Pharmacology: Nervous System

Front 1

Agent:
Norepinephrine

Back 1

Therapeutic Use:
Hypotension, pressor agent

Hint 1

Notes:
Adrenoceptor Agonist
a / b1 b3 (b2) neuronal, non-circulating, I: MAOI, TCA

Front 2

Agent:
Epinephrine

Back 2

Therapeutic Use:
Allergic reactions (DOC), shock, CPR

Hint 2

Notes:
Adrenoceptor Agonist
a / b1 b2 (b3) adrenal medulla, circulating; I: MAOI, TCA

Front 3

Agent:
Dopamine

Back 3

Therapeutic Use:
Shock (DOC)

Hint 3

Notes:
Adrenoceptor Agonist
a1 / b1 / D, NE precursor, renal vasodilatation? I: MAOI

Front 4

Agent:
Bromocriptine


x

Back 4

Therapeutic Use:
Parkinsons, RLS

Hint 4

Notes:
Adrenoceptor Agonist
D-receptors agonist, SE: drowsiness. Dopamine is parent drug. Other similar drug is pramiprexole which is also used for Parkinson's.

Front 5

Agent:
Isoproterenol

Back 5

Therapeutic Use:
Asthma, cardiac stimulant

Hint 5

Notes:
Adrenoceptor Agonist
b, synthetic, not endogenous; BP(down), HR (up)

Front 6

Agent:
Phenylephrine

Back 6

Therapeutic Use:
Nasal decongestant, hypotension

Hint 6

Notes:
Adrenoceptor Agonist
a1 not commonly use for hypotension; S:CV, reflex bradycardia. Methoxamine is related to this parent compound.

Front 7

Agent:
Methoxamine

Back 7

Therapeutic Use:
Hypotension, pressor agent

Hint 7

Notes:
Adrenoceptor Agonist
a1 not commonly use for hypotension; S:CV, reflex bradycardia. Phenylephrine is the parent compound.

Front 8

Agent:
Clonidine

Back 8

Therapeutic Use:
Hypertension

Hint 8

Notes:
Adrenoceptor Agonist
a2 decreases CNS sympathetic outflow, inhibits NE release, rebound HT; S: dry mouth, sedation, impotence. a-methyl-dopa is metabolized to a-methyl-NE (an a2-agonist, positive Coombs test). This is parent drug to Guanfacine and a-methyl-dopa.

Front 9

Agent:
Dobutamine

Back 9

Therapeutic Use:
CHF, cardiac stimulant

Hint 9

Notes:
Adrenoceptor Agonist
b1 iv infusion, tolerance, desensitization. Is parent drug to prenalterol.

Front 10

Agent:
Albuterol

Back 10

Therapeutic Use:
Asthma - bronchodilator

Hint 10

Notes:
Adrenoceptor Agonist
b2-selective, oral 1-2 hours onset --> 4-6 hrs duration, inhalation 5-10 min onset --> 3-4 hours duration
S: cardiovascular, less via inhalation. Parent drug to Ritodrine, Metaproterenol, Terbutaline. Note that Terbutaline not FDA approved for premature labor though it is cheaper and longer lasting than Ritodrine.

Front 11

Agent:
Ritodrine

Back 11

Therapeutic Use:
Premature labor

Hint 11

Notes:
Adrenoceptor Agonist
b2-selective, oral 1-2 hours onset --> 4-6 hrs duration, inhalation 5-10 min onset --> 3-4 hours duration
S: cardiovascular, less via inhalation. Parent drug is albuterol.

Front 12

Agent:
Metaproterenol

x

Back 12

Therapeutic Use:
Asthma

Hint 12

Notes:
b2-selective, oral 1-2 hours onset --> 4-6 hrs duration, inhalation 5-10 min onset --> 3-4 hours duration
S: cardiovascular, less via inhalation. Parent drug is albuterol.

Front 13

Agent:
Terbutaline

x

Back 13

Therapeutic Use:
Asthma, (premature labor)

Hint 13

Notes:
Notes:
b2-selective, oral 1-2 hours onset --> 4-6 hrs duration, inhalation 5-10 min onset --> 3-4 hours duration
S: cardiovascular, less via inhalation. Parent drug is albuterol.

Front 14

Agent:
Guanfacine

x

Back 14

Therapeutic Use:
Hypertension

Hint 14

Notes:
a2, decreases cns sympathetic outflow, inhibit NE release, rebound HT; S: dry mouth, sedation, impotence.
a-methyl-dopa is metabolized to a-methyl-NE (a2-agonist, positive Coombs test). Parent drug is Clonidine.

Front 15

Agent:
a-methyl-dopa

Back 15

Therapeutic Use:
Hypertension

Hint 15

Notes:
a2, decreases cns sympathetic outflow, inhibit NE release, rebound HT; S: dry mouth, sedation, impotence.
a-methyl-dopa is metabolized to a-methyl-NE (a2-agonist, positive Coombs test). Parent drug is Clonidine.

Front 16

Agent:
Prenalterol

x

Back 16

Therapeutic Use:
CHF, cardiac stimulant

Hint 16

Notes:
b1, iv infusion, tolerance, desensitization. Parent drug is dobutamine.

