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161 Cards in this Set

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how Tx Alz?
carbamate, and other AChase inhibitors like donepezil
chol agonists
CarbaCHOL
BethaneCHOL
MethaCHOLine
methacholine
methaCHOLine=Ach+

*Dx asthma (d/t bronchoconstriction<==Ach)

S/E: Ach+ ==>
flushing
sweating (SNS CHOLinergic)
salivation,
GI cramping,
bronchoconstriction
bethanechol
Tx: urinary retention
(muscarinic agonist)
Tx: urinary retention
bethanechol
Tx Park Dz
benztropine
(muscarinic antagonist;
in Park Dz: no DA, so ACh predominates)
Tx psychotic pt
typical antipsychotic (thioridazine)
choline esters
-ex?
-affects what receptors?
-PE?
eg- ACh, CarcbaCHOL

-affects nicotinic/muscarinic receptors

PE:
*decr BP via NO released from vascular endothelial cells (muscarinic receptors)

*decr BP blocked by atropine
what can block the decr BP caused by ACh or carbachol (choline esters)?
atropine (muscarinic antagonist)
pilocarpine
(pilocarpine=chol agonist)

Tx: glaucoma

PE:
*miosis (via sphincter pupillae)
*cycloplegia (paralysis of ciliary muscle) via contraction of ciliary muscle
==>decr IOP via incr AH outflow

S/E: bronchoconstrict, salivation
nicotine
-desc
-PE
-S/E
tertiary amine; not hydrolyzed by plasma AChase, metabolized by liver

PE:
-incr SNS: incr HR/BP, cutaneous vc
-incr resp & GI motility

S/E:
-muscle fasciculations folloed by depolarization blockade (large doses)
-CNS: convulsions (OD)
carbamates
-what are they
-ex's
=types of AChase -

-ex:
physostigmine(3')-ENTERS brain
==>CNS effects

neostigmine (4')-does NOT enter brain
edrophonium (4')-does NOT enter brain
==>NO CNS effects, only peripheral effects

(reversible)
physostigmine
3' AChase -

==>enters brain
edrophonium:
4' AChase -does NOT enter brain
==>NO CNS effects, only peripheral effects

(reversible)

*diagnosis of myasthenia gravis (MG)
*differentiate b/w
“myasthenic” & “cholinergic” crisis in patients tx w
neostigmine
*used with atropine (musc-) to reverse NMB caused by non-depolarizing drugs (d-tc, pancuronium)
neostigmine
4' AChase -does NOT enter brain
==>NO CNS effects, only peripheral effects

(reversible)

Tx:
*MG (always used with atropine to prevent indirect musc S/E)
*used w/glycoporrolate to reverse NMB caused by non-depolarizing drugs
organophosphates
-ex?
malathion
parathion
isofluophate (DFP)

organophosphate=AChase inhibitor
- irreversible due to phosphorylation (covalent bond) of AChase active site
USMLE: Scientist tries to commit suicide with “common laboratory chemical” or “chemical used in protein reactions.” What do you Tx him with?
The chemical was isofluophate (organophosphate). Tx him with atropine and pralidoxime
What do these Sx indicate:

lacrimation, salivation, miosis, dyspnea, no change BP, skeletal muscle fasciculations

-how Tx?
no change BP (N1)
SkM fascic (N2)

These indicate organophosphate (OP) poisoning.

-organophosphate=AChase inhibitor
* irreversible due to phosphorylation (covalent bond) of AChase active site


Tx w/atropine and pralidoxine (2-PAM): regenerates phosphorylated AChase
how Tx poisoning with plants that causes incr Ach?
(incr Ach is like giving physostigmine: 3' AChase inhibitor ==>DOES enter brain)

Tx w/atropine (3' musc - ==>cross BBB, placenta)
how Tx poisoning with plants that causes decr Ach?
decr ACh is like giving atropine (3' musc - ==>enters brain)

Tx w/physostigmine (3' AChase inhibitor: DOES enter brain)
muscarinic antagonist
3' (cross BBB, placenta)
aTROPINE
benzTROPINE
cyclopentolate
scopolamine

4' (do not cross BBB)
"N-METHYL-PIG: imagine a PIG with methyls on it" :

N-methylATROPINE
Propantheline - GI spasticity
Ipratropium - (Tx bronchoconstriction in asthma)
Glycopyrrolate
Sx of muscarinic receptor blockade
OD of atropine-like drugs
(atropine=musc - ==>incr SNS):

*red as a beet (cutaneous dilation bc shunting blood to skin==>sweat and reduce heat)

*hot as a pistol (hot skin bc cant sweat away heat; sweating=sympathetic CHOLINERGIC innervation, & atropine inhibits cholinergics)

*dry as a desert:
--inhibition of sweating
--saliva is thick (not watery)==>mouth feels dry
==>difficulty swallowing

*mad as a hatter (hallucinations/delerium)
(think how cocaine (incr SNS)==>hallucinations/delerium)
Tx glaucoma:
-ex?
-MOA
A. Decr production of AH:

1. BB: timolol, propanolol
2. CA-: acetoZOLAMIDE, dorZOLAMIDE


B.Inc outfow of AH via nl path:
1. A1 receptor:
EpinEPHRINE
dipivEFRIN

2. OP ACHase - :
isofluOPHATE
echothiOPHATE

(mneum: "OP"=OP ACHase-)

3. Musc agonist: pilocarpine

C. Inc outflow of AH via uveoscleral pathway
(contract ciliary muscle SmM):

Latanoprost (PGF2a analog)
ganglionic blocking drugs:
ex's?
effects?
trimethaphan
hexamethonium (mneum: put an “hex” on the autonomic NS)

These block SNS and PSNS:
1. Block SNS:
-arteriodilation lowers TPR
-venodilation==>decr preload
-decr dp/dt
-decr preload & dp/dt ==> decr CO
-decr TPR & CO==>hypotension
-decr sweating
-impotence (no ejaculation)

2. Block PSNS:
tachycardia
mydriasis & cycloplegia
decr GI motility
constipation, urinary retention
decr salivation & lacrimation
impotence (no erection)
NMB drugs
Depolarizing (non-comp):
*succinylcholine
*dexamthenoium

-Stage 1: MEP depol
-Stage 2: repol, but still refractory

-fasciculations prior to flaccid paralysis (b/c depol)
-Uses: NMB, ECT


Non-depolarizing (competitive)
"the --curiums & --roniums":
*d-tubocurarine (d-tc; curare)
*pancuronium

-MEP never depol==>no fasciculations prior to flaccid paralysis
-Use: NMB
effects of
a) succinylcholine
b) curare

on
1) MG,
2) burns,
3) denervation?
1) MG
*decr Ach receptor density
*succinylcholine: effect decr
*curare: effect incr

2) burns
*incr Ach receptor density
*succinylcholine: effect incr (hyperkalemia)
*curare: effect decr

3) denervation
*incr Ach receptor density
*succinylcholine: effect incr (hyperkalemia)
*curare: effect decr


*↓ Ach receptor density ==>
↑ effect of curare b/c not as many receptors to stimulate, so works really well

• Ach receptor density is directly related to effect of succinylcholine and inversely related to effect of curare

With burns and denervation, you get hyperkalemia with succinylcholine.

