Final Exam - Section III and IV Flashcards
What are the catecholamines?
What receptors do they effect?
- Epinephrine – α1, α2, β1, β2
- Norepinephrine - α1, α2, β1
- Isoproterenol - β1, β2
- Dopamine – D1-5, Higher doses: α1, β1
- Dobutamine - β1
What alpha antagonist is irreversibly bound?
- Phenoxybenzamine
-recovery requires new receptors due to covalent bonding
What is the clinical use for phenoxybenzamine? What is important to know about this drug?
- Hypertension associated with pheochromocytoma (tumors producing NE)
- It is covalently bound and irreversible
What are the reversible alpha antagonists?
- Phentolamine
- Prazosin
- Tolazoline
- Labetalol
Beta antagonist effect on the heart?
Blood vessels?
Heart:
* Negative inotropic
* Negative chronotropic
Blood vessels:
* Opposes B2 vasodilation
* Acute: increases peripheral resistance
* Chronic: decreases peripheral resistance
Describe MOA of propanolol, metoprolol, atenolol, and esmolol
- Propanolol-Works on β1 and β2 receptors
- Metoprolol- Mainly β1 selectivity; safer in COPD, diabetics
- Esmolol – Beta-1 selective, ultra short acting
What are the direct acting cholinomimetics and their MOA?
- Esters of choline
- Alkaloids
- Bind and activate muscarinic or nicotinic receptors
What are the indirect acting cholinomimetics MOA?
- Inhibit action of acetylcholinesterase
- Prolongs effects of ACh released at junction
What are the effects of cholinomimetics on the eye?
- Muscarininc agonist cause miosis
- Increases intraocular drainage
What are the cholinomimetic effects on the CV system?
- Reduction in peripheral vascular resistance
- Vasodilation – reduction in BP – reflexive increase in HR
- Large doses - bradycardia
What are the classes of indirect cholinomimetics and examples?
- Simple alcohols - Edrophonium
- Carbamic acid esters of alcohols - Carbamates and Neostigmine
- Organophosphates
What are the major uses for cholinomimetics?
- Disease of the eye
- GI and urinary tracts
- Neuromuscular junction – Myasthenia gravis (autoimmune against ACh receptor)
- Atropine overdose
What are the symptoms of cholinomimetic overdose?
Causes?
Treatments?
- SLUDGE-M
- Organophosphate exposure - TX: atropine, pralidoxime
- Poisonous mushrooms (muscarinic excess) - TX: atropine
What can cause atropine OD?
Symptoms?
TX?
- Belladona
- Sx: BRAND (Blind, Red, Absent bowel sounds, Nuts, Dry)
- Tx: Physostigmine
Describe the 3 differenent angina classifications?
What is the MOA of nitrates?
Activate GC, increase cGMP - Relaxation
WHat is the MOA of beta-2 agonists o smooth muscle?
GPCR – cAMP – Relaxation (mainly respiratory)
Describe the MOA of CCB on smooth muscle?
Less total calcium - Relaxation
Describe the MOA of sildenafil?
Blocks PDE5, increase cGMP - Relaxation
What is the good and bad of nitrates/nitrites?
The Good:
↑ venous capacitance, ↓ ventricular preload
↓ heart size, ↓ CO
The Bad:
Orthostatic hypotension, syncope, HA
Reflex tachycardia
What are the 4 mechanisms for drugs to relax vascular tone?
- Block Ca influx
- Increase cAMP
- Increase cGMP
- Prevent depolarization by potassium efflux
What CCB effects on the heart?
↓ contractility
↓ SA node pacemaker rate
↓ AV node conduction velocity
Reduce blood pressure
What are the 2 main classes of CCB and where they work?
- Dihydropyridines: more peripheral vasculature
- Verapamil and Diltiazem: more cardiac
How are beta blockers useful for angina?
decrease oxygen demand:
↓ HR
↓ BP
↓ Contractility
What are the 4 antihypertensive control sites?
How do drugs work that act here?
- Diuretics: deplete sodium
- Sympathoplegics: decrease PVR, reduce CO
- Direct Vasodilators: relax vascular smooth muscle
- Anti-angiotensins: block activity or production
What is the hydraulic equation?
BP=COxPVR
What are the 2 centrally acting sympathoplegics and their MOA?
