Pharm Chapter 5-10, 13

Front 1

Is the autonomic nervous system under voluntary control?

Back 1

no

Front 2

What does the ANS regulate?

Back 2

the cardiovascular and digestive systems, controls body temp and glandular secretion, involved in regulating metabolism

Front 3

What are the components of the central nervous system?

Back 3

brain and spinal cord

Front 4

What are the components of the peripheral nervous system?

Back 4

somatic (skeletal muscle) and autonomic (smooth and cardiac muscle and exocrine glands)

Front 5

What is the origin of the parasympathetic nervous system?

Back 5

craniosacral (CN III, VII, IX, and X)

Front 6

Where are parasympathetic ganglia located?

Back 6

near the effector organ

Front 7

What has long preganglionic fibers and short postganglionic fibers?

Back 7

parasympathetic

Front 8

What is the origin of the sympathetic nervous system?

Back 8

thoracolumbar

Front 9

Where are the ganglia of the sympathetic nervous system located?

Back 9

distant from effector organ in paravertebral chain

Front 10

Where does teh enteric nervous system originate?

Back 10

from the neural crest

Front 11

What are some of the neurotransmitters in the enteric system?

Back 11

neuropeptide Y, substance P, serotonin, adenosine, triphosphate, and nitric oxide

Front 12

Where is the enteric nervous system located?

Back 12

in the wall of the GI tract

Front 13

What system is the adrenal medulla a part of?

Back 13

the sympathetic nervous system

Front 14

What do the preganglionic fibers to the adrenal medulla release?

Back 14

acetylcholine

Front 15

What does the adrenal medulla release?

Back 15

epinephrine and norepinephrine

Front 16

Does the adrenal medulla have fibers?

Back 16

no it "spits" out catecholamines into blood

Front 17

What has trophotropic action and what does it mean?

Back 17

parasympathetic nervous system, means vegetative

Front 18

Which system has wide spread activation?

Back 18

sympathetic

Front 19

What system functions on an organ-specific basis?

Back 19

parasympathetic

Front 20

What system has ergotropic action and what does it mean?

Back 20

sympathetic system, means energy expenditure

Front 21

What is released at ALL post-ganglionic junctions in the parasympathetic system?

Back 21

ACh

Front 22

Sweat glands are anatomically ________ but chemically ___________.

Back 22

sympathetic but cholinergic (can be treated w/ atropine)

Front 23

Cholinergic neurons release ___________ and adrenergic neurons release __________.

Back 23

ACh and NE

Front 24

What is acetyl CoA derived from?

Back 24

mitochondria via pyruvate dehydrogenase

Front 25

How is choline obtained?

Back 25

by uptake from extracellular space or by release from phosphatidylcholine

Front 26

How is acetylcholine stored?

Back 26

by storage in nerve terminal vesicles (recycled choline)

Front 27

How is acetylcholine released?

Back 27

by exocytosis

Front 28

Where is NE released?

Back 28

in most sympathetic postganglionic nerve endings (except sweat glands and blood vessels in skeletal muscle around the face)

Front 29

How is acetylcholine made in the sympathetic system?

Back 29

from dietary tyrosine

Front 30

What is teh main way NE is removed?

Back 30

by taking it back up (it is captured whole and not metabolized)

Front 31

What are the steps in the process of neurotransmission?

Back 31

synthesis, storage, release from nerve terminal, receptor interaction and activation, signal transduction, and metabolism/regulation of neurotransmitter levels

Front 32

What does cocaine block?

Back 32

the reuptake process of NE

Front 33

What drugs affecting cholinergic and adrenergic neurotransmission inhibit synthesis of neurotransmitter?

Back 33

hemicholinium (C) and metyrosine (A)

Front 34

What drugs affecting cholinergic and adrenergic neurotransmission prevent vesicular storage of neurotransmitter?

Back 34

vesamicol (C) and reserpine (A)

Front 35

What drugs affecting cholinergic and adrenergic neurotransmission inhibit release of neurotransmitter?

Back 35

botulinum toxin (C) and bretylium and guanethidine (A)

Front 36

What drugs affecting cholinergic and adrenergic neurotransmission stimulate release of neurotransmitter?

Back 36

Black Widow spider venom (C) and amphetamine (A)

Front 37

What drugs affecting adrenergic neurotransmission inhibit reuptake of neurotransmitter?

Back 37

antidepressants and cocaine (A)

Front 38

What drugs affecting cholinergic and adrenergic neurotransmission inhibit metabolism of neurotransmitter?

Back 38

cholinesterase inhibitors (C) and monamine oxidase inhibitors (A)

Front 39

What drugs affecting cholinergic and adrenergic neurotransmission activate postsynaptic receptors?

Back 39

acetylcholine, bethanechol, pilocarpine (C) and albuterol, deobutamine, Epi, phenylephrine (A)

Front 40

What drugs affecting cholinergic and adrenergic neurotransmission block postsynaptic receptors?

Back 40

atropine, tubocurarine (C) and phentolamine, propranolol (A)

Front 41

Does the dual innervation of the ANS work together or in opposition usually?

Back 41

in opposition to each other

Front 42

What does the net effect depend on?

Back 42

innervation present, predominant tone (central activation), and receptors present

Front 43

Do blood vessels have parasympathetic innervation?

Back 43

NO

Front 44

What does sympathetic do to the eye?

Back 44

contracts the radiator muscles causing dilation

Front 45

What does parasympathetic do to the eye?

Back 45

contracts circular muscle to constrict

Front 46

What innervated virtually all vascular beds in the blood vessels?

Back 46

sympathetics

Front 47

What does parasympathetic affect primarily in the heart?

Back 47

rate and conduction

Front 48

Where does parasympathetic innervate in the heart?

Back 48

SA node, atrial wall, AV node, and ventricular conducting system

Front 49

What does sympathetic affect in the heart?

Back 49

rate, conduction, and force of contraction

Front 50

What does sympathetic innervate in the heart?

Back 50

SA node, atrial wall, AV node, ventricular conducting system, and ventricular wall

Front 51

What is the M1 receptor and where is it located?

Back 51

"neural" in autonomic ganglia, presynaptic nerve terminals and CNS

Front 52

What is the M2 receptor and where is it located?

Back 52

"cardiac" in cardiac tissue (SA and AV nodes)

Front 53

What is the M3 receptor and where is it located?

Back 53

"glandular" in smooth muscle and glands

Front 54

What muscarinic receptor activates phospholipase C and breaks it down into IP3 and DAG?

Back 54

M1 and M3

Front 55

What muscarinic receptor increases potassium efflux or decreased cAMP?

Back 55

M2

Front 56

With a low dose in cardiovascular system of muscarinic receptor, what results?

Back 56

reflex tachycardia (positive chronotropy)

Front 57

What do high doses of muscarinic yield in cardiac?

Back 57

bradycardia, dec rate of spontaneous depolarization of SA node and dec rate of conduction of impulses from SA node through AV node

Front 58

In low doses, nicotine acts like an __________.

Back 58

agonist

Front 59

What does muscarine do in the GI system?

Back 59

inc smooth muscle tone, inc muscle contraction amplitude, inc peristaltic activity in stomach and intestines, elevated secretory activity

Front 60

What are some side effects of muscarine in the GI system?

Back 60

nausea, belching, vomiting, cramps, and defecation

Front 61

What are effects of muscarine on the respiratory system?

Back 61

bronchoconstriction and inc tracheobronchial secretion

Front 62

What are effects on the skin from muscarine?

Back 62

inc sweating

Front 63

What are effects of muscarine on the urinary tract?

Back 63

inc ureter peristalsis and inc urination

Front 64

What are the effects of muscarine in the eyes?

Back 64

miosis and accomodation

Front 65

What are the 2 subdivisions of nicotinic receptors?

Back 65

Nm (muscles) and Nn (neurons)

Front 66

What is Nm and what is the mechanism?

Back 66

nicotinic in the somatic neuromuscular junctions and mech is inc Na influx

Front 67

What is Nn and what is the mechanism?

Back 67

nicotinic in autonomic ganglia and mech is inc Na influx

Front 68

What nicotinic receptor causes contraction of skeletal muscle?

Back 68

Nm

Front 69

What nicotinic receptor causes excitation of postganglionic neurons and stimulation of adrenal medulla to release Epi and NE?

Back 69

Nn

Front 70

What are direct acting cholinergic agonists?

Back 70

choline esters (ACh and synthetic esters) and naturally occurring alkaloids

Front 71

What is an indirect acting cholinergic agonist?

Back 71

cholinesterase inhibitors

Front 72

Are choline esters specific?

Back 72

not very

Front 73

ALL choline esters are _______ ______ compounds and can't cross the _______-_______ __________.

Back 73

quaternary ammonium and blood-brain barrier

Front 74

How are choline esters administered?

Back 74

PO or SC or topical to the eye

Front 75

What are some examples of choline esters?