-Succinylcholine binds and constantly depolarizes; you try to repolarize (by ship K+ out of the cell to try to make cell interior (-) again), but it doesn’t repolarize, so just keep shipping out K+ ==>hyperkalemia.

-Since burns and denervation have increased succinylcholine effect (d/t incr Ach receptor density), ship out even more K+.
metyrosine
inhibits production of DA, NE, and Epi via:

1. inhibit Tyrosine Hydroxylase
[catalyzes Tyrosine==>DA]

2. inhibit DA Hydroxylase
[catalyses DA==>NE]

3.prevent release of ATP with NE release
causes incr NE overflow
AngII & B2 stimulation
a1 block (3 P's)
cocaine (blocks NE uptake1)
TCA's
causes decr NE overflow
musc (ACh) & a2 stimulation (clonidine)
PGE's
site of action at sympathetic nerve jxn:

-a1, a2, B1, B2
-D1, D2
-MAO-A and MAO-B
site of action at sympathetic nerve jxn (Module 1, p.209)

*a1 [IP3 & DAG]...Semo: DAG caues DIRECT incr Ca2+ in SR


-SNS post-jxn sites @ effector organs, tissues, & glands

*a2:

-SNS post-jxn on effector organs, tissues, & glands
[inhibit AC==>decr cAMP]

-SNS pre-jxn= "Autoreceptors"
[Gi increaed K+ conductance]

-PSNS post-jxn= "Heteroreceptors" [Gi ==> incr K+ conductance] at:
--SA node
--sphincter muscle of iris
--GI


*B1 [AC]:
-post-jxn @
--cardiac
--adipocytes
--JG cells of renal aff art

*B2:

-Post-jxn @
--arterioles, venules
--lung (bronchioles)
--liver
--GI
--uterus

Prejxn on sympathetic neuron="Heteroreceptors"

*D1 [AC]
-Post-jxn @
--VSM of renal aff art==>vd

*D2 [inhibit AC==>incr K+]
-At synapse in CNS:
--corpus striatum,
--hypothalamus
--CTZ (4th ventricle & limbic system)

-MAO-A and MAO-B vacuum up xs Epi and NE in pre-synaptic cytoplasm
-Thus, MAOi
==>incr Epi and NE in pre-synaptic cytoplasm
==>Epi & NE leaks out into synapse via channel
==>incr Epi and NE in synapse
what is rate-limiting step of catecholamine syntehsis ?
-what prevents it
(catecholamines=NE, Epi)

rate-limiting step in syntehsis is tyrosine hydroxylase, which converts
L-TYRO==>DA

MeTYROSINE inhibits TYROSINE hydroxylase
CV effects of Epi, NE, DA
*Epi: (B2>B1>A)
-Incr: ("fight-or-flight")
*VR (relax hepatic resistance)
*dp/dt (B1)
*CO/SV==>incr SBP/PP
*incr coronary blood flow

-Decr:
*TPR/DBP (B2>A, so B2 effects of vd SkM,liver outweighs A effect of constricting kidney/GI)

*NE: (A >>> B)
-NE via IV decr HR via baroreflex (NE==>vc==>incr BP==>decr HR via baroreflex)
--this decr HR blocked by atropine

*DA: (D1>B1>B2>A)
-low dose: D1 incr RBF/GFR
-med dose: B1 incr CO/SV, D1 incr RBF/GFR
-high dose: A==>vc==>incr TPR==>decr CO/SV
USMLE:
-Give drug iv
==>incr BP, decr HR

-Then give atropine.
==>incr BP, incr HR

What is the drug
NE

(BP incr, but decr HR d/t baroreflex. Atropine blocks muscarinic effects like the baroreflex)
what blocks incr RBF/mesenteric BF caused by DA?
haloperidol (DA antagonist)
effects of epi
Epi: B2>B1>A

incr SkM BF (B2)
decr skin, renal, GI BF (A)

-incr dp/dt, SV/CO (B1)
-incr VR (relax hepatic resistance) (B2)
-decr DBP (relax arteriole resistance) (B2)
what's the advantage of DA
can incr BP without decreasing RBF

(both NE and Epi decr RBF [via A] a lot--very bad)


*DA: (D1>B1>B2>A)

-low dose: D1 incr RBF/GFR
-med dose: B1 incr CO/SV, D1 incr RBF/GFR
-high dose: A==>vc==>incr TPR==>decr CO/SV
Epi + what drug can cause arrhythmias?
halothane (inhalational anesthetic)
Epi reversal + phentolamine==>what effects?
phentolamine= alpha blocker

(Epi: B2>B1>A)

Thus, Epi + alpha blocker==>
only B effects:
B2:
*incr VR (decrease hepatic resistance)
*decr TPR/DBP (vd SkM,liver)

B1: incr dp/dt, SV/CO
Epi + propanolol
propanolol=B blocker

Epi+ B blocker==>only a effects (incr BP)
what add to local anesthetic
Epi (to prevent systemic absorprtion b/c Epi vc)
phenylephrine
=a1-agonist= mydriasis w/o cycloplegia
ritodrine
=B2-agonist=decr uterine contraction in premature labor
bronchodilation w/incr HR caused by what drug
isoproterenol (B1=B2, AKA non-selective B1 and B2 agonist)
bronchodilation w/very little HR-->caused by what drug
albuterol, terbutaline (selective B2 agonists)
clonidine
pre and post-synaptic a2 agonist (Module 1 syll,p. 209: alpha-2 is inhibitory to SNS)

-this α2-agonist enters & works in brain to DECREASE SNS
==>decr BP and HR

mneum: "get clobbered by clonidine"

(give to psych pts to calm them down)
indrect adrenergic agonists
-ex?
-MOA
-Tyramine (in fermented foods: beer, cheese)
-amphetamine

MOA: release of stored NE

*NO EFFECT if pre-treat with:

1. reserpine/guanethidine (sympatholytic: thus can't release stored NE)

2. cocaine (blocks NE uptake1, so NE is in the cytoplasm instead of in the pre-synaptic strores)

3. "3 P's" (alpha blockers): phentolamine, prazosin, phenoxybenzamine (PBZ)
For what drugs are you not supposed to eat cheese or beer?
Fermented foods like cheese and beer contain Tyramine (indirect adrenergic agonist: release stored NE).

