Exam 3 Flashcards
1
Q
Adrenergic receptor type and response: SA node
A
beta 1, increased rate
2
Q
Adrenergic receptor type and response: AV node
A
beta 1, Increased conduction
3
Q
Adrenergic receptor type and response: Ventricles
A
beta 1, increased contractiity and automaticity
4
Q
Adrenergic receptor type and response: Blood Vessels (skin and mucosa)
A
alpha 1, constriction
5
Q
Adrenergic receptor type and response: Blood vessels, skeletal muscle
A
beta 2- dilation; alpha 1- constriction
6
Q
Adrenergic receptor type and response:Blood vessels, abdominal viscera (inc renal)
A
alpha 1- constriction; beta 2- dilation
7
Q
Adrenergic receptor type and response: Pulmonary blood vessels
A
alpha 1- constriction
8
Q
Adrenergic receptor type and response: Kidney
A
beta 1- renin release
9
Q
Adrenergic receptor type and response: GI tract
A
alpha 1, beta 2: decreased motility and tone, decreased secretion, contraction of sphincters
10
Q
Adrenergic receptor type and response: Uterus (pregnant)
A
alpha 1- contraction; beta 2- relaxation
11
Q
what are alpha 2 receptors?
A
Adrenergic receptors on the presynaptic neuron terminus that is responsible for feedback inhibition (reduces NE release). They are also present in the CNS, inhibiting NE.
12
Q
How are catecholamines metabolized after release (2 enzymes)
A
Monoamine oxidase (MAO) and Catechol-o-methyl-transferase (COMT). All postsynaptic. MAO can also be presynaptic.
13
Q
Guanethidine: Target/Mechanism
A
Guanethidine is brought into presynaptic cells via norepinephrine transmitter, where it is packaged into vesicles and basically crowds-out norepinephrine, which is degraded by MAO
14
Q
Reserpine: Target/Mechanism
A
Reserpine crosses into presynaptic neurons spontaneously and blocks vesicle membrane transport proteins, preventing concentration of NE into vesicles.
15
Q
Tyramine and Amphetamine: target/mechanism
A
Enters presynaptic cell via NE transporter, where it displaces NE from vesicles (crowds-out), causing a short-term massive NE release from cell by NE transporter.
16
Q
Cocaine, imipramine, atomoxetine: Target/mechanism
A
Blocks norepinephrine transporter (responsible for norepinephrine reputake. This increases the amount of norepinephrine in the synapse.
17
Q
Phenylephrine: target/mechanism
A
it is an agonist of alpha adrenergic receptors (blood vessels constrict peripherally)
18
Q
phentolamine: target/mechanism
A
alpha adrenergic receptor antagonist
19
Q
Norepinephrine: target/mechanism
A
Agonist for alpha 1 and beta 1 receptors. This increases contractility AND resistance, causing increased blood pressure. HR increases initially, but there will be a vagal reflex reducing within a minute.
20
Q
Epinephrine: target/mechanism
A
low doses it is an agonist for beta 1 and beta 2 (CO and HR will increase, but there will also be vasodilation via beta 2, so DBP decreases and SBP climbs). At high doses, it activates alpha 1 receptors which begin to decrease CO. There will be a vagal reflex about a minute later dropping HR. Half life is short so epi will be gone by then.
21
Q
Dopamine: target/mechanism
A
At low doses it is selective agonist for dopamine receptor, with some activity on beta 2. This will cause a slight decrease in BP, heart contractility, and HR. At high doses it is an agonist for alpha, beta1 and beta2. First BP will decrease due to beta 2, then an increase due to alpha 1 receptors. Contractility will increase and HR will initially increase, then decrease (vagal reflex).
22
Q
Dobutamine: target/mechanism
A
At low doses it is an agonist for beta1 receptors, selectively affecting contractility without affecting RATE. At higher doses it affects alpha 1 and beta 1, as well as some activity against beta2 and alpha receptors.
23
Q
Isoproterenol: targtet/mechanism
A
Agonist for beta receptors (1 and 2).
24
Q
Beta 1 receptors: which catacholamines does it have highest affinity for?
A
Iso>epi=NE
25
Beta 2 receptors: which catacholamines does it have highest affinity for?
iso>epi>>NE
26
Alpha 1 receptors: which catacholamines does it have highest affinity for?
epi>NE>>iso
27
In general, what do beta 1 receptors do when activated?
Increase heart contractility and rate increasing CO and BP with a stimulatory g-protein linked pathway (in heart). In kidney: release renin
28
In general, what do beta 2 receptors do when activated?
Vasodilation to decrease total peripheral resistance. Bronchodilation.
29
In general, what do alpha 1 receptors do when activated?
They cause vasoconstriction to increase peripheral resistance and increase blood pressure.
30
In general, what do alpha 2 receptors do when activated?