Back 75

bethanechol, carbachol, methacholine, and acetylcholine

Front 76

What is bethanachol used for?

Back 76

urinary retention, gastric atony and retention, and coronary angiography

Front 77

What is carbachol used for?

Back 77

treatment of non-congestive wide-angle glaucoma, miosis during surgery

Front 78

What is methacholine used for?

Back 78

test for bronchial reactivity

Front 79

What is acetylcholine used for?

Back 79

production of rapid and brief miosis during ophthalmic surgery

Front 80

Can choline esters also activate muscarinic receptors?

Back 80

yes

Front 81

What are naturally occuring direct acting cholinergic agonists?

Back 81

nicotine, muscarine, pilocarpine

Front 82

Is nicotine selective?

Back 82

yes, VERY

Front 83

Is muscarine broken down in the body?

Back 83

No

Front 84

What receptor is pilocarpine selective for?

Back 84

muscarinic receptors

Front 85

What is pilocarpine used for?

Back 85

reducing IOP in open-angle glaucoma and treatment of xerostomia

Front 86

What are some cholinesterase inhibitors?

Back 86

organophosphates, carbamates, and edrophonium

Front 87

What is the mechanism of action of cholinesterases?

Back 87

ester to an alcohol and carboxylic acid

Front 88

Is hydrolysis of ACh by acetylcholinesterase fast or slow and what is the enzyme?

Back 88

fast and serine esterase

Front 89

What are the 2 active sites in serine esterase?

Back 89

anionic site to attract quaternary ammonium and esteric site to hydrolysis of ester linkage

Front 90

What are short-acting competitive inhibitors of acetylcholinesterase?

Back 90

edrophonium (tensilon) and ambenonium (mytelase)

Front 91

How does edrophonium work?

Back 91

competes for ACh binding at anionic site but contains no ester linkage so it's not hydrolyzed and inhibition is rapidly reversible

Front 92

What is edrophonium used for?

Back 92

to test for diagnosis of myasthenia gravis

Front 93

What are some intermediate acting inhibitors of Acetylcholinesterase?

Back 93

neostigmine, physostigmine (pyridostigmine and carbaryl), tacrine (cognex), donepezil (aricept), rivastigmine (exelon), and galantamine (reminyl)

Front 94

What do tacrine and donepezil treat?

Back 94

Alzheimer's disease

Front 95

_______ ester linkage is hydrolyzed by AChE.

Back 95

carbamyl

Front 96

Do carbamate inhibitors have slow or long lasting inhibition?

Back 96

long

Front 97

Are physostigmine and neostigmine CNS permeable?

Back 97

only physostigmine and they treat glaucoma and MG

Front 98

What are some long-acting "irreversible" inhibitors of AChE?

Back 98

echothiophate, isoflurophate, malathion, parathion, sevin, DFP, sarin, and soman

Front 99

What is the only irreversible inhibitor of AChE that is used therapeutically?

Back 99

echothiophate

Front 100

Why do irreversible inhibitors of AChE have good CNS penetration?

Back 100

highly lipid soluble

Front 101

Irreversible inhibitors of AChE form ________ attachment of phosphate group to the ________ site of the enzyme?

Back 101

covalent, esteratic

Front 102

What can prevent the process of "aging" and making the bond permanent?

Back 102

2-PAM or pralidoxime

Front 103

Phosphorylation is generally slow and _______.

Back 103

irreversible

Front 104

How do drugs primarily alter nervous sytem function?

Back 104

by affecting neurotransmitters or their receptors

Front 105

What is the nickname for sympathetics?

Back 105

"fight or flight"

Front 106

What is the nickname for parasympathetics?

Back 106

"rest and digest"

Front 107

Parasympathetic stimulation ________ the ENS, whereas sympathetic __________ the ENS.

Back 107

activates, inhibits

Front 108

What is the principal catecholamine released from the adrenal medulla in response to activation of the symp nervous system?

Back 108

epinephrine

Front 109

What are the 2 cholinergic receptors?

Back 109

muscarinic and nicotinic

Front 110

What are muscarinic receptors activated by and where are they located?

Back 110

muscarine, at parasymp neuroeffector junctions

Front 111

What are nicotinic receptors activated by and where are they located?

Back 111

nicotine, in all autonomic ganglia and at somatic neuromuscular junctions

Front 112

What does the M3 muscarinic receptor produce?

Back 112

smooth muscle contraction (except sphincters) and gland secretion

Front 113

What does the M2 muscarinic receptor mediate?

Back 113

cardiac slowing

Front 114

What is the M1 muscarinic receptor concerned with?

Back 114

modulation of neurotransmission at central and peripheral sites

Front 115

The alpha-1 adrenergic receptors mediate smooth muscle ________, whereas beta-2 adrenergic receptors mediate smooth muscle _________.

Back 115

contraction, relaxation

Front 116

Acetylcholine is synthesized from ________ and ________ in the neuronal __________ by choline acetyltransferase and then it is stored in vesicles.

Back 116

choline and acetate, in cytoplasm

Front 117

During exocytosis, the vesicle membrane and _______ _______ fuse, and the neurotransmitter is released into the synapse through an opening in the fused membranes.

Back 117

plasma membrane

Front 118

________ blocks choline transport into the neuron and thereby inhibits the synthesis of ACh, whereas _______ prevents the vesicular storage of ACh.

Back 118

hemicholinium, vesamicol

Front 119

Black widow spider venom contains _______ which stimulates vesicular release of ACh producing excessive activation of cholinergic receptors in ab muscles and other tissues.

Back 119

latrotoxin

Front 120

What drugs can mimic the effect of ACh at muscarinic and nicotinic receptors?

Back 120

bethanechol and pilocarpine (direct-acting cholinergic receptor agonists)

Front 121

What do cholinesterase inhibitors prevent?

Back 121

the breakdown of ACh and thereby increase the synaptic concentration of ACh (called indirect-acting cholinergic receptor agonists)

Front 122

What is the most important group of drugs that inhibit cholinergic neurotransmission?

Back 122

cholinergic receptor antagonists

Front 123

What are the 2 subgoups of cholinergic receptor antagonists?

Back 123

muscarinic receptor antagonits (atropine) and nicotinic receptor antagonists (ganglionic blocking agents and neuromuscular blocking drugs)

Front 124

How is NE synthesized?

Back 124

tyrosine, dopa, dopamine, NE

Front 125

What are the enzymes that inactivate NE that is not sequestered by presynaptic neurons?

Back 125

catechol O-methyltransferase (COMT) and monoamine oxidase (MAO)

Front 126

What inhibits the synthesis of NE?

Back 126

metyrosine (copetitive inhibitor of tyrosine hydroxylase)

Front 127

What blocks the storage of NE in vesicles?

Back 127

reserpine (inhibits transporter for amines)

Front 128

What are albuterol, dobutamine, and epi?

Back 128

direct-acting adrenergic receptor agonists (directly activate alpha and beta receptors)

Front 129

What are some drugs that indirectly increase the activation of adrenergic receptors by increasing the synaptic concentration of NE?

Back 129

amphetamine and cocaine (indirect-acting adrenergic receptor agonists)

Front 130

What are some examples of adrenergic receptor antagonists?

Back 130

phentolamine, propranolol, and labetalol

Front 131

If a drug lowers the BP sufficiently, it may reduce the baroreceptor tone and thereby produce an acceleration of the HR and activation of the symp vasoonstriction. The effect on the HR is called ___________.

Back 131

reflex tachycardia

Front 132

In the ANS, there are several nonadrenergic-nonchlinergic neurotransmitters, including __________, _______, and _______.

Back 132

peptides, nitric oxide, and serotonin

Front 133

What do indirect-acting drugs do?

Back 133

have effects on neurotransmitter synthesis, storage, release, or metabolism

Front 134

What do indirect-acting agonists require to exert their effects?

Back 134

the presence of a functinoal postganglionic neuron

Front 135

What are the M1, M3, and M5 receptors coupled with?

Back 135

Gq proteins

Front 136

What are M2 and M4 receptors coupled with?

Back 136

Gi proteins

Front 137

What does nicotinic receptor activation lead to?

Back 137

Na influx, membrane depol, and excitation of autonomic postganglionic neurons and skeletal muscle

Front 138

__________-acting agonists bind and activate cholinergic receptors, whereas the _______-acting agonists increase the synaptic concentration of ACh.

Back 138

direct, indirect

Front 139

What do direct-acting agonists include?

Back 139

choline esters and plant alkaloids

Front 140

Are choline esters absorbed from the GI tract?

Back 140

poorly

Front 141

Does ACh have a short or long duration of action?

Back 141

extremely short

Front 142

Is ACh effective by topical ocular admin?

Back 142

no, b/c it is hydrolyzed by corneal cholinesterase

Front 143

What is the vasodilative effect of ACh mediated by?

Back 143

muscarinic receptors in vascular endothelial cells

Front 144

What is teh vasospastic effect of ACh caused by?

