
o Anthracycline+doxorubicin+other drugs
A
Triple negative tumors
• Classic regimen
• Incidence of cardiac issues post-treatment is a concern
18
Q
• Medroxyprogesterone (Depo-Provera)
A
Endometrial cancer
– progestin contraceptive which can bind to progestin receptors to block GnRH release; causes cessation of menstrual cycle
19
Q
• Megestrol
A
Endometrial cancer
– synthetic oral progestin which suppresses LH release and enhances estrogen degradation; may cause low estrogen/signs of menopause; may also be use in ER+ breast cancer treatment
20
Q
• Carboplatin
A
Epithelial Ovarian Carcinoma/Testicular Cancer
– DNA intrastrand crosslinks; more myelosuppression, nephro/ototoxicity, less peripheral neuropathy; use amifostine (free radical scavenger) and saline diuresis to minimize these
21
Q
• Cisplatin
A
Epithelial Ovarian Carcinoma/Testicular Cancer
– DNA intrastrand crosslinks; identical but less myelosuppression and more peripheral neuropathy, thrombocytopenia
22
Q
• Cyclophosphamide
A
Epithelial Ovarian Carcinoma
– prodrug (needs liver activation) of DNA crosslinker at N-7 guanine residue; myelosuppression, hemorrhagic cystitis; use MESNA to bind toxic metabolites and protect bladder
23
Q
• Doxorubicin
A
Epithelial Ovarian Carcinoma
– free radical generator to cause DNA strand breaks; myelosuppression, dilated cardiomyopathy; use dexrazoxane (iron chelator) to prevent cardiotoxicity
24
Q
• Paclitaxel
A
Epithelial Ovarian Carcinoma/Testicular Cancer
– stabilize polymerized microtubules in M-phase of cell division so mitotic spindle cannot breakdown and cell cannot divide; myelosuppression, hypersensitivity
25
• Mitomycin C
Bladder Carcinoma
o Trans-urethral resection followed by intravesical installation of high concentration of chemo. To eradicate any residual neoplastic uroepithelium
– alkylating agent; pancytopenia, chemical cystitis, contact dermatitis with palmar/plantar erythema
26
• Bacillus Calmette-Guerin (BCG)
Bladder Carcinoma
o Trans-urethral resection followed by intravesical installation of high concentration of chemo. To eradicate any residual neoplastic uroepithelium
– binds uroepithelial cells, attracting antigen-presenting cells to produce CTLs/NKs/LAKs/BCG-killer cells. Patient must have an intact immune system. Immune response can occur within hours and last for days.
27
• Thiotepa
Bladder Carcinoma
o Trans-urethral resection followed by intravesical installation of high concentration of chemo. To eradicate any residual neoplastic uroepithelium
– small molecular weight so it easily penetrates bladder
– alkylating agent; pancytopenia, dysuria/urinary retention/chemical and hemorrhagic cystitis, renal dysfunction
28
o Total cystectomy with life-style changes needed when bladder sparing measures do not work
Bladder Carcinoma
29
• Surgery is the definite treatment for any solid tumor!
o Often the entire affected testicle will be removed
o Best used if disease is confined to single testicle
o Removing one testicle does NOT impact fertility in an appreciable manner
Testicular Cancer
30
o Bleomycin
Testicular Cancer
31
o Etoposide
Testicular Cancer
32
o Ifosfamide
Testicular Cancer
33
o Vinblastine
Testicular Cancer
34
o “Train your bladder” to be continent
o Fluid management (not drinking too much at any given time)
o Pelvic floor exercises (strong muscles means good retention)
o Timed bladder emptying (get those neural pathways en pointe with normal firing)
Urinary Incontinence
35
o Oxybutynin
Urinary Incontinence
– blocks muscarinic Ach receptors (M3 to stop detrussor muscle contraction)
o Adverse Effects
• Peripheral: dry mouth, mydriasis, constipation, urinary retention, tachycardia
• Central: sedation, confusion, hallucinations, slow cognitive function, poor sleep
o Concerns with these drugs
• Elderly patients taking multiple anti-cholinergics can be extremely difficult to manage-
• Contradindications: narrow-angle glaucoma, GU/GI obstruction, alzhemer’s dementia, need for mental alertness (they’re an airplane pilot)
36
o Tolterodine
Urinary Incontinence
– blocks muscarinic Ach receptors (M3 to stop detrussor muscle contraction)
• Strong oral bioavailabilty (75%)
o Adverse Effects
• Peripheral: dry mouth, mydriasis, constipation, urinary retention, tachycardia
• Central: sedation, confusion, hallucinations, slow cognitive function, poor sleep
o Concerns with these drugs
• Elderly patients taking multiple anti-cholinergics can be extremely difficult to manage-
• Contradindications: narrow-angle glaucoma, GU/GI obstruction, alzhemer’s dementia, need for mental alertness (they’re an airplane pilot)
37
o Fesoterodine
Urinary Incontinence
– blocks muscarinic Ach receptors (M3 to stop detrussor muscle contraction)
o Adverse Effects
• Peripheral: dry mouth, mydriasis, constipation, urinary retention, tachycardia
• Central: sedation, confusion, hallucinations, slow cognitive function, poor sleep
o Concerns with these drugs
• Elderly patients taking multiple anti-cholinergics can be extremely difficult to manage-
• Contradindications: narrow-angle glaucoma, GU/GI obstruction, alzhemer’s dementia, need for mental alertness (they’re an airplane pilot)
38
o Trospium
Urinary Incontinence
– blocks muscarinic Ach receptors (M3 to stop detrussor muscle contraction)
• Quatrinary amine that cannot cross BBB (no central side effects!)