Alpha 2 are autoreceptors for NE on pre and postsynaptic neurons in the brain. They BLOCK sympathetic outflow in CNS. In post-ganglionic neurons they are found only on presynaptic neurons and INHIBIT NE release.
31
Epinephrine: indication
Anaphylactic shock: Beta 2 stimulation opens airways, supresses histamine and renin release. Incidental increase in blood pressure via alpha 1.
Asthma/hypersensitivity (same)
Topical hemostasis: Shrinks mucosa via alpha 1
Cardiac arrest: resusitate heart via Beta 1
32
Epinephrine: toxicity
Arrhythmia, cerebral vascular accident. Less serious: anxiety, fear, palpitations, HA, tremors.
33
Norepinephrine: indication
Remember: beta1 and alpha1 only (no effect on beta 2s). Typically used in shock (neurogenic). Increases heart rate and contractility, increases blood pressure, no change in cardiac output due to vasoconstriction (alpha 1). Decreases glycogen synthesis via alpha 1.
34
Norepinephrine: toxicities
Similar to Epinephrine
35
Isoproterenol: indication
Agonist of beta 1 and 2. Increases heart rate but decreases blood pressure via vasodilation. Relaxes bronchi. It is used in emergencies to stimulate heart in patients with heart block or to prepare for insertion of pacemaker.
36
Isoproterenol: toxicity
Arrhythmia, tachycardia, palpitations, angina.
37
Dopamine: indication
at high enough doses to stimulate alpha and beta receptors: Increases heart rate, decreases blood pressure (via DA, unless at higher doses and activates alpha 1). Used in cardiogenic shock (drug of choice)
38
Dopamine: toxicities
Due to excessive sympathetic stimulation (tachycardia, angina, arrhythmias) and DA receptor stimulation of chemotrigger zone (causes nausea and vomiting). Does not cross BBB)
39
Dobutamine: indication
In certain types of heart failure (open heart surgery) and acute infarct. Selective for B1 receptors and basically increases contractility without affecting rate.
40
Dobutamine:
Arrythmias. Does not cross BBB, so no CNS effects.
41
Alpha 1 agonists: indication
Decongestion of mucous membranes, raises blood pressure, dilates pupils
42
Alpha 1 agonists: toxicities
Elevate blood pressure
43
Phenylephrine: indication
decongestant, pupilary dilator
44
Ephedrine: indication
(weak alpha and beta agonist). Used as a nasal decongestant and a pressor (increases blood vessel constriction)
45
Non-catecholamine alpha agonists: drug list
Phenylephrine, Ephedrine, Amphetamine
46
Catecholamines: drug list
Epinephrine, Norepinephrine, isoproterenol, dopamine, dobutamine.
47
Catecholamines: ADME
Route: IV, IM, topical, inhaled. Epinephrine and NE cross into CNS, dopamine, dobutamine, and isoproterenol do not. All are rapidly metabolized by catecholamine-o-methyl transferase (COMT) and methyl-amine transferase (MAO) EVERYWHERE including in the blood. Very short half-life ~2 mins
48
Beta 2 stimulators: indication
Bronchial asthma, anaphylaxis, relaxation of pregnant uterus (delays labor)
49
beta2-stimulators: toxicity
related to incidental beta 1 activation.
50
Beta 2 stimulators: drug list
ephedrine, terbutaline, albuterol
51
CNS stimulants: drug list
Amphetamine, methylphenidate, atomoxetine (mech only)
52
Amphetamine: indication
Narcolepsy, weight reduction
53
Methylphenidate: indication
ADHD
54
CNS stimulants: toxicities
Excessive cardiovascular effects.
55
Xanthines: drug list
caffeine, theophylline
56
Xanthines: target/mechanism
Inhibits phosphodiesterase (which breaks-down cAMP), which is the second messenger for beta receptors. This causes a similar effect to beta agonists. Also antagonists of adenosine receptors (sleepiness). This is responsible for CNS stimulation. It will cause a decrease in BP (due to decreased vascular resistance from Beta2 receptors) an INCREASE in contractility (beta1 receptor) and an increase in HR.
57
Xanthines: indication
bronchial asthma, acute and chronic.
58
Selective alpha blockers: target/mechanism
Reversibly block alpha 1 receptors only (which are generally responsible for vasoconstriction). . In general this will decrease BP, and cause reflex tachycardia.
59
If a drug affects alpha and beta receptors equally, which effect will predominate?
Alpha1s are distributed much more widely than beta2s, so alpha (constriction) effects will predominate.
60
Alpha blockers (irreversible): target/mechanism
block alpha 1 receptors (somewhat selective over alpha 2) irreversibly. Drug action continues until new alpha 1s can by synthesized (24 hrs)
61
Selective alpha blockers: drug list
prazosin
62
Alpha blockers (irreversible): drug list
phenoxybenzamine. phentolamine
63
Non-selective alpha blockers: mechanism
Block alpha 1 AND alpha 2 receptors (will prevent feedback inhibition of NE release). Will decrease BP but increase NE onto Beta 1 receptors, causing a greater tachycardia than you would see with a selective alpha blocker.
