Pharmacology quiz 3

Question 1

Describe the dose dependent effect of DA

Indications?

Answer 1

Low - D1 receptors -> dilation of renal + splanchnic vessels

Mid - beta-1 adrenergic receptors -> tachy + inc contractility

High - alpha-1 adrenergic -> increase peripheral vascular resistance

Used for hypotensive shock and acute HF

Question 2

Alpha-2 vs beta1,2 receptors on the presynapse in CNS

Answer 2

Alpha-2 -> inhibit NE release

Beta -> stimulate more NE release

Question 3

Clonidine

• MoA
• indications
• major adverse effects
• compare to alpha-methyldopa

Answer 3

presynaptic alpha-2 adrenergic agonist -> reduces SANS outflow in CNS

• also reduces renin release
• lowers heart rate and CO (better than methyldopa)

Indications
-HTN

Adverse effects

• rebound HTN on abrupt w/drawal due to:
  1) downregulation of central presynaptic alpha-2 receptors
  2) upregulation of peripheral post synpatic alpha-1 receptors on vascular smooth muscle

Alpha-methyldopa

• same MoA
• different presynaptic alpha-2 receptor (not as good)
• used in pregnancy HTN
• contraindicated in liver disease

Question 4

Phentolamine vs prazosin

Answer 4

Both are alpha-adrenergic receptor ANTAGONISTS

PHENTOLAMINE -> non-selective

• reflex tachy observed
• given w/ beta-blocker and diuretic (retention of salt/water can occur without it)

Indications/Uses

• pheochromocytoma
• prevention of dermal necrosis after IV NE or DA

Contraindications
-CAD (hypoTN can evoke angina and AMI) -> make ischemic insult worse

Adverse rxn

• HypoTN -> b-2 activation/high NE levels
• Tachy + arrhythmia -? high NE at beta-receptors

PRAZOSIN -> alpha-1 selective

• no reflex tachy -> alpha-2 not blocked
• used w/ other HTN agents

Indications

• 2nd line HTN
• BPH

Adverse rxns

• 1st dose hypoTN, dizziness and syncope
• nasal congestion -> unopposed beta-receptor action of NE

Question 5

Compare the beta-adrenergic receptor antagonist

Answer 5

First generation beta blockers - propranolol
-nonselective

Second-generation agents: metoprolol
-selective for cardiac beta-1 receptors when given in low doses

Third-generation compounds: Carvedilol and labetalol
-Block beta and alpha receptors

Question 6

Which beta blockers reduce mortality after an MI?

Answer 6

Propanolol metoprolol timolol

Question 7

Which beta blockers reduce mortality in patients with heart failure?

Answer 7

Carvedilol (non-selective) and metoprolol (beta-1 selective)

Question 8

List three side effects of beta blockers

Answer 8

1. Smooth muscle spasm
2. exaggeration of cardiac actions including bradycardia, heart block and negative inotropic effect
3. CNS effects including insomnia and depression

Question 9

Which beta blocker has a high risk of sexual dysfunction

Answer 9

Metoprolol

Question 10

Why do beta blockers decrease renin release

Answer 10

Presence of beta-1 receptors on the kidneys

Question 11

List the vascular relaxation mechanisms and associated drug classes

Answer 11

1. cGMP (nitrates/nitrites)
   - inc cGMP -> dephosphorylation of myosin light chain -> prevents myosin-actin ix
2. intracellular Ca++ (calcium channel antagonists, Na channel blockers)
   - reduction intracellular Ca++ -> reduced MLC kinase efficacy -> reduces myosin-actin ix
3. cell membrane potential (direct vasodilators)
   - inc K+ permeability -> hyperpolarization
4. cAMP (b-2 adrenergic agonists)
   - inc cAMP -> inc rate of MLC kinase inactivation -> reduce myosin-actin ix

Question 12

List 3 Ca++ channel blockers
-which one has the greatest suppression of contractility and conduction?
least?

Answer 12

1. Verapamil - greatest
2. Diltiazem
3. Nifedipine - least
   - dihydropyridine -> vascular selectivity

Question 13

What can dec metab of Ca++ channel blockers?

Answer 13

inhibitors of P450

Question 14

Verapamil inc plasma levels of?

Answer 14

digoxin

Question 15

Which Ca++ blocker can cause peripheral dependent edema?

Myocardial depression?

constipation?

reflex tachy?

Which one should NOT be given w/ beta-blocker

Answer 15

Nifedipine

verapamil and diltiazem

verapamil

nifedipine

Verapamil (diltiazem ok)

Question 16

Hydralazine

• administration?
• dilates which vessels?
• combined with what to tx HF (in which population?)
• side effects and CIs?