• Poor oral bioavailabilty (
39
o Solifenacin
Urinary Incontinence
– blocks muscarinic Ach receptors (M3 to stop detrussor muscle contraction)
• Strong oral bioavailability (90%)
o Adverse Effects
• Peripheral: dry mouth, mydriasis, constipation, urinary retention, tachycardia
• Central: sedation, confusion, hallucinations, slow cognitive function, poor sleep
o Concerns with these drugs
• Elderly patients taking multiple anti-cholinergics can be extremely difficult to manage-
• Contradindications: narrow-angle glaucoma, GU/GI obstruction, alzhemer’s dementia, need for mental alertness (they’re an airplane pilot)
40
o Darifenacin
Urinary Incontinence
– only blocks muscarinic M3 Ach receptor to stop detrussor muscle contraction
o Adverse Effects
• Peripheral: dry mouth, mydriasis, constipation, urinary retention, tachycardia
• Central: sedation, confusion, hallucinations, slow cognitive function, poor sleep
o Concerns with these drugs
• Elderly patients taking multiple anti-cholinergics can be extremely difficult to manage-
• Contradindications: narrow-angle glaucoma, GU/GI obstruction, alzhemer’s dementia, need for mental alertness (they’re an airplane pilot)
41
o Mirabegron
Urinary Incontinence
– B3 agonist – relaxes detrusor muscle to increase holding capacity
• 50-hour half-life (super long!)
• Increased Blood pressure/tachycardia (concern in HTN patients)
42
o Pseudoephedrine
Urinary Incontinence
– a>B agonist, can stimulate B3/a1 but is non-specific
• Hypertension, Atrial fibrillation, insomnia, anxiety
• Interacts with MAOIs, must check patient history
43
o Ephedra
Urinary Incontinence
– indirect a/B agonist – can stimulate B3/a1 but non-specific
• Hypertension, Atrial fibrillation, CHF/MI, insomnia
• Interacts with MAOIs, must check patient history
44
o Ma Huang
Urinary Incontinence
– indirect a/B agonist – can stimulate B3/a1 but non-specific
• Hypertension, Atrial fibrillation, CHF/MI, insomnia
• Interacts with MAOIs, must check patient history
45
o Botox
Urinary Incontinence
– stops Ach release by cutting pre-synaptic SNARE/SNAP proteins, halting vesicle fusion
• Injections into urothelial wall to limit Ach receptor signaling
• Patients responding the anti-cholinergic drugs but cannot tolerate adverse effects are the best candidates for this therapy
• May result in initial hyper-responsive bladder due to initial cholinergic firing not occurring to keep the bladder retaining urine
46
o Methionine
Urinary Incontinence
– acidifies urine (decrease pH) to eliminate ammonia, limits odor/dermatitis/ ulceration from leaking urine
• Take with milk/food
• Adverse effects: drowsiness, nausea, vomiting
47
o Bovine Collagen
Urinary Incontinence
– injected into urethra to increase bulk of sphincter, aiding with incontinence due to intrinsic sphincter deficiency
• Used in patients that fail other therapies for >1 year
48
• Bethanechol
Urinary Retention
– muscarinic agonist for bladder and GI tract (stimulates M3 receptors)
o Does not cross BBB so no central side effects
o Super short half life (1 hour orally)
o Adverse effects: syncope, diarrhea, dizziness, excessive tear production, urgent urination
49
• Neostigmine
Urinary Retention
– acetylcholinesterase inhibitor to increase Ach effect on muscarinic receptors (M3)
o Super short half life (
50
• Goserelin
Prostate Cancer
– GnRH agonist (feedback inhibition for androgen production via hypothalamus/ant. pit.)