Front 17

Which drugs are not commonly used for hypotension and have side effects that include the CV system and reflex bradycardia?

A. Pramiprexole and Fenoldopam
B. Phenylephrine and Methoxamine
C. Pramiprexole and Methoxamine
D. Pheylephrine and Fenoldopam

Back 17

B. Phenylephrine and Methoxamine

Front 18

Which of the adrenoceptor agonist drugs listed decreases CNS sympathetic outlow, inhibits NE release, has rebound HTN and side effects of dry mouth, sedation, and impotence?

A. alpha-methyl-dopa
B. Clonidine
C. Dexmedetomidine
D. Isoroterenol
E. Methoxamine
F. Phenylephrine
G. Tizanidine

Back 18

A. alpha-methyl-dopa
B. Clonidine

Hint 18

Both are used for HTN. Clonidine is also used for opioid withdrawal.

Front 19

Which of the following drugs are beta2 selective?

A. Albuterol
B. alpha-methyl-dopa
C. Fenoldopam
D. Metaproterenol
E. Methoxamine
F. Ritodrine
G.Terbutaline
H. Salmeterol

Back 19

A. Albuterol
F. Ritodrine
G.Terbutaline

H. Salmeterol

Hint 19

Notes:
Adrenoceptor Agonist
b2-selective, oral 1-2 hours onset --> 4-6 hrs duration, inhalation 5-10 min onset --> 3-4 hours duration
S: cardiovascular, less via inhalation. Parent drug is albuterol.

for H. Salmeterol, has 12 hr duration, and high adverse risk/death

Front 20

________ is not yet FDA approved for premature labor though it is cheaper, longer lasting than _____________.

Back 20

Terbutaline is not FDA approved yet..... longer lasting than Ritodrine

Front 21

How is the neurotransmitter NE symthesized?

Back 21

Tyrosine --> DOPA --> Dopamine -->NE

enzymes: tyrosine hydroxylase (limiting step) , then DOPA decarboxylase, then dopamine beta hydroxylase

Hint 21

tyrosine is actively transported into neuron. In cytosol is where first two steps happen. Then dopamine is actively transported into storage vesicles where it is turned into NE. 50% of dopamine synthesized is metabolized by MAO before entering storage vesicle.

Front 22

In the tyrosine ------> NE synthesis pathway, what effect does reserpine have if introduced?

Back 22

Reserpine inhibits the transport of dopamine into the storage vesicle where dopamine can be converted into NE via dopamine beta hydroxylase.

Front 23

The conversion of NE to epinephrine occurs only in the _______ and _______.

Back 23

adrenal medulla and some brain regions

Front 24

In the tyrosine ------> NE synthesis pathway, what effect does metyrosine have if introduced?

Back 24

Metyrosine inhibits the first step of Tyr ---> DOPA.

Front 25

Released NE can activate presynaptic alpha 2 receptors and beta2 receptors. What is the effect of each?

Back 25

Presynaptic alpha2 receptor activation INHIBITS further transmitter release.

Presynaptic beta2 receptor activation ENHANCES futher transmitter release.

Front 26

True or False:

When NE activates a presynaptic alpha2 receptor, further transmitter release is inhibited.

Back 26

True

Front 27

With regards to the termination of transmitter response, which is the most important/significant?

A. active transport into the effector cells
B. reuptake into noradrenergic neuron
C. passage into circulation and enzymatic destruction in liver

Back 27

B. reuptake into noradrenergic neuron

accounts for 70-80%. also called neuronal uptake, uptake1.

Front 28

Regarding the two enzymes that metabolize catecholamines, where is each
A. located in the cell?
B. located in the body?

Back 28

A. MAO: outer mitochondrial membrane
COMT: cytosol

B. MAO: sympathetic nerve, placenta (MAOa) , platelets (MAOb), liver kidney and brain (both a and b)
COMT: most tissues, not in sympathetic nerves

Front 29

Regarding the two enzymes that metabolize catecholamines, what is the effect of each's inhibition on NE levels?

Back 29

MAO: Increases NE level in sympathetic neuron, potentiates release by tyramine-like drugs.

COMT: minor small effect

Front 30

NE tends to favor [ alpha / beta / both ] receptors at [ low / high / any ] dose.

Back 30

NE tends to favor ALPHA receptors at ANY dose.

EPI favors beta at low doses and both at high doses; ISO is a good beta agonist in general.

Front 31

EPI tends to favor [ alpha / beta / both ] receptors at low doses and [ alpha / beta / both ] receptors at high doses.

Back 31

EPI favors beta at low and both at high.

NE tends to favor alpha receptors at any dose and ISO is a good beta agonist in general.

Front 32

_______ is a good beta agonist in general.

A. EPI
B. ISO
C. NE

Back 32

B. ISO

NE tends to favor alpha receptors at any dose. EPI favors beta at low and both at high.

Front 33

All adrenergic receptors are coupled to GPCR. Which receptor has a Gq GPCR? What is its second messenger system?

Back 33

Gq is coupled to alpha1 recpetors. The second messenger system is: increase in Ca, increase in IP3, DAG.

