Cumulative Material Flashcards
What are the indications for use of a loop diuretics?
Edema, hypercalcemia, hyperkalemia, anion overdose (fluoride, bromide, iodide).
MOA of loop diuretics
Inhibits sodium/potassium/chloride transporter at the thick ascending limb of the loop of henle.
Which loop diuretic should be used when concerned about sulfonamide allergy (even though there is no cross reactivity between loops and sulfa abx)?
Ethacrynic Acid (Edecrin)
Indications for the use of Spironolactone
Primarily hypokalemia (px and tx); hyperaldosteronism, PCOS
What are Eplerenone, Triamterene, and Amiloride indicated for? (All potassium sparing diuretics)
Hypokalemia px and tx
What is Conivaptan indicated for?
CHF, SIADH
Drugs that induce ED
Beta blockers,Clonidine, methyldopa, haloperidol, chlorpromazine, thioridazine, Fluphenazine, SSRIs, SNRIs, Finasteride, Dutasteride, Silodosin, Opioids (esp Methadone), nicotine, excess alcohol
Onset and Duration of Sildenafil (Viagra)
onset in 30 m - 1 hour; duration 4 hours
MOA of PDE Inhibitors
inhibits phosphodiesterase enzymes, slowing the breakdown of cGMP and allowing for the depression of calcium, leading to smooth muscle relaxation, allowing erection (arteriodilation + venoconstiction)
MOA of Alprostadil (injectable PGE-1)
increases cAMP leading to a drop in calcium
meds that induce BPH
testosterone, alpha agonists (pseudoephedrine, ephedrine, phenylephrine), anticholinergics (antihistamines, phenothiazine, TCAs), large doses of diuretics
ADE of Tamsulosin (and other alpha 1 adrenergic antagonists)
dizziness, hypotension, syncope with first dose, muscle weakness, H/A, floppy iris syndrome
indication for Finasteride (5-alpha reductase inhibitor)
BPH
MOA of 5-alpha reductase inhibitors
relax smooth muscle, decrease prostate size, halt disease process, and decrease PSA
What is the most commonly used herbal supplement in the tx of BPH?
Saw Palmetto
Drugs that cause/worsen Urinary Incontinence
diuretics, alpha receptor antagonists, sedation hypnotics, antidepressants, TCAs, alcohol, angiotensin converting enzyme inhibitors
first-line agent in the tx of stress induced urinary incontinence
Duloxetine (Cymbalta)
first-line tx for overactive bladder
Oxybutynin (Ditropan)
agents that cause vasodilation of the efferent arteriole
ACE-Is, ARBs, Diltiazem, Verapamil
drug class that affects blood/urine pH through the movement of H+ ions with K+ at the collecting duct
Potassium Sparing Diuretics
drug class that acts on the distal convoluted tubule and enhances calcium reabsorption into the blood stream
thiazide diuretics
Cholinesterase Inhibitor that is reversible and has specificity for only acetylcholine
Donepezil Hydrochloride (Aricept)
Cholinesterase Inhibitor that comes in capsule, solution, and patch forms
Rivastigmine
Rivastigmine Tartrate (Exelon) ADE
N/V/D, dizziness, H/A, insomnia, depression, somnolence
What drug is FDA approved for the tx of moderate to severe AD?
Memantine (Namenda)
What should all Alzheimer’s patients receive?
ASA therapy to improve vascular function
Which drug used to tx Alzheimer’s Disease is considered medical food?
Caprylidene (Axona)
Caprylidene (Axona) ADE
risk of DKA in diabetics, may increase TGs
drugs that cause visual abnormalities
Carbamazepine, Eslicarbazepine, Locasamide, Lamotrigine, Oxcarbazepine, Phenytoin, Pregabalin, Tiagabine, Vigabatrin
Anticonvulsants that cause weight loss
Ethosuximide, Felbamate*, Topiramate, Zonisamide
Anticonvulsants that cause weight gain
Gabapentin, Pregabalin, Valproic Acid, Vigabatrin
Why does Cimetidine cause significant DI’s?