Back 144

stimulation of muscarinic receptors that are located on vascular smooth muscle and mediate smooth muscle contraction

Front 145

Bethanechol and carbachol are ________ to hydrolysis by cholinesterase and their duration of action is relatively ________.

Back 145

resistant, short

Front 146

What receptors does bethanechol activate?

Back 146

muscarinic to stimulate bladder and GI muscle w/out significantly affecting BP or HR

Front 147

What is carbachol used?

Back 147

in chronic open-angle glaucoma and to produce miosis during ophthalmic surgery

Front 148

Does muscarine have any current medical use?

Back 148

no

Front 149

How is pilocarpine well absorbed?

Back 149

after topical ocular and oral admin

Front 150

Pilocarpine is a second line drug for what diseases?

Back 150

chronic open-angle glaucoma and sometimes used for acute angle-closure glaucoma (can also be used for xerostomia)

Front 151

What is a new synthetic direct-acting muscarinic receptor agonist and how is it admin?

Back 151

cevimeline (evoxac) PO to treat dry mouth

Front 152

What are some examples of reversible cholinesterase inhibitors?

Back 152

edrophonium, neostigmine, physostigmine, pyridostigmine, and donepezil

Front 153

What is edrophonium?

Back 153

positively charged quaternary alcohol that reversibly binds to a negatively charged site on cholinesterase

Front 154

What is the duration of action of edrophonium?

Back 154

short

Front 155

What does edrophonium prevent?

Back 155

the hydrolysis of ACh

Front 156

Why is edrophonium used?

Back 156

for diff diagnosis of muscle weakness in pts suspected of having MG

Front 157

What is a cholinergic crisis?

Back 157

when muscle weakness results from and ACh excess that causes prolonged depol of skeletal muscle

Front 158

Neostigmine, Physostigmine, and Pyridostigmine are esters of _______ ________.

Back 158

carbamic acid

Front 159

What is a plant alkaloid with a tertiary amine that is well absorbed from the gut and penetrates the blood-brain barrier?

Back 159

physostigmine

Front 160

Neostigmine and pyridostigmine are synthetic _______ compounds that are less well absorbed from the ____ and do not cross the ________.

Back 160

quaternary amine, gut, blood-brain barrier

Front 161

How long do carbamates prevent the breakdown of ACh?

Back 161

several hours

Front 162

What are neostigmine and pyridostigmine used for?

Back 162

to counteract curariform drug toxicity, neo used for postop urinary retention and ab distention

Front 163

What is physostigmine used for?

Back 163

glaucoma and sometimes to counteract seizures and other CNS effects caused by an atropine OD

Front 164

The irreversible cholinesterase inhibitors are ALL ____________.

Back 164

organophosphates

Front 165

What are irreversible cholinesterase inhibitors that have been used therapeutically?

Back 165

echothiophate, isoflurophate, and malathion

Front 166

What are irreversible cholinesterase inhibitors esters of?

Back 166

phosphoric acid

Front 167

Where are organophosphates absorbed?

Back 167

all sites in the body b/c they are highly lipid-soluble

Front 168

What kind of bond to organophosphates form with the catalytic site of cholinesterase?

Back 168

covalent

Front 169

What stabilizes the covalent bond of organophosphates?

Back 169

"aging" --one of the organic groups ("leaving" group) is hydrolyzed from the phosphate

Front 170

What does systemic exposure to organophosphates produce?

Back 170

salivation, lacrimation, miosis, accommodative spasm, bronchoconstriction, bradycardia, intestinal cramps, and urinary incontinence

Front 171

What is the primary clinical use of organophosphates?

Back 171

treatment of ocular conditions

Front 172

Malathion is usually a pesticide but has been used to treat what?

Back 172

head lice

Front 173

How do you manage organophosphate poisoning?

Back 173

decontamination of the pt, support of cardiovascular and respiratory function, use of a cholinergic receptor antagonist to block excessive ACh, and use of pralidoxime (2-PAM) to regenerate cholinesterase

Front 174

How does 2-PAM work?

Back 174

breaks phosphorus bond with cholinesterase and regenerates the enzyme

Front 175

What was the first phosphodiesterase inhibitor to be developed and what did it treat?

Back 175

sildenafil (viagra) for ED

Front 176

How do sildenafil (viagra), tadalafil (cialis), and vardenafil (levitra) work?

Back 176

potentiate vasodilative effect of ACh release from sacral parasymp neurons and increase penile blood flow and facilitate penile erection during sexual stimulation

Front 177

What do the ED drugs inhibit?

Back 177

the breakdown of cyclic GMP by type 5 phosphodiesterase (5-PDE)

Front 178

What is sildenafil's bioavailability?

Back 178

40% PO

Front 179

What reduces the absorption of sildenafil?

Back 179

if taken w/ a high fat meal (does not affect vardenafil or tadalafil)

Front 180

When do the ED drugs start acting?

Back 180

about 30-60 min after admin

Front 181

What is the half-life and duration of action of sildenafil and vardenafil?

Back 181

t1/2 4hrs and action 4-6 hrs

Front 182

What is the t1/2 and duration of action of tadalafil?

Back 182

t1/2 17hrs and action of 36 hrs

Front 183

What are some side effects of the ED drugs?

Back 183

headache, nasal congestion, dyspepsia, myalgia, back pain, and visual disturbances

Front 184

What is a contraindication of 5-PDE inhibitors or the ED drugs?

Back 184

men who take nitroglycerin or another organic nitrate (could cause profound hypotension , reflex tachycardia, and worsening of angina pectoris)

Front 185

What metabolizes sildenafil and related drugs?

Back 185

CYP3A4

Front 186

How do cholinesterase inhibitors indirectly activate cholinergic receptors?

Back 186

by increasing the synaptic concentration of ACh

Front 187

How is organophosphate toxicity treated?

Back 187

atropine and a cholinesterase regenerator called pralidoxime

Front 188

What is able to pass through biological membranes such as the blood-brain barrier?

Back 188

lipid soluble substances

Front 189

What is the only treatment after covalent bond is formed in irreversible inhibitors of AChE?

Back 189

symptomatic treatment

Front 190

Hoe does 2-PAM work?

Back 190

it competes for binding site and can prevent process of making covalent bond permanent

Front 191

What is the effect of low concentrations of cholinesterase inhibition?

Back 191

enhanced cholinergic transmission (enhance ACh effect)

Front 192

What is the effect of high concentrations of cholinesterase inhibition?

Back 192

blocked cholinergic transmission (primarily occurs @ nicotinic receptors)

Front 193

What are the classes of effects of cholinesterase inhibition?

Back 193

muscarinic stimulation of organs, nicotinic stimulation followed by antagonism of ganglionic and neuromuscular transmission, and CNS stimulation of cholinoceptors

Front 194

What are cardiovascular effects of cholinesterase inhibition?

Back 194

bradycardia and cardiogenic shock

Front 195

What are the respiratory effects of cholinesterase inhibitors?

Back 195

bronchoconstricion, increased secretion, and paralysis of diaphragm

Front 196

What are the GI effects of cholinesterase inhibition?

Back 196

increased tone, increased motility, and increased secretions

Front 197

What are the skin effects of cholinesterase inhibition?

Back 197

increased sweating

Front 198

What are the effects on the eye of cholinesterase inhibition?

Back 198

miosis and near accommodation

Front 199

What are the CNS effects of cholinesterase inhibition?

Back 199

tremor, anxiety, confusion, convulsions, and coma (last 2 follow when organs are not reactivated)

Front 200

What is the treatment for poisoning by cholinesterase inhibitors?

Back 200

atropine to block muscarinic effects and pralidoxime for reactivation enzyme then respiratory support

Front 201

Does 2-PAM enter the CNS?

Back 201

NO! it can't so it will not decrease CNS symptoms

Front 202

What are acetylcholine releasers (myenteric neurons)?

Back 202

cisapride and metoclopramide (increase GI motility)

Front 203

How do the ED drugs work?

Back 203

prevent cyclic GMP from breaking down and potentiate the vasodilating effect of ACh via alterations in signal transduction (5-PDE)

Front 204

What will ED drugs in conjuction w/ organic nitrates cause?

Back 204

"unhealthy drop in BP"

DEATH

Front 205

What are anti-muscarinics?

Back 205

alkaloids (atropine, scopolamine--nonselective) and synthetic (some of these are selective)

Front 206

What are some anti-nicotinics?

Back 206

ganglionic blockers, neuromuscular blockers, and partial agonists

Front 207

Are atropine and scopolamine selective?

Back 207

no, they are equilibrium competitive antagonists

Front 208

Which (scopolamine or atropine) produces a dream-like state b/c it crosses the BB-barrier?

Back 208

scopolamine

Front 209

How long is the duration of atropine?

Back 209

about a week

Front 210

What is the first side effect of atropine?