64
Prazosin: indication
Hypertension
65
Phenoxybenzmine: indication
pheochromaocytoma (adrenal tumor) or BPH (to relax smooth muscle in bladder)
66
Non-selective beta blockers: drug list
propranolol, timolol
67
Alpha-blockers: toxicity
postural hypotension, reflex tachycardia (WORSE with non-selective), nasal congestion, inhibition of ejaculation.
68
Epi reversal?
effects of epinephrine in the presence of an alpha blocker. Normally you get a drop in BP due to action on beta2, then an increase in BP (pressor) with increasing concentration due to alpha 1 receptor response. With alpha 1s blocked, effect of epi is only a depressor effect (beta 1).
69
Non-selective beta blocker: target/effect
Decreases HR due to B1 block, decreased CO, decreases conduction velocity (HR) and decrease oxygen demand. There is also a decrease in plasma RENIN (causing vasodilation). Finally, there is a decrease in sympathetic tone due to effects in the CNS. There is a "direct" effect of beta2 receptors that increases resistance, but it is slight.
70
Beta-blockers: contraindication
Asthmatics (bronchospasm)
71
Timolol: indication
treatment of glaucoma via action on beta 1 receptors.
72
Selective beta-blockers: drug list
Atenolol
73
Selective beta blocker: target/effect
Cardiac effects are similar to non-selective, but there is less danger of respiratory side effects. At high doses, it is no longer "selective"
74
Beta-blockers: indication
Hypertension (usually with diuretics and vasodilators), cardiac arrhythmias, angina, prophylaxis of migraine (low dose), may inhibit cancer progression, early MI or after, Pheochromocytoma, glaucoma, heart failure, performance anxiety.
75
Beta-blockers: toxicity
decrease CO, heart block, bradycardia (all due to beta 1 block); bronchoconstriction (due to beta 2 block), CNS depression/lethargy
76
Alpha 2 agonists: target/mechanism
Bind pre and post synaptically to norepinephrine alpha 2 receptors in the brain, reducing sympathetic outflow and increases feedback inhibition of norepinephrine.
77
Alpha 2 agonists: drug list
Clonidine (directly against alpha 2); and alpha-methyl-dopa (prodrug).
78
Alpha 2 agonists: indication
Essential hypertension (alpha-methyl-dopa is safe in pregnancy), opioid withdrawal (clonadine), open angle glaucoma, ADHD,
79
Alpha 2 agonists: toxicity
Dry mouth, sedation. Clonidine can cause hypertensive crisis if withdrawn abruptoly, alpha-methyl-dopa can cause a positive Coombes test (autoimmune).
80
Isoproterenol: target
Selective for beta 1 and beta 2 receptors.
81
How does heart failure look on a Frank-Starling curve? What about stroke volume and ejection fraction?
The curve is very flat. Compensatory sympathetic tone does not yield increased cardiac output. Renin-angiotensin system activates (due to sympathetic tone) and volume increases along with arteriole constriction. Initially End diastolic volume, end diastolic pressure, end systolic volume, and end systolic pressure all increase. The result is the same stroke volume with a drastically decreased ejection fraction.
82
Describe the general treatment approach to CHF (3 parts)
Decrease preload (diuretics, ACE inhibitors, AR antagonists, Aldosterone antagonists); Decrease OR stabilize contractility (decrease in mild, stabilize if afib); DECREASE afterload (Combined vasodilators, AR antagonists). Polytherapy is the norm.
83
Spironalactone: effect in CHF
Reduces renal Na absorption by blocking aldosterone RECEPTOR. Optimal effect at low concentrations when diuretic effect is minimal. Protects heart from fibrosis caused by excessive aldosterone.
Mortalitiy benefit in CHF when used along with ACE inhibitor, beta-blocker, diuretics)
84
Esmolol: useful for
emergency procedures due to its 8 min half life.
85
Aquired long QT syndrome
Caused by specific mutations in cardiac Na or K channels. Sx include syncope and sudden cardiac death due to Torsades de Pointes. Treatment is genetic testing to determine which receptor is mutated. Then treat with beta blockers for K+ channel mutation or mexiletine/implanted defibrillator for Na+ type.
86
For typical, uncomplicated HT, what are the two first-line classes?
Diuretics, beta-blockers
87
Why choose a diuretic as fist line?
Generally a good call. Especially good for systolic HT and in patients with heart failure.
88
Why choose a beta-blocker as first line?
Best for patients with Hx of MI, angina, tachycardia, fibrillation/arrhythmia.
