Pharmacology Flashcards
Tx for HSV
acyclovir, vala-, and fam- = not curative, can decr. symptoms
MOA for acyclovir and vala-
inhibit viral DNA polymerase action (preferentially over host DNA polym.) by inserting into the growing chain and preventing further elongation.
how is acyclovir spec for virally infected cells?
dependant upon viral thymidine kinase for the first of three phosphorylations needed to be active drug.
has 100xs greater affinity for the viral polymerase than the hosts
MOA for famciclovir
metabolized to penciclovir,competitive inhib of viral DNA polymerase, does not cause chain termination (ACV does)
why does ACV have two dosing regimens?
the higher the does of ACV the less its bioavailability, so if you want to increase the dose, you have to give less but more frequently.
Mechanism of resistance to ACV, vala-, fam-
mutation of viral thymidine kinase (70%), or mut of viral DNA polymerase so that it won’t take up the modified bases.
AE of ACV and vala-
access the CNS- neurotoxicity, limited solubility so can precip. in kidneys and cause nephropathy
AE for famciclovir
really none, maybe headache. why isn’t this used then? more expensive and not as well studied as ACV
Tx for syphillis
PCN (the benzathine formulation = IM producing a extended release over 2 weeks)
AE for PCN
hypersens is biggest problem - if pt must be treated, then desensitize and give anyway.
renally excreted - caution in renal problems
jarisch-herxheimer rxn
70-90% of pts w/ 2 syph treated w/ PCN = chills, fever, HA, myalgias and arthralgias, cut. lesions become more brilliant. prob due to rel of spirochete antg. and do not discont. PCN tx.
tx for chlamydia
azithro or doxy (can sub erythro, levofloxacin, ofloxacin)
* assume co-infection w/ GC and give ceftriaxone as well until proven otherwise
contraindications for doxycycline in Ct tx, AE
pregnancy, replace w/ amoxicillan, photosens, hepatic damage in high doses
MOA of azithro, erythro (macrolides)
inhib the 50s ribosomal subunit, bacteriostatic
MOA of doxy (tetracycline)
binds the 30s ribo. subunit, bacteriostatic
MOA of -floxacins
flouroquinolones, inhibit DNA gyrase (topo II), bacteriocidal
levo= gram neg
oflo= gram pos (topo IV)
cipro= both pos and neg
AE of -floxacins
BBW for incr. risk of tendonitis and rupture and musc weakness
Preg cat C - animal studies show damage, not recomm.
Erythromycin AE
CYP inhibitor and P-gp
ceftriaxone, cefixime MOA
3rd gen cephalosporin, bacteriocidal beta lactam- causes cell lysis thru cell wall disruption.
tx for GC
ceftriaxone (IM) or cefixime PLUS Azithro or doxy
- the others are oral.
- azithro and doxy are incl. for coverage of Ct which is presumed present until proven otherwise, also helps reduce devlmpt of resistance in GC
tx for trichomoniasis
metronidazole or tinidazole
MOA for metronidazole, tinidazole
bacterio- ameb- and trichomonacidal, reduced to active form inside the cell and disrupts DNA helix
AE for metro and tinidazole
preg. cat B, not recomm during 1st trimester or breastfeeding, may predispose to malignancy
BV tx
metronidazole (or tinid), or clindamycin
MOA and AE for Clindamycin
binds 50s ribo subunit (similar to macrolide but is a lincosamide), bacteriostatic,
AE= C. diff is classically assoc. with this, not recommended for vaginal use after the 1st trimester in pregnancy can cause complications
tx for candidiasis
Azoles, OTC or prescription
MOA for conazoles
block ergosterol synthesis through inhib the cyp enzyme necc for converting it to this necc membrane component
AE for conazoles
- avoid in 1st trimester - birth defects
- can weaken latex condoms - unintended prey
- fluconazole - potent cyp 2C9 inhibitor
What is the antigenic component of the HPV vaccine?
recombinant L1 protein ( a capsid protein) - the only component of the virus found in the vaccine so it is incapable of causing any dz
diff btwn gardisil an cervarix vaccine
Gardisil - covers HPV 6, 11, 16, 18
Cervavix - 16 and 18 only
*$300 not covered by insurance, three shots
recommended for m and f < 26 y/o
tx for genital warts
- 90% caused by HPV 6,11
- don’t elim. infectivitiy but can reduce
- Imiquimod (immune resp modifier)
- Podofilox - box MT in keratinocytes
- Sinecatchins - antioxidant green tea extract
three types of estrogen
estradiol E2
estrone E1
estriol E3
which is the weakest estrogen and also made by the placenta
Estriol E3, also made by conv. of 2 and 3 in the liver and adipose
what enzyme converts androstenedione and T into estrone and E2
aromatase
what effect does administr. of E2 have on Sex Hormone Binding Globulin
it increases its transcription, thus the amount of free estrogen and androgens goes down.
what molecule binds Progesterone in the blood
transcortin, same as cortisol
where is E Recp. B located primarily? ERa?