Back 210

dry mouth and decreased sweating

Front 211

What are the stair steps for effects of atropine?

Back 211

1. dry mouth and dec sweating
2. inc HR and very dry mouth
3. blurred vision, bradycardia, and palpitations
4. urinary retention, hot and dry skin, restlessness, and fatigue
5. rapid and weak pulse, ataxia, hallucinations, delirium, and coma

Front 212

What are the effects in the CNS of low doses of anti-muscarinic drugs?

Back 212

drowsiness, amnesia, and dreamless sleep

Front 213

What are the CNS effects of high doses of anti-muscarinic drugs?

Back 213

excitement, confusion/disorientation, hallucinations, and coma

Front 214

What are effects on the eye of muscarinic receptor antagonism?

Back 214

mydriasis, paralysis of accommodation, and increased intraocular pressure (relatively short t1/2 in the eye ~6hrs)

Front 215

What are effects on the cardiovascular system of muscarinic receptor antagonism?

Back 215

tachycardia, antagonized vasodilation and hypotension

Front 216

What are effects on the respiratory system from muscarinic receptor antagonism?

Back 216

bronchodilation and inhibits secretion and reduces mucociliary clearance

Front 217

What are effects on the GI and urinary tracts from muscarinic receptor antagonists?

Back 217

inhibition of GI tone and peristalsis, complete blockade of salivary gland secretion, inhibition of gastric acid secretion, and urinary retention

Front 218

What is an effect on the skin from muscarinic receptor antagonism?

Back 218

inhibits sweating

Front 219

What are the adverse effects of antimuscarinics in order? (a simple saying)

Back 219

"Dry as a bone, Red as a beet, Blind as a bat, and Mad as a hatter"

Front 220

What are some therapeutic uses of muscarinic cholinoceptor antagonists?

Back 220

prevent motion sickness, produce sedation, amnesia, tranq, mydriasis, and cycloplegia during opth. exam, inhibit salivation and resp tract secretions (prior to and during surgery), Tx of cholinomimetic poisoning (esp bradycardia and hypotension)

Front 221

What are some synthetic muscarinic antagonists?

Back 221

ipratropium, tiotropium, pirenzipine, tolterodine, dicyclomine, oxybutynin, cyclopentolate, and tropicamide

Front 222

What are the effects of ipratropium and tiotropium?

Back 222

similar to atropine with less inhibition of mucociliary clearance (caution in pts w/ peanut/soy allergy)

Front 223

What is pirenzipine used for?

Back 223

it is a selective M1 receptor antagonist used to block gastric acid secretion and to treat IBS

Front 224

What is a newer agent used to treat urinary frequency, urgency, and incontinence?

Back 224

tolterodine

Front 225

What are dicyclomine and oxybutynin used for?

Back 225

they are tertiary amines (ionized at most pH so won't cross BBB) used to treat irritable bowel, urinary bladder spasms

Front 226

What are cyclopentolate and tropicamide used for?

Back 226

for ophthalmological exam b/c it's short-acting causing mydriasis and cycloplegia

Front 227

What are 2 sub groups of ganglionic blockers and neuromuscular blockers?

Back 227

non-depolarizing antagonists and depolarizing antagonists

Front 228

What is an example of a partial agonist under nicotinic antagonists?

Back 228

varenicline or chantix

Front 229

Is nicotinic antagonist action very rapid or very slow?

Back 229

very rapid (microseconds)

Front 230

What is hexamethonium?

Back 230

a noncompetitive antagonist of the Nn receptor that blocks the open ion channel state

Front 231

What are trimethaphan and mecamylamine?

Back 231

competitive antagonists of the Nn receptor

Front 232

What is nicotine?

Back 232

agonist at Nn receptors in low concentrations, stimulates catecholamine release and baroreceptors leading to vasoconstriction and tachycardia

Front 233

What do higher concetrations of nicotine lead to?

Back 233

ganglionic blocking action that proceeds through two distinct phases

Front 234

What is Phase I blockade of depolarizing antagonists and what is it due to?

Back 234

persistent depolarizing action, blocks all excitatory input, due to inactivation of voltage-gated sodium channels

Front 235

What is Phase II blockade of depolarizing antagonists and what is it due to?

Back 235

parial repolarization, permits receovery of sensitivity to all other inputs except nicotinic receptors, due to receptor desensitization

Front 236

What are the effects of ganglionic Nn blockade and what do they depend on?

Back 236

both parasymp and symp Nn ganglia are blocked and it depends on the predominant tone

Front 237

What is the predominant tone in arterioles and veins and what is the observed effect from a ganglionic block?

Back 237

sympathetic: vasodilation, postural hypotension, reduced venous return

Front 238

What is the predominant tone in the heart (SA node) and what is the observed effect from a ganglionic block?

Back 238

parasympathetic: tachycardia

Front 239

What is teh predominant tone in the iris and ciliary muscle and what is the observed effect from a ganglionic block?

Back 239

parasympathetic: mydriasis and cycloplegia

Front 240

What is the predominant tone in the GI tract and what is the observed effect from a ganglionic block?

Back 240

parasympathetic: reduced tone and motility, constipation, abdominal discomfort, and nausea

Front 241

What is the predominant tone in the urinary bladder and what is the observed effect from a ganglionic block?

Back 241

parasympathetic: urinary retention

Front 242

What is the predominant tone in the salivary glands and what is the observed effect from a ganglionic block?

Back 242

parasympathetic: dry mouth

Front 243

What is the predominant tone in the sweat glands and what is the observed effect from a ganglionic block?

Back 243

sympathetic (cholinergic): decreased sweating

Front 244

What is the historcal use of canglionic Nn blockers therapeutically?

Back 244

tx of HTN

Front 245

Are ganglionic Nn blockers used therapeutically now?

Back 245

not really b/c of broad range of effects produced by blocking ganglionic transmission in both symp and parasymp ganglia, can be good for smoking cessation

Front 246

What is varenicline (chantix)?

Back 246

partial agonist at Nn receptors producing constant low level of activation

Front 247

Are non-depolarizing antagonists non-competitive or competitive?

Back 247

competitive

Front 248

What are some facts about depolarizing antagonists?

Back 248

do NOT produce analgesia or anesthesia, most are poorly absorbed and do not cross BBB, usually admin IV

Front 249

What are some non-depolarizing neuromuscular blocking drugs?

Back 249

d-tubocurare, mivacurium, doxacurium, pancuronium, vecuronium, and atracurium

Front 250

what is the least selective amonth the non-depolarizing neuromuscular blocking drugs?

Back 250

curare b/c it alos produces some ganglionic blockade and will induce the release of histamine

Front 251

What are some traits of non-depolarizing neuromuscular blocking drugs?

Back 251

competitive inhibition of ACh binding at the Nn receptor and they rapidly develop muscle weakness followed by flaccid paralysis

Front 252

What does adenosine produce when admin?

Back 252

asystole for about 10sec

Front 253

What are 2 depolarizing neuromuscular blocking drugs?

Back 253

succinylcholine and nicotine

Front 254

What do succinylcholine and nicotine do?

Back 254

inhibit activation of Nm receptor similar to the blockade of ganglionic Nn transmission (muscle fasiculations may develope w/ initial depol phase followed by inc weakness and paralysis)

Front 255

Is depolarizing neuromuscular blocking drugs blockade competitive or noncompetitive?

Back 255

noncompetitive and will not be reversed by anticholinesterase agents

Front 256

What is succinylchoine's structure?

Back 256

2 ACh attached

Front 257

What are some therapeutic uses of neuromuscular blocking agents?

Back 257

relax skeletal muscle during surgery, permit reduction in anesthetic doses, assist w/ orthopedic procedures, facilitate procedures involving skeletal muscle (succ will work for hrs. if pt does not have cholinesterase and diaphragm will be paralyzed)

Front 258

What are some adverse effects associated with neuromuscular blocking agents?

Back 258

prolonged apnea (caution if pseudocholinesterase deficiency) and electrolyte imbalances due to excessive K release

Front 259

What is the only neuromuscular blocking agent that cannot be reversed by cholinesterase inhibitors?

Back 259

succinylcholine and it is depolarizing

Front 260

Where is Beta-1 found?

Back 260

heart

Front 261

Where is Beta-2 found?

Back 261

lungs and smooth muscle (especially bronchioles and vasculature of skeletal muscle)

Front 262

What is the primary receptor for chronotropic response, inotropic response, cardiac conduction, and cardiac arrhythmias?

Back 262

Beta-1

Front 263

What is the primary receptor for vasoconstriction?

Back 263

alpha-1

Front 264

What is the primary receptor for skeletal muscle arterial vasodilaton?

Back 264

beta-2

Front 265

What is the primary receptor of vasoconstriction of veins?

Back 265

alpha-1 and some alpha-2

Front 266

What is the primary receptor of radial muscle contraction?

Back 266

alpha-1

Front 267

What is the primary receptor of ciliary muscle relaxation?