Front 34

All adrenergic receptors are coupled to GPCR. Which receptor has a Gi GPCR? What is its second messenger system?

Back 34

Gi is coupled to alpha2 receptors and D2, D3, D4 receptors. When activated, lowers cAMP levels.

Front 35

All beta receptors are coupled to what type of GPCR? What is the second messenger system?

Back 35

All beta receptors are coupled to Gs and thus increase cAMP levels when activated.

Front 36

D1 and D5 receptors are coupled to what type of GPCR? What is the second messenger system?

Back 36

D1 and D5 are coupled to Gs and thus increase cAMP levels when activated.

Front 37

Which adrenergic and cholinergic receptors utilize the phospholipase C second messenger system?

Back 37

Adrenergic: alpha1

Cholinergic: Odd-numbered muscarinic receptors (M1, M3, M5)

Front 38

Which adrenergic receptors stimulate adenylate cyclase?

(Note: no cholinergic receptors stimulate adenylate cyclase)

Back 38

all beta receptors,
D1, D5 receptors

Front 39

Which adrenergic and cholinergic receptors INHIBIT adenylate cyclase?

Back 39

Adrenergic: alpha2,
D2, D3, D4 receptors

Cholinergic: M2, M4 receptors

Front 40

What is the DOC for
A. septic shock?
B. allergic reactions?

Back 40

A. Dopamine
B. Epinephrine

Front 41

Dopamine at moderate dose prefers [ alpha1 / beta 1 ] receptor and at high dose prefers [ alpha1 / beta1 ] receptor too. What is it the DOC for?

Back 41

moderate dose = beta1
high dose = alpha1 also

remember that alpha1 when stimulated yields vasoconstriction and increased TPR and BP. Thus, dopamine is DOC for septic shock.

Front 42

In the catecholamines, ________ is used as pressor agent, shock.

Back 42

NE

Front 43

In the catecholamines, ________ is used as the DOC for allergic reactions.

Back 43

EPI

Front 44

In the catecholamines, ________ is used as DOC for septic shock.

Back 44

Dopamine

Front 45

In the catecholamines, ________ is used for asthma and as cardiac stimulant.

Back 45

Isoproterenol

Front 46

Slective beta2-agonists are used for asthma or premature labor. In asthma, activationof beta2 recpetors quickly dilate bronchioles as rescue inhalers. In pregnancy, causes relaxation of uterine muscles.

Name the 1 bold, 2 plain and 2 italicized selective beta2 agonists.

Back 46

Albuterol
salmeterol (LABA), ritodrine
terbutaline, metaproterenol

Adverse effects: extension of effects. Cardiovascular effects.

Front 47

Name the selective beta1 agonists. (1 bold, 1 italicized) What are they used for?

Back 47

*Dobutamine*
prenalternol

Used for CHF to increase force ONLY, no change in HR or oxygen demand though.

Front 48

For acute heart failure, what is the first line drug? What drug should NOT be used?

Back 48

Dobutamine is first line for CHF because it ONLY INCREASES FORCE of contraction, not HR or oxygen demand. Isoproterenol shouldn't be used because it increases HR.

Front 49

Name the two alpha1 agonists. What are they used for?

Back 49

Methoxamine and phylephrine.

Used for nasal decongestants or hypotension.

Front 50

Name the two alpha2 agonists. What is the prototype? What are they used for? What are adverse effects?

Back 50

*Clonidine*
alpha-methyl-dopa
Used for: chronic hypertension (CNS action), and decreases opioid withdrawal severity.
Adverse effects: impotence, dry mouth, rebound HT, sedation

Front 51

What selective agonist class has side effects of impotence, dry mouth, rebound HT, and sedation and thus should be discountinued gradually?

Back 51

alpha2 agonists like Clonidine and alpha-methyldopa used for chronic hypertension and opioid withdrawal.

Front 52

Dexmedetomidine and tizanidine are optimized/tweaked selective ____ agonists. What do they do?

Back 52

alpha2 agonists.
Dexmedetomidine is used for sedation/ analgesia in surgery.
Tizanidine: muscle relaxant acting on CNS.

Front 53

True or False:
Alpha2 agonists are a mixed bag and include Clonidine and alpha-methyldopa.

Back 53

True

Used for: chronic hypertension (CNS action), and decreases opioid withdrawal severity.
Adverse effects: impotence, dry mouth, rebound HT, sedation.
Special drugs are: Dexmedetomidine is used for sedation/ analgesia in surgery.
Tizanidine: muscle relaxant acting on CNS.

Front 54

Dopamine agonists include what two compounds?

Back 54

Pramiprexole and fenoldopam.

Fenoldopam: D1 agonist but no action on alpha1 or beta receptors. Used for acute hypertension and only used short term IV infusion. SE: increased ocular pressure and increased HR.
Pramiprexole is used for Parkinson's Disease and RLS.

Front 55

Which of the following dopamine agonists is used for acute hypertension as a short term IV infusion?

A. Bromocriptine
B. Fenoldopam
C. Pramiprexole

Back 55

B. Fenoldopam

Is a D1a receptor agonist.
SE: increased ocular pressure and increased HR.
Dopamine is parent drug.