it is a CYP inhibitor
tx algorithm for early-established seizures
0-10 minutes: IV lorazepam (or diazepam)
10-30 minutes: IV phenytoin or fosphenytoin
30-60 minutes: additional dose of hydantoin 5 mg/kg, IV phenobarbital 20 mg/kg at a rate of 100 mg/min
treatment algorithm for refractory seizures > 60 minutes wit 10-15% GCSE
additional dose of phenobarbital 10 mg/kg every hour until sz stop
or
IV valproate 15-25 mg/kg followed by 1-4 mg/kg/hr
or
medically induced coma
only class that should be used in the elderly to tx sx of anxiety, restlessness, and insomnia in AD
Benzodiazepines (Lorazepam, Diazepam, Temazepam)
use of anticonvulsants (Carbamazepine, VA) in non-elderly AD pts
agitation or aggression
use of anitpsychotics (Aripiprazole, Olanzapine, Quetiapine, Risperidone) in non-elderly pts with AD
disruptive behavior, agitation, aggression
medications associated with memory loss
anticholinergics, benzos, other sedative hypnotics, opioid analgesics, antipsychotics, anticonvulsants, NSAIDs, H2 receptor antagonists, digoxin, amiodarone, corticosteroids, antihypertensives (dizziness)
Indications for Rasgiline (Azilect - MAOB Inhibitor)
mono tx in early PD or adjunct to LD in advanced PD (typically first-line in early disease)
medication used for Parkinson’s that is an antiviral
Amantidine (Symmetrel)
drug used to tx PD for which tachyphylaxis may be expected in 4-8 weeks
Amantidine (Symmetrel)
drug of choice in PD if resting tremor is the initial presenting sx
Benztropine Mesylate (Cobentin) or Trihexylphenidyl* (Artane)
Pt population in which Benztropine and Trihexyphenidyl (Anticholinergics) should be avoided.
pts with cognitive deficits
MOA of Ergot Derivative Dopamine Agonists (Bromocriptine, Pergolide)
Moderate affinity for D2 and D3 receptors.
What needs to be done for patients who have renal issues and are taking Pramipexole (Mirapex)?
dose adjust
Drug class of Ropinerol (Requip)
Non-Ergot Derivative Dopamine Agonists
Indication for Rotigotine (Neupro - Non-Ergot Derivative Dopamine Agonist)
early stage idiopathic PD and advanced stages
Which Non-Ergot Derivative Dopamine Agonist comes in patch form?
Rotigotine (Neupro)
indication for Apomorphine (Apokyn)
rescue med for “delayed on”/”no on” or “freezing episodes” (PRN)
What prophylaxis is required when using Apomorphine (Apokyn)?
Trimethobenzamide 3 days prior
Indication for CD/LD
cornerstone of tx of PD, required by nearly all PD pts at some point in dz but use as first-line is controvertial d/t ADE
MOA of CD/LD
CD inhibits decarboxylase, delaying the conversion of LD to dopamine prior to crossing the BBB, increasing its bioavailability once on the other side of the BBB
ADE of CD/LD
N/V, orthostasis, confusion, postural hypotension, vivid dreams, wearing-off fluctuations, dyskinesias (5-10%), random motor oscillations possible with chronic use; issues with dose gap (add DA’s)
Special Recommendations for pts taking CD/LD
avoid high protein meals, take 30 m before or 60 m after meals d/t competition with other aa’s for GI absorption
major ADE of COMT Inhibitors (Entacapone, Tolcapone)
brownish-orange urinary discoloration, potential for serious liver dysfunction (monitor LFTs!)
Stalevo
CD/LD + Entacapone
What is the purpose of COMT Inhibitors in PD therapy?
increases the “time on” by 1-3 hours when used as an adjunct to CD/LD (Entacapone*)
drugs that extend the effects of CD/LD
DA’s and COMT-I’s
appropriate tx in a Parkinson’s pt experiencing freezing or start hesitation who is on CD/LD
increase CD/LD dose, add DAs or MAO-B-Is, PT, sensory cues, walking devices
For a pt presenting with tremor who is already being tx’d for PD, how does age change the tx’s available?