• All GnRH agonists have similar properties
o SC or IM injection
o Adverse effects mainly relate to low testosterone
• Deceased estrogen = decreased bone mineral density (risk for fracture)
• Increased serum lipids/weight gain/diabetes mellitus = cardiovascular disease
• Sexual dysfunction/reduced libido/gynecomastia = low testosterone
• Disease flare (bone pain, sexual organ tenderness) = initial agonist effect
• Injection site reactions (not uncommon with any injection drug)
• Pregnancy category X
51
• Histrelin
Prostate Cancer
– GnRH agonist (feedback inhibition for androgen production via hypothalamus/ant. pit.)
• All GnRH agonists have similar properties
o SC or IM injection
o Adverse effects mainly relate to low testosterone
• Deceased estrogen = decreased bone mineral density (risk for fracture)
• Increased serum lipids/weight gain/diabetes mellitus = cardiovascular disease
• Sexual dysfunction/reduced libido/gynecomastia = low testosterone
• Disease flare (bone pain, sexual organ tenderness) = initial agonist effect
• Injection site reactions (not uncommon with any injection drug)
• Pregnancy category X
52
• Leuprolide
Prostate Cancer
– GnRH agonist (feedback inhibition for androgen production via hypothalamus/ant. pit.)
• All GnRH agonists have similar properties
o SC or IM injection
o Adverse effects mainly relate to low testosterone
• Deceased estrogen = decreased bone mineral density (risk for fracture)
• Increased serum lipids/weight gain/diabetes mellitus = cardiovascular disease
• Sexual dysfunction/reduced libido/gynecomastia = low testosterone
• Disease flare (bone pain, sexual organ tenderness) = initial agonist effect
• Injection site reactions (not uncommon with any injection drug)
• Pregnancy category X
53
• Triptorelin
Prostate Cancer
– GnRH agonist (feedback inhibition for androgen production via hypothalamus/ant. pit.)
• All GnRH agonists have similar properties
o SC or IM injection
o Adverse effects mainly relate to low testosterone
• Deceased estrogen = decreased bone mineral density (risk for fracture)
• Increased serum lipids/weight gain/diabetes mellitus = cardiovascular disease
• Sexual dysfunction/reduced libido/gynecomastia = low testosterone
• Disease flare (bone pain, sexual organ tenderness) = initial agonist effect
• Injection site reactions (not uncommon with any injection drug)
• Pregnancy category X
54
• Degarelix
Prostate Cancer
– reversible GnRH receptor antagonist
o Reduces LH/FSH to mute androgen production within 3 days
o Does not have initial disease flare that agonists have
o Adverse effects
• QT prolongation (arrhythmias)
• Hepatic enzyme changes
• Deceased estrogen = decreased bone mineral density (risk for fracture)
• Increased serum lipids/weight gain/diabetes mellitus = cardiovascular disease
• Low testosterone = Sexual dysfunction/reduced libido/gynecomastia
55
• Estramustine
Prostate Cancer
– estradiol conjugated with an alkylating agent (raises estrogen levels to depress HPA axis and kills cancerous cells in prostate)
o Oral drug
o Prostate cancers can express estramustine binding protein (EMBP) so when the drug hits the prostate, it enters the cancerous cells via this cell surface protein to gain entry and deliver the conjugated alkylator, inhibiting microtubules and inducing DNA strand breakage
o Adverse effects:
• Gynecomastia/mastalgia/infertility = increased estrogen levels
• Edema, thromboembolic disease (PE/DVT/stroke), MI = increased estrogen levels
56
• Bicalutamide
Prostate Cancer
– androgen receptor blocker (decreased androgen effect but normal androgen levels)
o Antagonist with some agonist activity; Prostate > central action
o Teratogenic
57
• Enzalutamide
Prostate Cancer
– androgen receptor blocker (decreased androgen effect but normal androgen levels)
o Pure antagonist with prostate and central action
o Male and female mediated teratogenicity
o Adverse effects:
• Dizziness insomnia, seizures (due to CNS action)
58
• Flutamide
Prostate Cancer
– androgen receptor blocker (decreased androgen effect but normal androgen levels)
o Pure antagonist with prostate action only
o May be used hirsutism or polycystic ovary syndrome as well (women’s diseases)
o Adverse effects:
• Myelosuppression
• Teratogenic
59
• Nilutamide
Prostate Cancer
– androgen receptor blocker (decreased androgen effect but normal androgen levels)
o Pure antagonist with prostate and central action
o Adverse effects:
• HTN/heart failure, myelosuppression
• Increased time to accommodate from light to darkness
• Respiratory insufficiency/interstitial pneumonitits
60
• Sipuleucel-T
Prostate Cancer
– T-cell stimulatory treatment to prime cell-mediated response against prostate
o Process of treatment
• Leukapherese patient’s APCs, thus culture them with Prostatic Acid Phosphasase (PAP) mixed with GM-CSF
• APCs will take up antigen and express fragments on their surface
• APCs then re-infused to stimulate CD-8 T-cell immune response against prostate cancer
o Note that prostate cancer expresses higher amounts of PAP, allowing for specificity
o Adverse effects
• Mild infusion reactions
• Paresthesias, citrate toxicity, fatigue
61
• Abiraterone
Prostate Cancer
– 17a-hydroxylase (CYP17) inhibitor causing decreased androgen production
o Stops conversion of adrenal intermediates to androsteidione, thus lowering testosterone/DHT
o Produces hyper-mineralocorticoid state
• HTN, increased Na+, decreased K+ levels, fluid retention
• Do not use in people with existing heart problems
o Corticosteroid administration can suppress ACTH to stop hyper-mineralocorticoid effects
o Other adverse effects
• Elevated hepatic liver enzymes
• Category X drug – women should not take this AND it can pass through semen!
