Random pharmacology Flashcards
Fulvestrant
- A “pure” estrogen antagonist
- Associated with a much lower risk of causing endometrial pathology, including cancer than raloxifene or toremifene
Ranolazine
- MECHANISM: inhibits late phase of sodium current thereby reducing diastolic wall tension and oxygen consumption; does not affect HR or contractility
- CLINICAL USE: angina refractory to other medical therapies
- ADVERSE EFFECTS: constipation, dizziness, headache, nausea, QT prolongation
Cinacalcet
- MECHANISM: sensitizes Ca2+ sensing receptor (CaSR) in parathyroid gland to circulating Ca2+, leads to decrease in PTH
- CLINICAL USE: primary or secondary hyperparathyroidism
- ADVERSE EFFECTS: hypocalcemia
Orlistat
- MECHANISM: inhibits gastric and pancreatic lipase and leads to a decrease in breakdown and absorption of dietary fats
- CLINICAL USE: weight loss
- ADVERSE EFFECTS: steatorrhea, decreased absorption of fat-soluble vitamins
Ursodiol (ursodeoxycholic acid)
- MECHANISM: nontoxic bile acid that increases bile secretion and decreases cholesterol secretion and absorption
- CLINICAL USE: primary biliary cirrhosis, gallstone prevention or dissolution
Cladribine
- MECHANISM: purine analog that works through multiple mechanisms (eg inhibition of DNA polymerase, DNA strand breaks); an antimetabolite
- CLINICAL USE: hairy cell leukemia
- ADVERSE EFFECTS: myelosuppression, nephrotoxicity, neurotoxicity
Cytarabine (arabinofuranosyl cytidine)
- MECHANISM: pyrimidine analog that leads to the inhibition of DNA polymerase; an antimetabolite
- CLINICAL USE: leukemias (AML), lymphomas
- ADVERSE EFFECTS: myelosuppression with megaloblastic anemia (“CYTarabine causes panCYTopenia”)
Nitrosureas (carmustine, lomustine, semustine, streptozocin)
- MECHANSIM: requires bioactivation; works as an alkylating agent; crosses blood brain barrier into the CNS where it crosslinks DNA
- CLINICAL USE: brain tumors (including glioblastoma multiforme)
- ADVERSE EFFECTS: CNS toxicity (convulsions, dizziness, ataxia)
Erlotinib
- MECHANISM: EGFR tyrosine kinase inhibitor
- CLINICAL USE: non-small cell lung cancer
- ADVERSE EFFECTS: rash
Cetuximab
- MECHANISM: monoclonal antibody against EGFR
- CLINICAL USE: stage IV colorectal cancer (wild-type KRAS), head and neck cancer
- ADVERSE EFFECTS: rash, elevated LFTs, diarrhea
Vemurafenib
- MECHANISM: small molecule inhibitor of BRAF oncogene (+) melanoma
- CLINICAL USE: metastatic melanoma
Leflunomide
- MECHANISM: reversibly inhibits dihydroorate dehydrogenase, preventing pyrimidine synthesis; suppresses T cell proliferation
- CLINCIAL USE: rheumatoid arthritis, psoriatic arthritis
- ADVERSE EFFECTS: diarrhea, hypertension, hepatotoxicity, teratogenicity
Teriparatide
- MECHANISM: recombinant PTH analog given subcutaneously daily, increases osteoblastic acitivity
- CLINICAL USE: osteoporosis; causes increase in bone growth compared to antiresorptive therapies (eg bisphosphonates)
- ADVERSE EFFECTS: transient hypercalcemia
Etanercept
- MECHANISM: TNF-alpha inhibitor; fusion protein (receptor for TNF-alpha + IgG1, Fc), produced by recombinant DNA; acts as a TNF decoy receptor
- CLINICAL USE: rheumatoid arthritis, psoriasis, ankylosing spondylitis
Infliximab, adalimumab