Front 56

Which of the following dopamine agonists is used to treat Parkinson's disease and RLS?

A. Clonidine
B. Fenoldopam
C. Pramiprexole

Back 56

C. Pramiprexole

Front 57

Why is dopamine DOC for shock but fenoldopam, a dopamine agonist, is used for acute hypertension as a short term IV infusion?

Back 57

Dopamine elevates blood pressure because it hits the alpha1 receptors. Fenoldopam is selective for D1 and doesn't hit the alpha1 recpetors thus doesn't vasoconstrict.

Front 58

For Parkinson's disease, what is the initial drug combination used? After a few years, the effect will wear off and dopamine agonist _____ will be started. When that wears off then ______ is started. ________ is used as the last resort drug for Parkinson's.

Back 58

Initially: L-dopa + carbidopa.
Then dopamine agonists bromocriptine and pramiprexole.
Then MAO inhibitors.
Last resort COMT inhibition.

Front 59

List the indirectly-acting sympathomimemtics (agents that displace the transmitter). Three bullet points.

Back 59

- Amphetamine, methamphetamine, methylpenidate (ritalin)
- ephedrine (has mixed effects)
- tyramine (not a drug but need to be aware that it adversely interacts with MAO inhibitors)

Amphetamines are CNS stimulant, performance enhancer, and have potential for physical and mental abuse. Increases alertness, mood, self-confidence and concentration.

Front 60

Of the indirectly acting sympathomimetics, which is used for ADHD and narcolepsy?

Back 60

Amphetamine, methamphetamine, methylpenidate

These are CNS stimulants, performance enhances and increase alertness, mood, self-confidence, concentration. Toxicity includes CV, restlessness, tremor, insomnia

Front 61

Of the indirectly acting sympathomimetics, which is used for nasal decongestant?

Back 61

Ephedrine

Front 62

Of the indirectly acting sympathomimetics, which has particularly adverse interaction with MAO inhibitors?

Back 62

tyramine is VERY cautioned against.

Note that ephedrine also has drug interactions with MAOI and TCA.

Front 63

What agents inhibit NE reuptake? (3)

Back 63

Cocaine,
tricyclic antidepressants,
atomoxetine

Hint 63

So if you want to potentiate cocaine, take amphetamine before cocaine. (Easy as ABC)

Front 64

What do cocaine, TCA and atomoxetine have in common?

A. They all act to displace NE
B. They all inhibit neuronal reuptake / (Uptake1)

Back 64

B. They all inhibit neuronal reuptake / (Uptake1)

Cocaine is a drug of abuse and local anaesthetic. Atomoxetine is used for ADHD and is considered non-stimulant. Examples of TCAs are imipramine and amitriptyline. Used for depression.

Front 65

Of the indirectly acting sympathomimetics, which two are used for ADHD?

A. Amphetamine
B. Atomoxetine
C. Ephedrine
D. Methamphetamine
E. Methylphenidate

Back 65

B. Atomoxetine
E. Methylphenidate

Front 66

What are the clinical uses of MAO and COMT inhibitors?

Back 66

Depression (nonselective or MAOa selective such as tranylcypromine)
or
Parkinson's disease (MAOb selective) like Selegiline. COMT inhibitor is only a last resort! Tolcapone

Hint 66

Note: MAO inhibitors potentiate effects of tyramine due to blocking metabolism of tyramine by MAO in the liver) can precipitate a Hypertensive Crisis

Front 67

What type of agents are best to use to treat asthma?

A. alpha1 selective agents
B. alpha 2 selective agents
C. beta1 selective agents
D. beta 2 selective agents

Back 67

B. beta2 selective agents (albuterol, ritodrine, salmeterol)

Hint 67

alpha1 selective agents are phenylephrine and methoxamine.
alpha2 selective agents are clonidine, alpha-methyl-dopa
beta1 selective agent is dobutamine

Front 68

What are therapeutic agents to be used for nasal decongestants? (2)

Back 68

ephedrine (indirectly acting sympathomimetic that displaces NE),
phenylephrine (selective alpha1 agonist along with methoxamine)

Front 69

What therapeutic agents would you use for:
A. Chronic hypertension?
B. Acute hypertension?

Back 69

A. Chronic HTN: alpha2 agonists (Clonidine, alpha-methyldopa

B. Acute: fenoldopam (D1a agonist)

Front 70

What therapeutic agents would you use for shock/hypotension? (3)

Back 70

dopamine (DOC)
EPI
NE

Front 71

What therapeutic agent would you use for acute CHF?

Back 71

dobutamine

beta1 selective agent that increases contractile force but doesn't increase HR. Never use isoproterenol in this situation!!

Front 72

What therapeutic agent would you use for cardiac heart block and cardiac arrest? (2)

Back 72

EPI
ISO

Front 73

What therapeutic agent would you use for Parkinson's disease?

Back 73

L-Dopa + Carbidopa
MAOb inhibitor: selegiline
D-agonists: pramiprexole
COMT inhibtior: tolcapone

Front 74

Regarding eye pupil musculature, just keep in mind: the inner circular muscular layer innervated by parasympathetic NS. Has muscarinic receptors. Contraction Activation causes pinpoint pupils (miosis).
The radial muscle layer of the iris is innervated by sympathetic NS. Contraction causes dilated pupils (mydriasis).

