Autonomic Cardiac Pharmacology

Front 1

Sympathetic receptors important to note:

Back 1

B1 - in heart, increase CO
A1 - contraction in peripheral arterioles
B2 - bronchial smooth muscle, certain GI, and in blood vessels supply skeletal muscles

Front 2

What does the adrenal medulla predominately secrete?

Back 2

MOSTLY epinephrine (2/3)
1/3 norepinephrine

Front 3

Describe synthesis of NE?

Back 3

Tyrosine converted to L-dopa by tyrosine hydroxylase (RLS)

Front 4

Major ways to terminate NE signal?

Back 4

Major way - NE transporter, uptake 1
Extraneuronal transporter - uptake 2
Alpha 2 receptors (negative feedback, inhibit NE release)

Front 5

Drugs that decrease NE transmission:

Back 5

a-methyltyrosine
carbidopa, a-methyldopa
disulfiram
reserpine
guanethidine
receptor antagonist

Front 6

Drugs that increase NE transmission:

Back 6

Amphetamine, tyramine
Cocaine
Receptor agonist

Front 7

alpha-methyl tyrosine

Back 7

MOA: inhibit tyrosine hydroxylase, affecting NE synthesis
Uses: pheocromocytoma
ASE: hypotension, sedation

Front 8

Reserpine

Back 8

MOA: affects NE release by depleting NE stores via VMAT inhibition
Uses: hypertension (obsolete)
ASE: same as methyldopa, depression, parkinson disorders

Front 9

Imipramine

Back 9

Drug affecting NE uptake by blocking neuronal transport.
Uses: Depression
ASE: atropine like side effects, arrhytmias

Front 10

Guanethidine

Back 10

MOA: affects NE release, neuronal damages
Uses: hypertension (obsolete)
ASE: same as methyldopa, initial increase in BP

Front 11

Cocaine

Back 11

MOA: blocks NET
Uses: drug abuse
ASE: hypertension, excitement, convulsion

Front 12

Methyldopa

Back 12

MOA: false transmitter precursor to inhibit NE synthesis
Uses: hypertension in pregnancy
ASE: hypotension, drowsiness, diarrhea impotence

Front 13

Carbidopa

Back 13

MOA: inhibits DOPA decarboxylase, affecting NE syntehsis
Uses: adjunct to LDOPA for peripheral effects. Whatever

Front 14

Where do you find a1 receptors, and what do they do?

Back 14

VSM - contraction (IP3/DAG)
Pupillary dilator muscle -Contraction (dilates pupil)
Pilomotor smooth muscle - erects hair

Front 15

What do you find a2 receptors and what do they do?

Back 15

Postsynaptic CNS adrenoceptors - decrease cAMP
Platelets - aggregation (decrease cAMP)
Adrenergic/cholinergic nerve terminals - inhibition of trasmitter release
Some VSM - Decrease cAMP and decrease contraction?
Fat cells - inhibition of lipolysis, decrease cAMP

Front 16

Where do you find B1 receptors and what do they do?

Back 16

Heart, fat cells, glomerular cells - activate adenylate cyclase

Front 17

Where do you find B2 receptors and what do they do?

Back 17

respiratory, uterine, and VSM - activate adenylate cyclase

Front 18

Where do you find B3 receptors, what do they do?

Back 18

Fat cels - activates lipolysis

Front 19

Where do you find B4 cells, what do they do?

Back 19

CNS - involved in long term memory

Front 20

Where do you find D1 receptors?

Back 20

smooth muscle - dilates renal blood vessels

Front 21

Where do you find D2 receptors?

Back 21

CNS nerve endings - modulates transmitter release

Front 22

Dobutamine

Back 22

B1 agonist

Front 23

Methoxamine

Back 23

a1/a2 agonist

Front 24

Phenylephrine

Back 24

a1/a2 agonist

Front 25

Isoproterenol

Back 25

b1/b2 agonist

Front 26

Epinephrine

Back 26

a1/a2/b1/b2 agonist

Front 27

Norepinephrine

Back 27

a1/a2/b1 agonist

Front 28

What isomers of beta blockers actually work?

Back 28

S (L) isomer.

Front 29

What as the differences in isomers of Propanolol?

Back 29

L isomer - has B blocking action
D isomers - doesn't, but still has local anesthetic function

Front 30

What drugs are not susceptible to MAO?