- MECHANSIM: TNF-alpha inhibitor; anti-TNF-alpha monoclonal antibody
- CLINICAL USE: inflammatory bowel disease, rheumatoid arthritis, psoriasis, ankylosing spondylitis
Rasburicase
- MECHANISM: recombinant uricase that catalyzes metabolism of uric acid to allantoin
- CLINICAL USE: prevention and treatment of tumor lysis syndrome
Cyclobenzaprine
- MECHANISM: centrally acting skeletal muscle relaxant; structurally related to TCAs, similar to anticholinergic side effects
- CLINICAL USE: muscle spasms
Varenicline
- Atypical antidepressant
- Nicotinic ACh receptor partial agonist
- Used for smoking cessation
- TOXICITY: sleep disturbance
Clomiphene
- Selective estrogen receptor modulator
- Antagonist at estrogen receptors in hypothalamus
- Prevents normal feedback inhibition and increases release of LH and FSH from pituitary, which stimulates ovulation
- Used to treat infertility due to anovulation (eg PCOS)
May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances
Tamoxifen
- Selective estrogen receptor modulator
- Antagonist at breast
- Agonist at bone, uterus
- Increase risk of thromboembolic events and endometrial cancer
- Used to treat and prevent recurrence of ER/PR (+) breast cancer
Raloxifene
- Selective estrogen receptor modulator
- Antagonist at breast, uterus
- Agonist at bone
- Increase risk of thromboembolic events but no increased risk of endometrial cancer (vs tamoxifen)
- Used primarily to treat osteoporosis
Anastrozole, letrozole, exemestane
- Aromatase inhibitor
- MECHANISM: inhibit peripheral conversion of androgens to estrogens
- CLINICAL USE: ER(+) breast cancer in postmenopausal women
Mifepristone, ulipristal
- Antiprogestin
- MECHANISM: competitive inhibitors of progestins at progesterone receptors
- CLINICAL USE: termination of pregnancy (mifepristone with misoprostol); emergency contraception (ulipristal)
Terbutaline, ritodrine
- Beta-2 agonists that relax the uterus
- Used to decrease contraction frequency in women during labor
Danazol
- MECHANISM: synthetic androgen that acts as partial agonist at androgen receptor
- CLINICAL USE: endometriosis, hereditary angioedema
- ADVERSE EFFECTS: weight gain, edema, acne, hirsutism, masculinization, decreased HDL levels, hepatotoxicity
Minoxidil
- MECHANISM: direct arteriolar vasodilator
- CLINICAL USE: androgenetic alopecia, severe refractory hypertension
Bosentan
- Pulmonary hypertension drug
- MECHANISM: competitively antagonizes endothelin-1 receptors which leads to a decrease in pulmonary vascular resistance
- CLINICAL NOTES: hepatotoxic (monitor LFTs)
Sildenafil
- MECHANISM: inihibits cGMP PDE-5 and prolongs vasodilatory effect of NO
- CLINICAL NOTES: used for pulmonary hypertension as well as erectile dysfunction
Epoprostenol, iloprost
- Pulmonary hypertension drug
- MECHANISM: PGI2 (prostacyclin) with direct vasodilatory effects on pulmonary and systemic arterial vascular beds, also inhibits platelet aggregation
- ADVERSE EFFECTS: flushing, jaw pain
Fluticasone, budesonide
- Inhaled corticosteroids used for asthma
- Inhibit synthesis of virtually all cytokines
- Inactivate NF-KB , the transcription factor that induces production of TNF-alpha and other inflammatory agents
- 1st line therapy for chronic asthma
Omalizumab
- Anti-IgE monoclonal therapy for asthma