62
o Carbazitaxel
Prostate Cancer
• Conventional Chemotherapy typically involves taxanes
• Keeps microtubules polymerized so cytokinesis cannot occur and cells cannot divide
• Poor substrate for P-gp efflux pump often seen in resistant cancers; which may aid in treating resistant cancers
• Also crosses BBB, which may be useful in brain tumors
63
• Prazosin
Benign Prostatic Hypertrophy
• Alpha-1 adrenergic receptor blockers - Blocking receptors can relax the penile urethra/prostate aiding in voiding
• All drugs thought to be similarly efficacious
• Adverse effects:
o GI - xerostomia/nausea
o CNS – dizziness, headache, insomnia
o Abnormal ejaculation (retrograde, lack of ejaculation)
o Floppy iris syndrome – if patient on a1-receptor getting cataract surgery, their iris can billow/prolapse in response to operative incisions/irrigation
• Stopping the a-blocker before surgery does NOT provide benefit
• Surgical technique modification may be the best treatment
64
• Alfuzosin
Benign Prostatic Hypertrophy
• Alpha-1 adrenergic receptor blockers - Blocking receptors can relax the penile urethra/prostate aiding in voiding
• All drugs thought to be similarly efficacious; clinically alfuzosin is thought to be superior
• Adverse effects:
o GI - xerostomia/nausea
o CNS – dizziness, headache, insomnia
o Abnormal ejaculation (retrograde, lack of ejaculation)
o Floppy iris syndrome – if patient on a1-receptor getting cataract surgery, their iris can billow/prolapse in response to operative incisions/irrigation
• Stopping the a-blocker before surgery does NOT provide benefit
• Surgical technique modification may be the best treatment
65
• Terazosin
Benign Prostatic Hypertrophy
• Alpha-1 adrenergic receptor blockers - Blocking receptors can relax the penile urethra/prostate aiding in voiding
• All drugs thought to be similarly efficacious
• Adverse effects:
o GI - xerostomia/nausea
o CNS – dizziness, headache, insomnia
o Abnormal ejaculation (retrograde, lack of ejaculation)
o Floppy iris syndrome – if patient on a1-receptor getting cataract surgery, their iris can billow/prolapse in response to operative incisions/irrigation
• Stopping the a-blocker before surgery does NOT provide benefit
• Surgical technique modification may be the best treatment
66
• Doxazosin
Benign Prostatic Hypertrophy
• Alpha-1 adrenergic receptor blockers - Blocking receptors can relax the penile urethra/prostate aiding in voiding
• All drugs thought to be similarly efficacious
• Adverse effects:
o GI - xerostomia/nausea
o CNS – dizziness, headache, insomnia
o Abnormal ejaculation (retrograde, lack of ejaculation)
o Floppy iris syndrome – if patient on a1-receptor getting cataract surgery, their iris can billow/prolapse in response to operative incisions/irrigation
• Stopping the a-blocker before surgery does NOT provide benefit
• Surgical technique modification may be the best treatment
67
• Tamsulosin
Benign Prostatic Hypertrophy
• Alpha-1 adrenergic receptor blockers - Blocking receptors can relax the penile urethra/prostate aiding in voiding
• All drugs thought to be similarly efficacious
• Adverse effects:
o GI - xerostomia/nausea
o CNS – dizziness, headache, insomnia
o Abnormal ejaculation (retrograde, lack of ejaculation)
o Floppy iris syndrome – if patient on a1-receptor getting cataract surgery, their iris can billow/prolapse in response to operative incisions/irrigation
• Stopping the a-blocker before surgery does NOT provide benefit
• Surgical technique modification may be the best treatment
68
• Silodosin
Benign Prostatic Hypertrophy
• Alpha-1 adrenergic receptor blockers - Blocking receptors can relax the penile urethra/prostate aiding in voiding
• All drugs thought to be similarly efficacious
• Adverse effects:
o GI - xerostomia/nausea