Answer 16

• orally
• dilates arterioles
• combined w/ isosorbide dinitrate to tx HF in AA

Side effects

• lupus-like syndrome
• reflex tachy
• CI in CAD and rheumatic valve disease

Question 17

Name 2 activators of vascular ATP-sensitive K+ channels

• dilate which vessels?
• IV or oral?
• tx use?

Answer 17

• Minoxidil and Diazoxide
• arterioles
• diazoxide = IV and minoxidil = oral

Question 18

Minoxidil, diazoxide or both?

1. Hypertrichosis
2. Reflex tachy
3. Salt+water retn
4. hyperglycemia
5. subendocardial necrosis (reflex catecholamine)
6. LVH and pericardial effusion
7. gynecomastia

Answer 18

1. Hypertrichosis - M
2. Reflex tachy - B
3. Salt+water retn - B
4. hyperglycemia - D
5. subendocardial necrosis(reflex catecholamine)-D
6. LVH and pericardial effusion - M
7. gynecomastia - M

Question 19

Ranolazine

• MoA
• tx use
• side effects and CI

Answer 19

Moa - blocks VG Na channel -> minimizes Na+ coming in to the cell

Tx use -> chronic angina

Side effects
-QTc prolongation

CI
-hepatic impairment

Drug-Drug ix

• drugs that inhibit P450
• Verapamil
• Digoxin

Question 20

Name 2 nitrovasodilators

• mech
• artery vs vein selectivity?
• indications
• side effects/toxicities
• tolerance?

Answer 20

NITROGLYCERIN

• mech -> stimulates intracellular cGMP production
• dilates veins (low conc.) and arteries (higher conc)
• dec preload and afterload

Use

• acute angina pectoris
• angina prophylaxis
• IV for CV surgery to lower BP

Adverse effects (unique to NG)
-headache 

NITROPRUSSIDE
-non-selective vasodilator 
-use -> HTN crisis (not angina!!!)
-toxicity -> cyanide with prolonged use 
NO TOLERANCE -> doesn't affect thiol stores 

BOTH can cause methemoglobinemia

Question 21

How can we decrease the reflex increase in heart rate associated with nitrates?

contractility?

Answer 21

Add beta blocker or Ca++ channel blocker

Question 22

In patients with CAD which drug should never be combined with nitrovasodilators? Why?

Answer 22

• Nitroglycerine and Sildenafil (Viagra) drug rxn
  
  • cGMP increase the phosphatase leading to vasodilation
  • Sildenafil blocks breakdown of cGMP
  • Double whammy combination leading to massive VSM relaxation
  • Potent lowering of BP leading to heart attack
    • Exacerbation of ischemia

Question 23

Dobutamine

• class
• MoA
• side effects

Answer 23

class -> Beta1 adrenergic agonist

MoA

• inc rate and force of contraction (Ca++ induced Ca++ release)
• inc rate of relaxation (phospholamban-P reuptake of Ca++)

Side effects

• arrhythmias-> can result in sudden cardiac death
• worsen ischemic injury
• tolerance due to beta receptor down regulation

Question 24

List the beneficial actions of beta blockers in HF (6)

Answer 24

• Bradycardia by inhibiting conduction
• Too much catecholamine can hurt myocytes - beta blockers reduce this
• Blocking beta receptor leads to up regulation leading to preservation of beta signaling
• Renin release blocks which prevents AGII from forming
  
  • AGII is a potent vasoconstrictor
• Slow down the remodeling process which is bad in the long run
• Decreasing sympathetic tone also beneficial

Question 25

List the the drug ix of metoprolol

Answer 25

1) Cimetidine (Histamine H2 antagonist): Increase the bioavailability of metoprolol by affecting hepatic blood flow 2) Hydralazine (vasodilator): Increase the bioavailability of metoprolol by affecting hepatic blood flow 3) Calcium channel blocking agents: Increase risk of conduction disturbances 4) Rifampin (antibiotic): Decrease plasma levels of metoprolol 5) Phenytoin (anticonvulsant) or Phenobarbital (anticonvulsant): Decrease plasma levels of metoprolol 6) Cholestyramine (bile acid sequestrant): decrease absorption of metoprolol

Question 26

Carvedilol drug ix

Answer 26

1) Antidiabetic agents: The beta-blocking effect may increase the hypoglycemic effects 2) Calcium channel blocking agents: Increase risk of conduction disturbances 3) Clonidine: Potentiation of BP and heart rate lowering effects 4) Cyclosporine: Increase cyclosporine blood levels due to decrease liver breakdown 5) Digoxin: Increase digoxin levels 6) Rifampin: Decrease plasma levels of carvedilol