Thus, tyramine is contraindicated if taking phenelzine or tranylcypromine, which are MAOi and thus incr NE in synapse. Since cheese/beer (Tyramine) release stored NE, this would increase NE even more==>hypertensive crisis
incr BP d/t tyramine and amphetamine can be blocked by
(Recall: tyramine and amphetamine are indirect adrenergic agonists, MOA=released stored NE)

*NO EFFECT if pre-treat with:

1. reserpine/guanethidine (sympatholytic: thus can't release stored NE)

2. cocaine (blocks NE uptake1, so NE is in the cytoplasm instead of in the pre-synaptic strores)

3. "3 P's" (alpha blockers): phentolamine, prazosin, phenoxybenzamine (PBZ)
Tx ADHD?
-S/E:
methylphenidate (Ritalin)

MOA: stim NE release and block NE uptake1

S/E: insomnia, decr linear growth rate, depression
amphetamine toxicity
-Sx?
-how Tx?
-nervous, excited, agitated
-convulsions
-formication (think have ants under skin)==>excoriation (cut yourself)

Tx w/chlorpromazine (typical antipsychotic: blocks DA in brain)
the following are Sx of toxicity/withdrawal from what?

-nervous, excited, agitated
-convulsions
-formication (think have ants under skin)==>excoriation (cut yourself)
amphetamine toxicity (looks like cocaine)
ephedrine
diret B1 and B2
indirect a--thus no a effects after reserpine
alpha blockers
-ex?
-PE?
-S/E?
"3 P's":
phentolamine
prazosin
phenoxybenzamine (PBZ):

-PBZ causes IRREV (non-competitive) blockade of alpha receptors

-phentolamine/phenoxybenzamine (PBZ) incr HR via baroreflex
-prazosin has no effecton HR

Epi reversal: These REVERSE the vasopressor (vasopressor=incr BP via vc) of supraphysiological dose of Epi (B2>B1>A)
==>VASODEPRESSOR

S/E: orthostatic hypotension
(alpha receptors prevent you from fainting when you stand up)
Tx migraine
partial a agonists:
ERGOTAMINE
dihydroERGOTAMINE

("ERG, you GOT A MINE migraine pills")
Tx BPH
-Rx?
-MOA
tamsulosin

MOA: block a1A receptors in GU tract==>void
pheo tumor
-Tx?
-PE?
phentolamine (A-blocker)

PE: decr BP (Epi reversal)
how reverse Epi?
A-blockers: "3 P's"
phentolamine
phenoxybenzine (PBZ)
prazolin

These REVERSE the vasopressor (vasopressor=incr BP via vc) of supraphysiological dose of Epi (B2>B1>A)
==>VASODEPRESSOR
selective B1 blockers
atenolol, metaprolol (sp?)

mneum: ppl get heart attacks in he morning (AM), so give “AM” drugs to block B1 (heart attack)
block B1 and B2
timolol, propanolol
Beta blockers
-Rx?
-Tx?
-S/E
B1-selective:
*Atenolol
*Metoprolol

non-selective (B1 and B2):
*propnaolol
*timolol- decr IOP w/o cycloplegia (do not use propanolol b/c causes local anesthesia of cornea)

Tx:
1. angina: decr O2 demand by decr dp/dt & HR, but LV-EDV incr (d/t decr HR)

2. decr HR, AV conduction, dp/dt

3. Hyperthyroidism: decr tachycardia and tremor, also prevents conversion of T4-->T3

4. block incr HR caused by hemorrhage, minoxidil, hydralazine, diazoxide, nitroprusside, nitroglycerin

5. decr Oxygen demand via decr HR, dp/dt, afterload/DBP
[Nitroglycerin decr O2 demand by decr VR and LV-EDV)

-S/E:
-CHF, AV block
-bronchospasm
-delayed recovery of [glucose] in Type I DM after s.c. injxn of too much insulin
Pt Tx w/BB for angina, then d/c drug. Now, angina and MI.

Why?
BB Withdrawal Syndrome
(Sx=tachycardia, palpitations, tremor, chest pain)

BB==>upreg B receptors
==>d/c drug
==>incr cardiac B receptor stimulation
==>incr O2 demand
`==>Angina and MI
reserpine
sympatholytic:

1. decr NE release by poisoning NE storage vesicles

2. no effect of TAP drugs (Tyramine, Amphetamine, Propanolamine= Indirect Adrenergic Agonist) if pre-Tx with reserpine

3. no alpha effects of ephedrine if pre-Tx with reserpine
guanethidine
sympatholytic:

1. decr nerve-stimulated release of NE

2. competitive inhibitor of NE uptake1 (vs. cocaine=non-competitive inhibitor of NE uptake1)
==>inhibits vesicular storage of NE (sympatholytic)

3. anti-HTN effect blocked by TCA's b/c TCA's block entry of guanethidine into neuron
cocaine
-PE
-MOA
-toxicity
-withdrawal
1. blocks uptake1 of NE, Epi, DA, adn 5-HT in CNS

2. blocks uptake1 in peripheral sympathetic neurons--potentiates effects of NE and Epi, but not isoproterenol (B1=B2 agonist)

3. euphoria via DA release in nucleus accumbens

4. local anesthetic effect via blockade of Na channels in sensory neurons

Toxicity:
dilated pupils
excitation, euphoria,
halo vision
itchy skin
incr BP/HR
convulsions

Withdrawal:
sleepiness
depression
anhedonia (inability to feel pleasure)
what do these Sx indicate:
-dilated pupils
incr BP/HR
euphoria
hallucinations
halo vision
itchy skin
convulsions
cocaine toxicity
what do these Sx suggest:
sleepiness
depression
anhedonia
(anhedonia=inab to feel pleasure)

cocaine withdrawal
MAOi's
-Rx?
-Tx
-MOA
-S/E
Rx
-inhibit MAO-A and MAO-B:
*phenelzine
*tranylcypromine

-inhibit MAO-B to prevent breakdown of DA in CNS:
*selegiline

Tx: depression

S/E:
cheese rxn (cheese, pickled herring): inhibition of MAO-A (thus, phenelzine and tranylcypromine (not selegiline)) allows dietary tyramine to enter circulation and release NE==>HTN and tachycardia
clonidine
Tx: HTN (give to psych pts to calm them down: "get CLObbered by CLOnidine")

MOA: decr SNS activity via stim of a2 receptors in CNS (mimics baroreceptor input==>decr SNS)
==>decr NE and renin activity,
decr HR

s/E: sedation, dry mouth, edema

Withdrawal syndrome: sweating, incr HR, abrupt return of BP to HTN value,
abdominal pain,
tremor,
H/A,
apprehension