o CNS – dizziness, headache, insomnia
o Abnormal ejaculation (retrograde, lack of ejaculation)
o Floppy iris syndrome – if patient on a1-receptor getting cataract surgery, their iris can billow/prolapse in response to operative incisions/irrigation
• Stopping the a-blocker before surgery does NOT provide benefit
• Surgical technique modification may be the best treatment
69
• Finasteride (Type II)
Benign Prostatic Hypertrophy
• 5-a reductase inhibitors - Normally 5-a reductase converts [testosterone → DHT], which has a longer/stronger action and some different specificities of site of action. Two types are identified:
o Type I: non-genital skin, liver, and bone
o Type II: urogenital tissue and male/female genital skin
o Inhibition of DHT production can help decrease prostate size
o Adverse effects:
• Category X teratogen; not carried in semen
• Low DHT = Ejaculation dysfunction/erectile dysfunction/libido/gynecomastia
• Decreased PSA = problem if using PSA to follow prostate cancer monitoring
70
Dutasteride (Type I and II)
Benign Prostatic Hypertrophy
• 5-a reductase inhibitors - Normally 5-a reductase converts [testosterone → DHT], which has a longer/stronger action and some different specificities of site of action. Two types are identified:
o Type I: non-genital skin, liver, and bone
o Type II: urogenital tissue and male/female genital skin
o Inhibition of DHT production can help decrease prostate size
o Adverse effects:
• Category X teratogen; not carried in semen
• Low DHT = Ejaculation dysfunction/erectile dysfunction/libido/gynecomastia
• Decreased PSA = problem if using PSA to follow prostate cancer monitoring
71
Beta-sitosterols (South Africa start grass, Hypoxis rooperi, Pinus/Picea species)
Benign Prostatic Hypertrophy
• 100% B-sitosterol shown to be efficacious for improving urinary symptoms, but not for reducing prostate size
• No known long term effects
72
Saw-Palmetto
Benign Prostatic Hypertrophy
| • not enough evidence to show any benefit from this herbal supplement
73
• Avanafil
Erectile dysfunction
– PDE-5 inhibitor (stops cGMP breakdown to increase smooth muscle relaxation)
o Contraindication with organic nitrates/a-blockers (profound hypotension, QT prolongation)
o Adverse effects:
• Sudden loss of hearing and vision
• Cardiovascular issues
• Male hormone replacement may improve the efficacy of PDE-5 inhibitors
74
• Tadalafil
Erectile dysfunction and Benign Prostatic Hypertrophy
– PDE-5 inhibitor (stops cGMP breakdown to increase smooth muscle relaxation)
o Contraindication with organic nitrates/a-blockers (profound hypotension, QT prolongation)
o Adverse effects:
• Sudden loss of hearing and vision
• Cardiovascular issues
• Male hormone replacement may improve the efficacy of PDE-5 inhibitors
75
• Vardenafil
Erectile dysfunction
– PDE-5 inhibitor (stops cGMP breakdown to increase smooth muscle relaxation)
o Contraindication with organic nitrates/a-blockers (profound hypotension, QT prolongation)
o Adverse effects:
• Sudden loss of hearing and vision
• Cardiovascular issues
• Male hormone replacement may improve the efficacy of PDE-5 inhibitors
76
• Silenafil
Erectile dysfunction
– PDE-5 inhibitor (stops cGMP breakdown to increase smooth muscle relaxation)
o Contraindication with organic nitrates/a-blockers (profound hypotension, QT prolongation)
o Adverse effects:
• Sudden loss of hearing and vision
• Cardiovascular issues
• Male hormone replacement may improve the efficacy of PDE-5 inhibitors
77
Alprostadil
– PGE1 analogue that stimulates [Adenylate cyclase → increased cAMP→ PKA activation → decreased intracellular Ca2+ → smoother muscle relaxation]
• Delivered by local application via the urethra (suppository insertion) or injection to the side of the penis (not the top or the bottom!!)
