Exam 2 Flashcards
Which ion contributes most to resting potential?
Potassium.
Which ions are most concentrated inside the cell? ECM?
Potassium. Sodium, Chloride, and Calcium.
Which mechanisms maintain resting membrane potential?
Sodium Potassium ATPase pumps, leak channels, and potassium inward rectifying channels.
How does the Na/K ATPase pump keep the membrane negative?
By pumping out 3 sodiums and pumping in 2 potassiums.
How do leak channels keep the membrane negative?
There is much more potassium leak channels so positive charge is leaking out of the cell more than it’s leaking in.
What do inward rectifying channels do?
Open in response to the membrane becoming too negative. This allows potassium to leak in.
What is the difference between a closed and inactive conformation of a voltage-gated ion channel?
When it is closed, it’s able to open. When inactive, it cannot open due to the refractory period.
What ends the depolarization phase of a myocyte action potential?
Inactivation of Sodium channels.
Why do myocytes action potential have a plateau phase?
Slow calcium influx and most potassium channels closed.
What causes repolarization for myocyte action potentials?
Inactivation of calcium ion channels and opening of inward rectifying potassium channels.
Why do the atria and ventricle contract at different times?
Conduction pause between SA and AV node.
What is considered the pacemaker of the heart? Why? What else influences heart rate?
SA node because it generates the fastest action potential. ANS also affects HR.
What is the pacemaker potential? What does this mean about these cells resting membrane potential?
Slow depolarization from opening of funny/leak sodium channels and closing of potassium channels.
What signifies the start of depolarization for pacemaker cells? What does it involve?
When threshold is reached. Involves opening of calcium ion channels.
What does repolarization of pacemaker cells entail?
Inactivation of calcium ion channels and opening of inward rectifying potassium channels.
How does the ANS generally work?
Preganglionic neuron from CNS releases AcH at ganglion (synapse). AcH binds to nicotinic receptor on postganglionic neuron.
For the parasympathetic system, what does the postganglionic neuron release upon activation? What effects does this have?
Releases AcH that binds to muscarinic (M-2) receptors. This slows heart rate.
For the sympathetic system, what does the postganglionic neuron release upon activation? What effects does this have?
Releases norepinephrine that binds to adrenergic (beta-1) receptors. This increases cAMP and PKA production which promotes the opening of calcium and sodium ion channels. This increases cardiac output.
Which G-protein do muscinic receptors couple with? What about adrenergic receptors?
Gi. Gs.
What is mean arterial pressure (MAP) a product of? What is equivalent to MAP?
Cardiac output (CO) and systemic vascular resistance (SVR). Equivalent to blood pressure.
What is cardiac output a product of?
Heart rate (bpm) and stroke volume (blood volume per beat).
What is ionotropy?
Force of contractions (SV).
What is chronotropy?
Rate of contractions (HR).
What is dromotropy?
Electrical conductance (related to SVR).
What are the 3 extrinsic controls which cause vasoconstriction? How do they work?
Angiotensin II, norepinephrine, and L-type calcium channels. All increase calcium ion concentrations which causes contraction.
What is angiotensin II’s receptor? What about norepinephrine?
At-1. Adrenergic alpha-1.
What are the 4 factors that increase MAP? What is each factor a function of?
Increased heart rate, contractility, SVR, and fluid volume. The first three are a function of the sympathetic nervous sytem. SVR and fluid volume are also a function of angiotensin II. Fluid volume also a function of aldosterone.
What are the 3 general mechanisms of treatment for hypertension? What are the agents of each mechanism?
- Reduction of fluid volume. (diuretics)
- Negative ionotropic/chronotropic agents. (2 calcium channels and beta blockers)
- Vasodilation. (1 calcium channel, ACE-inhibitors, AT-1 blockers, and alpha blockers)
What is sympatholytics?
Blocking of the sympathetic nervous sytem.
What does the sympathetic system release? What are the receptors and effects of these neurotransmitters?
Norepinephrine and epinephrine (from adrenal glands). Increase rate and force of contraction (beta-1 receptors) and also cause vasoconstriction (alpha-1 receptors).
What is the function of the beta-1 receptor?
Couples with Gs protein to increase heart rate, force of contraction, and conduction.
What is the function of the beta-2 receptor?
Couples with Gs protein for smooth muscle relaxation in the lungs, etc. Also glucose breakdown in liver.
What is the function of the alpha-1 receptor?
Couples with Gq protein to cause vasoconstriction.
What is the function of the alpha-2 receptor?
Couples with Gi protein to inhibit neurotransmitter release and insulin release.
What are the modifications of the R3 group? What do they indicate?