89
Compelling indications for ACE inhibitor:
Diabetes, heart failure, cardiac hypertrophy, MI
90
Compelling indicators for Ca channel antagonists:
arrhythmia
91
For whom are beta-blockers contraindicated?
Asthma, depression, pregnancy (category C)
92
For whom are ACE inhibitors contraindicated?
Pregnancy, renal stenosis.
93
For whom are alpha-2 antagonists contraindicated?
Depression
94
For whom are Ca channel blockers contraindicated?
Heart failure.
95
For whom are AII receptor antagonists CI?
Pregnancy.
96
-one
Aldosterone antagonists
| Spironalactone and eplerenone
97
-sartan
Angiotensin II receptor antagonists
| Candesartan, losartan
98
-lol
beta blockers
99
Which beta blockers are selective?
Met-at-es (metoprolol, esmolol, atenolol)
100
Which beta blockers are antiarrhythmics?
(Sota and Metopro) Metoprolol- Class II; Sotalol: Class III
101
-pril
ACE inhibitors
102
Digoxin: mechanism
Blocks Na/K ATPase increasing Na and decreasing drivng forsce of Na/Ca exchanger. This causes ↑d intracellular Ca and ↑d contractility. Indirectly, it ↑s vagal stimulation of heart, decreasing pacemaker activity at SA node and decreasing conduction through AV node. Improved CO and ↓d sympathetic done cause reduced renin secreation, decreasing preload and afterload. RATE CONTROL in A-fib.
103
Milrinone: mechanism
Blocks PDE in cardiac and smooth muscle causing an ↑ in cAMP in both. In cardiac muscle this is similar to β-1 stimulation (↑s contractility) and to β-2 stimulation in arterioles which leads to dilation of arterioles (reducing afterload).
104
Vasodilators: list
Nitroglycerin, Isosorbide dinitrate, sodium nitroprusside, hydralazine, minoxidil
105
-ide
Diuretics
106
Amiloride
K-sparing diuretic
107
Furosemide
Loop diuretic
108
-pine
Dihydropyridine class of Ca channel blockers
109
Verapamil
non-dihydropyridine Ca channel blocker, Class IV antiarrhythmic.
110
Diltiazem
non-dihydropyridine Ca channel blocker, Class IV antiarrhythmic.
111
Adenosine: mechanism
Increases K+ conductance. Acute cardioversion of arrhythmias involving AV node.
112
Warfarin
Vitamin K antagonist. Essential part of Afib treatment.
113
Dabigatran
Thrombin inhibitor. Approved for use in aFib. Easier to administer, no way to handle toxicity.
114
Rivaroxaban
Blocks clotting factor Xa. Approved for use in aFib. Easier to administer, no way to handle toxicity.
115
What do you do if your patient does not tolerate a HTN drug well or has NO response?
Substitute with another drug from a different class.
116
What do you do if your patient tolerates a HTN drug well but does not have an adequate response?
Add a diuretic. If a diuretic is what is already being used, then add a drug from another class.
117
Where are Nicotinic receptors found?
Nm at neuromuscular junctions of somatic NS. Also the receptor of postganglionic neurons in sympathetic and parasympathetic. Also widespread in CNS.
118
Where are Muscarinic receptors found?
Target organs for parasympathetic NS (often receptors are there without innervation!).
119
Where are alpha3 nicotinic receptors found?
Autonomic ganglia
120
Where are alpha4 and alpha7 nicotinic receptors found?
CNS
121
Spironolactone
Aldosterone antagonist. Reduces effect of aldosterone on Na and H2O, but optimal effect when diuretic effect is minimal. Protects heart from fibrosis due to excessive aldosterone stimulation. Used in CHF. Causes hyperkalemia and AV block with digoxin.
122
Epelerenone.
Aldosterone agonist Similar to spironolactone, but more specific for aldosterone receptors. Approved by FDA for CHF following acute MI and for HTN. Can cause hyperkalemeia and AV block with digoxin.
123
Candesartan
Angiotensin II receptor antagonist. Effect similar to ACE inhibitor but newer with less data behind it. May be tolerated in patients who do not tolerate ACEi's. Contraindicated in pregnancy.
124
Losartan
Angiotensin II receptor antagonist. Effect similar to ACE inhibitor but newer with less data behind it. May be tolerated in patients who do not tolerate ACEi's. Contraindicated in pregnancy.
125
Non-selective beta blockers: mechanism
Block β1, β2 (and α1 if carvedilol) receptors. This inhibits adverse cardiac remodeling (hypertrophy) that results from chronic catacholamine stimulation in CHF. ↓ HR, CO, conduction velocity, O2 demand, plasma renin (direct β1 block). β2 block increases resestance, but block on renin predominates. . HTN mechanism: ↓ CO, ↓ renin, ↓ overall sym tone through CNS effects. Main effect in angina is ↓ O2 demand. ↑Preload! Don't work in elderly and AA.
