1-2 and 3 Flashcards
How does increasing vascular radius affect vascular resistance?
Increasing vascular radius decreases vascular resistance
What type of drugs are: Furosemide, Torsemide, and Ethacrynic Acid?
Effect?
- Thick Ascending Limb - LOOP Diuretics (Na/K/Cl)
- Prevent reabsorption of ions
Target of thiazide diuretics?
Na/Cl Carrier (Distal Convoluted Segment)
What are the two major AE for Loop and Thiazide Diuretics?
1) Hypokalemia
2) Ischemic Ventricular Fibrillation
What channel do K Sparing diuretics target?
-Effects on Na/K?
ENaC
-Prevents Na reabsorption
-Prevents loss of K
True or False: Hypokalemia is an adverse effect of K sparing diuretics
False - Hyperkalemia is an adverse effect of K sparing diuretics
True or False: Beta 1 selective blockers will reduce myocardial contraction, HR, and CO
True
How does using beta blockers on JG of the kidney affect Ang II and renin secretion?
Decreases renin secretion and Ang II synthesis
How do beta blockers affect peripheral resistance and arterial pressure?
Beta blockers decrease both peripheral resistance and arterial pressure
Rebound HTN is an adverse affect associated with sudden discontinuation of which drug class?
Beta blockers
What causes Rebound Hypertension
-Sudden discontinuation leads to:
1) up-regulation of beta receptors (adaptive)
2) enhance sensitivity to endogenous catecholamine
True or False: Rebound HTN can exacerbate CAD
True
Two contraindications for Beta receptors?
1) Reactive airway disease
2) Myocardial conduction defects (SA/AV Nodal Dysfunction)
What type of drug, when given in combination with epinephrine, can cause hypertension due to alpha adrenergic receptor stimulation.
Non-selective beta blocker
What drug should NOT be administered with beta blockers?
A. Diltiazem
B. Verapamil
C. Prazosin
D. Torsemide
A. Diltiazem
B. Verapamil
How do alpha 1 blockers affect arteriole resistance and venous capacitance in VSM?
Arteriole resistance: Reduces
Venous capacitance: Increases
Postural hypotension and retention of water and salt are associated with what drug class?
Alpha 1 blockers
Which drug is an equimolar mixture of four stereoisomers, including an alpha blocker and non-selective beta blocker?
Clinical use?
Labetolol
- HTN emergency or crisis
What drug is a beta receptor antagonist with alpha 1 receptor antagonist activity that can be used as an adjunctive therapy with diuretics and ACE Inhibitors
Carvedilol
True or False: Carvedilol can be given to patients with decompensated heart failure or who are dependent on sympathetic stimulation
False
What are the four centrally acting adrenergic agents?
1) Methyldopa
2) Clonidine
3) Guanabenz
4) Guanafacine
What enzyme converts the prodrug methyldopa from alpha-methyldopamine to alpha methylnorepinephrine?
L-aromatic amino acid decarboxylase (adrenergic neurons)
How does the active form of methyldopa (alpha-methylnorepinephrine) affect NE release from pre-synaptic alpha neurons in the CNS?
Effect on vasoconstriction?
Since methyldopa is an alpha 2 agonist, it will prevent further NE release and reduce VC signals
Which class of drugs stimulate the alpha 2a receptor in the brainstem, leading to reduced NE?
Centrally-acting adrenergic agents
Bradycardia, sinus arrest, and hepatotoxicity are associated with which drug class?
Centrally-acting adrenergic agents
What type of drugs are Guanadrel and Reserpine?
Adrenergic neuron blocking agents
Which adrenergic neuron blocking drug acts as exogenous, false NT that is accumulated, stored, and released like NE but is inactive at adrenergic receptors?
Guanadrel
True or False: Guanadrel activates the peripheral post-ganglionic adrenergic neuronal activation
False - Guanadrel INHIBITS the peripheral post-ganglionic adrenergic neuronal activation
True or False: Intermittent hypotension and sexual dysfunction are AE’s associated with Reserpine
False - associated with Guanadrel
Drugs that compete with the catecholamine transporter on the pre-synaptic region (tricyclic antidepressants, cocaine) will reduce the effects of what drug?
Guanadrel
True or False: Guandrel can be used to treat pheochromocytomas
False - because Guanadrel can promote NE release, not use in patients with pheochromocytomas
Which drug was the first known to interfere with SNS?
Reserpine
True or False: Reserpine only remains tightly bound to vesicles in CNS neurons
False - Reserpine remains tightly bound to vesicles in CNS neurons AND peripheral neurons
Reserpine causes irreversible binding to vesicles in CNS/PNS, followed by LOF of which transporter?
VMAT2 (known to store and accumulate catecholamines)
AE associated with reserpine?
Psychotic depression and suicide
Which CCB is ultra short acting drug with a high specificity to vasculature, which belongs to the dihydropyridine class?