(vs. BB withdrawal syndrome:
incr HR w/palpitations,
but not tremor, sweating, ab pain, or incr BP)
alpha methyl-dopa
Tx: HTN in pregnant women
MOA: decr SNS by stim a2 receptors in CNS (mimics baroreceptor input)
==>decr NE and renin,
decr HR

S/E: (+)Coombs test (Goljan),
heptatitis, "flu" syndrome
drugs that decr plasms NE
clonidine
alpha methyl-dopa
reserpine
guanethine
drugs that incr plasma NE
-alpha blockers (3 P's: phenotolamine, phenoxybenzine, prazosin)
-arterial vasodilators (hydralazine, minoxidil, diazoxide)
-HCTZ (anti-HTN: inhibit NA abs)
-sodium nitroprusside
-
arterial vasodilators
-Rx?
-PE?
-MOA?
-SE?
arterial vasodilator (hydralazine, minoxidil, diazoxide)

-dilate resistence vessels (arterioles)
==>decr TPR, BP
==>incr dp/dt, CO, PRA, NE

-S/E:
*hydralazine (sHip drug):
==>lupus-like syndrome
==>d/c hydralazine & tx with steroid

minoxidil: hirsuitism, effective additive w/finasteride; edema

diazoxide: inhibit insulin release==>hyperglycemia;
edema
hydralazine
arterial vasodilator (hydralazine, minoxidil, diazoxide)

-dilate resistence vessels (arterioles)
==>decr TPR, BP
==>incr dp/dt, CO, PRA, NE

-S/E:
*hydralazine (sHip drug):
==>lupus-like syndrome
==>d/c hydralazine & tx with steroid
minoxidil
-dilate resistence vessels (arterioles)
==>decr TPR, BP
==>incr dp/dt, CO, PRA, NE

S/E of minoxidil:
-hirsuitism
-effective additive w/finasteride
-edema
diazoxide
arterial vasodilator (hydralazine, minoxidil, diazoxide)

-dilate resistence vessels (arterioles)
==>decr TPR, BP
==>incr dp/dt, CO, PRA, NE

S/E: inhibit insulin release==>
hyperglycemia; edema
sodium nitroprusside
Tx:
*hypertensive emergency (Goljan)
*CHF

MOA: dilates artieres & veins via release of NO from sodium nitroprusside molecule

PE: balanced vasodilation
dilate arteries==>decr TPR/DBP
dilate veins==>decr VR

In normotensive pt, these effects cancel out, so no change in CO.

In CHF pt, CO incr (b/c VR is too high in CHF pt, can't pump blood out, so reducing VR actually helps incr CO (good!).

Thus, both the decrease in DBP and decrease in VR lead to incr CO in CHF pts.)
what happens in infuse sodium nitroprusside into a pt with poor renal fxn
-how tx?
thiocyanate toxicity (muscle weakness, spasm, disorientation)

Tx with thiosulfate
how Tx cyanide toxicity
Tx with nitrate or thiosulfate
Ca++ blockers
verapamil
diltiazem
nifedipine

(mneum: "Valentine's Day" (heart)="VD"=Verapimil, Diltiazem)

Tx:
-HTN
-exertional & vasospastic angina
-AVNRT

1. block Ca++ channels at SA/AV nodes, cardiac myocytes, arterial VSM
2. decr BP: Nifedipine>Diltiazem>Verapamil
3. decr AV conduction via incr ERP: verapamil>diltiazem
4. nifedipine- incr HR with little/n.c. AV conduction
5. angina-decr O2 (decr dp/dt, HR, afterload) w/incr O2 delivery via dilation of coronary artieres
Rx that decr dp/dt
BB,
Ca++ blockers
diisopyramide
effects of AngII
relese ALDO & ADH
incr BP
incr SNS
incr NE release
block NE uptake 1
decr mesenteric BF
Tx GI bleeding
-rx?
-MOA?
MOA: decr mesenteric BF

Rx:
NE & AngII (get escape),
ADH (AKA AVP) & octreotide--no escape
Tx Portal HTN
-rx?
-MOA?
MOA: constrict arterial BF to GI tract-->less blood going from GI to liver

Rx: ADH & octreotide (somatostatin analog)--
"no escape"
ACEi
"--pril": captopril, enalapril

Tx:
*lower BP;
*CHF (incr CO by decr preload and afterload; reverses cardiac remodeling caused by AngII)
*HTN w/DM (ACEi lowers BP and proteinuria (protects kidney))

MOA: prevent conversion of AngI==>AngII in every vascular endothelial cell

PE:
-decr BP/TPR without changing CO, HR
-
S/E:
fetal toxicity (Category X)
K+retension
cough (ACEi blocks metabolism of bradykinin==>incr BK==>incr PG==>cough)
*can prevent cough by giving aspirin, or d/c ACEi and switch to ARB (sartan, i.e.losartan)
person on ACEi develops cough. what do you do?
d/c ACEi switch to ARB (sartan)
what can you give along with ACEi to prevent cough?
aspirin
why give ACEi to CHF pt?
*incr CO by decrasing preload and afterload
*reverse cardiac remodeling by AngII
what give to HTN pt w/DM
ACEi:
*decr BP
*decr proteinuria (protects kidney)
acetozolamide
Tx:
glaucoma
aspirin OD
altitude sickness

MOA: inh CA in PT and DT to prevent reabs of bicarb

PE:
*inhibits formation of aq humor and CSF (CA invovled in production of aq humor & CSF)
==>Tx glaucoma
*incr excretion of bicarb, Na, K
*makes urine more alkaline==>enhances clearance of aspirin (acid)
*prevents reabs of bicarb and Na
*causes met acid==>stimulates resp alkalosis (good for altitude sickness)

S/E:
-metabolic acid
-hyperchloremic
what Rx stimulates respiration?
caffeine, theophylline
nicotine
Epi
acetozolamide (met acid==>compensatory resp alk)
what Tx depress respiration?
EtOH
baribiturates
opiates (i.e. morphine)
benzodiazepine (ie. diazepam)
how enhance renal clearance of acidic drugs?
make urine alkaline via CA inhibitor or Na bicarbonate
how enhance renal clearance of basic drugs?
make urine acidic via ammonium cloride (NH3Cl)
furosemide
Loop diuretic (furosemide, ethacrynic acid)

Tx:
*fluid overload d/t CHF, pulmonary edema, periph edema
*hypercalcemia (Goljan)

MOA:
*inhibits Tri-transporter in TAL (Na:K:2Cl)
*inhibits Na transport in macula densa of DT

