Lee's Lectures Flashcards
which drugs are known as boosters?
Ritonavir and Cobacistat
-inhibit CYP3A4 increasing [] of other drugs
NRTIs
-Tenofovir, Abacavir, Emtricitabine, Lamivudine, Didanosine, Stavudine, Zidovudine
- COMPETITIVE inhibition of reverse transcriptase
- need phosphorylation to become active
which 2 NRTIs have mitochondrial toxicities?
Didanosine and Stavudine
-both are also contraindicated in pregnancy
side effects of NRTIs
- hepato-steatosis (fatty liver)
- lactic acidosis
- lipodystrophy
Tenofovir
- thymidine NUCLEOTIDE
- NO phosphorylation needed
- NEPHROTOXIC (not used w/ GFR <60) and BONE LOSS
what do drugs can treat HIV-1 and chronic hepB?
Tenofovir and Lamivudine
Abacavir
- HLA:B5701 allele -> HYPERSENSITIVITY
- Hyperlipidemia -> risk of CAD
Emtricitabine
-HYPERPIGMENTATION (palms/soles)
Lamivudine
-GI side effects
Didanosine
- Mitochondrial toxicity
- fatal PANCREATITIS
- Peripheral Neuropathy
Stavudine
- Mitochondrial toxicity
- also peripheral neuropathy and less severe pancreatitis
NNRTIs
-Efavirenz, Etravirine, Delavirdine, Nevirapine
- highly selective, NON-COMPETITIVE (allosteric) binding to reverse transcriptase
- NOT need phoshphorylation to be active
Efavirinz
- not used w/ hypersensitivity (SJS, erythema multiforme)
- strong CYP3A4 inhibition
- Neural tube defects in pregnancy
- VIVID DREAMS
Etravirine
-active against HIV strains that are resistant to 1st gen NNRTIs
Nevirapine
- not used w/ HEPATIC impairment (child-Pugh) -> increase cholesterol and ALT
- not used w/ postexposure prophylaxis (PEP)
protease inhibitors
- Atazanavir, Darunavir, Lopinavir, Ritonavir
- REVERSIBLE inhibitors of HIV aspartyl protease
- CYP3A4, 2C9 inhibition -> interact w/ many drugs
- NOT used w/ Rifampin
adverse effects of protease inhibitors
- parasthesias
- hyperglycemia (diabetes)
- hypertriglyceridemia, hypercholesterolemia
- BUFFALO HUMP
Atazanavir
-UNBOOSTED
Darunavir
- for HIV-1 and HIV-2
- must be administered w/ Ritonavir
which 2 PIs do you not want to use w/ hypersensitivities like SJS and erythema multiforme?
Atazanavir and Lopinavir
Ritonavir***
-BOOSTER of PIs -> increase drug []
integrase inhibitors
Raltegravir, Dolutagravir
-both inhibit integrase
Raltegravir
- prevent integration of prevail gene into host DNA
- well tolerated
Dolutagravir
-binds to integrase active site and inhibits strand transfer step of HIV-1 DNA integration needed for HIV replication cycle
- QT PROLONGATION (torsades)
- neural tube defects if pregnant
Fusion inhibitors.
Enfuvirtide, Maraviroc
Enfuvirtide
- block confirmational change in gp41
- injection site pain
Maraviroc
- CCR5 antagonist -> inhibit gp120 conformational change
- not used w/ Renal impairment -> end stage renal disease (ESRD)
water soluble vitamins
Vit. B
fat soluble vitamins
vit. A,D,E,K
vit. B1
thiamine
- BERIBERI and WERNICKE-KORSAKOFF syndrome
- high risk in alcoholics and malnutrition
- banana bag
vit. B2
riboflavin
vit. B3
niacin
- deficient -> HARTNUP disease, pallagra
- excess -> facial flushing
vit. B5
pantothenic acid
vit. B6
pyridoxine
-peripheral neuropathy due to isoniazid
vit. B7
biotin
vit. B9
folate
-supplemented to decrease neural tube defects
vit. B12
cobalamin
-defiiency -> abnormal myelin
vit. D
-deficient -> rickets, osteomalacia, hypocalcemic tetany
vit. K
- required for clotting
- deficient -> neonatal hemorrhage; due to CEPHALOSPORIN use
- Warfarin inhibits synthesis
vit. A
retinol
- deficient -> Nyctalopia (night blindness)
- excess -> toxicity from polar bear/beef liver, vit. supplement
vit. C
ascorbic acid
- needed for COLLAGEN synthesis
- deficient -> SCURVY
- excess -> Ca2+ oxalate stones
vit. E
tocopherols
- anti-oxidant
- can increase effects of warfarin on vit. K
St. John’s Wort (Hypericum)
- antidepressant, antiviral, anti carcinogenic
- many DRUG INTERACTIONS -> CYP450 inducer
- AE -> photosensitization, mania, arousal
volume of distribution (Vd)
low Vd -> CENTRAL compartment
high Vd -> PERIPHERAL compartment
what is the metabolite of acetaminophen w/ toxic effects?