126
Carvedilol
Alpha1 AND non-selective beta blocker. Use in CHF only in patients already stabilized by other drugs. Start wioth small dose. Can cause bronchospasm due to beta2 block, hypotension, fluid retention, bradycardia. Contraindicated in Asthma
127
Timolol
non-selective beta blocker. Can cause bronchospasm, hypotension, fluid retention, bradycardia. Contraindicated in asthma.
128
Sotalol
Non-selective beta blocker AND class III antiarhythmic. Rate control in Afib. Blocks K+ efflux during phase 3. Reduces risk of death in pts with implantable cardiac defibrillaters. Can cause bronchospasm. CI in asthma.
129
Selective beta blockers
Blocks 100x more β1 than β2 at therapeutic doses (loses selectivity at ↑ doses. ↓ HR, CO, conduction velocity, O2 demand, plasma renin. No increase on vascular resistance, beta 2 not blocked. Dont work well in elderly and AA.
130
Atenolol
Selective beta blocker. Less bronchospasm than non-selective.
131
Esmolol
Selective beta blocker. Less bronchospasm than non-selctive.
132
Metoprolol
Selective beta blocker. Class II antiarrhythmic. Decreases SA nodal rate (Rate control in AFib) and AV conduction through block of sym. Proven effectiveness in reducing mortality in post-MI patients. CI in Wolff-Parkinson-White.
133
Phenoxybenzamine
Non-selective, irreversible alpha inhibitor (somewhat selective for alpha 1.This blocks vasoconstriction, causing a ↓ in BP and a reflex tachycardia. Duration of action is 24hrs (new receptor synthesized).
134
Phentolamine
Non-selective alpha blocker. Block α 1 and 2 receptors. Prevents vasoconstriction (reducing BP) and PREVENTS feedback inhibition by α2 on NE, causing ↑NE and tachycardia WORSE than selective.
135
Prazosin
Selective alpha 1 blocker (reversible). Block α 1 receptors (reversibly), preventing vasoconstriction, reducing BP and causing reflex increase in HR. Also evoke Na and water retention. Can cause postural hypotension, refl;ex tach, nasal stuffiness, and increase fluid retention.
136
Ace inhibitors
↓d afterload by reducing arteriole constriction. Reduces aldosterone secretion reducing Na and H2O retention. Protects against adverse remodeling of heart.
Monitor K, creatinine, BUN always. Extra effective in DIABETICS. Reverses LV hypertrophy.
Adverse: Cough (ace also breaks down bradykinin). Hyperkalemia (same mech as Aldosterone antagonists), reflex tachycardia. Can be used in mild/moderate renal failure, but does reduce GFR 15% leading to possible renal insufficiency.
CI: PREGNANCY.
137
Captopril
ACE inhibitor.
138
Enalapril
ACE inhibitor
139
Digoxin
Blocks Na/K ATPase increasing Na and decreasing drivng forsce of Na/Ca exchanger. This causes ↑d intracellular Ca and ↑d contractility. Indirectly, it ↑s vagal stimulation of heart, decreasing pacemaker activity at SA node and decreasing conduction through AV node. Improved CO and ↓d sympathetic done cause reduced renin secreation, decreasing preload and afterload. RATE CONTROL in A-fib.
Last resort drug with narrow therapeutic window. Long half life.
High doses can cause heart block and ↑ likelihood of ventricular arrhythmia. Toxicity more likely in hypokalemia (due to ACEi or ARa)
140
Milrinone
Blocks PDE in cardiac and smooth muscle causing an ↑ in cAMP in both. In cardiac muscle this is similar to β-1 stimulation (↑s contractility) and to β-2 stimulation in arterioles which leads to dilation of arterioles (reducing afterload).
Use only for short term.
141
Isosorbide dinitrate
↑d NO causes venous dilation, reducing preload. . 2-3 hr half life. Requires 8hr drug free period.
142
Hydralazine
Arteriole dilation, reduces afterload. Also reduces oxidation of NO. Causes reflex ↑ in HR, contractility, and renin (fluid retention).
Adverse: Reflex tachycardia, ↑ in HR, contractility, and renin (fluid retention).
143
BiDil
Isorbide dinitrate + Hydralazine
144
Nitroglycerin
3 Mechanisms: Systemic venodilation reduces preload; reduced oxygen demand due to lower preload; selective dilation of large epicardial vessels.
Requires 8-12 hour drug-free period
Adverse: headache, dizziness, weakness.
Low Bioavailability.
145
Sodium nitroprusside
Metabolized into NO. Evokes vasodilation in arterioles AND venules. ↓preload, O2 demand.
Continuous infusion ONLY
146
minoxidil
Activates ATP-modulated K channel causing hyperpolarization and relaxation of vascular smooth muscle (no effect on veins). Used topically (Rogaine) to treat pattern baldness.
