- 2 contraindications for all ca++ channel blockers: - 3 Contraindications for Verapamil/Diltiazem:

ALL: 1. Hypotension 2. Severe Hepatic Disease Verapamil / Diltiazem: 1. CHF 2. AV block/ LV dysfunction 3. Sick Sinus Syndrome

Vasodilator Drugs- Melissa (3)* Flashcards by Leah Stalnaker

What is the overall mechanism of vasodilators?

BP= TPR x CO

Aterial dilation–> LOWER TPR
Venous Dilation–> LOWER Venous Return
- -> LOWER CO

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Amlodipine:

Drug class?

Ca++ Channel blocker: Dihydropyridines*

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Verapamil, Diltiazem:

Drug Class?

Ca++ Channel blocker: Non-dihydropyridines

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Describe the direct effects (MOA) of Ca++ Inhibitors on vasculature (1) and the heart (3):

Vasculature:
1. INHIB L-Type Ca++ Channels–> vasodilation (more arteries)–> LOWER TPR (DHPs > non-DHPs)

Heart:

INHIB L-Type Ca++ Channels (Verapamil>Diltiazem»>DHPs)
INHIB Phase 2 (plateau) of AP in atrial/vent muscle (slow cntrxn)
INHIB Phase 0 Depolarization (slow HR/AV block)

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3 therapeutic uses for ca++ channel blockers:

Angina
(coronary dilation, vasodilation–> ^O2 supply + lower O2 demand)
Supraventricular tachy (A-fib, PSVT)–>Verapamil
HTN

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2 contraindications for all ca++ channel blockers:

- 3 Contraindications for Verapamil/Diltiazem:

ALL:

Hypotension
Severe Hepatic Disease

Verapamil / Diltiazem:

CHF
AV block/ LV dysfunction
Sick Sinus Syndrome

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Verapamil Cardio Effects:

vasodilation
HR
Cardiac contractility
AV nodal conduction

\+ = Increase
- = DECREASE
0 = NONE

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Diltiazem Cardio Effects:

vasodilation
HR
Cardiac contractility
AV nodal conduction

++
0/ -
0/ -
-

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Amlodipine (DHPs) Cardio Effects:

vasodilation
HR
Cardiac contractility
AV nodal conduction

+++
0/ +
0/ +
0

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Rank severity of HypoTN caused by ca++ blockers:

Verapamil/ Diltiazam/ Amlodipine

Verapamil: ++
Diltiazam: +
Amlodipine (DHPs): +++ (responsible for decreasing TPR!)

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Rank severity of CHF caused by ca++ blockers:

Verapamil/ Diltiazam/ Amlodipine

Verapamil: ++
Diltiazam: +
Amlodipine (DHPs): 0/+

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Rank severity of AV block caused by ca++ blockers:

Verapamil/ Diltiazam/ Amlodipine

Verapamil: ++
Diltiazam: +
Amlodipine (DHPs): 0

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Why do DHPs have more balanced vascular and cardiac effects?

Trigger baroreceptor reflex

Meaning—-increased HR/ fluid retention (edema possible)

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Which two ca++ channel blockers DECREASE HR/ contractility / O2 demand?

Verapamil + Diltiazem

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4 drug-drug interactions with ca++ channel blockers:

CYP3A4 inhibitors/ inducers
B blockers (V, D)
Digoxin (V) -Antiarrythmics

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Minoxidil:
Drug class
Effects (2)

K+ Channel ACTIVATOR–> hyperpolarization of vascular SM

Potent arterial dilator–> LOWER TRP
^ compensatory: HR, CO, fluid retention

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Minoxidil: 3 clinical applications

Refractory HTN (combo tx)
Malignant HTN
ROGAINE for baldness!

(probably causes too much fluid retention to use for acute CHF)

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4 ADRs of Minoxidil + drugs to coadmin in order to avoid them:

^ Fluid Retention (COADMIN diuretic)
Tachy*** (COADMIN B-blocker)
Cardiac tamponade (due to fluid retention)
Hypertrichosis (bad unless you’re bald)

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MOA Guanylyl Cyclase Activators:

^ Gualylyl Cyclase–> ^ cGAMP–> ^ Vasodilation

Sodium Nitroprusside:
Drug Class
Effects (1)
ROA

Guanylyl Cyclase Activators:

Arteriodilation = venodilation

DECREASE TPR, BP, CO
^ HR

*IV infusion only, very short t1/2

3 Therapeutic uses for Sodium Nitroprusside:

HTN Crises, Acute CHF, MI

Adverse rxns to Sodium Nitorprusside:

Acute (1), Chronic (1)

Acute: Severe HypoTN
Chronic: Thiocyanate/ CN toxicity

Sx. Thiocyanate toxicity:

N / weakness

2. Disorientation / Delirium

Sx. CN- toxicity:

CN-cytochrome oxidase–> cytotoxic anoxia
Hypoxia/Resp. Arrest
Convulsions

Describe the mechanism by which Nitroprusside becomes toxic CN / thiocyanate: Where does this mechanism occur? By what enzyme is it catalyzed

Nitroprusside + SN--> CN CN + Thiosulfate--> Thiocyanate **Rhodenase in the liver**