Back 74

keep in mind is all

Front 75

Toxic effects of sympathomimetics are basically extensions of their receptor mediated effects.

A. Cardiovascular: give examples
B. CNS, especially those that cross the BBB yields....
C. What are SE of alpha2receptor agonists?

Back 75

A. cardiac overstimulation by beta agonists --> arrhythmias. hypertension can occur with alpha agonists --> hemorrhage
B. restlessness, dizziness, insomnia
C. alpha2 agonists like Clonidine and alpha-methyldopa have SE: dry motuh, sedation, impotence

Front 76

What type of agonists can be utilized in hypertensive crises, chronic hypertension and benign prostate hypertophy?

Back 76

alpha-adrenergic receptor agonists like
phenoxybenzamine, phentolamine, tolazoline, prazosin, terazosin, doxazosin, yohimbine.

Front 77

What is pheochromocytoma?

Back 77

Tumor (usually benign) of the adrenal gland. Occurs in ppl ~40-60 yrs of age. Basically causes increased synthesis, storage and release of EPI and NE thus results in increased BP and HR. Treatment can return BP to normal. Treatment for long-term diffuse tumor is administration of alpha-methyl-p-tyrosine (or metyrosine) which directly inhibits NE synthesis.

Front 78

True or False:
Alpha blockers interfere with baroreceptor reflex response. Individuals that take alpha blockers must be careful of orthostatic hypotension.

Back 78

True!

Remember alpha1 vasoconstricts and increases TPR and BP normally.

Front 79

Which of the following is an irreversible alpha1 blocker?

A. Doxazosin
B. Phenoxybenzamine
C. Phentolamine
D. Prazosin
E. Terazosin
F. Tolazoline
G. Yohimbine

Back 79

B. Phenoxybenzamine

is an alpha-adrenergic receptor antagonist. also blocks Ach, histamine and serotonin and Uptake 1 and 2. Decreases BP, reflex postural hypotension and resulting tachycardia. generally used only in treatment of pheochromocytoma.

note: Treatment for long-term diffuse tumor is administration of alpha-methyl-p-tyrosine (or metyrosine) which directly inhibits NE synthesis.

Front 80

True or False:
All alpha adrenergic receptor antagonists cause a decrease in blood pressure, postural hypotension and tachycardia.

Back 80

True

Front 81

What are the features of most alpha adrenergic receptor antagonists? (3)

Back 81

All alpha adrenergic receptor antagonists cause a decrease in blood pressure, postural hypotension and tachycardia.

Most because remember prazosin, terazosin, doxazosin class generally do not have reflex tachycardia.

Front 82

What alpha adrenergic receptor antagonist is nonselective and equally acts upon alpha1 and alpha2 receptors? (2)

A. Doxazosin
B. Phenoxybenzamine
C. Phentolamine
D. Prazosin
E. Terazosin
F. Tolazoline
G. Yohimbine

Back 82

C. Phentolamine and F. Tolazoline (competitive)

Front 83

Which are used for primary HTN and benign prostate hypertrophy?

A. Doxazosin
B. Phenoxybenzamine
C. Phentolamine
D. Prazosin
E. Terazosin
F. Tolazoline
G. Yohimbine

Back 83

D. Prazosin
E. Terazosin
A. Doxazosin

This class is highly selective for alpha1 moreso than alpha2. Generally no reflex tachycardia occurs.

Front 84

Regarding alpha blockers, name the
A. irreversible alpha1 blocker
B. nonselective alpha antagonist (does both 1 and 2 equally)
C. selective for alpha1 over alpha2
D. selective alpha2 antagonist

Back 84

A. phenoxybenzamine (noncompetitive)
B. Phentolamine and Tolazoline (competitive)
C. Prazosin, Terazosin, doxazosin (competitive)
D. Yohimbine (competitive)

Hint 84

Phenoxybenzamine is used for pheochromocytoma.

Prazosin, Terazosin, doxazosin are the most clinically useful and used class of alpha antagonists. Has higher selectivity for alpha1 than alpha2 so generally no reflex tachycardia occurs.
Yohimbine was used for impotence but was d/c ed clinically. Can still get in herbal section of stores.

Front 85

What are alpha antagonists utilized for clinically? (3)

Back 85

Hypertensive crises (pheochromocytoma, tyrmaine +MAOi)
Chronic HTN
Benign prostate hypertrophy

Front 86

In general, beta-blocking agents end in the suffix _______ . What are the three exceptions? Additionally, agents beginning with letters ________ are selective for [which beta receptor]. What are the three exceptions?

Back 86

end in -olol except for Sotalol, Labetalol, Carvedilol.
Agents beginning with A-M are beta1 selective except for Carteolol, Labetalol, Carvedilol.

Front 87

For the beta blocker class, what is the
A. prototype drug?
B. two commonly rxed drugs?
C. drug used for glaucoma treatment?
D. partial agonist action prototype?
E. two drugs that have some alpha blocking properties as well?