Reflex ↑ in HR, contractility, and renin (fluid retention).
147
Hydrachlorathiazide
Diuretic. Inhibits Na-Cl co-transport in distal convoluted tubule of kidney. Initial response is due to decreased volume, and is maintained by reduced vascular resistance.
Adverse: Hypokalemia (kaluria) , which can increase risk of arrythmia
148
Amiloride
K-sparing diuretic. Block Na channels in collecting duct and reduce K efflux. Use in combination with a thiazide.
149
Furosemide
Loop diuretic
150
Quinidine
Class 1A antiarrhythmic. Blocks Na+ channels (only in regular cardiac muscle, not pacemaker cells), in both normal and "sick"(depolarized) cells by locking them in "inactive position". The channel must be active before this can occur (use-dependent). Prolongs repolarization due to some blockade of K+. Increases refractory period. Effect is rate dependent (more effict with higher rate). RHYTHM CONTROL
Less anticholinergic than procainamide.
Adverse: There is a risk of increasing ventricular rate if Afib supressed. Solution is to lower conduction with a Ca bloceker, beta blocker, or digoxin. Fever, diarrhea, long QT syndrome-->torsades de pointes
151
Procainamide
Class 1A antiarrhythmic. Blocks Na+ channels (only in regular cardiac muscle, not pacemaker cells), in both normal and "sick"(depolarized) cells by locking them in "inactive position". The channel must be active before this can occur (use-dependent). Prolongs repolarization due to some blockade of K+. Increases refractory period. Effect is rate dependent (more effict with higher rate). RHYTHM CONTROL
More anticholinergic than quinidine.
Adverse: There is a risk of increasing ventricular rate if Afib supressed. Solution is to lower conduction with a Ca bloceker, beta blocker, or digoxin. Fever, diarrhea, long QT syndrome-->torsades de pointes
152
lidocaine
Class 1B antiarrhythmic. Blocks Na+ channels in DEPOLARIZED cells only. Increases K+ permeability so decreases QT length and increases sodium channel recovery time. RHYTHM CONTROL. IV ONLY.
153
mexiletine
Class 1B antiarrhythmic. Blocks Na+ channels in DEPOLARIZED cells only. Increases K+ permeability so decreases QT length and increases sodium channel recovery time. RHYTHM CONTROL.
Available PO (unlike lidocaine)
154
Flecainide
Class Ic antiarrhythmic. Blocks Na+ channels in normal AND sick cells. AP duration increases, but does not effect length of repolarization. RHYTHM CONTROL.
Adverse:Ataxia, (lower risk of long QT)
155
Amiodarone
Class III antiarrhnythmic: Blockated of K+ efflux. Increases AP duration, refractory period. Actas as RHYTHM control in afib.
Adverse: long QT syndrome-->torsades de pointes; pulmonary fibrosis; Rhabdomyolysis with simvastatin.
156
Verapamil
```
(non dihydropyridine) Ca Channel blocker, plus class IV antiarrhythmic. Blockade calcium influx. RATE control in Afib. Also causes systemic vasodilation (no venodilation). ↓ heart contractility, reducing O2 demand. Do not evoke tachycardia because of a direct, negative chronotropic effect.
CI: CHF
```
157
Diltiazem
```
(non dihydropyridine) Ca Channel blocker, plus class IV antiarrhythmic. Blockade calcium influx. RATE control in Afib. Also causes systemic vasodilation (no venodilation). ↓ heart contractility, reducing O2 demand. Do not evoke tachycardia because of a direct, negative chronotropic effect.
CI: CHF
```
158
Nifedipine
Dihydropyridine Ca channel blocker. Relaxation of areterioles systemically, including coronary arteries. ↓ heart contractility initially, but cause a reflex increase in HR, and contractility. Reflex tachycardia is less severe in long lasting dihydropyridines.
159
Amlodipine
Dihydropyridine Ca channel blocker. Relaxation of areterioles systemically, including coronary arteries. ↓ heart contractility initially, but cause a reflex increase in HR, and contractility. Reflex tachycardia is less severe in long lasting dihydropyridines.
160
Nimodipine
Dihydropyridine Ca channel blocker. Has ↑ affinity for cerebral vessels and reduces vasospasm in subarachnoid hemorrhage.
161
Adenosine
Increases K+ conductance. Acute cardioversion of arrhythmias involving AV node.
Half-life is SECONDS
162
Warfarin
Anticoagulant for Afib. Vit K antagonist.
163
dibigatran
Anticoagulant for Afib. Thrombin inhibitor
164
Rivaroxaban
Blocks Xa. Use in Afib for anticoag.
165
Clonidine
Alpha2 agonist. Inhibit release of NE peripherally and sympathetic tone centrally. The effect is a broad-anti adrenergic effect causing ↓ contractility, HR, BP.