Back 267

beta-1

Front 268

What is the primary receptor of bronchiole dilation?

Back 268

beta-2

Front 269

What is the primary receptor for renin release?

Back 269

beta-1

Front 270

What is the primary receptor of ureter contraction?

Back 270

alpha-1

Front 271

What is the primary receptor of GI sphincter contraction?

Back 271

alpha-1

Front 272

What is the primary receptor of intestinal relaxation?

Back 272

alpha-1 and some beta-2

Front 273

What is the primary receptor of decreased insulin release?

Back 273

alpha-2

Front 274

What is the primary receptor of increased insulin release?

Back 274

beta-1

Front 275

What is the primary receptor for activation of lipolysis?

Back 275

beta-1 and beta-3

Front 276

What is the primary receptor of lipolysis inhibition?

Back 276

alpha-2

Front 277

What is the primary receptor of increased glycogenolysis in liver and muscle?

Back 277

beta-2

Front 278

What is the primary receptor of platelet aggregation?

Back 278

alpha-2

Front 279

What is the primary receptor for pilomotor erection, nasal secretion, prostatic capsule, vas deferens, and uterus contraction?

Back 279

alpha-1

Front 280

What is the primary receptor for uterus relaxation?

Back 280

beta-2

Front 281

What is the signal transduction mechanism and the effects of alpha-1?

Back 281

increased IP3 and DAG (elevated intracellular release of Ca) causing contraction of smooth muscle

Front 282

What is the mechanism and effect of alpha-2?

Back 282

decreased cAMP causing inhibition of NE release, decreased secretion of aqueous humor, dec insulin secretion, mediation of platelet aggregation and meiation of central nervous system effects

Front 283

What is the mechanism of B1 and its effects?

Back 283

inc cAMP causing inc in secretion of renin and inc in heart rate, contractility, and conduction

Front 284

What is the mech of B2 and its effects?

Back 284

inc cAMP causing glycogenolysis, relaxation of smooth muscles, and uptake of K in skeletal muscle

Front 285

What is the mech of B3 and its effects?

Back 285

inc cAMP causing lipolysis

Front 286

What is the mech and effect of dopamine 1 receptors?

Back 286

inc cAMP causing relaxation of vascular smooth muscle

Front 287

What is the mech and effects of dopamine 2 receptors?

Back 287

dec cAMP, inc K currents and dec Ca influx causing modulation of neurotransmission in the symp and CNS

Front 288

What is the mech and effect of imidazoline receptors?

Back 288

uncertain, possibly inc DAG causing natriuresis and dec of sympathetic outflow from the CNS

Front 289

What is the response of cutaneous vascular bed to catecholamines?

Back 289

receptors A1 and A2, constriction with epi and NE, no response with ISO

Front 290

What is the response of splanchnic vascular bed to catecholamines?

Back 290

receptors A1, A2, some B2, constriction with epi and NE and weak dilation with ISO

Front 291

What is the response of skeletal muscle vascular bed to catecholamines?

Back 291

receptors A1, A2, and B2, dilation with epi and ISO and constriction with NE

Front 292

What are direct acting adrenergic agonists?

Back 292

alpha agonists anad beta agonists

Front 293

What are indirect acting adrenergic agonists?

Back 293

releasers and reuptake inhibitors (stim release of NE)

Front 294

Does epi have selectivity?

Back 294

no, it has affinity for all receptors

Front 295

What is NE selective for?

Back 295

A1, A2, and B1

Front 296

What is isoproterenol selective for?

Back 296

B1 and B2

Front 297

What is albuterol selective for?

Back 297

B2

Front 298

What is terbutaline selective for?

Back 298

B2

Front 299

What is dobutamine selective for?

Back 299

B1

Front 300

What is phenylephrine selective for?

Back 300

A1 (OTC cold meds)

Front 301

What is clonidine selective for?

Back 301

A2

Front 302

What is alpha-methyl-NE selective for?

Back 302

A2

Front 303

What happens if you substituet meta and para groups with OH-?

Back 303

makes it a catecholamine

Front 304

What happens if you sub at meta, para, or beta?

Back 304

makes it a direct agonist

Front 305

What happens if you sub at alpha?

Back 305

makes it not be a substrate for MAO

Front 306

If you sub anything of 2 carbons what happens?

Back 306

agonist becomes antagonist

Front 307

What happens when you add larger and larger groups on the N?

Back 307

the more B-selective it becomes

Front 308

Muscarinic receptor antagonists compete with ______ for muscarinic receptors at _______ neuroeffector junctions and inhibit the effects of ______ nerve stimulation.

Back 308

ACh, parasympathetic, parasymp

Front 309

What are muscarinic receptor antagonists obtained from plants called and what are some examples?

Back 309

belladonna alkaloids: atropine, scopolamine, and hyoscyamine

Front 310

What are belladonna alkaloids esters of?

Back 310

tropic acid

Front 311

Do people with darker irises bind more or less atropine?

Back 311

more

Front 312

What causes pardoxical slowing of the HR?

Back 312

low doses of atropine

Front 313

What drug reduces lower esphageal muscle tone and can cause GERD?

Back 313

atropine

Front 314

What is now used instead of atropine to treat asthma and why?

Back 314

ipratropium b/c atropine impaired ciliary action and had other negative effects

Front 315

What drug is used to prevent motion sickness?

Back 315

scopolamine

Front 316

Will atropine counteract the effects of nicotinic receptor activation caused by cholinesterase inhibition?

Back 316

no

Front 317

What is hyoscyamine primarily used for?

Back 317

intestinal spasms and other GI disorders

Front 318

What are 2 quarternary amines and what are they used for?

Back 318

ipratropium and tiotropium admin by inhalation for obstructive lung diseases

Front 319

What does glycopyrrolate block?

Back 319

muscarinic receptors

Front 320

Why was tropicamide developed?

Back 320

for topical ocular admin as a mydriatic bc it has a short duration of action

Front 321

Blockade of ________ ganglia causes _______ whereas blockade of ____________ ganglia produces dry mouth, blurred vision, and urinary retention.

Back 321

sympathetic, hypotension, parasympathetic

Front 322

What is occasionally used in cases of hypertensive emergencies?

Back 322

trimethaphan

Front 323

The curariform drugs act as ________ antagonists of ACh at Nm receptors in skeletal muscle accounting for their muscle-_______ effects.

Back 323

competitive, relaxing

Front 324

What patients show pronounced effects of curariform drugs?

Back 324

those that have nueromuscular disorders

Front 325

What curariform drug is seldom used?

Back 325

tubocurarine b/c of adverse effects

Front 326

What curariform drugs have longer duration of action?

Back 326

doxacurium, pancuronium, and tubucuranine

Front 327

What is the only depolarizing agent available for clinical use today and what is its duration of action?

Back 327

succinylcholine, 5-10 minutes

Front 328

Why is succ used?

Back 328

to produce muscle relaxation before and during surgery

Front 329

What can succ cause in patients with unhealed skeletal muscle injury?

Back 329

hyperkalemia sufficient to cause cardiac arrest

Front 330

What do muscarinic receptor antagonists do?

Back 330

relax smooth muscle, increase HR and cardiac conduction, and inhibit exocrine gland secretion

Front 331

What do muscarinic receptor blockers treat?

Back 331

bradycardia, obstructive lung diseases, intestinal spasms, urinary bladder spasms, and peptic ulcers

Front 332

What is used to produce controlled hypotension during surgery and to treat HTN emergencies?

Back 332

trimethaphan

Front 333

What are neuromuscular blockers primarily used for?

Back 333

muscle relaxation during surgery

Front 334

Curariform drugs competitively block _______ receptors in skeletal muscle and do not cause muscle _______, and their effects can be _______ by cholinesterase inhibitors.

Back 334

nicotinic, fasiculations, reverse

Front 335

Does succ produce muscle fasiculations?

Back 335

yes, followed by muscle paralysis and cannot be reversed by cholinesterase inhibitors

Front 336

Where are alpha-1 receptors primarily located?

Back 336

in postjunctional smooth muscle

Front 337

Where are alpha-2 receptors primarily located?

Back 337

on presynaptic neurons as well as in some postsynaptic tissues and blood platelets

Front 338

What are autoreceptors?

Back 338

A2, leads to feedback inhibition of NE release from nerve terminals

Front 339

What does activation of B1 produce?

Back 339

cardiac stimulation

Front 340

What does B2 do?

Back 340

mediates relaxation of bronchial, uterine, and vascular smooth muscle

Front 341

What do D1 receptors do?

Back 341

mediate muscle relaxation in vascular smooth muscle

Front 342

What do D2 receptors do?

Back 342

modulate neurotransmitter release

Front 343

Where are teh imidazoline receptors found?

Back 343

in the CNS and a number of peripheral tissues

Front 344

How do indirect-acting agonists work?