prostate gland and ovary, female reprod. tract = ovary, uterus, vagina
Effect of E’s on lipid
incr. HDL and decr. LDL
Effects of E on bone
decr. # and activity of osteoclasts, hastens bone maturation and closure of epiphyseal plates of long bones
Effects of E on liver
incr. synth. of TBG, transcortin, SHBG, and clotting factors (hypercoagulable)
Effects of E on sexual devlpmt
stim breast tiss ( and tumors) as well as the dvlpmt of the endometrium during the proliferative phase. increases libido
action of P on carb/lipid metab
enhances storage and transfer into tissues - thus it incr. insulin and incr glycogen synth. it also decr HDL and incr LDL while stimulating LPL so that the tissues can take up more lipid
effects of P during pregnancy
released initially by the rescued corpus luteum and then by the placenta itself. maintains the decidua of the uterus, inhibits uterine contraction, alveolobular dvlmpt of the breast but inhibits lactation, thickens cervical mucous
SERMs
selective E Receptor Modulators. tamoxifen, raloxifene, torimifene
-selective b/c they have estrogenic effects in tiss. where it is beneficial (bone, brain, liver), but block its effect in the breast or endometrium (useful for those cancers)
clomiphene, fulvestrant
true anti estrogens, pure antagonist in all tissues. –b/c it blocks the feedback of ER on the hypothalmus it stimulates the release of GnRH and thus LH/FSH and thus stimulates ovulation, incr. E levels
anastrozole, letrozole
aromatase inhibitors. used for breast CA after SERM failure
estrogens incr risk of ________ in women, esp those who _________
clots (DVT, stroke, PE), smoke
synthetic E for use in BC
ethinyl estradiol, mestranol
synthetic progestin for BC
norethindrone, norgestrel, levonorgestrel
side effects of E/P BC
incr. risk of thromboembolic events (E), GI disturbance (both), changes in lipid levels (P), breast enlgmt (E), acne and weight gain (P)
non-contraceptive uses of BC, benefits
regular cycles, decr. acne, incr hgb, reduce risk of ovarian and endometrial CA
drugs that reduce effectiveness of BC
antibiotics (PCNs, Tetracyclines), Rifampin (CYP inducer), Anticonvulsants, St. Johns wort
emergency contraception
lg dose of progestins (levonorgestrel), 50-80% effective if taken w/in 24-72 hrs of intercourse, prevents ovulation, no effect on implantation
mifepristone
antiprogestin, RU 486, for termination of pregnancy 49 days or less, blocks binding of P to recp.
side effects of T administration to men
feminization bc conv to E2, suppr. of LH/FSH leads to decr. testis size, decr spermatogenesis, decr. endog T, decr. HDL and incr LDL
5-a-reductase inhibitors
finasteride, dutasteride. antag of the enzyme that conv. T to DHT (the more active form). Used for BPH, male patt. baldness
- teratogenic to male fetuses (no contact w/ pregnant F) no blood donation
spironolactone
aldo antag for 1/2 hyperaldosteronism but also competes w/ T recp.
what antimycotic has effects on the cyp p450 enzymes and thus inhibs T synthesis (and other steroid hormones)
ketoconazole - antitestosterone effects are a side effect of antifungal tx. not useful as primary tx
what role does the parasymp. NS play in urination?
ps nn. stim M3 recp on the bladder and stim contraction of (detrusor) sm. musc and bladder emptying
Role of sympathetic NS in urination
sympathetics act on B3 recp in the bladder and inhibit detrusor musc contraction Also act on a1 recp causing contraction of the urethra.
Role of somatic NS in urination
the somatic (voluntary) NS controls the external urethral sphincter thru pudendal N action on Nicotinic recp (+)
AE of anticholinergics
dry mouth, tachycardia, constipation, urinary retention, sedation, slowed cognition, mydriasis
which of the antichol. has the most selectivity for M3 as opposed to the rest which are non-selective
darifenacin
Which of the antichol. has almost no CYP metabolism as opposed to the rest?
trospium
which two antichol. have ER formulations to make up for their otherwise extremely short 1/2 lives?
oxybutynin, tolterodine
which antichol. drug is metablized to another form and not detectable in systemic circ?
fesoterodine
contraindications of antichol.
- angle closure or narrow-angle glaucoma
- urinary or gastric obstruction
- need for mental alertness
- alzheimers type dementia (already a cholinergic defect)
in which type of pt does botox tx for bladder dysfunction work best?
recomm. for those unresp. to antimuscarinics, but only worked in 60% of those pts, as opposed to 86% of pts for whom the antimuscarinics merely had too many side effects but were otherwise effective.
what do sympathomimetics do for bladder control?
they activate the B3 recp causing relaxation of the detrusor muscle and they also activate the a1 recp causing contraction of the urethral sm musc.
mirabegron, pseudoephedrine, ephedra, Ma-Huang
sympathomimetics for urinary incontinence
AE of sympmim
epi like effects, incr BP, HR, anxiety, insomnia, interact w/ MAOIs.
methionine
creates ammonia-free urine (odorless) by acidifying urine pH.
which of the sympmim is less orally available than the others?
mirabegron, b/c has substancial CYP metabolism and is decr. by food also. Has a much longer 1/2 life than the others though.
two drugs used to tx urinary retention - strenghten cholinergic mediated detrussor musc contraction
neostigmine - inhib AChE
bethanechol - muscarinic agonist
both have short duration of action (adminst often)
and poor oral bioavailability
AE of the urinary retention drugs
syncope, diarrhea, stomach cramps, AV block, bradys, cardiac arrest, hypoTN, dizziness
what effects do opiates have on the urinary system?
can cause urinary retention by inhibiting PS outflow from the spinal cord (s1-3) and hence detrussor activation