Adverse: reduced labido, dry mouth, sedation, can cause HTN crisis with abrupt withdrawal.
166
Methyldopa
Alpha2 agonist. Prodrug. Use for HTN in pregnancy.
167
Albuterol
Selective beta2 Agonist. β 2 stimulation dilates airways and inhibits release of mediators from mast cells.
Adverse: Less than perfect specificity for β 2 receptors. Also activates β 1 receptors ↑ng HR and contractility
168
Terbutaline
Selective beta2 Agonist. β 2 stimulation dilates airways and inhibits release of mediators from mast cells.
Adverse: Less than perfect specificity for β 2 receptors. Also activates β 1 receptors ↑ng HR and contractility
169
Amphetamine
Substrate for NET in presynaptic neurons. ↑s synaptic NE, basically increasing adrenergic effects of NE on α and β receptors.
MAO metabolized. Used for narcolepsy.
170
Methylphenidate
Inhibits reuptake of NE and dopamine in CNS. Used for ADHD, narcolepsy.
171
Cocaine
Block NET, increasing NE in synapse.
172
Ephedrine.
Weak α and β agonist, plus releaser of NE. Used as nasal decongestant and pressor agent. No MAO or COMT metabolism.
173
Xanthines:
Theophylline, Caffeine. Phosphodiesterase inhibitors ↑ cAMP in smoth muscle and cardiac muscle similar to β 2 stimulation. Causes vasodilation, bronchodilation, incrased HR and contractility, ↓d TPR. Adenosine antagoinist
174
Acetylcholine
Agonist for muscarinic receptors at any dose and Nicotinic receptors at HIGH doses only.
175
carbachol
Agonist for muscarinic receptors at any dose and Nicotinic receptors at HIGH doses only. Used for glaucoma. Basically synthetic ACh, not metabolized by AChesterase.
Adverse: Hypotension (vasodilation), diarrhea, vomiting, bronchial constriction, sweating.
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bethanechol
Selective for muscarinic receptors ONLY. Use for postoperative paralytic ileus, urinary retention
Adverse: Hypotension (vasodilation), diarrhea, vomiting, bronchial constriction, sweating.
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nicotine
Agonist for all nicotinic receptors in CNS and PNS. Alpha4 receptors in mesolimbic rewoard system activated creating "pleasurable" sensation. Causes activation of sympathetic and parasympathetic ganglia- increased BP and HR, increased GI activity
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varenicline
Partial agonist of alpha4 receptors in brain. Activates (
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Mechanism of indirect cholinergic agonists
Anticholinesterases (Block activity of acetylcholineesterase), increasing activity of endogenous Ach. Little effect on vascular smooth muscle because there is no cholinergic innervation. At higher doses, get effects on nicotinic receptors including muscle contractions.
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edrophonium
Indirect cholinergic agonist. Dx myasthenia gravis. 5-15 min duration of action.
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neostigmine
Indirect cholinergic agonist. Tx mysanthenia gravis, paralytic ileus. Give with atropine to block muscarinic effects. Reverses paralysis due to vecuronium and tubocurarine.
0.5-2 hrs activity. Does not cross BBB.
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physostigmine
Indirect cholinergic agonist. Used for glaucoma. 0.5-2hrs activity, crosses BBB.
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Donepezil
Indirect cholinergic agonist. Alzheimer's. 12hr half life
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Rivastigmine
Indirect cholinergic agonist. Alzheimer. 24hr
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Galantamine
Indirect cholinergic agonist. Alzheimer. Also enhances Ach activation of nicotinic receptors by binding to allosteric site. 24hr.
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Sarin
Irreversible cholinergic agonist. SLUDGE- salivation, lacrimation, urination, defecation, gi distress, emesis
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botulinum toxin
Binds to pre-synaptic terminals preventing exocytosis of Ach. Result is muscle relaxation in skin and reduced wrinkles.
Also used for chronic migraine.
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Atropine
Muscarinic antagonist. Crosses BBB. Used as preanesthetic medication (relax bronchi, reduce secretions) antispasmodic, antidiarrheal. No effect on circulatory system.
Used to treat Sarin exposure
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Ipratropium
Muscarinic antagonist. Does not ender CNS. Used as bronchodilator in COPD. Suspended inhalational aerosol- no CNS effcts.
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Hexamethonium
Nicotinic antagonist. Binds to alpha3 (ganglionic) receptors. Blockades sympathetic tone in arterioles and venules (dilation), and parasympathetic tone in heart causing tachycardia.
Not used.
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tubocurarine
Binds to Nm and some alpha3(ganglionic) receptors. Drops BP rapidly. Blocks sympathetic and parasympathitic tone (no reflexes). Histamine relase.
Used in acute dissecting aortic aneurysm to rapidly control BP and block reflexes. Produces hypotension
Paralyzes patient. Hypotension, histamine release.