N-acetyl-p-benzoquinone imine (NAPQI)
Dimercaprol (BAL) - chelator
- Bidentate chelator
- for ARSENIC and MERCURY poisoning (also LEAD w/ EDTA)
Succimer
- H2O soluble
- binds LEAD, CADMIUM, MERCURY
- less toxic than dimercaprol
Penicillamine
- Bidentate chelator
- for COPPER poisoning and WILSON’S disease
Edetate (EDTA)
- Polyadentate chelator -> Ca2+ signaling
- for LEAD poisoning
- AE -> NEPHROTOXIC -> renal tubular necrosis
Deferoxamine
- Polyadentate chelator
- for Fe toxicity
Deferasirox
- Tridentate chelator
- for Fe toxicity
both Deferoxamine and Deferasirox
- chelate Fe
- AE -> SKIN RXNS (blushing, urticaria) and NEUROTOXIC (retinal degeneration)
Lead
- dust and paint
- lead ENCEPHALOPATHY (death)
- treat w/ Succimer or EDTA (if severe)
Arsenic
- known carcinogen
- garlic odor, rice water stools
- treat w/ Dimercaprol
- arsine gas -> MASSIVE HEMOLYSIS
Mercury
acute -> hemorrhagic gastroenteritis…treat w/ Dimercaprol or Succimer
chronic -> treat w/ Succimer and UNITHIOL** (no dimercaprol)
Iron
- seen in SMALL CHILDREN
- treat w/ Deferoxamine
Organophosphates and Carbamates
- neurotoxic pesticides
- bind to and inhibit AChE**
clinical présentation of organophosphates and carbamates
-pinpoint pupils, muscle fasciculations, diaphoresis, emesis, diarrhea, salivation, lacrimation, urinary incontinence, garlic odor
how do you rescue AChE?
2-PAM** -> binds to AChE and removes organophosphate -> reactivates AChE
carcinogens vs. mutagens
- mutagens -> DNA mutations
- carcinogens -> tumor development…affects cell cycle
NOT all carcinogens are mutagens
IARC - group 1
KNOWN carcinogen
WORSE ones
IARC - group 2A
PROBABLY carcinogen
IARC - group 2B
POSSIBLY carcinogen
IARC - group 3
DATA LACKING to suggest carcinogenic
IARC - group 4
data says UNLIKELY carcinogenic
genotoxic agents
- absorbed -> initiate tumor formation by DNA damage
- INITIATION phase
non-genotoxic agents
- increase risk of cancer w/o DNA damage
- use tumor promoters
-PROMOTION phase
teratogens - drugs
- thalidomide
- phenytoin, fosphenytoin, ethotoin (antiepileptics)
teratogens - environment
fetal alcohol syndrome
what does insulin do?
-recruit GLUT4 to the membrane -> uptake glucose
adverse effects of insulin analogs (lispro, NPH, glargine)
hypoglycemia, hypokalemia, Lipodystrophy, Wt. gain
Lispro
-RAPID acting insulin analog
NPH
-INTERMEDIATE acting insulin analog
Glargine
- LONG acting insulin analog
- “peak less”
the main side effects w/ non-insulin drugs
- hypoglycemia
- GI probs
- weight gain
- nausea
- pancreatitis
Metformin
-decrease hepatic glucose production, decrease intestinal glucose absorption, improve insulin sensitivity
- 1st line for type 2 diabetes
- AE: DIARRHEA, NAUSEA, LACTIC ACIDOSIS
Glyburide
- stimulate insulin release from beta cells by blocking K+ channels, decrease hepatic gluconeogenesis, increase insulin sensitivity
- AE: life threatening HYPOGLYCEMIA, WEIGHT GAIN
Repaglinide
- same MOA as glyburide
- GLUCOSE-DEPENDENT
- for post-prandial peaks in blood glucose levels**
Exenatide
- analog of incretin
- not used w/ GI motility disorders or pancreatic tumors**
Sitagliptin
- inhibit DPP-4 -> increase insulin secretion, decrease glucagon secretion, decrease hepatic gluconeogenesis
- AE: PANCREATITIS
Pioglitazone
-activate PPARy
-not used w/ CHF***
AE: FLUID RETENTION/EDEMA, wt gain, OSTEOPOROSIS
Canagliflozin
- SGLT-2 inhibitor -> reduce renal absorption of glucose
- increase URINATION (diuretic)
-AE: female genital mycotic infections (Candida), UTI, urinary frequency
Acarbose
-inhibit alpha-amylase and alpha-glucosidase
- not used w/ GI disorders**
- AE: FLATULENCE, DIARRHEA
