exam 2: lecture 2 Flashcards
what is the MOA of CCB? how many subunit does CCB have ?
BLOCKS L type ca channel and T type ca channel
5 subunits- 2a b g d
V + D binds to the A1 subunit and dihydro binds to the a1 subunit but on a DIFF PLACE = accounts for specificity
what are the nondihydro and dibhydro CCB meds?
non-dihydro - VD - verapamil, diltz
Dihydro: NNFAC
nifedipine - 1st drug in class casues tachycardia since blood vessles dialte fast
nicardine
felodipine
amlodipine - LONGEST half life
clevidipijne - only in IV form
where does nondihyfro and dihydro work best?
nondihydro works best in myocardium
dihydro works best in peripheral vascualr smooth musucles
what binds to T type channels CCB?
they are found in SA and AV nodes and non-dihydro drugs bind to it more which accounts for tissue specificity
what are the effects on the myocardium, arterial smooth musucles, coronary aa from CCB?
mycardium - slows contraction, reduces O2 requirement, usefull in angina. slows AV/SA nodes, decreases HR, decreases O2 requiremetns
arteiral smooth muscules - STOPS ca influx so casues vasodilation which decreases aterial presure
coronary aa - stops contraction stops spasm helps w prinz metal angina
what does amlodipine do to NO?
amlodipine worsk as a ACEi which leads to buildup of bradykinin –> increases NO –>. vasodilation
how does Vereapamil and diltiazem have sympatehtic antagonist effects?
if you give someone diltiazem, there is no relfex tachycardia due to sympaethtic blockage = vasodialtion, no tachycarida!!!
unlike nifidepine which has tachy effect
what are some indication for CCB and how do some of them work?
- HTN = dihydro drugs like amlodipine
- variant angina = diltizaem + isosorbide dinitrate (will explain in diff card)
- supraventricular arrhytmias = dilz, vera = targets T CA channels (t challens leads to depolarization)
- raynauds = dihydro (nifedipine) prevetns constriction, casues dialtion to fingers
-achalasia= dihydro (nifedipine) presents vasocontriction and casues relaxation
- migraines
- intracranila vasospams = dihydro = prevetns spasm after a stroke
what are some untoward effects to CCB?
cardiac depression - can slow down condcution and casue bradycarida and heart block
Hypotension = orthostasisi
GERD - VERY COMMON
Hyperglycemia - CCB can block calcium channels to stop releasing insulin leading to hyperglycemia!! ==> Metabolic ketoacidosis!!
Edema = due to redistruction of fluid and space
when is non dihydro CCB contraindiacated?
AV NODE BLOCK
what is the sig to papaver somniferum? what does the opium contain?
its an illegal plant that contains a crude opium (morphone, codein, pavaverine, thebaine).
this is why in drug test its positive
in 1964 reserchers realzied that the opiates are great vasodilators and they modfied papaverine to verapamil
what was the first drug in the nondihydro (year) and dihydro class?
non dihydro - verapamil 1964 but FDA approved in 1982
dihydro - nifedipine
waht is the MOA and pharmokinetics for minoxdil? what year was it made?
made in the 60s which has an untaught effect of hypertrichosis!!
MOA = OPENS K channels in arterial smooth musucles which hyperpolarizes making it harder to transmit a signal.
AFFECTS ONLY ARTERIES NOT VEINS!
pharmokinetics = taken PO. its a prodrug so liver can convert it to active sulfate metabolite!
what are the indication and untowards effect for minoxdil?
indications are:
- HTN = NOT FIRST IN LINE, its used for refractory HTN. only give this is nothing else works
- +diuretic and BB - you need to give it w either these two drugs or else it will casue bad vasodilation –> bad edema and bad tachycardia
untoward effects:
- CV - tachycardia, palpitation, angina, death
- hypertrichosis
what is the MOA of hydralazine?
normally, Gq activates IP3 but hydralazine inhibits IP3 so theres less contraction OR IT COULD ALSO open up calcium channels who knows
net effect: arterioles vasodilators
what is the pharmokineteics for hydralazine? think about metformin (mommy)
PO
hydralzies is metabolzied in liver by acetylate
fast metabolism = 15%
slow metabolism = 35-40%
what are the indication for hydralazine?
you give it to someone wiht HTN w angina.
you would combine hydralazine +isosorbide dinitrate = BIDEL
whats the significance of BIDEL?
so normally tachypalaxis effect happen when you give someone NO and body respond by making ROS to cancel out NO.
but if you give someone BIDEL, then this cancels the ROS so BIDEL gets rid of tachyphalyaxis effect
why is BIDEL effective in black pt than white? think of the study
study showed that BIDEL decreased M/M sig in black pateitns
more in black bc black has more ROS than anyone else so BIDEL works better
what are the untoward effect for hydralazine?
HYPOtension, headahce, lupus like syndrome
which drug has lupus like syndrome as their untoward effect? explain
hydralazine!!
lupus like syndrome consist of malasie, rash, fever, muscule joint but NO RENAL DYSFUNCTION
its an auotimmune mediated reaction developing months after taking the rx
if you stop the drug lupus like syndrome can get back to normal
more prone in SLOW metabolizers since drug lingers in their body logner for effects to happen
which two vasodilator rx would you combine with +isosobirde dinitrate and what is it used for ?
CCB for variant angina: combine ditazem + Isosobide = FOR preventing tachycardia reflux
Hydralazine for HTN w angina: combine hydra + isosorbide = FOR preventing tachyphylaxsis
what is the MOA for milrinone?
normally in the cell, cAMP is converted to 5AMP by PDE3 (phosphodiesterase 3)
BUT milrinone inhibits PDE3
so the effect is increase cAMP therefore increase in PKA which will release MORE CA –> POSTIVE INOTROPIC EFFECT TO HEART
whats the pharmokinectic, when would u give it, and untwoard effect for milrinone?
given IV
given for HF or acute cardiac decompenstation for THAT JOLT for inotropic effect (contractility)
effects are GI disturbances :( and arrhythmias sine were contracting