PE:
-loss of Na, K, Cl, Ca, Mg, water

-K loss worsened b/c Na not reabosrbed in TAL, so later on CD principal cells reabsorb more Na (and thus wastes more K)
-blocks Na transport in macula densa of DT==>no Na sensed==>secondary hyper-ALDO worsens K loss

S/E:
-ototoxicity; potentiated by aminoglycosides (e.g. gentamicin)

-enhances digoxin toxicity:
loop diuretic causees hypokalemia, so less K to compete with digoxin
-hypochloremic met alkalosis
(lose Cl-, so retain HCO3-)
-hypomagnesemia
-hyperglycemia (d/t enhanced reabsorption in PT)
-dilutional hyponatremia--cannot make a dilute urine in order to excrete free water
-hyperuricemia (bad for gout) and Li+ toxicity b/c enhanced reabs in PT
ethacrynic acid
Loop diuretic

Tx:
*fluid overload d/t CHF, pulmonary edema, periph edema
*hypercalcemia (Goljan)

MOA:
*inhibits Tri-transporter in TAL (Na:K:2Cl)
*inhibits Na transport in macula densa of DT

PE:
-loss of Na, K, Cl, Ca, Mg, water

-K loss worsened b/c Na not reabosrbed in TAL, so later on CD principal cells reabsorb more Na (and thus wastes more K)
-blocks Na transport in macula densa of DT==>no Na sensed==>secondary hyper-ALDO worsens K loss

S/E:
-ototoxicity; potentiated by aminoglycosides (e.g. gentamicin)

-enhances digoxin toxicity:
loop diuretic causees hypokalemia, so less K to compete with digoxin
-hypochloremic met alkalosis
(lose Cl-, so retain HCO3-)
-hypomagnesemia
-hyperglycemia (d/t enhanced reabsorption in PT)
-dilutional hyponatremia--cannot make a dilute urine in order to excrete free water
-hyperuricemia (bad for gout) and Li+ toxicity b/c enhanced reabs in PT
hydrochlorothiazide
MOA:
-site of action=DT
-decr GFR in all pts

-blocks NaCl symporter in DT==> incr excretion of Na, Cl, Mg, K
-decreased free water clearance: urine always hypertonic
==>dilutional hyponatremia ("emia"=blood)
-decr Ca+ excretion (thus, decr formation of kidney stones)
-increased Na delivery to distal tubule worsens K loss
-blocks Na transport in macula densa
==>no Na sensed
==>secondary hyperALDO

S/E:
-hyponatremia, hypokalemia w/alkalosis, hypomagnesia, hyponatremia, hypergluyemia
==>all uniformly decr GFR

-enhances digoxin toxicity via hypokalemia - less K+ to compete with digoxin for
Na+-K+ ATPase binding sites
-hyperuricemia (bad for gout) and Li+ toxicity (bipolar) b/c enhanced reabs of uric acid and Li+ in prox tubule
K+ sparing diuretics
mneum: "the K+ STAys"

S=Spironolactone
*ALDO antagonist in CCT (Cortical Collecting Tubule)

T=triamterene & A=amiloride:
*block Na channels in CCT principal cells
==>no Na/K exchange (usually, Na is absorbed and K excreted via Na/K exchange)

*block Na channels in CCT intercalated cells
==>no Na/H exchange (usually, Na is absorbed and H excreted via Na/H exchange)
==>no H excreted
==>urine more alkaline

S/E: hyperkalemia! DO NOT USE IN RENAL INSUFFICIENCY B/C CAN CAUSE FATAL HYPERKALEMIA
Triamterene
K-sparing diuretic

mneum: "the K+ STAys"

S=Spironolactone
*ALDO antagonist in CCT (Cortical Collecting Tubule)

T=triamterene & A=amiloride:
*block Na channels in CCT principal cells
==>no Na/K exchange (usually, Na is absorbed and K excreted via Na/K exchange)

*block Na channels in CCT intercalated cells
==>no Na/H exchange (usually, Na is absorbed and H excreted via Na/H exchange)
==>no H excreted
==>urine more alkaline

S/E: hyperkalemia! DO NOT USE IN RENAL INSUFFICIENCY B/C CAN CAUSE FATAL HYPERKALEMIA
amiloride
mneum: "the K+ STAys"

S=Spironolactone
*ALDO antagonist in CCT (Cortical Collecting Tubule)

T=triamterene & A=amiloride:
*block Na channels in CCT principal cells
==>no Na/K exchange (usually, Na is absorbed and K excreted via Na/K exchange)

*block Na channels in CCT intercalated cells
==>no Na/H exchange (usually, Na is absorbed and H excreted via Na/H exchange)
==>no H excreted
==>urine more alkaline

S/E: hyperkalemia! DO NOT USE IN RENAL INSUFFICIENCY B/C CAN CAUSE FATAL HYPERKALEMIA
spironolactone
K+ sparing diuretic

MOA: ALDO-antagonist in CCT (Cortical Collecting Tubule)
==>incr Na excretion, decr K excretion
-no effect on adrenalectomized pts (b/c no adrenal cortex, so no ALDO for spironolactone to antagonize)

-Tx: secondary hyperaldosteronism assoc w/cirrhosis, nephrotic syndrome
-reverses cardiac remodeling caused by ALDO in HF pts

S/E:
-hyperkalemia
-spironolactone is a partial sex agonist, so can get==>
-males: gynecomastia
-females: hirsutism, deep voice
-can treat hirsutism in pts taking OCP's (OCP's contain the progestin northethindrone, which are sex hormone agonists; spironolactone is a partial sex agonist so can act as antagonist in presence of full agonist like norethindrone)
Tx: secondary hyperaldosteronism in pats with cirrhosis, nephrotic syndrome
spironolactone

spironolactone is a partial sex agonist so can act as antagonist in presence of full agonist
Tx: hirsutism in postmenopausal woman
spironolactone

spironolactone is a partial sex agonist so can act as antagonist in presence of full agonist
Tx: hirusutism in woman taking OCP's
spironolactone

spironolactone is a partial sex agonist so can act as antagonist in presence of full agonist
pt with adrenal tumor has high BP and low bicarb, K, and PRA, nl Na

-Dx?
-Tx?
conn's syndrome (adrenal tumor secreting ALDO)

Tx: spironolactone (ALDO antagonist)
how can you prevent hypokalemia from furosemide and HCTZ?
K-sparing diuretics,
ACEi,
BB,
po K supplements
graph on the effects of diuretics on
urinary flow, pH, and electrolyte composition

--how distinguish b/w diuretics?
A. Look at urine flow rate. 1. If flow=8-10 ml/min
==>fureosemide, mannitol
2. If flow=2-3 ml/min
==>acetozolamide, thiazide, K+ sparing