Clevidipine (admin as IV)
Which drug class can indirectly evoke baroreceptor mediated sympathetic discharge and tachycardia (SA Node activation)?
Calcium channel blockers
CCB’s given with what other drug can aggravate negative chronotropic effect (HR)?
Beta blockers
- can lead to heart block in patients with h/o MI, angina, SA nodal block
What drug is a direct renin inhibitor?
Aliskiren
Angioedema is an AE associated with which drug classes?
Direct Renin Inhibitors and ACE Inhibitors
True or False: Beta 1 specific blockers show similar effects as Aliskiren
True
What drug class do Enalapril and Lisinopril belong to?
ACE Inhibitors
Two benefits of ACE Inhibitors?
1) No VC due to Ang II binding to AT1R
2) No elevated aldosterone - therefore: no increase sodium uptake
Cough is a common adverse side effect associated with which drug class?
ACE Inhibitors (due to bradykinin accumulation)
True or False: ACE Inhibitors can cause hypokalemia when administered with K sparing diuretics
False - ACE Inhibitors can cause hyperkalemia when administered with K sparing diuretics
True or False: ACE Inhibitors are contraindicated in patients with compromised renal function
True
What receptor does Losartan, Valsartan, Telmisartan target (block)?
AT1R
Inhibition of AT1R prevents aldosterone synthesis, which promotes renal ____ and ____ excretions, reducing _____
salt/water ; plasma volume
How do AT1R blockers affect smooth muscle?
Relaxes smooth muscle (vasodilation)
Following AT1R inhibition, there is enhanced circulation of what two molcules?
1) Renin
2) Ang II
True or False: Hypotension, hypokalemia, and reduced renal function are associated with AT1R inhibitors
False - Hypotension, hyperkalemia, and reduced renal function are associated with AT1R inhibitors
What are two arterial vasodilators?
1) Minoxidil
2) Hydralazine
Which drug is one of the most orally active?
Hydralazine
How does hydralazine affect intracellular calcium?
Decrease intracellular calcium by preventing IP3 mediated release of calcium from SR
What is the active form of Minoxidil?
Minoxidil Sulfate (via: hepatic sulfotransferase)
AE associated with Minoxidil Sulfate?
1) Hirsuitism
2) Pseudoacromegaly
3) Pericardial Effusion
Which drug is a K+/ATP channel opener that promotes efflux of K in VSM, as well as VSM hyperpolarization and relaxation?
Minoxidil Sulfate
Which drug is both an arterial and venous nitro-vasodilator?
Nitroprusside
How does nitroprusside work?
Release NO, which activates cGMP-PKG and leads to vasodilation
Thiosulfate in the system reacts with CN- to form what molecule?
Thiocynate (water soluble, less toxic than CN-)
- is eliminate via urination
CN toxicity is associated with which drug?
Nitroprusside
What causes the short-term effects of nitroprusside?
1) Excessive VD
2) Hypotension
A rare phenomenon of ___ is due to conversion of nitroprusside to cyanide and thiocyanate
Cyanide Toxicity
True or False: Accumulation of CN- causes lactic acidosis and can result in anorexia, nausea, fatigue, and toxic psychosis
True
Preventative measure for CN toxicity?
Preferred treatment?
Preventative: Administer thiosulfate
Preferred: Hydroxycobalamin
____: A disorder of pulmonary vasculature that is normally accompanied by cardiopulmonary, vascular, and inflammatory disorders
Pulmonary Hypertension
What two symptoms typically accompany PH?
1) Vessel narrowing
2) Ventricular hypertrophy
What type of drug is Riociguat?
Riociguat is a soluble guanyl cyclase stimulator
True or False: sGC Stimulators (riociguat) as well as Nitrovasodilators and PDE5 Inhibitors are associated with embro-fetal toxicity and hypotension
True
What two drugs are PDE-5 Inhibitors?
How do they work?
Sildenafil*/Tadalafil
-Prevent breakdown of cGMP to 5’-GMP
-Enhances cGMP and PKG signaing
-VSM relaxation
AE of PDE-5 Inhibitors?
Hypotension
What receptor do prostacyclins bind to?
IPR - on membrane of pulmonary artery VSM cells
How does activation of IPR via prostacyclin and prostacyclin receptor agonists affect cAMP, PKA, and pulmonary artery VSM?
-Increases cAMP to PKA
- VSM relaxtion
Selexipag is a ____ agonist
Iloprost and Treprostinil are ____ analogs
Selexipag: IPR agonist
Iloprost and Treprostinil: Prostacyclin analogs
What three drugs are endothelin receptor antagonists?
1) Bosentan
2) Ambrisentan
3) Macitentan
How do endothelin receptor antagonists affect VSM?
Relaxes VSM
AE associated with Endothelian Receptor Antagonists?
1) Pulmonary edema
2) Testicular atrophy
3) Infertility