Pharma Flashcards
maintenance dose formula
what unit will MD be in?
and what if certain dosing interval is given?
MD = Cpss x CL / [bioavailability fraction]
MD unit is mg/min
If dosing interval given, can calc. MD based on that
(eg, 2 mg/min x 60 min/hr x 6 hrs for an MD of 2 and an interval of 6 hrs)
Cpss is steady-state plasma conc.
CL is clearance
bioavailability is 1 if IV
half life formula + how many half-lives to reach Cpss
Vd x 0.7 / CL
steady state conc reached in 4-5 half lives
loading dose formula
changes in loading dose based on organ function?
Vd x Cpss / [Bioavailability fraction]
loading dose stays say, but maintenance dose changes in case of renal/liver issue affecting elimination
anastrozole, letrozole, exemestane
MOA, uses
aromatase inhibitor
postmenopausal breast cancer (blocks aromatization of androstenedione in liver, muscle, fat)
flutamide, cyproterone acetate + spironolactone
MOA, uses
androgen receptor antagonists
tx of metastatic prostate cancer
Cytarabine + Gemcitabine
MOA, differences
both pyrimidine analog antimetabolites; incorporated into DNA > strand termination (no effect on folate metab.)
cytarabine is S-phase specific; gemcitabine is NOT + also has ribonucleotide reductase inhibition
(“cyt” has S sound; “gem” is a real gem… works better)
Fludarabine
MOA, indication
deamination-resistant purine nucleotide analog
inhibits DNA polymerase, primase, ligase and ribonucleotide reductase
used for CLL
5-Fluorouracil
MOA, leucovorin effect
pyrimidine analog that inhibits thymidylate synthetase (after conversion to floxuridine monophosphate)
binds thymidylate synthetase in presence of reduced folate > leucovorin actually INCREASES its toxicity
Interleukin-2
MOA and indications as a drug
activation + differentiation of T-cells to help tumor destruction
approved for renal cell carcinoma and melanoma
Abciximab
MOA + indication
anti-GpIIb/IIIa receptor mAb; blocks final step in platelet aggregation (GpIIb/IIIa binds fibrinogen)
used during angioplasty in ACS
Colchicine
MOA, use, sfx
binds TUBULIN and prevents microtubule polymerization (impairs WBC migration + phagocytosis to reduce gout inflammation)
2nd line in gout, for pt with renal failure, PUD, other NSAID contraindications
GI microtubule disruption > diarrhea (less common nausea, vomiting + pain)
Hepatitis 2-3 days after surgery with anesthesia
cause, s/s, histo
Halothane Hepatitis - halothane is hi-risk, fluranes lower, but still some risk; CYP450 metab > intermediates > immune-mediated hepatitis
fever, nausea, jaundice, tender hepatomegaly OR liver atrophy if severe, anorexia, my-/arthralgia, rash
high LFTs and bilirubin, prolonged PT (may have leukocytosis and eosinophilia, probably and HS rxn)
centrilobular hepatic necrosis (like viral hep)
inflammation of portal tracts and parenchyma
Nitrous Oxide
MOA and toxicity
NMDA antagonism
prolonged exposure > inhibits methionine reductase > megaloblastic anemia
Succinylcholine
MOA, toxicity
depolarizing NMJ blocker
hyperkalemia (esp. burn or SC injury pt)
malignant hyperthermia (ANS issues, rigidity, high temp)
First-line for absence seizures
Detailed MOA, SFX, and 2nd line
Ethosuximide
blocks T-type Ca channels > inhibits rhythmic burst discharges in thalamic neurons
sfx are nausea, vomit, fatigue + hyperactivity
valproate is 2nd line
4 drugs assoc. with acute pancreatitis
azathioprine
sulfasalazine
furosemide
valproate
vinca alkaloids
MOA, phase specificity?
vincristine / vinblastine
inhibit microtubule FORMATION by binding beta-tubulin and preventing polymerization of microtubules
specific to M phase of cell cycle (chromosomes can’t align and segregate)
vincristine
side effect
peripheral neuropathy
disruption of neuronal microtubules > disrupts axonal transport
Cell Cycle + its related chemo drugs
each phase
G1 - cells prepare building blocks for DNA synth
G0 - resting phase
S - DNA replication; topoisomerase I + II inhibitors (etoposide, irinotecan, topotecan) and antimetabolites (MTX, 5-FU, etc.)
G2 - DNA checked for errors + corrections made or apoptosis occurs; intercalators + ROS formers work here (bleomycin, doxorubicin, etc.)