Back 87

A. prototype = propranolol
B. common = atenolol, metoprolol
C. Timolol
D. Pindolol
E. Labetalol and Carvedilol

Front 88

For the beta blocker class, what are the commonly prescribed drugs (2)?

A. Atenolol
B. Carvedilol
C. Labetalol
D. Metoprolol
E. Pindolol
F. Propranolol
G. Timolol

Back 88

A. Atenolol
D. Metoprolol

Front 89

For the beta blocker class, what is prescribed for glaucoma?

A. Atenolol
B. Carvedilol
C. Labetalol
D. Metoprolol
E. Pindolol
F. Propranolol
G. Timolol

Back 89

G. Timolol

Front 90

For the beta blocker class, what is the partial agonist action prototype?

A. Atenolol
B. Carvedilol
C. Labetalol
D. Metoprolol
E. Pindolol
F. Propranolol
G. Timolol

Back 90

E. Pindolol

Front 91

For the beta blocker class, what has partial alpha agonist action too? (2)

A. Atenolol
B. Carvedilol
C. Labetalol
D. Metoprolol
E. Pindolol
F. Propranolol
G. Timolol

Back 91

B. Carvedilol
C. Labetalol

Front 92

What does instrinsic sympathomimetic activity (partial agonist action) mean?

Back 92

The agent in addition to being a beta receptor antagonist, has also some partial agonist activity. Ex. in Pindolol. This feature was developed by pharm companies to diminish the downside of beta blockers as in supersensitivity effects.

Front 93

List some of the clinical uses beta blockers are indicated for. (5)

Back 93

Chronic HTN (produces gradual reduction of TPR and thus BP),
Arrhythmia (beta1 blockers with membrane stabilizing potential is better - ex. metoprolol),
Angina (beta1 selective blocker better - ex. atenolol, metoprolol okay too)
Glaucoma (Timolol)
Congestive Heart Failure / Heart Failure (tweaked nonselective or beta1, aka Carvediolol or metoprolol).

Hint 93

NOT propranolol which is a nonselective agent b/c it will overall increase BP which won't help the situation. Additionally, this contraindicated for unstable CHF, significant bronchospasm, bradycardia or depression.

Front 94

Beta blockers, together with ______, _____ and ________ are considered first line treatment for uncomplicated essential (chronic) hypertension.

Back 94

diuretics, Ca channel blockers, and ACE inhibitors

note: both nonselective and beta1 selective antagonists are effective. Usually effect is gradual reductionof TPR in spite of long term decrease in cardiac output.

Front 95

Which condition is best treated with beta1blockers with membrane stabilizing properties? What would be the agent to use?

A. Angina
B. Arrhythmia
C. Glaucoma
D. Heart Failure
E. Hypertension

Back 95

B. Arrhythmia

can use metoprolol since it is a beta1 antagonist with membrane stabilizing property

Front 96

Which condition is best treated with Metoprolol or Carvediolol?

A. Angina
B. Arrhythmia
C. Glaucoma
D. Heart Failure
E. Hypertension

Back 96

D. Heart Failure

Nonselective Carvedilol also blocks alpha receptors and metoprolol blocks beta1 receptors thus decreasing CO. Both will decrease load and oxygen demand of the heart which will help the situation.

Front 97

Besides angina, arrhythmia, glaucoma, heart failure and hypertension, what else can beta blockers be used for? (the more minor stuff, 4 things)

Back 97

tremor of peripheral origin (beta2 receptors in skeletal muscle), migraine prophylaxis, hyperthyroidism, panic attacks and stage fright

Front 98

What are some contraindications to the use of beta blockers?

Back 98

depression, sleep disturbances, bradycardia.

asthamtics and diabetics need to use beta1 blockers only. Why? see next side.

Other effects to watch out for: supersensitivity of remaining beta receptors (thus if d/ced should be gradual), effectiveness decreased with elderly due to age, may precipitate Raynaud's Syndrome

Hint 98

asthamtics and diabetics need to use beta1 blockers ONLY since beta2 blockers would precipitate an ashtma attack and prolong recovery from hypoglycemic episode since beta2 receptors in liver cells that, when activated, lead to glycogen breakdown to glucose, would be blocked.

Front 99

These two drugs are used for chronic HTN, CHF, and hypertensive crises and are better than alpha receptor blockers alone since can decrease both BP AND HR effects).

A. Atenolol
B. Carvedilol
C. Labetalol
D. Metoprolol
E. Pindolol

Back 99

B. Carvedilol
C. Labetalol

note: Carvedilol used moreso for heart fialure; Labetalol used moreso for HTN

Front 100

What are dopamine antagonists (Haloperidol, chlorpromazine) used for?

Back 100

treatment of schizophrenia and nausea

SE: tachycardia, hypo/hypertension. Need to discontinue gradually.

Front 101

What agent directly inhibits the synthesis of NE and is thus used in the long term treatment of pheochromocytoma when it is a diffuse tumor?

Back 101

Treatment for long-term diffuse tumor is administration of alpha-methyl-p-tyrosine (or metyrosine) which directly inhibits NE synthesis.

Front 102

What are false transmitters?

Back 102

These are agents that use the same pathway (thus enzymes) as tyrosine --> NE but DO NOT end up making NE! Results in change is in the quantity and quality of transmitter in storage vesicles.