Back 344

increase stim of adrenergic receptors by inc concentration of NE at symp neuroeffector junctions

Front 345

How does cocaine work?

Back 345

binds and inhibits catecholamine transporter protein located in plasma membrane of the presynaptic symp neuron and thereby inhibits the neuronal reuptake of NE and increases its synaptic concentration

Front 346

Do catecholamines have good PO bioavailability?

Back 346

no, and short half-lives

Front 347

Epi is a potent ______ at all alpha and beta receptors

Back 347

agoinst

Front 348

Is dopamine a direct or indirect acting agoinst?

Back 348

both

Front 349

What are the cardiovascular effects of NE?

Back 349

vasoconstriction and inc peripheral resistance inc systolic and diastolic BP

Front 350

Does epi increase both systolic and diastolic BP?

Back 350

no it may decrease DBP, buy SBP is due to inc HR and cardiac output

Front 351

Low doses of dopamine selectively activate ____ receptors in renal and other vascular bed while higher doses activate ____ receptors in the ____.

Back 351

D1, B1, heart

Front 352

What drugs can treat shock?

Back 352

catecholamines

Front 353

Will vasopressors be effective if hypovolemia is present?

Back 353

no

Front 354

What is used to treat septic or cardiogenic shock?

Back 354

dopamine

Front 355

What is used to treat anaphylactic shock?

Back 355

epi

Front 356

Do amphetamines have high lipid solubility?

Back 356

yes

Front 357

Where is ephedrine well absorbed?

Back 357

gut

Front 358

What are some side effects of ephedrine and pseudoephedrine?

Back 358

tachycardia caused by B1 receptor stimulation, inc BP, and urinary retention

Front 359

What do A1 cause?

Back 359

vasoconstriction, dilation of pupils, and contraction of the bladder sphincter muscle

Front 360

What do A2 cause?

Back 360

inhibits release of NE from spym neurons, dec secretion of aquaeous humor, and dec secretion of insulin

Front 361

What does B1 cause?

Back 361

cardiac stimulation, and inc secretion of renin

Front 362

What does B2 cause?

Back 362

smooth muscle relaxation

Front 363

What are the catecholamines?

Back 363

NE, epi, isoproterenol, dopamine, and dobutamine (rapidly metabolized and admin parenterally)

Front 364

Does dopamine increase renal blood flow?

Back 364

yes

Front 365

What are noncatecholamines resistant to degradation by?

Back 365

COMT

Front 366

What do imidazoline compounds activate?

Back 366

A-adrenergic and imidazoline receptors

Front 367

What are examples of imidazoline compounds?

Back 367

oxymetazoline, clonidine, and apraclonidine

Front 368

What increases the synaptic concentration of NE?

Back 368

indirect-acting adrenergic receptor agonists

Front 369

What indirectly activates reverse NE transport by catecholamine transportor whearas ______ blocks it?

Back 369

amphetamine, cocaine

Front 370

What are mixed-acting agoinsts used for?

Back 370

nasal decongestants

Front 371

What are some direct-acting catecholamines?

Back 371

dobutamine, dopamine, epinephrine, isoproterenol, and norepinephrine

Front 372

What is the pharm effect and clinical use of dobutamine?

Back 372

cardiac stim and vasodilation of B1 receptors used in cardiogenic shock, acute heart failure, and cardiac stim during heart surgery

Front 373

What is the pharm effect and clinical use of dopamine?

Back 373

renal vasodilation (D1), cardiac stimu (B1), and inc BP (B1 and A1)used in cardiogenic shock, septic shock, heart failure, and adjunct to fluid admin in hypovolemic shock

Front 374

What are the pharm effects and clinical use of epi?

Back 374

vasoconstriction and inc BP (A1), cardiac stim (B1), and bronchodilation (B2) used in anaphylactic shock, cardiac arrest, v-fib, reduction in bleeding during surgery, and prolongation of of the action of local anesthetics

Front 375

What are the pharm effects and clinical uses of isoproterenol?

Back 375

cardiac stim (B1) and bronchodilation (B2) used in asthma, refractory AV block and refractory bradycardia

Front 376

What are the pharm effects an clinical uses of NE?

Back 376

vasoconstriction and inc BP (A1) used in hypotension and shock

Front 377

What are some direct-acting noncatecholamines?

Back 377

albuterol, apraclonidine, clonidine, oxymetazoline, phenylephrine, ritodrine, terbutaline

Front 378

What are the pharm effects and clinical uses of albuterol?

Back 378

bronchodilation (B2) used for asthma

Front 379

What are the pharm effects and clinical uses of apraclonidine?

Back 379

dec aqueous humur formation (A2) used in chronic open-angle glaucoma

Front 380

What are the pharm effects and clinical uses of clonidine?

Back 380

dec symp outflow from CNS (A2 and imidazoline) used in chronic HTN

Front 381

What are the pharm effects and clinical uses of oxymetazoline?

Back 381

vasoconstriction (A1) used in nasal and ocular decongestion

Front 382

What are the pharm effects and clinical uses of phenylephrine?

Back 382

vasoconstriction, inc BP, and mydriasis (A1) used in nasal decongestion in viral and allergic rhinitis, ocular decongestion in allergic conjunctivitis, mydriasis during ophthalmologic exam, maintenance of BP during surgery, and treatment of drug-induced and neurogenic shock

Front 383

What are the pharm effects and clinical uses of ritodrine?

Back 383

bronchodilation and uterine relaxation (B2) used in asthma and premature labor

Front 384

What are the pharm effects and clinical uses of terbutaline?

Back 384

bronchodilation and uterine relaxation (B2) used in asthma and premature labor

Front 385

What are some indirect-acting agents?

Back 385

amphetamine and cocaine

Front 386

What are the pharm effects and clinical uses of amphetamine?

Back 386

inc in NE release used in CNS effects

Front 387

What are the pharm effects and clinical uses of cocaine?

Back 387

inhibition of NE uptake used in local anesthesia

Front 388

What are some mixed-acting agents?

Back 388

ephedrine, phenylpropanolamine, and pseudophedrine

Front 389

What are the pharm effects and clinical uses of mixed-acting agents?

Back 389

vasoconstriction (A1) used in nasal decongestion in viral and allergic rhinitis

Front 390

What are some alpha selective antagonist compounds?

Back 390

phentolamine, phenoxybenzamine, prazosin, tamsulosin, yohimbine, and idazoxan

Front 391

What are some beta selective antagonist compounds?

Back 391

propanolol, metoprolol, atenolol, butoxamine, labetalol (some affinity for A1) and carvedilol (some affinity for A1)

Front 392

What are some adverse effects of interference w/ symp function?

Back 392

postural hypotension, sedation and/or depression, inc GI motility and diarrhea, respiratory difficulties, inc blood vol. and Na retention, and sexual dysfunction

Front 393

Is the structure of alpha adrenoceptor antagonists predictable?

Back 393

no

Front 394

What are some alpha adrenergic receptor antagonists?

Back 394

doxazosin, phenoxybenzamine, phentolamine, prazosin, and terazosin

Front 395

What are the mech, pharm effects, and clinical uses of doxazosin?

Back 395

competitive A1 blocker, causing vasodilation, dec vascular resistance and BP, relaxes bladder neck and prostate, used in HTN, urinary retention due to BPH

Front 396

What are the mech, pharm effects, and clinical uses of phenoxybenzamine?

Back 396

noncompetitive A1 and A2 blocker, causing vasodilation, dec vascular resistance and BP and relaxes bladder neck and prostate, used in HTN episodes due to pheochromocytoma, urinary retention due to BPH

Front 397

What are the mech, pharm effects, and clinical uses of phentolamine?

Back 397

competitive A2 and A1 blockers, causing vasodilation, dec vascular resistance and BP, used in HTN episodes due to pheochromocytoma, necrosis and ischemia after injection of A-adrenergic receptor agonists

Front 398

What are the mech, pharm effects, and clinical uses of prazosin?

Back 398

competitive A1 blocker, causing vasodilation, dec vascular resistance and BP, and relaxes bladder neck and prostate, used in HTN, urinary retention due to BPH

Front 399

What are the mech, pharm effects, and clinical uses of terazosin?

Back 399

competitive A1 blocker, causing vasodilation, dec vascular resitance and BP, and relaxes bladder neck and prostate, used in HTN, urinary retention due to BPH

Front 400

What are drugs that end in -osin?

Back 400

selective A1 blocking agent

Front 401

What are some adverse effects of alpha adrenoceptor antagonists?

Back 401

postural hypotension, first dose syncope (HTN drugs), tachycardia, failure of ejaculation, and nasal stuffiness

Front 402

What do alpha and beta adrenergic receptor antagonists do?

Back 402

they both interact with symp just at different parts, both dec BP, alpha dec peripheral vascular resistance and beta dec cardiac output

Front 403

What are some B-blockers?