Back 30

Isoproternol (b/c if has big substitution group, though it can be oxidized by COMT)
Amphetamine - not susceptible to MAO OR COMT, and can cross BBB b/c it doesn't have hydroxyl group. Yikes. abused

Front 31

What are the indirect acting sympathomimetics (that act by increase NE)?

Back 31

Amphetamine
Methamphetamine
Tyramine
Phenylpropranolamine
Ephedrine (and pseudoephedrine)

Front 32

Amphetamine uses/ASE

Back 32

Use: narcolepsy, ADD, suppress appetite (no longer used)
ASE: restlessness, dizziness, insomnia, impotence, cardiac arrhythmias, hypertensive crisis with MAO inhibitors

Front 33

Ephedrine (pseudoephedrine)

Back 33

Use: vasoconstriciton, bronchodilation
ASE: hypertension, insomnia, tachyphylaxis

Front 34

Tyramine

Back 34

Present in wines, beer, cheese, no relevant clinical uses
ASE: incombo with MAO inhibitors could lead to sympathetic crisis and be potentially fatal

Front 35

Remember the qiss and qiq till your siq of sqs analogy:

Back 35

a1a2b1b2
m1m2m3
d1d2h1
h2v1v2

Front 36

What sympathetic receptors mediate lipolysis?

Back 36

B1

Front 37

What receptors on skeletal muscle cells can, when stimulated, uptake K and lead to hypokalemia?

Back 37

B2

Front 38

What two drugs were used in the lecture to test the baroreceptor reflex (ie they increase/decrease bp)?

Back 38

Phenylephrine - vasoconstriction and increase BP (increase PARA)
Histamine - vasodilation and decrease BP (increase SYMP)

Front 39

What receptors control peripheral resistance?

Back 39

a1 vasoconstricts
b2 vasodilates

Front 40

What receptors modulate blood pressure?

Back 40

systolic - b1 HR
diastolic - a1 TPR

Front 41

If you stimulate a1, a2, and b1 receptors together with norepi, what will happen to HR, BP, and TPR?

Back 41

BP will increase
HR will DECREASE (despite stimulating B1, because the baroreceptors reflex is also active due to increase BP. The B1 stimulation DOES cause increase contractility and CO, therfore systolic pressure INCREASES. I know this isn't intuitive
TPR also goes up and causes the BP to go up, you get this.

Front 42

If you stimulates a1, a2, b1, b2 receptors together with epi, what will happen to HR, BP?

Back 42

HIGH DOES - it acts JUST the same as NE (raises BP, TPR, and lowers HR)
BUT
LOW DOSE - accentuates action of B2 receptors (which vasodilate) - diastolic pressure goes down, systolic goes up

Front 43

If you stimulates JUST B receptors with isoproterenol, what will that do?

Back 43

It will dramatically decrease TPR (stimulating B2, and there is no more alpha action, only B2 relaxing)
AND
decrease in diasotlic BP, slight increase in systolic BP (BP goes down overall b/c of the combo effect of both B recepors)
HR will go up in response to low BP and B1 stimulation

Front 44

What do the 2 dopamine receptors do?

Back 44

D1 - mostly in BV, increase cAMP and cause vasorelaxation at lo doses and B1 activation at higher, a1 at high high doses
D2 - CNS, cause hypotension, decrease HR

Front 45

Dopaminergic receptor antagonist mentioned

Back 45

Haloperidol (used in low doses as renal vascular dilator, and medium doses to increase cardiac contraction), HIGH doses to increase vasconsriction (a1 recetors)

Front 46

What receptors are most sensitive to the drugs epi, norepi, and isop?

Back 46

A1 - Epi > NE >> Iso
A2 - Epi > NE >> Iso
B1 - Isop > Epi = NE
B2 - Isop > Epi >> NE

Front 47

A1 agonist

Back 47

Phenylephrine
Midodrine

Front 48

A2 agonist

Back 48

Clonidine
Dexmedetomidine

Front 49

A1 antagonist

Back 49

Prazosin
Terazosin
Phentolamine

Front 50

A2 antagonist

Back 50

Yohimbine
Tolazoline
Phentolamine

Front 51

B1 agonist

Back 51

Dobutamine

Front 52

B1 antagonist

Back 52

Metoprolol
Atenolol
Propranolol

Front 53

B2 agonist

Back 53

Terbutaline
Albuterol

Front 54

B2 antagonist

Back 54

Propranolol
Butoxamine

Front 55

Phenylephrine (neosynephrine)

Back 55

Alpha 1 agonist
Nasal decongestant, mydriatic agent (pupil dilation), vasconstriction to localize local anesthetic
ASE: Hypertension, headache, tissue necrosis

Front 56

Metaraminol

Back 56

alpha 1 agonist
both direction acting and releases NE (mixed acting). Treats hypotension, off-label use to relieve paroxysmal tachycardia

Front 57

Midodrine (prodrug)

Back 57

alpha 1 agonist
treats Orthostatic hypotension, chronic fatigue syndrome
ASE: supine hypertension, piloerection, urinary retention.