- Presence of 4’-OH indicates beta agonist.
- A lone 3’-OH indicates alpha agonist.
- Substitute at 4’-OH indicates an antagonist.
What are the modifications of the R1 group? What do they increase?
- 2-3 methyl groups increases beta selectivity.
2. Nitrogenous rings increases alpha selectivity.
What is the modification of the R2 group? What does it indicate?
Large alkyl and ring substitutions decrease beta receptor activity.
What is the modification of the beta position? What does it indicate?
Insertion of OCH2 favors beta antagonist.
What is SLUDGEM? Which system and receptor is it associated with?
Salivation, lacrimation (tears), urination, defacation, GI cramping, emisis (vomiting), muscle spasms and/or pinpoint pupils. Caused by parasympathetic - M-2 receptors.
What is the function of non-selective beta blockers? What are some of the common side effects? Give examples.
Block both beta receptors. Side effects include shortness of breath and exercise fatigue, major dose limiting factors. (ex: propranolol)
What is the function of selective beta blockers? Why are these advantageous? Give examples.
Higher affinity for beta-1 receptors. Reduces the side effects associated with beta-2 receptors. (ex: atenolol and metoprolol).
What is the function of selective beta blockers with intrinsic sympathomimetic activity (ISA)? What patients are these usually given to? Give examples.
Partial agonists that reduce the effects of beta receptors. Used for patients who become hypotensive easily or have severe bradycardia. (ex: acebutolol and pindolol).
What is the function of alpha-1 selective antagonists? What do they treat and what are their side effects? Give examples.
Relaxes smooth muscle to induce vasodilation (decrease SVR). Used as an add-on therapy or to treat difficult urination due to enlarged prostate.
Side effects: orthostatic hypertension from first dose effect & reflex tachycardia (increased heart rate).
Examples: terazosin, prazosin, doxazosin, lamsulosin
What is the function of mixed alpha/beta blockers? What are they used for and what are the side effects?
Vasodilation and increased stroke volume. Drug of choice for congestive heart failure. Less reflex tachycardia but not beta-1 selective so bad for patients with lung problems.
How does intracellular calcium increase MAP?
Cardiac nodal cells increased HR by reducing time till threshold. Cardiomyocytes increase SV by increasing myosin-actin coupling during systole. Smooth muscle contraction increases SVR and vasoconstriction.
What are dihydropyradines (DHP) selective for? (Hint: they are calcium channel blockers)
Vascular smooth muscle.
What are calcium channel blocker phenylalkamines selective for?
Heart.
What are calcium channel blocker benzothiazepines selective for?
Smooth muscle and heart.
Be able to draw the different calcium channel blocker’s structures.
Okay.
What are the binding sites of the different calcium channel blockers?
DHP: extracellular part of conductance pore.
Phenylalkamine: intracellular part of channel pore/gate.
What is the function of calcium channel blockers, dihydropyradines (DHP)? What do they treat and what are their side effects?
Vasodilation that reduces SVR. Used to treat angina (chest pain caused from low oxygen). Useless for arrhythmia. Side effects include dizziness/headache, increased HR, ankle edema (fluid buildup), & constipation.
What is the function of calcium channel blockers, phenylalkamines? What do they treat and what are their side effects?
Decreases SV and HR (shortens plateau phase). Used to treat arrhythmia. Side effects include dizziness/headache, fatigue, nausea, and constipation.
What is the function of calcium channel blockers, benzothiazepines? What do they treat and what are their side effects?
Decreases SV and SVR. Used to treat arrhythmia and angina. Side effects include dizziness/headache, bradycardia/hypotension, & potential drug-drug interactions.
What is the function of Renin? Where is it produced from?
Converts angiotensinogen into angiotensin I. Produced from the kidneys.
What is the function of ACE? Where is it produced from?
Converts angiotensin I into angiotensin II. Produced from the lungs.
How does angiotensin II increase MAP?
- Direct constriction of vascular smooth muscles from M-2 receptors. This causes vasoconstriction.
- Causes adrenal glands to release aldosterone which promotes sodium and water retention. This increases blood volume.
How do ACE inhibitors work? What are some general side effects
Replace c-terminal and don’t have a peptide bond at the corresponding cleavage site. This inhibits ACE from cleaving angiotensin I into the active form.
Why are ACE inhibitors considered prodrugs?
Because they are not active due to their ester group until they enter the bloodstream.
What are some general side effects of ACE inhibitors?
Dizziness, hypotension, syncope (fainting), dry cough, hyperkalimia (high potassium), and angiodema (rapid throat swelling). Also not given to pregnant women.