• Rapid/durable onset with minimal systemization
• Typically only penile, urethral, or testicular pain reported
78
Yohimbe
– alpha-2 agonist (older drug) that’s largely been replaced by PDE-5 inhibitors
• Works by blocking adrenergic receptors/pro-synaptic heteroreceptors on NANC nerves
• May be taken as a supplement by patients; is NOT a good idea
o Often the “natural extract” is extremely concentrated/processed
o High placebo effect with the drug
• Adverse effects
o Lots of CNS problems (crosses BBB)
o MAOI action with higher doses
79
Oral Estrogens for HRT
17-B-estradiol, ethinyl estradiol, conjugated estrogen
80
Transdermal Estrogen for HRT
17-B-estradiol (patch,gel,spray,emulsion)
81
Vaginal Application Estrogens for HRT
17-B-estradiol (cream, tablet, ring)
82
Oral Progesterone for HRT
medroxyprogosesterone acetate, norethindrone acetate, drospirenone, microionized progesterone
83
Transdermal Progesterone for HRT
norethindone acetate, levonogestril
84
Bazedoxiene for HRT
o SERM drug that recently gained FDA approval
85
Diesthylstverbutol (DES)
* Non-steroidal estrogen compound used in the 50s to prevent spontaneous abortion
* Thought that increasing estrogen influence would promote healthy uterus
* Daughters of women taking it has increased incidence of vagina clear cell adenocarcinoma, infertility, and ectopic pregnancy
86
Oxytocin
Oxytocics/Prostaglandins
• Used to induce labor in cases of:
o Premature membrane rupture/Fetal growth restriction/Uteroplacental insufficiency
o Pre-eclampsia/eclampsia
• Control post-partum uterine bleeding through muscular contraction
87
Pitocin
Oxytocics/Prostaglandins
• Used to induce labor in cases of:
o Premature membrane rupture/Fetal growth restriction/Uteroplacental insufficiency
o Pre-eclampsia/eclampsia
• Control post-partum uterine bleeding through muscular contraction
88
Dinoprostone (PGE-2)
Oxytocics/Prostaglandins
• Used to induce labor in cases of:
o Premature membrane rupture/Fetal growth restriction/Uteroplacental insufficiency
o Pre-eclampsia/eclampsia
• Control post-partum uterine bleeding through muscular contraction
89
Misoprostol (PGE-1)
Oxytocics/Prostaglandins
• Used to induce labor in cases of:
o Premature membrane rupture/Fetal growth restriction/Uteroplacental insufficiency
o Pre-eclampsia/eclampsia
• Control post-partum uterine bleeding through muscular contraction
90
Carboprost tromethamine (15-methylPFG-2)
Oxytocics/Prostaglandins
• Used to induce labor in cases of:
o Premature membrane rupture/Fetal growth restriction/Uteroplacental insufficiency
o Pre-eclampsia/eclampsia
• Control post-partum uterine bleeding through muscular contraction
91
OTC Oxytocics/Prostaglandins
- Caster Oil, Blue Cohosh, Black Cohosh, Oil of Evening Primrose, Castor Oil, Bethroot
92
Magnesium sulfate
Tocolytics
• Inhibit uterine contractions
o Mg-sulfate – mechanism not understood; huge risk of Mg2+ toxicity (Deep tendon reflex loss, drowsiness, respiratory depression, coma, cardiac arrest)
o Indomethacin – COX-1/2 inhibitor to stop prostaglandin signaling of labor onset
• Used to delay/prevent premature pregnancy in order to get the mom to a place for advanced neonatal care
• Slow or arrest delivery for brief periods to administer drugs for reducing premature birth complications (glucocorticoid/pulmonary surfactant administration)
93
Indomethacin
Tocolytics
• Inhibit uterine contractions
o Mg-sulfate – mechanism not understood; huge risk of Mg2+ toxicity/other problems
o Indomethacin – COX-1/2 inhibitor to stop prostaglandin signaling of labor onset
• Used to delay/prevent premature pregnancy in order to get the mom to a place for advanced neonatal care
• Slow or arrest delivery for brief periods to administer drugs for reducing premature birth complications (glucocorticoid/pulmonary surfactant administration)
94
Mifepristone (RU-486)
• Competitive inhibitor of progesterone/glucocorticoids at progesterone receptor
• Used for medically induced abortion (abortifacient)
• Combined with misoprostol = 95% successful abortions of early pregnancy (up to day 49 post menstruation)
• Adverse effects – mainly due to misoprostol
o Nausea, vomiting, diarrhea
o Vaginal cramping/bleeding due to passing the pregnancy
o Rare but severe infection
95
Onapristone
• Competitive inhibitor of progesterone/glucocorticoids at progesterone receptor
• Used for medically induced abortion (abortifacient)
• Combined with misoprostol = 95% successful abortions of early pregnancy (up to day 49 post menstruation)
• Adverse effects – mainly due to misoprostol
o Nausea, vomiting, diarrhea
o Vaginal cramping/bleeding due to passing the pregnancy
o Rare but severe infection
96
Danazol
* CYP450 inhibitor of gonadal steroid synthesis; androgen receptor partial agonist
* Used to treat endometriosis and hereditary angioedema