Back 403

acebutolol, atenolol, esmolol, metoprolol, nadolol, pindolol, propanolol, timolol

Front 404

What is the pharm effect of B-blockers?

Back 404

dec cardiac rate, output, AV node conduction, and O2 demand, dec BP, and timolol also dec intraocular pressure

Front 405

What are most B-blockers used for?

Back 405

to treat HTN, angina pectoris, AMI, and cardiac arrhythmias

Front 406

What are some non-selective B-blockers?

Back 406

nadolol, pindolol, propranolol, and timolol

Front 407

What are some selective B1-blockers?

Back 407

acebutolol, atenolol, esmolol, and metoprolol

Front 408

What is a side effect of B-blockers especially if lipid soluble?

Back 408

depression

Front 409

What are some therapeutic uses of B-adrenoceptor antagonists?

Back 409

HTN, angina pectoris, cardiac arrhythmias, glaucoma, protection following MI, CHF, and migraine

Front 410

What are some contraindications of B-adrenoceptor antagonists?

Back 410

CHF, asthma, cardiac conduction disturbances, and hypoglycemia

Front 411

What are some adverse effects of B-adrenoceptor antagonists?

Back 411

exercise intolerance, tiredness, insomnia, hallucinations, and sexual dysfunction

Front 412

What are the mech, pharm effects, and clinical uses of carvedilol?

Back 412

B1, B2, and A1 blocker, causing vasodilation, dec HR and BP in pt w/ HTN, inc cardiac output in pt w/ heart failure, used for HTN and heart failure

Front 413

What are the mech, pharm effects, and clinical uses of labetalol?

Back 413

B1, B2 blocker w/ MSA and A1 blocker, causing vasodilation, dec HR and BP, used in HTN

Front 414

What are diuretics?

Back 414

agents that elevate the rate of urine excretion

Front 415

What are physiologic effects of diuretics on electrolytes?

Back 415

most inhibit Na reabsorption, several inc kaliuresis, and alter excretion of Mg, Ca, Cl, and bicarb

Front 416

What are diuretics used to manage?

Back 416

edema (CV, renal, endocrine), HTN, glaucoma

Front 417

What is the functional unit of the kidney?

Back 417

nephron

Front 418

What are the processes regulating ions, nutrients, and toxic metabolites?

Back 418

glomerular filtration, secretion, and reabsorption

Front 419

What is nephron function regulated by?

Back 419

hormones, neurotransmitters, drugs, and prostaglandins

Front 420

What is the function of the nephron?

Back 420

reabsorption of Na and other electrolytes into circulation via active and passive processes

Front 421

What is the direction of ion channels determined by?

Back 421

electrochemical gradient

Front 422

How are proteins transported?

Back 422

symporters and antiporters

Front 423

What happens in the proximal tubule?

Back 423

reabsorption of Glu, AAs, and other organic solutes, secretion of organic acids, bases, and drugs into lumen (drugs targeting site: CAIs, osmotic diuretics)

Front 424

What happens in the loop of henle?

Back 424

reabsorption of NaCl, absorption of H2O, (drugs targeting site: loop diuretics)

Front 425

What happens in the distal tubule?

Back 425

reabsorbs 5-10% of NaCl (drugs targeting site: thiazides)

Front 426

What happens in the collecting duct?

Back 426

adjustment of final comp and vol. of urine, regulation of extracellular fluid comp and pH, maintenance of homeostasis, Na retention, H2O conservation and urine concentration (durgs targeting site: K sparing drugs)

Front 427

What is the most commonly used diuretics?

Back 427

thiazides

Front 428

What are some facts about thiazides?

Back 428

sulfonamide compounds, favorable PO bioavailability, moderate natriuretic effect, few adverse effects

Front 429

What are some thiazide drugs?

Back 429

hydrochlorothizide (Esidrix), inapamide (Lozol), and metolazone (Mykrox)

Front 430

How do thiazides work?

Back 430

inhibit Na/Cl symporter, inc NaCl-enriched fluid deliverd to late DT and collecting duct, K secretion and Na reabsorption and kaliuresis

Front 431

What can hypokalemia, an adverse effect of thiazide, lead to?

Back 431

hypokalemic metabolic alkalosis

Front 432

What are some metabolic abnormalities from thiazide?

Back 432

inc blood glucose levels (caution in diabetes), inc uric acid levels (consider gout), inc serum lipid levels (consider hyperlipidemia)

Front 433

What are indications for thiazides?

Back 433

CV and renal diseases: HTN, edema, nephrolithiasis, nephrogenic diabetes insipidus, and impaired renal function

Front 434

Do thiazides prolong life?

Back 434

yes

Front 435

What are loop diuretics?

Back 435

all but one are sulfonamide compounds

Front 436

What are the sulfonamide loop diuretics?

Back 436

furosemide (Lasix), bumetanide (Bumex), and Torsemide (Demadex)

Front 437

What is the 1 non-sulfonamide loop diuretic?

Back 437

Ethacrynic acid (Edecrin)

Front 438

What are some facts about loop diuretics?

Back 438

favorable PO bioavailability, actively secreted into nephron, act on ascending loop of Henle, greater natriuretic effect than other diuretics, used when intensive diuresis is needed and cannot be affected by other diuretics, very high efficacy

Front 439

What is the most potent diuretic?

Back 439

loop, dose-dependent diuretic effect throughout therapeutic dosage range

Front 440

How do loop diuretics work?

Back 440

inhibit Na, K, Cl symporter, inc K secretion and Na reabsorption, kaliuresis

Front 441

What are adverse effects of loop diuretics?

Back 441

dec K, Ca, and Mg, metabolic alkalosis, inc blood glu, inc uric acid, ototoxicity

Front 442

What are some drug interactions of loop diuretics?

Back 442

diuretic effect dec by NSAIDs and admin with ACE inhibitors may cause excessive hypotension

Front 443

What are indications for loop diuretics?

Back 443

pulmonary edema, renal impairment, edema caused by HF, cirrhosis, and other disorders, HTN (thiazides are usually prefereed b/c better long term), hypercalcemia

Front 444

Sulfonamide loop diuretics are admin by?

Back 444

oral or IV

Front 445

When are non-sulfonamide loop diuretics used?

Back 445

seldomly b/c causes more ototoxicity, when pt is sensitive to sulfonamide derivatives

Front 446

What are the 2 types of K-sparing drugs?

Back 446

epithelial Na channel antagonists and aldosterone receptor antagonists

Front 447

How doe epithelial Na channel blockers work?

Back 447

promote natriuresis and dec kaliuresis by inhibiting Na reabsorption and indirectly dec K secretion

Front 448

What are the prototypes of epithelial Na channel blockers?

Back 448

amiloride (Midamor)-renally excreted and triamterene (dyrenium)-metabolized

Front 449

What are indications for epithelial Na channel blockers?

Back 449

prevention/Tx of hypokalemia caused by thiazide and loop diuretics

Front 450

What are adverse effects of epithelial Na channel blockers?

Back 450

hyperkalemia associated with dietary K, drugs that inc serum K, and renal disorders predisposing pt to hyperkalemia

Front 451

How do aldosterone receptor antagonists work?

Back 451

promote natriuresis and dec kaliuresis by competitively block binding of aldosterone to MR, inhibit transcription of genes encoding proteins of epithelial Na channels, Na, K ATPase and related compounds involved in Na reabsorption and K secretion

Front 452

What are 2 aldosterone receptor antagonists?

Back 452

spironolactone (aldactone) and eplerenone (inspra)

Front 453

What are some indications for spironolactone?

Back 453

prevention of hypokalemia, 1st degree hyperaldosteronism in HF, polycystic ovary dz, and hirsutism

Front 454

What are adverse effects of spironolactone?

Back 454

hyperkalemia, gynecomastia, and impotence

Front 455

What is eplerenone?

Back 455

new drug that has less endocrine side effects and counteracts effects of excessive aldosterone in HF pts

Front 456

How do osmotic diuretics work?

Back 456

inc osmotic pressure of plasma, attract H2O from interstitial, transcellular fluids, and ocular fluids, dec intraocular vol and pressure, attract H2O from renal tubules, dec tubular Na concentration and conc gradient between tubular fluid and cells, dec Na reabsorption

Front 457

How is glycerol (osmotic diuretic) eliminated and when is it used?

Back 457

metabolized, used in cerebral edema and acute glaucoma (PO)

Front 458

How is mannitol (osmitrol) eliminated and when is this osmotic diuretic used?

Back 458

renal excretion, acute glaucoma (IV), oliguria of acute renal failure, renal transplantaion, adjunct to IV fluids to maintain renal functino, drug OD to inc renal excretion of toxins

Front 459

What are adverse effects of mannitol?

Back 459

excessive plasma volume expansion (due to drug being admin too rapidly or excessive IV fluid vol), can lead to HF, pulmonary congestion, and edema

Front 460

What do carbonic anhydrase inhibitors (CAIs) inhibit?

