drug dosing is mostly based on
CrCl
PK changes
- bioavailability (absorption)
- drug distributio
- metabolism (Phase 1 & II slowed)
- renal elimination
volume of distribution
- reduction in tissue binding
- body composition altered
- protein binding (decreased binding of acidic drugs, altered binding of basic drugs)
normal phenytoin concentration
- 10-20mcg/mL
- 90% bound normally
- low albumin-> difference in ratio
renal elimination
- decreased glomerular filtration, renal tubular secretion & reabsorption
- accumulation of metabolites
- efficacy (codein, procainamide)
- toxicity (meperidine, propoxyphene)
pts on dialysis have CrCl of
intermittent dialysis
maintains a high concentration until dialysis then drops
continuous dialysis
more like normal kidney function
drug characteristics that affect removal in HD
- MW
- water solubility
- protein binding
- Vd
PD is
not as effective as HD at removing substances
Metformin is contraindicated with
SCr>1.4 in females 1.5 in males
- risk of lactic acidosis
drugs needing dose adjusted
- warfarin, LMWH
- phenytoin
- spironolactone, digoxin, procainamide
- NSAIDs, meperidine, morphine
- insulin, glyburide, metformin
- ABX: AGs, cephs, PCN, FQs, vanc
- gout: colchicine & allopurinol
Metformin is contraindicated with
SCr>1.4 in females 1.5 in males
- risk of lactic acidosis
is overactive bladder (OAB) more common in M/F ?
=
is OAB with incontinence more common in M/F?
females
urge urinary incontinence
- OAB
- detrusor contracts during filling phase
stress urinary incontinence
- urethra or urethral sphincters cannot sufficiently impede urine flow
overflow incontinence
- bladder underactivity
- bladder outlet obstruction (BOO)
functional
unrelated to urethral or bladder capability
symptoms of urge urinary incontinence
- frequency (>8Xday) & urgency
- nocturia (>1/night) &/or enuresis (nocturnal incontinence)
- usually large volume due to complete emptying
stress urinary incontinence
- urethral underactivity
- UI during activities
- small volume
overflow incontinence
- bladder is full but unable to empty
- bladder underactivity (loss of function of detruser muscle)
- BOO(BPH)
- difficulty initiating stream, dribbling, small amounts of urine leaking constantly
pelvic floor muscle rehab is used in
stress UI
bladder training is used in
urge UI
urge UI treatment
- anticholinergics/ antispasmodics 1st line (oxybutynin or tolterodine)
- oxybutynin IR (ditropan): gold standard
adverse effect of oxybutynin
orthostatic hypotension
oxybutynin IR
- ditropan
- 2.5-5mg PO 2-3x/day
oxybutinin ER
- ditropan XL
- 5-10mg PO QD
- decreased ADE
oxybutynin transdermal
- oxytrol
- OTC
tolterodine
- detrol, detrol LA
- IR: 2mg PO BID
- ER: 4mg PO QD
- alternative 1st line for urge UI
- no orthostatic hypotension
fesoterodine
- toviaz
- alt 1st line for urge UI
solifenacin
- vesicare
- urge UI
darifenacin
- enablex
- urge UI
trospium
- sanctura
- urge UI
mirabegron
- myrbetriq
- beta3 agonist
- consider in those intolerant of anticholinergic effects
- 25-50mgPO QD
- urge UI
tricyclic antidepressents
- urge UI
- reserved in those with a concurrent indication (peripheral neuropathy, depression)
- orthostatic hypotension
- overdoses are potentially life-threatening
- desipramine & nortiptyline preferred due to
tricyclic antidepressents
- urge UI
- reserved in those with a concurrent indication (peripheral neuropathy, depression)
- orthostatic hypotension
- overdoses are potentially life-threatening
- desipramine & nortiptyline preferred due to decreased side effects
duloxetine
- cymbalta
- 1st line is stress UI
- 40mg PO BID
alpha-adrenergic agonist
- stress UI
- pseudoephedrin 15-60mg TID
- phenylephrine 10mg QID
topical estrogens
- Stress UI in combo with urethritis or vaginitis due to estrogen deficiency
overflow incontinence treatment
- intermittent self catherization 3-4X/day
- bethanechol: rarely used
epithelial tissue of prostate
produces prostatic secretions
stromal tissue of postate
smooth muscle c ontraction if alpha-adrenergic receptor stimulated
capsule tissue of prostate
- fibrous, connective tissue that also contracts when alpha-adrenergic receptor stimulated
pathophys of BPH
- static factors: growing prostate
- dynamic factors: alpha stimulation
- detrusor factors: 2* to BOO
symptoms of BPH
- obstructive: diminished stream, urinary hesitancy, incomplete bladder voiding
- irritative: urinary frequency & urgency, nocturia
mild BPH
- aymptomatic
- peak urinary flow rate 25-50mL
moderate BPH
- all of mild plus obstructive or irritative voiding symtoms
severe BPH
- all of moderate plus one or more complication of BPH
mild BPH treatment
- watchful waiting
- behavior modification
severe BPH symptoms & complications treattment
surgery
alpha- adrenergic antagonists
- do not reduce prostate side
- relax intrinsic urethral sphincter & prostatic smooth muscle
3rd generation alpha blockers
- tamsulosin (flomax) & silodosin
2nd generation alpha blockers
prazosin, terazosin (Hytrin), doxazosine (Cadura), alfuzosin
- terazosin & doxazosin 1 mg PO at bedtime
- orthostatic hypotension
3rd generation alpha blockers
- tamsulosin (flomax) & silodosin
- tamsulosin 0.4mg PO QD
- avoid in sulfa allergy
- good in pts at risk for hypotension
5- alpha reductive inhibitors
- reduce size of prostate
- decrease intraprostatic DHT & SDHT
- takes 6-12 months to take effect
- second line in sexually active men
- pregnancy X
- dutasteride (Avodart) 0.5mg PO QD
- finasteride (proscar) 5mg PO QD
BPH treatment not commonly used
- GNrh antagonists
- antiandrogens