M - division; vinca alkaloids + taxanes
Thiazolidinediones
MOA + effects
PPARy agonist
increased: FA uptake
adiponectin (adipokine that increases adipocyte insulin response + stimulates FA oxidation)
insulin sensitivity
decreased: TNF-alpha and leptin (adipokine that acts on hypothalamus to decrease appetite)
Succinylcholine side effects
Malignant Hyperthermia - especially with halothane co-admin; in genetically susceptible patients
Severe hyperkalemia + life-threatening arrhythmia - in patients with burns, myopathies, denervation or crush injuries
(upregulation of nAChR in denervation > great drug effect)
Bradycardia (PSNS stim) -or- tachycardia (SNS stim)
UFH binds both ATIII and thrombin, increasing ATIII inactivation of thrombin AND factor X
LMWH primarily affects inactivation of which factor?
Mostly just factor X
it has the AT-III binding pentasaccharide, but is shorter and doesn’t bind thrombin
inhibitor of ALCOHOL DEHYDROGENASE
inhibitor(s) of ACETALDEHYDE DH
fomepizole (alcohol DH)
disulfiram (acetaldehyde DH)
metronidazole (acetaldehyde DH)
heparin induced thrombocytopenia mechanism + tx
heparin-PLATELET FACTOR 4 complex causes IgG autoantibodies (about 3-5 days after heparin initiation)
Ab then binds Fc receptor on platelets > activation and clot formation > platelet consumption causes -penia
stop heparin and give direct thrombin inhibitors (bivalirudin or ARGATROBAN) or LMW heparinoids (fondaparinux, danaparoid) to control thrombosis
(don’t give warfarin because necrosis risk is high when thrombosis is already present!)
Trastuzumab
MOA, toxicity
anti-EGFR-2 (HER-2) mAb
cardiotoxicity - HER2 plays role in minimizing cardiomyocyte oxidative stress > antagonism causes DECREASED CONTRACTILITY without signs of destruction or fibrosis
usually ASYMPTOMATIC LV EF REDUCTION, but heart failure can occur
not related to cumulative dose and is often reversible with discontinuation (unlike anthracyclines)
Cholestyramine, Colesevelam, Colestipol
MOA, effects on LDL, VLDL, TAGs
bind GI bile acids > hepatic cholesterol diverted to new bile acid synth > increased LDL uptake > lower LDL
hepatic TAG production increases > HIGHER TAGs and VLDL in circ
Common drug class associated with OLIGOHYDRAMNIOS? why?
results in fetus/child?
ACE inhibitors and ARBs
AT-II is important in fetal renal development > renal maldevelopment > reduced diuresis
results in PULMONARY HYPOPLASIA, skeletal defects, impaired cranial vascularization + hypocalvaria
A patient with epilepsy also has osteoporosis
Why?
Some anticonvulsants (phenobarbital, phenytoin, carbamazepine) also INDUCE CYP450
this can result in INCREASED VITAMIN D CATABOLISM and thus impaired calcium homeostasis
Mechanisms of Isoniazid Resistance (2)
when can isoniazid monotherapy be used?
Decreased catalase-peroxidase - mycobacterial enzyme for activation of drug
Modified protein binding site for isoniazid
Pt with positive PPD but a negative chest x-ray + no other evidence of clinical disease
Bupropion
MOA, most significant side effect + pts at higher risk of it
NE and DA reuptake inhibitor for major depression
SEIZURE - especially at high doses, or in patients with epilepsy or EATING DISORDER
Terbinafine
MOA, uses
inhibits squalene epoxidase
common for dermatophytosis; topical or oral; accumulates in skin/appendages
Theophylline
toxicity effects? tx of toxicity?
nausea/vomiting, abd. pain, diarrhea, ARRHYTHMIA or SEIZURE (seizure is main COD)
activated charcoal
beta blockers
BZD / barbiturate for seizures
DOCs for bacterial vaginosis
their MOAs?
Clindamycin - binds 50s ribosomal subunit; bacteriostatic
Metronidazole - damages DNA of facultative anaerobes; bactericidal
DRESS syndrome
when + how? general sx? other organs affected? labs?
Drug Reaction with Eosinophilia and Systemic Symptoms
2-8 wks after exposure to ANTICONVULSANTS (carbamazepine, phenytoin), ALLOPURINOL, SULFONAMIDES and ABX (minocycline, vanco)
drug-induced HERPESVIRUS reactivation with clonal T-cell expansion cross-reacting with drug
FEVER
generalized LAP
FACIAL EDEMA
generalized morbilliform SKIN RASH (may progress to confluent erythema with follicular accentuation)
may have…
hepatomegaly + jaundice
acute interstitial nephritis
cough + dyspnea
labs - EOSINOPHILIA, atypical lymphocytes, high ALAT
Drug-Induced ANCA vasculitis
which drugs? sx?