- Clonidine and Methyldopa
- Primary antihypertensive activity due to α agonist activity in brainstem, decreasing sympathetic stimulation. Bind more tightly to α2 than α1
What is the MOA of α1 blockers used for HTN?
Drugs?
- Prazosin, Terazosin, Doxazosin, phenolamine, labetalol, phenoxybenzamine
- Block α1 receptors in arterioles and venules
- Dilates both resistance and capacitance vessels
- BP is reduced more in upright position
What is the MOA of minoxidil and hydralazine?
Minoxidil: Opens K+ channels in smooth muscles, stabilizes potential, less likely to contract.
Dilates arteries, arterioles
Hydralazine: Dilates arterioles (NO production)
What is the MOA and uses of sodium nitroprusside?
- HT emergencies, Cardiac failure
- Dilates arterial and venous vessels
- Relaxes vascular smooth muscle
- Breaks down in blood to release NO
- Increases intracellular cGMP
Can cause CN toxicity
What is the MOA and uses of sodium fenoldopam?
- Agonist of D1 receptors, causing diuresis
- Peripheral arteriolar dilator
- HTN emergencies, post-op HTN
Describe the RAAS pathway and drugs that work here.
Describe the normal intracellular cardiac contractility cycle?
- “Trigger” calcium enters cell
- Binds to channel in SR, release stored calcium
- Frees actin to interact with myosin
Describe the differences between systolic and diastolic heart failure?
Systolic: typical of acute failure, MI (Ex: thin, dilated left ventricle)
↓ CO, ↓ Ejection fraction
Diastolic (Ex: hypertrophy of myocardium)
↓ CO, Normal Ejection fraction
Does not respond well to positive inotropic drugs
What is MOA and effects of digoxin?
- Inhibits Na+/K+ ATPase
- Slows down removal of calcium by NCX
- Maintains normal resting potential
- Positive inotrope
What are the EC50 and TC50 of digoxin?
EC50 – 1 ng/mL
TC50 – 2 ng/mL
What drug is a bypyridine?
Milrinone
How do PDE inhibitors increase inotropy?
- Inhibt enzymes that inactivate cAMP and cGMP
- Positive inotropic effects
- Main action from vasodilation
Explain the phases of cardiac action potentials and the ion channels participating?
What are the 4 classes of antiarrythmics and their MOA?
Class I – sodium channel blockade
Class II – sympatholytic
Class III – prolong action potential duration (other mechanisms besides sodium channels – K+)
Class IV – block cardiac calcium channel currents
What class are quinidine, lidocaine, and flecaninde in?
Effects on cardiac cycle?
Dissociation?
Class I - Na+ channel blockers
What is the MOA of amiodarone?
Uses?
DOC for VT
Explain the MOA of carbonic anhydrase inhibitors?
Where do they work?
Proximal convuluted tubule
Loop diuretics MOA?
Examples?
- Inhibit NKCC2 in thick ascending loop of henle
- Furosemide (sulfa)
- Ethacrynic acid (non-sulfa)
What electrolytes are reabsorbed via the paracellular route in the ascending loop of henle?
How?
Ca++ and Mg++
The secretion of K+ creates a positve lumen potential and drives Ca and Mg through paracellular route
Thiazaides MOA?
Example?
- Inhibit NaCl transport in DCT (NCC)
- Some inhibition of CA activity
- Hydrochlorothiazide
Describe upstream diuretic effects on the collecting tubule?
- Diuretics upstream result in excess Na+ in CT
- Some block NaCl
Cl- leaves via paracellular route - Some block NaHCO3
- HCO3 can’t exit via paracellular route - Drives K+ depletion
How do aldosterone and spirinolactone affect the collecting tubule?
Aldosterone:
* Increase Na+ and water reuptake (ENaC)
* Increases blood volume
Spironolactone
* Block aldosterone receptors
* Potassium sparing
What are ADH affects at the collecting tubule?
Its antagonist?
- Increases water reabsorption
- Adds preformed AQP2 to apical membrane
- Increases blood volume
- Makes more concentrated urine
- Antagonist: Conivaptan
What are the uses and toxicities of mannitol?
- Used mainly to reduce intracranial pressure
- Promote removal of renal toxins
Toxicity - Extracellular volume expansion
- Rapidly distributed to extracellular compartments
- Dehydration