Organic nitrates: | Drug class + 2 Drugs in this group

Guanylyl Cyclase Activators: 1. Nitrolglyceride 2. Isosorbide Dinitrate (ISDN)-- long acting, most used

Describe the effects of organic nitrates on CV system in low and high doses:

Venodilation>>Arteriodilation LOW Dose: VENOUS DILATION-- Practice step question!!!! Do not be tricked, doesn't dilate coronary ARTERIES. 1. ^ venous dilation --> *DECREASE* CO 2. ^ HR, TPR, ~BP (***MONDAY DISEASE***) HIGH Dose: 1. Arterial AND venous dilation --> DECREASE CO, TPR, BP 2. ^ HR (reflex)

How are organic nitrates metabolized? What are the long acting nitrates metabolized into? What is their ROA?

``` Hepatic metabolism (glutathione-organic nitrate reductase) long acting nitrates denitrated to active metabolites (ISDN, ISMN) ``` IV/ subling/ transderm (*avoid hepatic portal sx*)

3 Therapeutic applications for organic nitrates:

1. Angina 2. CHF 3. acute MI

2 ADRs of organic nitrates:

1. Excessive HypoTN/ Angina | 2. Tolerance (do patch on/ patch off long term)

``` Nitric Oxide: Drug Class ROA? t1/2? Excretion? ```

Gualylyl Cyclase Activator | Inhalation; t1/2= seconds; renal excretion

Therapeutic indication for NO? What are 2 ADRS?

Hypoxic Resp Failure w/ pulm HTN in near term neonates ADRS: 1. pulm edema (from NO2 formation) 2. hypoxemia (from sudden w/drawal)

Hydralazine: Drug class? Effects? 2 Therapeutic uses?

Gualylyl Cyclase Activator * Potent ARTERIAL (only!) vasodilator TX: CHF, HTN

What is the most important ADR associated with Hydralazine? Which patients are most susceptible? Is it reversible?

+ANA--> LUPUS LIKE SYNDROME*** (spares the kidneys) - Generally reversible Higher risk: Slow acetylators taking than 200mg/ day

``` Fenoldopam: Drug Class? ROA? Therapeutic Use? ADR? ```

FenolDOPAM - *D1-R AGONIST (peripheral vasodilation) - Admin IV for HTN Emergency *Can cause hypersensitivity rxn (via sodium metabisulfate)

Sildenafil, Tadalafil, Vardenafil: Drug Class + MOA? Therapeutic use (2)?

INHIB *PDE Type 5*--> ^NO-induced cGAMP (stop breakdown) --> sm muscle relaxation 1. Erectile dysfunction 2. BPH (induces micturition) "SildenaFIL, TadalaFIL, VardenaFIL keep the penis FILLED"

3 DD interactions with PDE inhibitors?

1. Organic nitrates 2. A- blockers 3. CYP3A4 interactions

Lisinopril, Enalapril, Captopril: Drug Class? MOA + 6 Effects?

``` ACE Inhibitor! ACEi--> DECREASE ANG II--> DECREASE: 1. Aldo 2. ANG II vasocnstrxn 3. ANG II adrenergic vasocnstrxn 4. ANG II cardiac remodeling (via decrease NE/catechol.) 5. Bradykinin metabolism 6. ^ PGs ``` NOTE: Look for ending in *pril* = ACEi

Therapeutic indications for ACEi (4) ?

1. HTN 2. CHF 3. Post-MI 4. Prevent Diabetic Nephropathy

4 important ADRs associated with ACEi?

1. Fetopathic nephrotoxicity- in DIT warm up ?s 2. Hypersensitivity: rash/ pruritus / angioedema 3. COUGH! (^ Bradykinin + ^ PGs) 4. Renal vascular stenosis (renal excretion)

2 contraindications for ACEi?

1. preggos 2. K+ supplements BECAUSE: ACEi decreases Aldo, therefore increases K+

``` Losartan, Valsartan: Drug class? MOA (2)+ Effects? Therapeutic use? ADRs? Contras? ```

ANG-R Blockers MOA: 1. Block ANG II-R 2. Competative inhib ANG I-R Effects, therapeutic use, ADRs, Contras are SAME AS ACEi w/ *less cough*

``` Aliskiren: Drug Class? Effects? Therapeutic uses? Contras? ```

Renin Inhibitor--> DECREASE AG I Effects, ADR, Contras same as ACEi w/ *less cough* Tx: HTN "AlisKIREN = KIlls RENin"

Which drugs do we admin to prevent diabetic nephropathy?

ACEi's

Which vasodilators are influenced by CYP3A4 inhib/inducers?

1. Ca++ channel blockers | 2. PDE-5 inhibitors

Which vasodilator is used to treat baldness?

Minoxidil

To which vasodilator do patients develop tolerance with long term use?

Organic nitrates (patch on patch off) **This concept will be presented on boards as "Monday's Disease"--patient works in explosives factory/somewhere where they are exposed to NG, develops tolerance to vasodilation effects during work week and becomes DESENSITIZED over the weekend. This results in patient feeling the rebound effects--tacky, dizzy, HA, maybe heart palpitations every Monday when he/she returns to work. Don't miss this!**