Blockade AUGMENTED by aminoglycosides and inhaled anaesthetics
does not cross BBB. Long acting
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vecuronium
Binds to Nm only. Agonist without activation.
Used as anaesthesia adjuvant. Aids intubation. Paralyzes patient. Better tolerated than tubocurarine. Blockade AUGMENTED by aminoglycosides and inhaled anaesthetics
1-1.5 hrs duration.
Metabolized in minutes by cholinesterase
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pralidoxime
Cholinesterase reactivator
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Amphotericin B
Polyene. Forms pores in membrane by binding to ergosterol. Broad spectrum fungicidal.
Broades spec. Use for serious infections and IN PREGNANCY
Chills, fever, muscle spasms, vomiting HT. Can be controlled by slowing infusino an dpremed with antipyretics and antihistamines. Can cause renal damage (preload with Na)- limit cum. Dose to 2 grams.
IV (oral poorly absorbed). Slow excretion
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Nystatin
Polyene. Topical only.
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Azoles- mechanism
Inhibits ergosterol synthesis by blocking conveersion of Lanosterol to Ergosterol
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Fluconazole
best CNS penetration, highest therapeutic index. Drug of choice for cryptococcal meningitis, prophylaxis in high risk groups.
Good CNS pen. P450i
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Itraconazole
Use for bimorphic fungi: histoplasma, blastomyces, sporothrix
Adverse: Ventricular dysfunciton
Poor CNS pen. P450i
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Voriconazole
Broadest azole. Use for invasive aspergillosis (less toxic than amphotericin)
200
Casponfungin
Binds to β-glucan synthase, preventing cell wall synthesis.
Use for Aspergillus and candida, and invasive aspergillosis if not responsive to Voriconazole
Hepatotoxicity
IV only. P450i
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Griseofulvin
Inhibits microtubule synthesis. Deposited in newly growing keratin in skin and nails
Dermatophytosis only. Tx persists until old tissue is gone (6mo- 1 yr)
PO. P450 Inducer!
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Terbinafine
Inhibits ergosterol synthesis by inhibiting squaline oxidase. Squalene accumulates, is toxic.
Dermatophytosis only, esp oncychomycosis. Shorter Tx.
***NO p450 interactions
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Flucytosine
Taken up by cytosine permease, metabolized to nucleotide that blocks DNA/RNA synthesis. NARROW spec- only use in combination.
Use only in combination (eg cryptococcus neoformans)
Serious hematotoxiciy, esp in cases of renal insufficiency and in AIDS
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Fiber
Absorbs dietary cholesterol an dbile acids, facilitating excretion. When fermented by microflora, inhibit hepatic FA synthesis. Increase speed of GI pass, slowing absorption of cholesterol, glucose etc.
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Omega-3 PUFAs (Lovaza)
Increase clearance of TGs Lowers TGs!
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Atorvastatin
Most lipid soluble. Better.
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Adverse: Jyopathy, esp with gemfibrozil. P450 interactions. Cognitive effects, memory loss in >50. DM (small risk).
P450 metabolized (CYP3A4). Protein bound. 14h half life (administer any time). Cross BBB.
CI: Pregnancy
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Pravastatin
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Fewer interactions (not p450 metabolized)
Adverse: Myopathy (less than Atorvastatin).Cognitive effects, memory loss in >50. DM (small risk)/
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Metabolized by sulfation, NOT p-450 dependent. Not protein bound. 2hr half-life- administer at night. More hepatoselective (does not cross BBB)
CI: Pregnancy
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Ezetimibe
Blocks absorption of cholesterol from GI tract. Localized at brush border.
Used in combination.
Glucuronidated. Hepatic circulation.
May lower LDL, def in combo.
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Cholestyramine
Bile acid sequestrants/resins
Sequesters bile acids and cholesterol in GI tract, preventing absorption. Depletes store of bile acids, requiring more to be produced from cholesterol, upregulating LDL receptor in liver. Can also lead to upregulation of HMG-CoA reductase (so combine with statin).
Used in combination.
Adverse: Constipation, bloating. Malapsorption of vitamin K and folate.
Not absorbed
May lower LDL.
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Niacin
Inhibits TG siynthesis, VLDL secretion, and decreases HDL catabolism.
Adverse: Flushing due to vasodilatory effects. Hepatotoxicity (esp taking >2g of OTC preps)
CI: Pregnancy
211
Gemfibrozil
Ligand for PPAR-alpha receptor, proliferates peroxisomes, stimulates fatty acid oxidation. Increases LPL synthesis, increases clearance of TG and VLDL, enhances LDL receptor expression. Lowers VLDL, LDL, and TG
Never use with STATIN! Inhibits OATP transporter (inhibits statin uptake)
Myopathy and rhabdomyolysis with STATIN
CI: Pregnancy, children, renal and hepatic dysfunction