If under 65 consider an anticholinergic or Amantadine, if over 65 anticholinergics should not be used
monitoring for Phenytoin (Dilantin)
CBC, LFTs, albumin, and serum concentration
What disturbing oral ADE is Phenytoin (Dilantin) associated with?
Gingival Hyperplasia
What would be seen if Carbamazepine were to be given concomitantly with CYP inhibitors (ex: Cimetidine)?
increase in serum concentration
Pan-Inducers used to tx seizure disorders
Carbamazepine and Phenobarbital
Topiramate (Topimax) ADE
weight loss, cognitive functioning impairment, kidney stones, ataxia, somnolence
Lamotrigine (Lamictal) ADE
rash (SJS, TENS), coordination abnormalities, anxiety, mania, diplopia, insomnia, drowsiness, fatigue
Indication for Valproic Acid/Divalproex Sodium/Valproate Sodium in sz disorders
primary generalized sz (myoclonic, atonic, absence); partial sz, mixed disorders
What is unique about the metabolism of Valproic Acid/Divalproex Sodium/Valproate Sodium?
undergoes gluconuridation and inhibits glucuronidation in other agents
Valproic Acid/Divalproex Sodium/Valproate Sodium ADE
dose related: N/V, abdominal pain, heartburn, sedation, fine hand tremor, weight gain and increased appetite, hair loss, hepatotoxicity, thrombocytopenia
Gabapentin ADE
somnolence, ataxia, tremor, dizziness, H/A
Pregabalin ADE
dizziness, ataxia, somnolence, peripheral edema, weight gain, H/A (NO DIPLOPIA!!)
Zonisamide ADE
fatigue, dizziness, ataxia, somnolence, anorexia, weight loss, psychomotor slowing
Indication for Ethosuximide (Zarontin)
absence sz
Risk Factors for Iron Deficiency Anemia
premature infants, children in rapid growth periods, pregnant and lactating women, pts undergoing chronic hemodialysis, pts after gastrectomy, pts with small bowel disease, menstruation, occult GI bleeding
Which form of parenteral iron requires a 25 mg test dose for anaphylaxis?
Iron Dextran
How long is the tx of B12 Deficiency Anemia with cyanocobalamin?
typically for life
Indications of Nasocobal (nasal spray) Use
maintenance therapy in Vit B12 Deficiency Anemia tx
What is the difference in half life of ESAs (Darbepoetin and Epoetin Alfa)?
Darbe has a much longer half life allowing for less frequent dosing
What are the supportive tx’s used in Sickle Cell Anemia?
NS for hydration
Acetaminophen and NSAIDs for mild-moderate pain
Opioids for moderate to severe pain
What causes reduced efficacy of cancer drugs on cancer cells?
cancer cells can alter their characteristics to reduce their susceptibility
Where in the cell cycle do Alkylating Agents (Carmustine, Lomustine, Mechlorethiamine, Melphan, Thiotepa, Procarbizine, Chlorambucil, Cyclophosphamide, Bendamustine, Temozolamide, Dacarbazine) act?
cell cycle non-specific
Ankylating Agent (Cyclophosphamide) ADE
bone marrow toxicity, mucositis, sterility, N/V, tissue damage following extravasation, risk of secondary malignancies
Where in the cell cycle do Platinum Analogs (Carboplatinum) act?
cell cycle non-specific
ADE of Carboplatinum
myelosuppression
Where in the cell cycle do Antimetabolites (Methotrexate, 5-FU, Cytarabine) act?
S phase (DNA synthesis)
Cytarabine (Ara-C) ADE
cerebellar toxicity
Indication of Leocorvin (Special Antimetabolite)
reduction of MTX toxicity and increased colon cancer tx
Cell cycle phase where Leocorvin is active
S phase/DNA phase
Leucorvin MOA
no anticancer action! rescues normal cells by bypassing the inhibition of DHFR by MTX. increases 5-FU activity against colon cancer by enhancing binding.