* Adverse effects: weight gain, edema, hirsutism, acne, masculinization, decreased HDL, hepatotoxicity
97
• Acyclovir
o Mechanism
• Phosphorylated via viral thyimidine kinase intracellularly for activation
• Inhibit viral DNA polymerase via insertion into viral DNA and halting of chain elongation
• Cannot be removed by DNA repair mechanisms
o Resistance
• Thymidine kinase mutation – cannot phosphorylate/activate the drug
• DNA polymerase mutation – does not halt at inserted drug/can remove inserted drug
o Toxicities – seizure/crystalline nephrophathy (hydrate patient well)
o Does not penetrate CSF
98
• Val-acyclovir
o Mechanism
• Phosphorylated via viral thyimidine kinase intracellularly for activation
• Inhibit viral DNA polymerase via insertion into viral DNA and halting of chain elongation
• Cannot be removed by DNA repair mechanisms
o Resistance
• Thymidine kinase mutation – cannot phosphorylate/activate the drug
• DNA polymerase mutation – does not halt at inserted drug/can remove inserted drug
o Toxicities – seizure/crystalline nephrophathy (hydrate patient well)
o Does not penetrate CSF
99
• Famciclovir
o Mechanism
• De-acetylated into penciclovir (the active form)
• Phosphorylated via viral thyimidine kinase intracellularly for activation
• Inhibit viral DNA polymerase via insertion into viral DNA and halting of chain elongation
• Cannot be removed by DNA repair mechanisms
o Resistance
• Thymidine kinase mutation – cannot phosphorylate/activate the drug
• DNA polymerase mutation – does not halt at inserted drug/can remove inserted drug
o No significant toxicities
100
• Bentzathine Penicillin G
o Mechanism
• B-lactam – binds Penicillin Binding Proteins (PBPs) on cell surface to disrupt bacterial membrane and cause bacteriolysis
o IM injection results in depot that lasts for approx. 2 weeks
o Doesn’t penetrate CSF (neurosyphillis cannot be treated with this)
o Toxicity – penicillin allergy
• Jarisch-Herxheimer Reaction
o Reaction to penicillin injection, typically in secondary syphilis patients (70-90% incidence
• Acute chills, fever, headache, myalgia/arthralgia
• Syphilitic lesions become edematous, brilliant in color, more prominent
o Lasts 24-48 hours then fades without recurrence
o Occurs due to release of spirochete antigens from antibiotic destruction, causing immune response
o Aspirin will give symptomatic relief; do NOT stop the penicillin
101
Azithromycin
```
o Mechanism – Bind to 23S rRNA of 50S ribosomal subunit; stop translocation, thus protein synthesis
o Toxicities (MACRO)
• Gastric Motility issues, Arrhythmia (prolonged QT), Cholestatic hepatitis, Rash, eOsinophilia
o Resistance – Methylation of 23S rRNA subunit; blocks binding of drug
```
102
Erythromycin
```
o Mechanism – Bind to 23S rRNA of 50S ribosomal subunit; stop translocation, thus protein synthesis
o Toxicities (MACRO)
• Gastric Motility issues, Arrhythmia (prolonged QT), Cholestatic hepatitis, Rash, eOsinophilia
o Resistance – Methylation of 23S rRNA subunit; blocks binding of drug
```
103
Doxycycline
o Mechanism – inhibit topoisomerase II (DNA gyrase) in Gram– and topoisomerase IV in Gram+
o Toxicities
• Cartilage damage/tendonitits or rupture (“fluoroquinolones hurt attachments to bones”); pregnanct/nursing mothers/children contraindicated (more cartilage in fetus/child)
o Resistanace – mutation in DNA gyrase (drug cannot bind), efflux pumps
104
Levofloxacin
o Mechanism – inhibit topoisomerase II (DNA gyrase) in Gram– and topoisomerase IV in Gram+
o Toxicities
• Cartilage damage/tendonitits or rupture (“fluoroquinolones hurt attachments to bones”); pregnanct/nursing mothers/children contraindicated (more cartilage in fetus/child)
o Resistanace – mutation in DNA gyrase (drug cannot bind), efflux pumps
105
Ofloxacin
o Mechanism – inhibit topoisomerase II (DNA gyrase) in Gram– and topoisomerase IV in Gram+
o Toxicities
• Cartilage damage/tendonitits or rupture (“fluoroquinolones hurt attachments to bones”); pregnanct/nursing mothers/children contraindicated (more cartilage in fetus/child)
o Resistanace – mutation in DNA gyrase (drug cannot bind), efflux pumps
106
Ceftriaxone
o Mechanism – B-lactam – binds Penicillin Binding Proteins (PBPs) on cell surface to disrupt bacterial membrane and cause bacteriolysis (less susceptible to penicillinases)
o Toxicities
• Penicillin allergy, disulfiram-like reaction (don’t drink alcohol), Vit.K deficiency, autoimmune hyemolytic anemia
o Resistanace – alteration of PBPs
107
• Metronidazole
o Mechanism – reduced into a toxic free radical causing bacterial DNA damage
o Toxicities
• Disulfram-like reaction – severe flushing/tachycardia/hypotension/vomiting with alcohol
• Metallic taste
o Resistanace – none listed
108
• Tinidazole
o Mechanism – reduced into a toxic free radical causing bacterial DNA damage
