Pharmacology quiz 3 Flashcards
Describe the dose dependent effect of DA
Indications?
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
Alpha-2 vs beta1,2 receptors on the presynapse in CNS
Alpha-2 -> inhibit NE release
Beta -> stimulate more NE release
Clonidine
- MoA
- indications
- major adverse effects
- compare to alpha-methyldopa
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
Phentolamine vs prazosin
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
Compare the beta-adrenergic receptor antagonist
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
Which beta blockers reduce mortality after an MI?
Propanolol metoprolol timolol
Which beta blockers reduce mortality in patients with heart failure?
Carvedilol (non-selective) and metoprolol (beta-1 selective)
List three side effects of beta blockers
- Smooth muscle spasm
- exaggeration of cardiac actions including bradycardia, heart block and negative inotropic effect
- CNS effects including insomnia and depression
Which beta blocker has a high risk of sexual dysfunction
Metoprolol
Why do beta blockers decrease renin release
Presence of beta-1 receptors on the kidneys
List the vascular relaxation mechanisms and associated drug classes
- cGMP (nitrates/nitrites)
- inc cGMP -> dephosphorylation of myosin light chain -> prevents myosin-actin ix - intracellular Ca++ (calcium channel antagonists, Na channel blockers)
- reduction intracellular Ca++ -> reduced MLC kinase efficacy -> reduces myosin-actin ix - cell membrane potential (direct vasodilators)
- inc K+ permeability -> hyperpolarization - cAMP (b-2 adrenergic agonists)
- inc cAMP -> inc rate of MLC kinase inactivation -> reduce myosin-actin ix
List 3 Ca++ channel blockers
-which one has the greatest suppression of contractility and conduction?
least?
- Verapamil - greatest
- Diltiazem
- Nifedipine - least
- dihydropyridine -> vascular selectivity
What can dec metab of Ca++ channel blockers?
inhibitors of P450
Verapamil inc plasma levels of?
digoxin
Which Ca++ blocker can cause peripheral dependent edema?
Myocardial depression?
constipation?
reflex tachy?
Which one should NOT be given w/ beta-blocker
Nifedipine
verapamil and diltiazem
verapamil
nifedipine
Verapamil (diltiazem ok)
Hydralazine
- administration?
- dilates which vessels?
- combined with what to tx HF (in which population?)
- side effects and CIs?
- 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
Name 2 activators of vascular ATP-sensitive K+ channels
- dilate which vessels?
- IV or oral?
- tx use?
- Minoxidil and Diazoxide
- arterioles
- diazoxide = IV and minoxidil = oral
Minoxidil, diazoxide or both?
- Hypertrichosis
- Reflex tachy
- Salt+water retn
- hyperglycemia
- subendocardial necrosis (reflex catecholamine)
- LVH and pericardial effusion
- gynecomastia
- Hypertrichosis - M
- Reflex tachy - B
- Salt+water retn - B
- hyperglycemia - D
- subendocardial necrosis(reflex catecholamine)-D
- LVH and pericardial effusion - M
- gynecomastia - M
Ranolazine
- MoA
- tx use
- side effects and CI
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
Name 2 nitrovasodilators
- mech
- artery vs vein selectivity?
- indications
- side effects/toxicities
- tolerance?
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
How can we decrease the reflex increase in heart rate associated with nitrates?
contractility?
Add beta blocker or Ca++ channel blocker
In patients with CAD which drug should never be combined with nitrovasodilators? Why?
- 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
Dobutamine
- class
- MoA
- side effects
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
List the beneficial actions of beta blockers in HF (6)
- 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
List the the drug ix of metoprolol
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
Carvedilol drug ix
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
Digoxin
- indication
- MoA
- excretion
- unique aspect
- toxicities
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
List 4 hemodynamic effects of digoxin in CHF
- Positive inotropy
- reduction in HR
- Vasodilation
- Diuresis
How to tx digitalis toxicity
- KCl
- Digoxin-specific Abs
Digitalis drug ix
1) Diuretics (thiazides and loop diuretics)
2) Sympathomimetics and catecholamines
3) Spironolactone (aldosterone receptor blocker) 4) Verapamil (Ca2+ channel blocker)
5) Insulin
Milrinone
- MoA
- use
- 3 tx actions
- Side effects
MoA -> intracellular PDE-III inhibitor
indication -> IV tx for short-term management of acute HF
- Pos inotropy
- Pos lusitropy
- 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
Levosimendan
-MoA
-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
Aliskiren
- MoA
- CI and adverse effects
MoA - inhibits renin
Adverse effects
-angioedema and GI disturbances
CI
- pregnancy
- diabetes -> hyperkalemia when combined with ACE inhibitor
- caution -> impaired renal fx
Lisinopril MoA clinical outcomes adverse effect CI
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)
Losartan
- ARB - block T1 AGII receptors
- metabolized in liver - metabolites have HIGHER potency
Endothelin receptor antagonists
- use
- list 2 and compare
- side effects
- drug ix
- biological actions
-use -> pulmonary arterial HTN
- Bosentan -> non-selective antagonist
- 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
BNP dxic of?
Heart failure
physiological actions of ANP/BNP
- vasodilation
- natriuresis/diuresis
- inhibition of the renin-angiotensin- aldosterone (RAA)
- inhibition of the sympathetic nervous system
Nesiritide
- clinical effects
- side effect
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)