Vincristine (Vinca Alkaloid) MOA
inhibit tubulin polymerization required for microtubule assembly; prevents microtubule formation, blocking cell division during metaphase, resulting in cell death
Cell cycle where Vinca Alkaloids are active
M phase
Vincristine ADE
potent vesicant action upon extravasation
Cell cycle where Taxanes (Pacitaxel) act
M phase
cell cycle where Antitumor Abx/Anthracyclines act
cell cycle non specific
Doxorubicin (Anthracycline) ADE
vesicant if extravasated
What is an important aspect of tx with Doxorubicin?
limit lifetime dose of anthracyclines in general and use in combo with dextrazoxane
cell cycle where Bleomycin (antitumor antibiotics) is active
cell cycle-non specific
What are the toxicity risks of Bleomycin?
persons > 70, cumulative dose > 400 units, underlying pulmonary disease, prior mediastinal radiation, supplemental disease
Indication for use of Imatinib (TKI)
Ph+ CML and ALL
MOA of TKIs
(Imatinib) binds to and blocks specific sites on various TKI’s that are needed to activate them, promotes cancer cell death via apoptosis (phosphorylate mostly cell surface receptors)
Tx for multiple myeloma
Thalidomide (Immunomodulators)
Tx for Breast Cancer that is HER-2/neu overexpressing
Monoclonal Antibodies
MOA of Monoclonal Antibodies
targets specific proteins in CA cells and blocks their standard function
Monoclonal Antibody ADE
Trastuzumab: infusion related rx (px with acetaminophen, diphenhydramine +/- dexamethasone), HF
Major warning associated with ESA use
increased mortality, increased CV and TEEs, increased tumor growth or loss of remission
translocation that occurs in CML
t9:22 = Philadelphia Chromosome
What is breast cancer tx based on?
pre or post menopausal status
What are the hormonal therapies for Breast Cancer?
Tamoxifen, Raloxifene, Anastrozole, Letrozole, Leuprolide
What is the goal of chemo tx in malignant melanoma?
prolong survival
How do secondary malignancies and de novo cancer differ?
secondary malignancies are more difficult to tx than de novo cancer
What kind of tx is chemo considered?
systemic
What is the principle of cancer cell growth that describes how the growth fraction of a tumor changes over time?
growth fraction decreases as tumor size increases, therefore fewer cells are susceptible to chemo (Gompertzian Model of tumor cell growth)
Define adjuvant therapy
used after local therapy to improve long term effect by eliminating any remaining undetected CA cells
define remission
complete response (CR), when the presence of cancer is undetectable
define palliation
used to reduce sx of disease, improve QOL, and prolong survival; cure unlikely
Cyclophosphamide (Ankylating Agent) MOA
targets DNA/RNA to transfer ankylating groups to other molecules in the strands, preventing their use in replication and cell division; = apoptosis
Methotrexate (Antimetabolite) MOA
inhibits dihydrofolate reductase which converts one form of folic acid to another (blocks purine synthesis), also inhibits thymidine synthase
Vincristine (Vinca Alkaloids) MOA
inhibits tubulin polymerization requried for M.T. formation, blocking cell division during metaphase
What is the mechanism by which resistance to TKIs may occur?
mutations in the AA sequence of TK may cause the site bound to be inadequate
What are two mechanisms of drug interactions with TKIs?
changes in metabolism secondary to other drugs affecting CYP450 3A4 and reduced absorption secondary to acid reducing drugs (ex: PPIs)
families of drugs with vesicant activity if extravasated
antitumor antibiotics, vinca alkaloids, alkylating agents
Carboplatin ADE
myelosuppression
Doxorubicin ADE
cardiotoxicity
Cytarabine ADE
cerebellar toxicity
What are two methods to reduce the risk of cardiotoxicity associated with Doxorubicin?
limit lifetime dose, use in combo with dextrazone
What occurs in phase III of drug trials?
assess efficacy of compound compound compared to standard tx
hormone sensitive cancers
breast and prostate
MOA of Carbonic Acid Anhydrase Inhibitors
Inhibits enzyme responsible for dehydration of H2CO3 (H2CO3 ->HCO3)