Hint 102

(Ex. are alpha-methyl-dopa ---> alpha methyl NE , alpha-methyl-m-tyrosine --> metaraminol, tyramine + MAOi --> octopamine)

Front 103

Regarding the cholinoceptors, what are the two nicotinic receptor subtypes?

Back 103

Nn (N1) which are located in ganglia cells (part of both divisions of the ANS- parasympathetic and sweat glands of the sympathetic),
Nm (N2) which are in the somatic division

Front 104

What is the rate limiting step of cholinergic synthesis?

Back 104

Active uptake of choline into the nerve terminal. This is the rate limiting step for Ach synthesis. Note: Hemicholinium can inhibit this uptake step. Though it is not used clinically, it inhibits the rate limiting step so need to know!

Front 105

What does hemicholimium do?

Back 105

Active uptake of choline into the nerve terminal. This is the rate limiting step for Ach synthesis. Note: Hemicholinium can inhibit this uptake step. Though it is not used clinically, it inhibits the rate limiting step so need to know!

Front 106

Choline + ________ (from _____) = ACh when what enzyme works?

Back 106

Choline + Acetyl CoA from the mitochondria = ACh when choline acetyltrasnferase (CHAT) is present in cytosol.

Front 107

What agent can prevent the fusion of ACh containing vesicle to the membrane?

Back 107

Botulinum toxin,
aka botox

Front 108

Regarding cholinoceptors, where are muscarinic receptors located and where are nicotinic recpetors located?

Back 108

Muscarinic: Ganglia cells, cardiac muscle, sweat glands

Nicotinic: Ganglia cells, neuromuscular junction

Front 109

What is different with regards to "recycling" between NE and ACh?

Back 109

There is NO recycling of ACh. Reuptake does not occur. Instead, enzymatic degredation occurs by acetylcholinesterase. But the breakdown product, choline, CAN BE TAKEN UP for recycling.

Front 110

Cholinergic receptors are muscarinic or nicotinic. Which is:

A. an ion channel?
B. GPCR coupled?

Back 110

A. nicotinic receptor is an ion channel (pentamer, needs alpha subunits because is opened only when two AChs bind to alpha subunits)
B. Muscarinic is GPCR coupled. M 1, 3, 5 have phospholipase C as a second messenger while M 2, 4 are of Gi and thus decrease adenylate cyclase activity.

Front 111

Which muscarinic receptors have a second messenger system that consists of

A. phospholipase C
B. adenylate cyclase

Back 111

A. M 1, 3, 5 is phospholipase C
B. M 2, 4 is adenylate cyclase (Gi, so decreases cAMP!)

Front 112

AChE rapidly hydrolyzes breaks down Ach. Found in [high] at all areas where Ach is released (nerve synaptic clefts, NMJs). Another form of AChE like pseudocholinesterase, butylcholinesterase is found where?

Back 112

in circulation

Front 113

What are muscarinic effects on:
A. heart
B. vasculature
C. eyes
D. GI tract
E. Lungs
F. Exocrine glands

Back 113

A. Heart: bradycardia, lower contractility
B. Vasculature (not innervated, but if ACh gets into circulation, can cause some vasodilation)
C. Eye: miosis
D. GI tract: increased tone to intestine and bladder but decreased tone to sphincters
E. Lung: contract bronchial smooth muscle (increased resistance and secretion)
F. increased sweating, increased salivation and gastric acid secretion.

Front 114

What are muscarinic effects on:
A. heart
B. vasculature
C. eyes
D. GI tract
E. Lungs
F. Exocrine glands

Back 114

A. Heart: bradycardia, lower contractility
B. Vasculature (not innervated, but if ACh gets into circulation, can cause some vasodilation)
C. Eye: miosis
D. GI tract: increased tone to intestine and bladder but decreased tone to sphincters
E. Lung: contract bronchial smooth muscle (increased resistance and secretion)
F. increased sweating, increased salivation and gastric acid secretion.

Front 115

Which muscarinic receptor agonist is used to kick start GI activity after surgery and is very potent and thus should be used only orally or subcutaneous and never IV or IM (leads to cardiac arrest)?

A. bethanechol
B. carbachol
C. methacholine
D. pilocarpine

Back 115

A. bethanechol

Front 116

What muscarinic receptor agonist is the DOC in a glaucoma emergency due to its ability to rapidly decrease intraocular eye pressure?

A. bethanechol
B. carbachol
C. methacholine
D. pilocarpine

Back 116

D. pilocarpine

Front 117

Which muscarinic receptor agonist is best to use for diagnostic belladonna poisoning?

A. bethanechol
B. carbachol
C. methacholine
D. pilocarpine

Back 117

C. methacholine

not really used otherwise besides this diagnostic belladonna poisoning

Front 118

What are some adverse reactions to cholinergics?

Back 118

SLUDE: salivation, lacrimation, urination, diarrhea, emesis.

Front 119

Which mnemonic(s) refer to the symptoms of parasympathetic toxicity?