B. Now look at quantitative changes in electroylate composition.
1. Distinguish b/w furosemide and mannitol b/c furosemide has more excretion of Na, K, Cl
2. Distinguish b/w acetozolamde, thiazide, and K+ sparing:
-high excretion of bicarb (thus high urine pH)==>acetozolamide
-less excretion of K+ sparing
==>K+ sparing
-the one that remains is thiazide
digoxin, digitoxin
Tx: control (decr) ventricular rate in pts with Atrial flutter/fib

Meet the 3 (Italian) Digitali bros.!!!
1. Good ME (incr dp/dt via inhibit Na/K)
2. Good EE (vagal activity, decr AV conduction)
3. Bad EE (PVCs/PACs, AV block)

MOA:
(1) acts centrally to incr PSNS

(2) acts centrally to decr SNS

(3) partial inhibition of Na/K ATPase:

==>can't pump out Na+
==>Na+ builds up inside cell
==>Na/Ca antiport cannot work (usually pumps out Ca, pumps in Na)
==>Ca builds up inside the cell
==>more Ca in SR, so DIRECTLY incr dp/dt!!


Automaticity in fast fibers
("bad EE": PVC's/PAC's, AV block) d/t:

a. Inhibited Na-K pump
==>Na builds up inside cell (decreases membrane potential (more +)==>depolarized)==>automaticity

b. Hypokalemia (low K+ outside the cell) potentiates inhibition of Na-K ATPase b/c not enough extracellular K+ to pump into cell in order to pump Na+ out
==>Na/K ATPase doesn't work
==>Na builds up inside the cell and makes it +
==>spontaneous depolarization= “automaticity”==>decr ERP in ventricles

d. High Ca++: Ca++ overload inside cells causes automaticity (Goljan: decreasing depolarization threshold)

d. Low Mg++: same as Ca++ overload inside cells - causes automaticity


PE:
(1)&(2):
*decr HR
*decr conduction velocity
*incr ERP in AV node >> controls (reduces) V rate in A fib/flutter

(3) incr SV via increased dp/dt (thus, OK for HF)

*half-life of digitoxin >> half-life of digoxin (7 days vs. 1 day);

mneum: digitoxin is a longer word than digoxin, so it has a longer half-life


*Digitoxin cleared hepatically
(reduce dose in CHF, cirrhosis)

*Digoxin is cleared renally (reduce dose if decr GFR);

-older pt on digoxin--
low Vd ==>decr loading dose
low GFR==>decr maintenance dose

-MOA: inhibits N-Ka pump
==>incr dp/dt,
==>but also incr automaticity

S/E:
AV block
PVC's (d/t automaticity)
N/V (CTZ)
CNS-abnl color vision, halo vision
*quinidine incr plasma digoxin from SkM and decr renal Cl==>incr digoxin (toxic!)
quinidine
Tx: A and V dysrhythmias
(A fib/flutter, PVC's)

MOA:
1. block Na channels (in fast fibers: A, V, Purk)
2. block K channels (in fast fibers: A, V, Purk)
3. block a-adrenoceptors
4. block musc-receptors

PE:
1. suppress spontaneous depol(incr depol threshold) & slope of phase 0
==>slows conduction velocity (wider QRS)
==>PVC's

2. incr APD/ERP (b/c no K+ to repolarize)
-in atria==>decr AV conduct
-in vent ==>incr QT (Toursaud)

3. dilate arterioles & venules

4. tachycardia, incr AV conduction

*SA Node: no direct effect
*AV node: decr AV conduction d/t block K+ receptors (#2), but incr AV condution d/t block muscarinic (#4)

*give digoxin before quinidine in A fib/flutter pt so that digoxin can prevent incr QT interval d/t atropine-like effect of quinidine casued by blocking musc receptors

S/E:
Toursaud (incr QT interval)
hypotension (a-block)
decr dp/dt
diarrhea
tinnitus
pt with A fib given quinidine to slow ventricular rate, but instead ventricular rate rises immediately.
-why?
-how Tx?
incr vent rate d/t immediate anti-muscarinic effect of quinidine

Tx w/verapamil or diltiazem (Ca+ channel blockers, Tx AVNRT) to decr AV conduction
procainamide
shiP: SLE and arthritis in slow aceylators, who cannot clear drug by hepatic biotransformation

Tx:
-ACUTE control of V rate in A fib/flutter and PVC's

MOA: block Na and K channels
==>suppress phase 4 automaticity in fast fibers
==>decr conduction veloc (widens QRS)
disopyramide
PE:marked decrease in dp/dt

S/E: marked antimuscarinic effects:
-dry mouth
-constip
-contraindicated in BPH and glaucoma
lidocaine
Tx: DOC for PVC's (only for ventricular arrthythmias)

MOA: block Na+ channnels in fast fibers (A,V,Purk)
-give IV d/t low F

PE:
-decr phase 4 automaticity (prevent PVC's)
-no effect on SA or AV nodes, BP, or dp/dt
-local anesthetic effect by blocking Na+ channels

S/E:
seizures (b/c blocks Na channels in brain too well)
==>tx w/BZ (benzodiazepine)
DOC for PVC's
lidocaine

MOA: block Na+ channnels in fast fibers (A, V, Purkinje)
-give IV d/t low F

PE:
-decr phase 4 automaticity
(prevent PVC's)
-no effect on SA or AV nodes, BP, or dp/dt
-local anesthetic effect by blocking Na+ channels

S/E:
seizures (b/c blocks Na channels in brain too well)
==>tx w/BZ (benzodiazepine)
amiodarone
Tx: recurrent V tach/fib

MOA: block Na and K channels in fast fibers

PE:
-block K fibers
==>can't repolarize
==>incr APD/ERP
==>incr QT (but never Toursaud!)
==>slows AV conduction (incr PR_

-block Na fibers
==>suppress phse 4 automaticity

S/E:
-pulmonary fibrosis
-hyper/hypothyroidism
-corneal microdeposits
verapamil
mneum: VD=Valentine's Day (heart=cardiovascular)
=Verapamil & Diltiazem

Ca+ Channel blockers

Tx: AVNRT
MOA: blocks L-type channels at SA and AV nodes & cardiac myocytes

PE:

block at SA node:
==>decr HR

block at AV node:
==>decr conduction velocity and incr ERP
==>fewer signals from A to V

block at myocytes:
==?decr dp/dt==>decr CO

S/E:
AV block
decr dp/dt
decr CO in HF
patient with A fib and no GR has palpitations and dizziness. Tx w/verapamil:

MOA?
incr ERP of AV node slows AV conduction
==>more time for ventricles to fill
==>incr CO
antiplatelet drugs
1. Aspirin:
irreversibly inhibits both COX-1 & COX-2
==>prevent conversion of AA to PG's (incl. TxA2)
==>lack of TxA2 inhibits GP2b/3a expression (which use fibrinogen to bind platelets together)
on activated platelets
==>platelets can't aggregate

2. Ticlopidine, clopidogrel :
irreversibly blocks ADP receptors
==>inhibits GP2b/3a expression (which use fibrinogen to bind platelets together)on activated platelets
==>platelets can't aggregate

3. Abciximab, Tirofiban, Eptifibatide ("ATE"):
antagonize GP2b/GP3a
==>no platelet aggregation

(AbcixiMAB is Monoclonal AB that binds GP2b/3a)
a patient requires antiplatelet rug after MI or drug, but they have aspirin hypreseensitivity. how tx?
clopidogrel or ticlopidine
heparin
Tx: MI, DVT's

MOA: enhances binding of ATIII to activated clotting factors 2, 9-12
(Intrinsic Path: 12,11,9)
(Common Path: 10, 2)

-must give iv (not po)
-incr aPTT (intrinsic pathway) > incr PT (extrinsic pathway)
-antagonist: protamine sulfate

S/E: bleeding
ticlopidine
Ticlopidine, clopidogrel :
irreversibly blocks ADP receptors
==>inhibits GP2b/3a expression (which use fibrinogen to bind platelets together)on activated platelets
==>platelets can't aggregate
clopidogrel
Ticlopidine, clopidogrel :
irreversibly blocks ADP receptors
==>inhibits GP2b/3a expression (which use fibrinogen to bind platelets together)on activated platelets
==>platelets can't aggregate
Abciximab,
Abciximab, Tirofiban, Eptifibatide ("ATE"):
antagonize GP2b/GP3a (which use fibrinogen to bind platelets together)
==>no platelet aggregation
Eptifibatide
Abciximab, Tirofiban, Eptifibatide ("ATE"):
antagonize GP2b/GP3a (which use fibrinogen to bind platelets together)
==>no platelet aggregation
Tirofiban
Abciximab, Tirofiban, Eptifibatide ("ATE"):
antagonize GP2b/GP3a (which use fibrinogen to bind platelets together)
==>no platelet aggregation
LMW heparins
="--PARINS" (~hePARIN)
-eg: ardeparin, dalteparinm, enoxaparin
clreaed by kidneys instad of RE system (ReticuloEndothelial syste)
-longer half-life than heparin
-wroks mostly on 10a, so little effect to incr aPTT
warfarin
MOA=alters shape of factors 2,7,9,and 10, so that Ca2+ cannot bind to them and thus they cannot be gamma-carboxylated by Vit K1
-incr PT/INR (extrinsic system) > incr aPTT (Goljan)
-OD with warfarin incr both PR and aPTT (according to Keeton, nl dose of
warfarin does not inc aPTT)
-antidote: Vit K1 (phytonadione)
-many drug-drug interactions==>displacement of warfarin from plasma protein has 2 effects:
1. incr PT
2. incr clearance of warfarin

-Tx:
*MI,
*DVT,
*prevent emboli in pts with cardiac valves
*prevent thrombotic stroke in pts with A fib

-metabolized by CYP450; thus warfarin & PT/INR incr if CYP450 inhibited

Inhibition of CYP450:
"I C a KEG"
-isoniazid (INH) (Tx tb)
-cimetidine
-ketoconazole
-erythromycin
-grapefruit juice

Induction of CYP450(==>decr warfarin/PT):
-chronic EtOH (smoking)
-benzopyrene (cig's)
-carbamazepine (tx seizure)
-phenobarbital (tx seizure)
-phenytoin (tx seizure)
-rifampin (tx TB)
what drug give post-DVT
warfarin
what drug give post-MI
warfarin
person OD's with rat poison. what happens to clotting times?
both aPTT and PT incr
(nl dose=only PT(INR) incr.
OD =both aPTT and PT incr
what cardiac dysrhythmia req Tx with warfarin?
A fib
things that inhibit CYP450
Inhibition of CYP450:

"I C a KEG"

-isoniazid (INH) (Tx tb)
-cimetidine
-ketoconazole
-erythromycin
-grapefruit juice
things that induce CYP450
-chronic EtOH (smoking)
-benzopyrene (cig's)
-carbamazepine (tx seizure)
-phenobarbital (tx seizure)
-phenytoin (tx seizure)
-rifampin (tx TB)
thrombolytic drugs
activate plasminogen==>plasmin

-plasmin destroys fibrin to lyse clots (fibrin catches RBC's into its net, just like a fishing net catches fish. Then plasmin acts like scissors to cut the fibrin (fishing net))

1. urokinase: directly activates plasminogen==>plasmin

2. tPA: (direct activator)
when tPA and plasminogen bind to fibrin in loose proximity, tPA activates plasminogen==>plasmin

3. streptokinase (indirect activator): exposes protease binding site on plasminogen,
which activates other plasminogen molecules==>plasmin

S/E: systemic destruction of clotting factors 5 & 8
-->bleeding, esp in CNS (hemorrhagic stroke)
pt with MI treated with several drugs, then develops intacranial bleeding. what drug casued this?
streptokinase (indirectly activates plasminogen==>plasmin)
anti-fibrolytic drug?
aminocaproic acid

MOA: lysine analog, binds lysine-binding sites on plasmin and prevents it from binding fibrin
aminocaproic acid
anti-fibrinolytic

MOA: lysine analog, binds lysine binding sites on plasmin
==>prevents plasmin from binding fibrin
lovastatin
(and all other statins)

MOA: inhibit hepatic HMG CoA reductase
==>decr intracellular hepatic sterol pool
==>upreg HMG CoA reductase & LDL receptors

-Net effect:
decr LDL, total cholest, TG;
slight incr HDL

S/E:
-myosities/myopathy: muscle pain and weakness d/t incr CPK
-muscle damange
==>incr CPK & myoglobinuria
==>can progress to rhabdomyolysis (can kill you)
ezetimibe
MOA: inhibit GI abs of chol
==>decr sterol pool
==>incr gene expression of hepatic LDL receptors
==>decr total chol & LDL
(but no change HDL)
-Tx pts who get myositis on a statin: if pt on statin gets myositis, you can lower statin dose to lowest level and give ezetimibe (just as effective as highest dose of statin!)
pt on lovastatin develops myosiit. what drug can you switch them to?
ezetimibe
if pt on statin gets myositis, what can you do?
you can lower statin dose to lowest level and give ezetimibe (just as effective as highest dose of statin!)
Tx hypertriglyceridemia
gemfibrozil, fenofibrate
dicumerol
same as warfarin:

MOA=alters shape of factors 2,7,9,and 10, so that Ca2+ cannot bind to them and thus they cannot be gamma-carboxylated by Vit K1
-incr PT/INR (extrinsic system) > incr aPTT (Goljan)
-OD with warfarin incr both PR and aPTT (according to Keeton, nl dose of
warfarin does not inc aPTT)
-antidote: Vit K1 (phytonadione)
-many drug-drug interactions==>displacement of warfarin from plasma protein has 2 effects:
1. incr PT
2. incr clearance of warfarin

-Tx:
*MI,
*DVT,
*prevent emboli in pts with cardiac valves
*prevent thrombotic stroke in pts with A fib

-metabolized by CYP450; thus warfarin & PT/INR incr if CYP450 inhibited

Inhibition of CYP450:
"I C a KEG"
-isoniazid (INH) (Tx tb)
-cimetidine
-ketoconazole
-erythromycin
-grapefruit juice

Induction of CYP450(==>decr warfarin/PT):
-chronic EtOH (smoking)
-benzopyrene (cig's)
-carbamazepine (tx seizure)
-phenobarbital (tx seizure)
-phenytoin (tx seizure)
-rifampin (tx TB)
gemfibrozil
Tx: hypertriglyceridemia

MOA: inhibits lipoprotein lipase (esp in SkM)
==>decr VLDL synthesis
==>decr total chol, LDL, VLDL, TG;
-slight incr HDL

S/E:
-myositis/myopathy = musc pain/weakness assoc w/high CPK
-muscle damage can progress to rhabdomyolysis
niacin
MOA: unknown
-used to incr HDL
-S/E: flushing itchiness in face and upper body
what drug used to incr HDL
niacin
antianginal drugs
*all decr O2 demand and/or incr O2 supply
*all incr endocardial blood flow (incr diastole & decr HR)

1. Beta blockers ("--olol")
atenolol, metoprolol,
timolol, propolol

MOA:
*negative chronotropic (HR) and inotropic (decr dp/dt)
==>decr rate-pressure product (HRxSBP)
==>decr O2 Demand
*decr afterload==>decr D(O2)

B. Nitrates=nitroglycerin
NITROGLYCERIN
AKA GLYCERyl triNITRATE
AKA isosorbide mono- and diNITRATE

MOA: NO donors selectively venodilate
==>decr VR (preload)
==>decr D(O2)

*drug tolerance is big problem

C. CCB:
Verapamil, Diltiazem,
amLODIPINE, feLODIPINE

Verapamid & Diltiazem
(Valentines Day):

1. negative chlonotropic (HR) and inotropic (decr dp/dt)
==>decr rate-pressure product (HRxSBP)
==>decr D(O2)

2. decr afterload==>decr D(O2)

3. dilate epicardial vessels
& small endocardial resistance vessels
==>incr S(O2)

amLODIPINE, feLODIPINE:
*decr afterload==>decr D(O2)

*dilate epicardial vessels
& small endocardial resistance vessels
==>incr S(O2)
atenolol
"--olol"=Beta blocker
(also metoprolol, timolol, propanolol)

MOA:
*negative chronotropic (HR) and inotropic (dp/dt)
==>decr rate-pressure product (HRxSBP)
==>decr O2 Demand
*decr afterload==>decr D(O2)
nitroglycerin
*all decr O2 demand and/or incr O2 supply
*all incr endocardial blood flow (incr diastole & decr HR)

NITROGLYCERIN
AKA GLYCERyl triNITRATE
AKA isosorbide mono- and diNITRATE

MOA: NO donors selectively venodilate
==>decr VR (preload)
==>decr D(O2)

*drug tolerance is big problem
Verapimil
*all decr O2 demand and/or incr O2 supply
*all incr endocardial blood flow (incr diastole & decr HR)

Verapamil & Diltiazem
(Valentines Day):

1. negative chlonotropic (HR) and inotropic (decr dp/dt)
==>decr rate-pressure product (HRxSBP)
==>decr D(O2)

2. decr afterload==>decr D(O2)

3. dilate epicardial vessels
& small endocardial resistance vessels
==>incr S(O2)
Diltiazem
*all decr O2 demand and/or incr O2 supply
*all decr O2 demand and/or incr O2 supply
*all incr endocardial blood flow (incr diastole & decr HR)

Verapamil & Diltiazem
(Valentines Day):

1. negative chlonotropic (HR) and inotropic (decr dp/dt)
==>decr rate-pressure product (HRxSBP)
==>decr D(O2)

2. decr afterload==>decr D(O2)

3. dilate epicardial vessels
& small endocardial resistance vessels
==>incr S(O2)
amlodipine
*all decr D(O2)and/or incr S(O2)
*all incr endocardial blood flow (decr HR==>incr diastole)

amLODIPINE, feLODIPINE:
-decr afterload==>decr D(O2)
-dilate epicardial vessels
& small endocardial resistance vessels
==>incr S(O2)
glyceryl trinitrate
*all decr O2 demand and/or incr O2 supply
*all incr endocardial blood flow (incr diastole & decr HR)

NITROGLYCERIN
AKA GLYCERyl triNITRATE
AKA isosorbide mono- and diNITRATE

MOA: NO donors selectively venodilate
==>decr VR (preload)
==>decr D(O2)

*drug tolerance is big problem
isosorbide dinitrate
AKA nitroglycerin
AKA glyceryl trinitrate

*all decr O2 demand and/or incr O2 supply
*all incr endocardial blood flow (incr diastole & decr HR)


MOA: NO donors selectively venodilate
==>decr VR (preload)
(decr D(O2))
*drug tolerance is big problem
Tx Congestive Heart Failure
=systolic dysfxn

1. decr preload w/diuretic
2. decr preload & afterload (balanced vasodilation) w/ACEi or ARB
3. incr cardiac dp/dt w/digoxin
4. reverse cardiac remodeling caused by AngII w/ACEi or ARB
5. reverse cardiac remodeling caused by ALDO w/spironolactone
6. reverse cardiac remodeling caused by SNS w/carvedilol
7. add digoxin to Tx when ACEi + diuretic isn't working or when pt is in chronic A fib
how decr preload in CHF
diuretics (preload only)
ACEi or ARB (balanced vd
==?decr preload & afterload)
how enhance dp/dt in CHF
digoxin
how reverse cardiac remodeling in CHF caused by AngII
ACEi or ARB
how reverse cardiac remodeling in CHF caused by ALDO
spironolactone
how reverse cardiac remodeling in CHF caused by SNS
carvedilol
what add to Tx in CHF when ACEi + diuretic not working?
digoxin
how Tx chronic A fib in CHF?
digoxin