Question 27

Digoxin - indication - MoA - excretion - unique aspect - toxicities

Answer 27

Indication - chronic CHF + chronic afib - sx control in HF and systolic dysfx - control ventricular rate in afib Excretion -> kidneys MoA - Na/K ATPase inhibitor -> inc intracellular [Ca++] -> inc F of contraction - Ach release at AV node -> enhance parasympathetic tone of heart -> relaxation - activation of Ach-mediated K+ current -> convert atrial flutter to afib Unique -> only oral positive inotropic drug for CHF ``` Toxicities Cardiac -> arrhythmias Extracardiac -GI -> N/V, diarrhea, anorexia -Neuro -> depression, disorientation paresthesias -Visual -Hyperestrogenism -> gynecomastia ```

Question 28

List 4 hemodynamic effects of digoxin in CHF

Answer 28

1. Positive inotropy 2. reduction in HR 3. Vasodilation 4. Diuresis

Question 29

How to tx digitalis toxicity

Answer 29

- KCl | - Digoxin-specific Abs

Question 30

Digitalis drug ix

Answer 30

1) Diuretics (thiazides and loop diuretics) 2) Sympathomimetics and catecholamines 3) Spironolactone (aldosterone receptor blocker) 4) Verapamil (Ca2+ channel blocker) 5) Insulin

Question 31

Milrinone - MoA - use - 3 tx actions - Side effects

Answer 31

MoA -> intracellular PDE-III inhibitor indication -> IV tx for short-term management of acute HF 1. Pos inotropy 2. Pos lusitropy 3. vasodilation -> inc cGMP in vascular smooth muscle Side effects 1) Exacerbate ischemic event (increase in myocardial O2 consumption) 2) Arrhythmogenesis (due to elevated Ca2+) 3) Thrombocytopenia 4) Hypotension 5) Headache

Question 32

Levosimendan | -MoA

Answer 32

-MoA -> sensitize contractile apparatus to prevailing level of Ca++ • At higher doses, appear to inhibit PDE-III • Opens ATP-sensitive potassium channels on blood vessels and myocytes o Reduces preload and afterload o Cardiomyocyte survival

Question 33

Aliskiren - MoA - CI and adverse effects

Answer 33

MoA - inhibits renin Adverse effects -angioedema and GI disturbances CI - pregnancy - diabetes -> hyperkalemia when combined with ACE inhibitor - caution -> impaired renal fx

Question 34

``` Lisinopril MoA clinical outcomes adverse effect CI ```

Answer 34

ACE inhibitor * Decreased mortality after myocardial infarction * Increased cardiac performance in heart failure * Kidney protected from deteriorating damage associated with sustained hypertension angioedema cough - noncompliance CI -> pregnancy (2nd + 3rd TM) chronic renal failure ONLY volume depleted (temporarily stop)

Question 35

Losartan

Answer 35

- ARB - block T1 AGII receptors | - metabolized in liver - metabolites have HIGHER potency

Question 36

Endothelin receptor antagonists - use - list 2 and compare - side effects - drug ix - biological actions

Answer 36

-use -> pulmonary arterial HTN 1. Bosentan -> non-selective antagonist 2. Ambrisentan -> selective for ETA Adverse effects - liver injury CI - pregnancy - metab by CYP2C9 and 3A4 Drug ix 1) Cyclosporine A (immunosuppressant): affects the activity of bosentan 2) Glyburide (anti-diabetic agent): affects the activity of bosentan 3) “Statins” (lipid-lowering agents): bosentan may decrease the effects of statins 4) Oral contraceptives: bosentan may prevent contraceptives from working properly and may result in an unplanned pregnancy Biological actions - vasodilation - dec cardiac contractility and remodeling - inhibition of aldosterone and dec in blood volume

Question 37

BNP dxic of?

Answer 37

Heart failure

Question 38

physiological actions of ANP/BNP

Answer 38

* vasodilation * natriuresis/diuresis * inhibition of the renin-angiotensin- aldosterone (RAA) * inhibition of the sympathetic nervous system

Question 39

Nesiritide - clinical effects - side effect

Answer 39

Clinical effect • Dilates veins & arteries • Reduces pulmonary capillary wedge pressure • Reduces systemic BP • Increases cardiac output & stroke volume, without increasing heart rate • Has natriuretic actions and promotes diuresis Side effect -hypotension (worse w/ ACEI)