o Toxicities
• Disulfram-like reaction – severe flushing/tachycardia/hypotension/vomiting with alcohol
• Metallic taste
o Resistanace – none listed
109
• Clindamycin
o Mechanism – blocks RNA translocation at 50S ribosomal subunit in bacteria
o Toxicities
• Pseudomembranous colitis (C.diff overgrowth), fever, diarrhea – kills all your gut bacteria
• Teratogenic
o Resistanace – none listed
110
• butoconazole
o Mechanism – Blocks CYP450, needed for [Lanosterol → ergosterol] to make fungal cell wall
o Toxicities
• Testosterone synthesis inhibition (Low T) – CYP450 needed in adrenal glands to make androgens, which serve at precursors for testosterone
• Liver dysfunction (blocks CYP450, screws up liver metabolism)
o Resistanace – none listed
111
• clotimazole
o Mechanism – Blocks CYP450, needed for [Lanosterol → ergosterol] to make fungal cell wall
o Toxicities
• Testosterone synthesis inhibition (Low T) – CYP450 needed in adrenal glands to make androgens, which serve at precursors for testosterone
• Liver dysfunction (blocks CYP450, screws up liver metabolism)
o Resistanace – none listed
112
• miconazole
o Mechanism – Blocks CYP450, needed for [Lanosterol → ergosterol] to make fungal cell wall
o Toxicities
• Testosterone synthesis inhibition (Low T) – CYP450 needed in adrenal glands to make androgens, which serve at precursors for testosterone
• Liver dysfunction (blocks CYP450, screws up liver metabolism)
o Resistanace – none listed
113
• tioconazole
o Mechanism – Blocks CYP450, needed for [Lanosterol → ergosterol] to make fungal cell wall
o Toxicities
• Testosterone synthesis inhibition (Low T) – CYP450 needed in adrenal glands to make androgens, which serve at precursors for testosterone
• Liver dysfunction (blocks CYP450, screws up liver metabolism)
o Resistanace – none listed
114
Ethinyl estradiol
• Synthetic estrogens with high bioavailability
• Steroid hormones that bind estrogen receptors and directly promote gene expression
• Used for:
o Hypogonadism/ovarian failure – no estrogen means you need to exogenously administer it
o Menstrual abnormalities caused by low estrogen
o Part of Hormone replacement therapy
o Part of Oral contraceptive
• Toxicity
o Premature closure of epiphyseal plates in adolescents
o Increased risk of endometrial and breast cancer
o Increased risk of myocardial infarction/stroke/DVT
• Contraindications
o Estrogen receptor positive breast cancer
o History of DVTs or hypercoagulable state
115
mestranol
• Synthetic estrogens with high bioavailability
• Steroid hormones that bind estrogen receptors and directly promote gene expression
• Used for:
o Hypogonadism/ovarian failure – no estrogen means you need to exogenously administer it
o Menstrual abnormalities caused by low estrogen
o Part of Hormone replacement therapy
o Part of Oral contraceptive
• Toxicity
o Premature closure of epiphyseal plates in adolescents
o Increased risk of endometrial and breast cancer
o Increased risk of myocardial infarction/stroke/DVT
• Contraindications
o Estrogen receptor positive breast cancer
o History of DVTs or hypercoagulable state
116
Levonorgestrol (Mirena IUD or Skyla IUD or Plan B)
Mirena
- Estrogen/progesterone birth control
- IUD needing replacement every 5 years
- Breakthrough pregnancy rate in 1st year = 0.2%
- Amenorrhea!
Skyla
- Estrogen/progesterone birth control
- IUD needing replacement every 3 years
- Breakthrough pregnancy rate in 1st year = 0.2%
- Amenorrhea!
- Smaller device designed for nulliparous, younger patients
Plan B
- Emergency Contraception OTC
- If taken within 72 hours, reduces pregnancy rate from 8/100 --> 2/100
117
Norethindrone
- Progestin-only birth control
- remember that it thickens cervical mucus/limits endometrium proliferation/increases body temerpature but DOES NOT STOP OVULATION
118
Norgestrel
- Progestin-only birth control
- remember that it thickens cervical mucus/limits endometrium proliferation/increases body temerpature but DOES NOT STOP OVULATION
119
Medroxyprogesterone (Depo-Provera)
- Estrogen/progesterone birth control
- IM injection every 3 months
- Breakthrough pregnancy rate in 1st year = 6% (user failure)
- Amenorrhea (80%) or light menses (20%)
- Adverse effect: Weight gain, increase in HIV infection risk
- BBW: Bone loss (need to come off it after 3 years)
120
Copper IUD
- Copper acts as spermicide
- IUD needing replacement every 10 years
- Breakthrough pregnancy rate in 1st year = 0.8%
- Adverse effects: dysmenorrhea/heavy periods
- Contraindications: copper allergy or Wilson's disease
- Extremely effective for emergency contraceptive; implantation must be done within 72hr
121
Male Mediated Contraception
- Vas deferens ligation = more easily reversed, extremely quick surgery
- ALWAYS recommend using condoms!