- Binds mostly unbound serum IgE and blocks binding to FcERI
- Used in allergic asthma with increased IgE levels resistant to inhaled steroids and long acting beta-2 agonists
- ADVERSE EFFECTS: anaphylaxis (mostly occurs on initial dose)
Tesamorelin
- GHRH analog
- Used to treat HIV-associated lipodystrophy
Glycyrrhetic acid
Inhibits aldosterone synthase, which normally converts corticosterone to aldosterone and cortisol to cortisone
Pegvisomant
Growth hormone receptor antagonist used to treat acromegaly
Hyoscyamine, dicyclomine
- Muscarinic antagonist
- GI
- Antispasmodic for irritable bowel syndrome
Oxybutynin, solifenacin, tolterodine
- Muscarinic antagonist
- Genitourinary
- Reduce bladder spasm and urge urinary incontinence (overactive bladder)
Adverse effects of non-dihydropyridine Ca2+ blockers
- Cardiac depression
- AV block
- Hyperprolactinemia
- Constipation
Adverse effects of dihydropyridine Ca2+ blockers
- Peripheral edema
- Flushing
- Dizziness
- Gingival hyperplasia
Pindolol and acebutolol
Partial β agonists contraindicated in angina
Which lipid lowering agent is associated with hyperuricemia
Niacin (B3)
Which lipid-lowering agents ↑ triglycerides
Bile acid resins (cholestyramine, colestipol, colesevelam)
Adverse effects of thionamides
- Skin rash
- Agranulocytosis
- Aplastic anemia
- Hepatotoxicity
- Methimazole is a possible teratogen (can cause aplasia cutis)
GH used to treat
- GH deficiency
- Turner syndrome
What does CUSHINGOID stand for
- C → cataracts
- U → ulcers
- S → striae, skin thinning
- H → hypertension, hirsutism
- I → immunosuppression, infection
- N → necrosis of femoral heads
- G → glucose elevation
- O → osteoporosis, obesity
- I → impaired wound healing
- D → depression/ mood changes
Fludricortisone can cause what skin changes
Those associated with glucocorticoids + hyperpigmentation
Adverse effects of proton pump inhibitors
- ↑ risk of C difficile infection
- Pneumonia
- ↓ serum Mg2+ with long term use
Adverse effects of aluminum hydroxide
- Constipation and hypophosphatemia
- Proximal muscle weakness
- Osteodystrophy
- Seizures
Adverse effects of calcium carbonate
- Hypercalcemia (milk-alkali syndrome)
- Rebound acid ↑
Adverse effects of magnesium hydroxide
- Diarrhea
- Hyporeflexia
- Hypotension
- Cardiac arrest
Adverse effects of sulfasalazine
- Malaise
- Nausea
- Sulfonamide toxicity
- Reversible oligospermia
Adverse effects of ondansetron
- Headache
- Constipation
- QT prolongation
Adverse effects of ADP receptor inhibitors
- Neutropenia (ticlopidine)
- TTP
Cilostazol, dipyridamole
- MECHANISM: phosphodiesterase III inhibitor; ↑ cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators
- CLINICAL USE: intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin), angina prophylaxis
- ADVERSE EFFECTS: nausea, headache, facial flushing, hypotension, abdominal pain
Azathioprine and 6-mercaptopurine are activated by what enzyme
HGPRT
Clinical use of azathioprine and 6-mercaptopurine
- Preventing organ rejection, rheumatoid arthritis, IBD, SLE
- Used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease
Hemorrhagic cystitis caused by cyclophosphamide and isofamide can be prevented with what
Mesna and N-acetylcysteine. Thiol group binds to toxic metabolites.