Back 119

Parasympathetic toxicity: SLUDGE (salivation, lacrimation, urination, diarrhea, gastric upset, emesis) , DUMBELLS (diarrhea, urination, miosis, bronchorrea, bradycardia, emesis, lacrimation, salivation/sweating)

Hint 119

Other mnemonics are:
Adverse reactions to cholinergics = SLUDE
Muscarinic excess = SLUGBAM
Nicotinic excess = MTWThF

Front 120

Which mnemonic(s) refer to the symptoms of adverse reactions to cholinergics?

Back 120

Adverse reactions to cholinergics: SLUDE (salivation, lacrimation, urination, diarrhea, emesis) and also cardiac slowing, nausea and cramps, bronchoconstriction, tremor, CNS induced convulsions

Hint 120

Other mnemonics are:
Parasympathetic toxicity = SLUDGE
Muscarinic excess = SLUGBAM
Nicotinic excess = MTWThF

Front 121

Which mnemonic(s) refer to the symptoms of muscarinic excess?

Back 121

Muscarinic excess = SLUGBAM
salivation/seizures, lacrimation, urination, GI distress (diarrhea, vomiting), bronchoconstriction, abdominal cramps, miosis

Hint 121

Other mnemonics are
Parasympathetic toxicity = SLUDGE
Adverse reactions to cholinergics = SLUDE
Nicotinic excess = MTWThF

Front 122

Which mnemonic(s) refer to the symptoms of nicotinic excess?

Back 122

Nicotinic excess = MTWThF
Mydriasis, Tachycardia, Weakness (muscle paralysis), HyperTHermia, Fasiculations.

Hint 122

Other mnemonics are
Parasympathetic toxicity = SLUDGE
Adverse reactions to cholinergics = SLUDE
Muscarinic excess = slugbam

Front 123

With regards to cholinergics, there are two types of indirectly-acting parasympathomimetics. What are the two categories and give an exmaple drug of each.

Back 123

Reversible inhibiors (like physostigmine),
Irreversible inhibitors (like organophosphatases)

Front 124

Which reversible cholinergic inhibitor is used for testing for myasthenia gravis?

A. Ambenonium
B. Edrophonium
C. Neostigmine
D. Physostigmine

Back 124

B. Edrophonium (trade name Tensilon)

Front 125

Regarding cholinergic reversible inhibitors, differentiate between the two carbamates physostigmine and neostigmine.

Back 125

Physostigmine has good lipid solubility so can cross BBB and has CNS activity as well as peripherally. On the contrary, neostigmine DOES NOT cross BBB due to charge so only works peripherally.

Front 126

Myasthenia gravis is better treated with [ neostigmine / physostigmine ].

Back 126

neostigmine. does not have CNS activity.

Front 127

True or False:
Organophosphates are highly lipid soluble.

Back 127

True!

This contributes to their dangerousness because they can have CNS effects! Most are nerve gases but two (malathion, parathion) are of note to know by name.

Front 128

Most irreversible AChE inhibitors are nerve gases. What are two agents that are actually pesticides in prodrug form? Which has a better safety margin?

Back 128

Malathion and Parathion

. Instead of O, malathion and parathion have Sulfur groups. When metabolized, S becomes O,! In humans, we can quickly inactivate this. (Insects don’t have the ability to inactivate it. Unfortunately fish also cannot inactivate em.) Humans are better able to inactivate malathion versus parathion. Malathion has a better saftey margin.

Front 129

For irreversible AChE inhibitors, completion of [what process] makes it irreversible?

Back 129

"Aging". Binds to enzyme, they undergo “aging” which converts a loosley bond compound to a tightly bound COVALENT (hence irreversible), bond to the enzyme. Once aging process is complete, the agent is irreversibly bound! Nerve gas ages in seconds to minutes. DFP ages in 30-40 minutes. Malathion ages in 4-6 hours. Compound 2PAM can regenerate AChE to normal status if aging process has not completed.

Front 130

At low doses, EPI favors which receptors compared to at high dose EPI?

Back 130

@ low dose, EPI favors beta receptors.

@ high dose, EPI will utilize both alpha and beta recpetors

Front 131

At high doses, what are the following agents' effects with regards to BP, HR and baroreflex activation?

A. Phenylephrine
B. EPI
C. ISO

Back 131

A. Phenylephrine is an alpha1 agonist so vasoconstriction --> increased BP. Reflex activated in attempt to lower HR.
B. BP will increase and reflex bradycardia will occur, but EPI is much stronger than reflex so net overall there will still be some tachycardia as well as raised BP
C. Beta agonist in general. Beta1 activation will raise systolic; Beta2 activation will lower diastolic. Overall beta2 action will be a bit more potent and thus overall BP goes down. Reflex activated to increase HR. Note that the reflex is thus working in the same direction as (part of) the drug (the beta1!)

Front 132

At high doses, which of these agents actually works (partly) in the same direction as the reflex activated?

A. Epinephrine
B. Isoproterenol
C. Phentolamine
D. Phenylephrine

Back 132

B. Isoproterenol

Front 133

If EPI were paired with an alpha blocker, what would be the outcome with respect to BP and HR?

Back 133

Normal response to EPI alone is a raise in BP and HR. But if an alpha blocker were present, it'd be lowered BP, and raised HR.