Renal Drugs Flashcards
volume dependence theory for essential hypertension
na retention
ECFV expansion
increased preload
increase CO
HTN!
- low renin!!!
failure to autoregulate and vasodilate
nitroprusside
arterial and venous dilator
NO release followed by increase cGMP generation
IV – use in emergencies
side effect of selective alpha 1 blocker
orthostasis - take first dose in bed
aliskerin
renin inhibitor
inhibits renin to increase AII generation
don’t really know place in therapy yet
biotransformation
makes it easier for things to leave the body through the kidney
build up in CKD and can get symptomatic
propranolol
Non-selective Beta Blockers
K sparing diuretics adverse effects
hyperkalemia
gynecomastia (spiro)
triametere - kidney stones
renin profiling?
classify by renin level for essential htn
if high - beta blockers, ACEI, ARBs
if low - diuretics
not proven! urine monitor
IV contrast
known nephrotoxin!
can cause AKI
can lead to drug toxicity if can’t clear what they are taking
Carbonic Anhydrase inhibitors
Acetazolamide
Mountain Sickness Prophylaxis
Glaucoma (lowers intraocular pressure)
Proximal Tubule Diuretic – blocks countertransport of Na-H
Not used much for diuretic (only when HCO3 is high)
hydralazine
arterial dilator
direct effect on smooth muscle, safe in pregnancy
adverse effects of loop diuretics
increases Ca excretion
Hypokalemia
Metabolic Alkalosis
Hearing loss
losartan
ARB
non-selective alpha blocker
Blocks activation of receptors for vasoconstriction and NE release,
First line for treatment of HTN associated with cocaine – leads to reflex tachycardia
Do not use unless pheo, cocaine. If you gave a beta blocker to a patient with cocaine toxicity and hypertension, then you would knock out the beta effect which is in part vasodilatory and leave them with the unrestricted alpha effect of norepi if they are having cocaine or pheo.
Is toxin dialyzable?
low MW (fit through filter)
low protein binding (only free drug is filtered)
small Vd (only blood compartment is filtered)
low endogenous clearance (why bother if it will come out fast)
what does resistance dependent essential htn look like?
RAS
K sparing diuretics
**not used alone for HTN
all work distally
Triameterene, Amiloride block ENaC
Spiro is an aldo antagonist (lowers mortality in CHF)
good in CHF!
lithium overdose
very small, small Vd - dialysis!
Vaptans
conivaptal, tolvaptan
block ADH by binding it its recepotr
useful for hyponaturemia from CHF and cirrhosis
may be used to prevent cAMP generation in PKD
calcium channel blocker types
non-dihydropyridines (verapamil, diltiazen)
dihydropyridines (nifedipine)
thiazides
1 to treat HTN!!
block NCC on distal tubule
best for elderly, SBP - reduce U(Ca) - increase bone mineral density!!
distal action makes them less potent
adverse effects of non-dihydropyridines
constipation, negative inotrope, conduction delays
be careful if CHF, heart block, old people
hemodialysis
first created for overdose then instituted for CKD
Dialysis = stuff on one side of membrane that CAN’T MOVE through, and stuff that CAN MOVE through.
Based on diffusion, things move from one side of the membrane to the other.
Hemodialysis goes a little further.
Blood comes out of IV. Use a pump, stuff it into a machine full of fibers with hollow pores. Things will move to the other side based on their ability to move.
Would have concentration of 0 on the other side so things can move as fast as possible. Want a dialysate COUNTERCURRENT to FLUSH OUT THE OTHER SIDE OF THE MEMBRANE à if the concentration on the other side of the membrane is 0, things will move very quick!
Here’s another trick: b/c this is under pressure (like how kidney is under BP), there will be an ULTRAFILTRATE à H2O is forced to other side b/c of pressure and THINGS MOVE W/ WATER!
It’s a simple concept – things move across a membrane b/c they can and other things are stuck.
pH and pKA of weak acids and bases
if pH < pKa - all have H - HA, BH+
if pH > pKa - no H - A- , B
If pH >>> pKa, mole will be CHARGED and TRAPPED in COMPARTMENTS!
(basic pH à charged drug mole à can’t cross lipid membrane à drug will be trapped)
PHASE I reaction
Phase 1 is taking LIPOPHILIC (simple long C molecules, big organic things) and ADDING POLAR SIDE GROUPS (electrophils – ketones, COOH, or nucleophiles, nitrogens and sulfars
- do this to slightly INCREASE H2O SOLUBILITY + ADD SIDE GROUP that will allow something big to be ADDED TO THE END!
Phase 1 à put something polar on molecule
Phase 2 à conjugate something EXTREMELY POLAR to the first polar molecule that was added on in phase 1 to ENHANCE H2O SOLUBILITY
PHASE II reaction
- big thing is PHASE 2 conjugation rxns aka adding a large residue to end of drug/biotransforming molecule (acetyl residues, glutathione residues, sulfyl residues) à these big side groups ENHANCE H2O SOLUBILITY SO IT CAN COME OUT OF THE KIDNEY
Phase 1 à put something polar on molecule
Phase 2 à conjugate something EXTREMELY POLAR to the first polar molecule that was added on in phase 1 to ENHANCE H2O SOLUBILITY
Good rebound
redistribution from intracellular stores
increase amount in blood but good because it’s coming from a place it wascausing harm
NO clinical deterioration following HD
opp for futher elimination!!
Urine alkalinization
trap charged! drag molecules out of brain into urine
Give bicarb à will force equillibrium reaction to create basic environment à drug will donate H+ and become charged à will trap drug in urineà guy wakes up.
This guy has all sorts of problems to deal with, but is acutely medically improved by pH.
This is about all things done by IV bicarb.
Concept – Henderson Hasselback à change drug from one species to another environment that is BASIC to enhance its ability to have urinary elimination.