propylthiouracil, methimazole, hydralazine
generalized sx, arthralgia/-itis, cutaneous vasculitis
Pharma tx for alcoholism
3 drugs, 3 mechanisms
Naltrexone - mu atg; blocks rewarding effects of alcohol + reduces cravings; depot injection available
Disulfiram - acetaldehyde DH inhibitor; aversion tx
Acamprosate - NMDA modulation
Side effects of maternal terbutaline use in newborn
4
B2 agonist > delays preterm labor
increases risk of…
- neonatal intraventricular hemorrhage (vasodilation)
- hypoglycemia (insulin secretion)
- hypocalcemia
- ileus (relaxes GI SM)
Complications of surfactant treatment in premature newborn (4)
- transient hypoxia (diffusion limitation)
- hypotension
- endotracheal tube blockage (obstruction)
- pulmonary hemorrhage
Thiazides
MOA, mechs of Ca reabs. (2), uses for Ca reabs.
blocks Na-Cl cotransporter in DCT
- Less Na-Cl reabs. apically > more Ca-Na exchange basally (Na into cell, Ca into circ.) > more Ca reabs. via apical channel
- Hypovolemia induced by drug > more Na/water abs. in PCT > more paracellular Ca reabs. in PCT
Ca reabs. by thiazides can…
- Improve osteoporosis
- PREVENT CALCIUM STONES
Linezolid
important drug interaction
Linezolid has MAOI activity > interaction with SSRIs, TCAs, other MAOIs can cause serotonin syndrome!
tx with cyproheptadine
(ex: pt with depression history tx for cellulitis; linezolid is good for Gram+)
hydroxyurea
indication, MOA
sickle cell anemia
increases production of HbF via unknown mech
MOA of non-hydroxyurea sickle cell anemia tx
Gardos channel blockers
Ca-dependent K channels regulate K and water flow across RBC membrane > block them and prevent RBC dehydration
Acyclovir
MOA, activation, resistance
guanosine analog for HSV1/2 and VZV
P-ated by viral THYMIDINE KINASE then double P-ated by host kinases > inhibits DNA polymerase
EBV and CMV do not have the same thymidine kinase
Maraviroc blocks what?
Enfuvirtide blocks what?
Maraviroc - CCR5 antagonist; blocks entry
Enfuvirtide - gp41 antagonist; blocks fusion
MOA of systemic progestins in birth control?
examples
suppress GnRH > FSH/LH > inhibit ovulation
Combined hormonal contraceptives (pill, patch, ring)
Progestin implants/injections
MOA of locally-acting progestins in birth control?
examples (2 categories, one with diff MOA)?
Thicken cervical mucus, impair sperm penetrations
Progestin-only pill (norethindrone)
Levonorgestrel IUD
(Copper IUD - cytotoxic inflammatory response in uterus impairs sperm migration)
Clomiphene citrate
what is it? MOA?
selective estrogen receptor modulator
stimulates FSH + LH production
used as a fertility drug, or to help ovulation occur in PCOS
SPECIFIC mechanism of action of NRTIs
not just chain termination / reverse transcriptase inhibition
NRTIs are nucleoside/-tide analogs that LACK A 3’ OH GROUP
this means they can not form a PHOSPHODIESTER BOND with the next nucleotide > chain termination
Tx for Wilson disease
D-penicillamine, trientine (copper chelators)
Zinc (decr. Cu absorption)
Cyanide poisoning
mechanism?
binds FERRIC (3+) iron > inhibition of CYTOCHROME C OXIDASE in mitochondria
disrupts oxidative phosphorylation > severe LACTIC ACIDOSIS and death
Cyanide poisoning
presentation?
labs?
REDDISH SKIN tachypnea HA tachycardia nausea/vom confusion + weakness
progress to seizure + CV collapse
severe LACTIC ACIDOSIS
NARROW AVPO GRADIENT - tissues can’t use O2
Cyanide poisoning
tx? (3 things)
inhaled AMYL NITRATE - makes METHEMOGLOBIN (Fe2+ becomes Fe3+) with high affin. for CN
HYDROXYCOBALAMIN and SODIUM THIOSULFATE create non-toxic metabolites with CN that are excreted in urine
What is Doxepin?
a TCA
Tx for delirium-associated agitation and psychosis in elderly
(Delirium is acute-onset confusion state secondary to infection etc.; more common in elderly or cognitive disorder)
first-gen antipsych (HALOPERIDOL)
some second gen antipsychs
Status epilepticus tx
first + fastest? good for maintenance?
- IV Benzo - lorazepam or diazepam, fast onset
- Phenytoin - slower onset, for maintenance
- Valproate
Mechanism and tx of TCA arrhythmias
FAST SODIUM CHANNEL blockade causes QRS and QT prolongation
SODIUM BICARBONATE tx - increases serum Ph > favors non-ionized, neutral form of the tca > can’t access sodium channels
(also increases EC sodium > overcomes the competitive blockade by tcas)
What are the 3 types of EPS that occur with antipsychotics?
ACUTE DYSTONIA - sudden-onset sustained muscle contraction
AKATHISIA - subjective restlessness; unable to sit still
DRUG-INDUCED PARKINSONISM - tremor, rigidity, bradykinesia