Front 58

Clonidine

Back 58

a2 receptor agonist, passes BBB and activates a2 in medulla, decrease sympathetic outflow to heart. Does NOT interfere with baroreceptor function, does NOT product postural hypotension
used: hypertension, opiate and benzodiazepine withdrawal
ASE: Xerostomia (dry mouth), sedation, constipation, sexual dysfunction

Front 59

Dexmedetomidine

Back 59

a2 agonist used as sedative during VN surgery

Front 60

Dobutamine

Back 60

Selective B1 agonist
Positive inotropy with less increase in HR.
It's short term treatment of cardiac decomp with little change in myocardial O2 demand. Can desensitize D receptors.
ASE: tachyarrhythmias, angina, hypertension

Front 61

B2 agonist mentioned, and how they funciton

Back 61

Terbutaline
Albuterol
Ritodrine
Treat bronchospasms/asthma, delays premature labor.
ASE: nausea, vomiting, tachycardia, palpitations, termors, hypertension.

Front 62

Phenoxybenzmine

Back 62

Irreversible alpha antagonist
Used: peripheral vascular disease and control complications associated with excessive (pheochromocytoma)
ASE: tacycardia, postural hypotension, miosis, nasal stuffiness, failure of ejaculations

Front 63

Phentolamine

Back 63

Reversible alpha antagonist
Use: peripheral vascular disease, pheochromocytoma treatment
ASE: tachycardia, postural hypotension, miosis, nasal stuffiness

Front 64

Prazosin

Back 64

Selective a1 antagonist

Front 65

Yohimbine

Back 65

Selective a2 anatagonist

Front 66

Prazosin

Back 66

a1 antagonist, dilates arterioles and venous circulation, decreases preload and afterload
Uses: treat hypertension, congestive heart failure, raynaud phenomenon, benign prostate hyperplasia
ASE: "first dose effect" (marked postural hypotension), fainting, dizziness, etc.

Front 67

Yohimbine

Back 67

a2 antagonist - increase NE release, no relevant clinical use. May improve male sexual function
Good antidote for clonidine toxicity

Front 68

The non-selective B-blockers (beta 1/2 antagonist)

Back 68

propranolol
nadalol
timolol

Front 69

Uses for non-selelctive b blockers

Back 69

antihyptensive (short term)
antiarrhythmic (supraventricular)
Antianginal
Hyperthyroidism
Open-angle Glaucoma (timolol)
Anxiety

Front 70

Major ASE for B receptor antagonist

Back 70

Cardiac related bradycardia, heart blocks, precipitate congestive heart failure
Bronchospasms
CNS - hallucinations, nightmares
Tiredness, dizziness
Potential hypoglycemia (delayed recovery from insulin induced hypoglycemia)
Abrupt withdrawl - receptor sensitivity and tacharrhytmias

Front 71

B1 antagonist (major 'beta blockers")

Back 71

Metoprolol
Atenolol
Esmolol
Nebivolol
Bisoprolol

Front 72

What do B1 antagnoist do, ASE, etc.?

Back 72

Treat hypertension, congestive heart failure (metoprolol), angina, arrhythmias
ASE: similar CNS effects of non-selective B blockers (vivid dreams, insomnia. BUT, no bronchoconstriciton and less vasoconstriction (no B2 block)

Front 73

B2 antagonist:

Back 73

Butoxamine -

Front 74

Which beta blockers are lipophillic?

Back 74

Propranolol, this drug also has low oral bioavailabilty

Front 75

What is the first cardioselective beta blocker?

Back 75

Metoprolol

Front 76

What can treat caffein overdose? Beta blockers, alpha blockers, or beta agonist, alpha agonist?

Back 76

Beta blockers

Front 77

This treats beta blocker toxicity

Back 77

Glucagon

Front 78

Combo adrenergic blockers to treat hypertenions and HF?

Back 78

Carvedilol - ASE - fatigue
Labetalol - ASE - less tachycardia, doesn't treat CHF

Front 79

What drugs treat CHF?

Back 79

Metoprolol
Bisoprolol
Carvedilol