Used for treatment of c-KIT GI stromal tumors
Imantib
Clinical uses of rituximab
- Non-Hodgkin lymphoma
- CLL
- ITP
- Rheumatoid arthritis
Mannitol
- MECHANISM: osmotic diuretic; ↑ tubular fluid osmolarity → ↑ urine flow, ↓ intracranial/ intraocular pressure
- CLINICAL USE: drug overdose, elevated intracranial/intraocular pressure
- ADVERSE EFFECTS: pulmonary edema, dehydration
- Contraindicated in anuria, HF
Contraindications of mannitol
- Anuria
- HF
Loop diuretics have what effect on the medulla
Abolish hypertonicity of medulla, preventing concentration of urine
Loop diuretics stimulate release of
Stimulate PGE release (vasodilatory effect on afferent arteriole)
What effect do loop diuretics have on Ca2+
↑ Ca2+ excretion
Adverse effects of loop diuretics
- Ototoxicity
- Hypokalemia
- Dehydration
- Allergy (sulfa)/ metabolic Alkalosis
- Nephritis (interstitial)
- Gout
“OH DANG”
What toxicity is more pronounced in ethacrynic acid than loop diuretics in general
Ototoxicity
Potassium sparing diuretics
- Spironolactone and eplerenone; triamterene and amilioride
- Spironolactone and eplerenone → competitive aldosterone receptor antagonists in cortical collecting tubule
- Tiramterene and amiloride → act at the same part of the tubule by blocking Na+ channels in the cortical collecting tubule
Diuretics that ↓ pH
- Carbonic anhydrase inhibitors: ↓ HCO3- reabsorption
- K+ sparing: aldosterone blockade prevents K+ secretion and H+ secretion → hyperkalemia additionally leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells
Diuretics that ↑ pH
Loop diuretics and thiazides cause alkalemia through several mechanisms
- Volume contraction → ↑ AT II → ↑ Na+/H+ exchanger in PCT → ↑ HCO3- reabsorption (“contraction alkalosis”)
- K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells
- In low K+ states, H+ (rather than K+) is exchanged for Na+ in cortical collecting tubule → alkalosis and “paradoxical aciduria”
Adverse effects of ACE inhibitors
- Cough
- Angioedema (↑ bradykinin; contraindicated in C1 esterase inhibitor deficiency)
- Teratogen (fetal renal malformations)
- ↑ Creatinine (↓ GFR by preventing ATII mediated constriction of efferent arterioles)
- Hyperkalemia
- Hypotension
- Used with caution in bilateral renal artery stenosis because ACE inhibtors will further ↓ GFR → renal failure
Angiotensin II receptor blockers
Losartan, candesartan, valsartan
Clinical use of leuprolide
- Uterine fibroids
- Endometriosis
- Precocious puberty
- Prostate cancer
- Infertility
Name estrogens
- Ethinyl estradiol
- DES
- Mestranol
Clinical use of estrogens
- Hypogonadism or ovarian failure
- Menstrual abnormalities
- Hormone replacement therapy in postmenopausal women
- Use in men with androgen dependent prostate cancer
Adverse effects of estrogens
- ↑ risk of endometrial cancer
- Bleeding in postmenopausal women
- Clear cell adenocarcinoma of vagina in females exposed to DES in utero
- ↑ risk of thrombi
Name progestins
- Levonorgestrel
- Medroxyprogesterone
- Etonogestrel
- Norethindrone
- Megestrol
Mechanism of progestins
- Bind progesterone receptors
- ↓ growth and ↑ vascularization of endometrium
- Thicken cervical mucus
Progestin challenge
Presence of withdrawal bleeding excludes anatomic defects (eg Asherman syndrome) and chronic anovulation without estrogen
Mechanism of combined contraception
- Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge
- No estrogen surge → no LH surge → no ovulation
- Progestins cause thickening of cervical mucus, thereby limiting access of sperm to uterus
- Progestins also inhibit endometrial proliferation → endometrium is less suitable to the implantation of an embryo
What can stimulate anabolism to promote recovery after burn or injury
Testosterone or methyltestosterone
What causes premature closure of epiphyseal plates
Testosterone or methyltestosterone
Used for PCOS to reduce androgenic symptoms
Ketoconazole → inhibits steroid synthesis (17,20-desmolase)
Spironolactone → inhibits steroid binding, 17alpha-hydroxylase, and 17,20-desmolase
Minoxidil
- MECHANISM: direct arteriolar vasodilator
- CLINICAL USE: androgenetic alopecia, severe refractory hypertension