Back 460

reabsorption of sodium bicarbonate

Front 461

What are 2 CAIs?

Back 461

acetazolamide (diamox) and dorzolamide (trusopt)

Front 462

How does acetazolamide work?

Back 462

PO-inhibits CA throughout body and eliminated renally

Front 463

How does dorzolamide work?

Back 463

ophthalmic solution (topical)-partly absorbed from eye in circulation, dec aqueous humor secretion, partly metabolized before excretion in urine (use in chronic ocular HTN and open-angle glaucoma)

Front 464

What are other indications of CAIs?

Back 464

alkalinization of urine, high-altitude sickness (metabolic acidosis counteracts resp alkalosis, counteract fluid retention, preent dec in pH of CSF), epilepsy (inc seizure threshold)

Front 465

What are adverse effects of CAIs?

Back 465

CNS effects (drowsiness and paresthesia), hypokalemia, hyperglycemia, hypersensitivity, blood cell deficiencies

Front 466

What are drug interactions of CAIs?

Back 466

drug toxicity: inc pH of renal tubular fluid and alkalinized urine (dec excretion of WB)

Front 467

What are 2 causes of edema?

Back 467

inc hydrostatic pressure in capillary beds (HF and certain reanl diseases cause Na and H2O retention) and inadequate colloid osmotic pressure in plasma (severe dietary protein deficiency and hepatic diseases, cirrhosis, nephrotic syndrome)

Front 468

What is the first degree tx for edema?

Back 468

correct the underlying disorder and restore plasma osmotic pressure and hydrostatic pressure to normal values

Front 469

How do you manage edema in acute life-threatening situations?

Back 469

immediate tx w/ diuretics and other drugs to prevent tissue hypoxia, injury, and death

Front 470

How do you treat milder forms of edema?

Back 470

diuretics as short-term adjunct to move fluid

Front 471

How do you manage mild peripheral forms of edema?

Back 471

usually no pharmacologic tx by correcting underlying problem or removing edema-causing drug

Front 472

The therapeutic effects of the antagonists primarily are caused by blockade of ___ and ___ whereas adverse effects tend to be related to blockade of ___ and ___ receptors.

Back 472

A1 or B1, A2 or B2

Front 473

What is the duration of action of phenoxybenzamine?

Back 473

3-4 days b/c of its stable covalent bonding w/ A-adrenergic receptors

Front 474

After IV admin of phentolamine, when does it start working?

Back 474

immediately, and duration is 10-15min, after IM or SC admin onset is 15-20min and duration is 3-4 hours

Front 475

What are the adverse effects of phentolamine mostly caused by?

Back 475

excessive vasodilation

Front 476

What is the duration of action of prazosin?

Back 476

about 6 hours

Front 477

What is the duration of action of doxazosin and terazosin?

Back 477

about 30 hrs and 20 hrs respectively

Front 478

How are B-blockers admin?

Back 478

all can be PO and propranolol can be parenterally

Front 479

Of the nonselective B-blockers, what is teh only one that has intrinsic sympathomimetic activity or partial agonist activity?

Back 479

pindolol--enables it to exert a weak agonist effect on B-receptors

Front 480

What has a greater local anesthetic effect than other B-blockers?

Back 480

propranolol

Front 481

Do alpha or beta blockers reduce BP?

Back 481

both

Front 482

What are nonselective alpha blockers mainly used to treat?

Back 482

HTN episodes due to pheochromocytoma

Front 483

What are A1-blockers used to treat?

Back 483

chronic essential HTN or treat urinary retention caused by BPH

Front 484

Do selective or nonselective B-blockers cause less bronchoconstriction?

Back 484

selective

Front 485

What does carvedilol block?

Back 485

A and B receptors and is useful in tx of MI and heart failure

Front 486

What is natriuresis?

Back 486

excretion of sodium in the urine

Front 487

Where does urine formation begin?

Back 487

glomerular filtration

Front 488

How much of filtered sodium bicarb is reabsorbed in the proximal tubule?

Back 488

85%

Front 489

Where do thiazide diuretics primarily work?

Back 489

early portion of the distal tubule

Front 490

Why are loop diuretics highly effective in tx of pulmonary edema?

Back 490

b/c of vasodilation that occurs when they are admin IV

Front 491

Is spironalactone absorbed from the gut?

Back 491

yes, and has a long duration of action despite short t1/2

Front 492

What is the primary adverse effect of mannitol?

Back 492

plasma volume expansion, occurs when drug is admin too rapidly or w/ too large a vol of IV fluid

Front 493

How do most diuretics work?

Back 493

inhibit reabsorption of Na from various sites in the nephron

Front 494

Where do thiazides work?

Back 494

distal tubule, dec Ca excretion

Front 495

Where do loop diuretics work?

Back 495

ascending limb and inc Na, Ca, Mg, and K excretion

Front 496

Where do K-sparing drugs work?

Back 496

collecting duct

Front 497

Where do osmotic diuretics work?

Back 497

inc osmotic pressure of plasma and retain water in nephron

Front 498

Where do CAIs work?

Back 498

weak diuretics that inhibit sodium bicarb reabsorption from the proximal tubule (can cause a mild form of metabolic acidosis)

Front 499

What can untreated hypertension lead to?

Back 499

blood vessel damage, accelerated atherosclerosis, LV hypertrophy, then ischemic heart disease, stroke, HF, and renal failure

Front 500

How do you calculate BP?

Back 500

cardiac output x total peripheral resistance

Front 501

Does prehypertension need drug tx?

Back 501

only if diabetic and lifestyle changes fail

Front 502

What is short term control of BP regulation?

Back 502

monitor momentary changes such as during exercise and stress

Front 503

What is long term control of BP regulation?

Back 503

sets BP levels for weeks or months like in chronic disease state

Front 504

What systems primarly regulate BP?

Back 504

autonomic nervous system, renin angiotensin system, and local/autoregulatory mechanism

Front 505

What system controls short term BP?

Back 505

autonomic nervous system

Front 506

Where are sensitive baroreceptors located?

Back 506

in the wall of the carotid artery and aortic arch respond to variations in Bp

Front 507

What do baroreceptors do when BP falls?

Back 507

send fewer impulses to CV center increasing symp and dec parasymp output to heart resulting in tachycardia and vasoconstriction

Front 508

Are baroreceptors efficient for controlling BP long term?

Back 508

no, b/c they reset to new pressures in 1-2 days

Front 509

What system is good for regulating BP long term?

Back 509

renin-angiotensin-aldosterone system (RAAS) - by altering plasma volume

Front 510

What does angiotensin II do?

Back 510

it is a potent vasoconstrictor that releases aldosterone and contributes to Na/Water retention and elevation of blood vol and finally BP returns to previous levels

Front 511

What is the metabolic theory of autoregulation?

Back 511

excessive blood flow provides other nutrients, vasoconstriction, and O2 which constricts blood vessels

Front 512

What is the myogenic theory of autoregulation?

Back 512

high blood flow produces a sudden stretch in the blood vessels which causes the smooth muscle of the vessels to constrict

Front 513

What local substances can dilate small vessels in the immediate viscinity?

Back 513

endothelin, NO, PGI2

Front 514

What are the blood bourne substances that can dilate small vessels in the immediate viscinity?

Back 514

ANP, BNP, epi, ADH

Front 515

What are some adrenergic receptor blockade?

Back 515

alpha blockers (prazosin, terazosin, phenoxybenzamine, phentalamine), beta blockers (propranolol, metoprolol, carvedilol)

Front 516

What are some central adrenergic nerve inhibitors?

Back 516

alpha2 agonists (methyldopa, clonidine, guanabenx, guanfacine) and I2 agonists (rilmenidine and moxonidine)

Front 517

What are 2 peripheral adrenergic nerve inhibitors?

Back 517

guanethidine and gunadrel

Front 518

What is a mixed central and peripheral inhibitor?

Back 518

reserpine

Front 519

What are some arterial vasodilators?

Back 519

hydralazine, minoxidil, and diazoxide

Front 520

What is one mixed venous/arterial vasodilators?

Back 520

sodium nitroprusside

Front 521

What groups of drugs act on RAAS?

Back 521

converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and aldosterone inhibitors

Front 522

What are some ACE-I?

Back 522

captopril, lisinopril, and enalapril

Front 523

What are some ARBs?

Back 523

candesartan, irbesartan, losartan, telmisartan, valsartan

Front 524

What is a renin inhibitor?

Back 524

aliskiren

Front 525

What are 2 aldosterone inhibitors?

Back 525

eplerenone and spironolactone

Front 526

What CCBs are more selective on vascular smooth muscles?

Back 526

dihydropyridine class and nifedipine

Front 527

What CCBs are more cardioselective?

Back 527

verapamil and dilitazem

Front 528

What do anti-HTN drugs act on to decrease BP?

Back 528

kidneys, SNS, RAA axis and vascular smooth muscle

Front 529

What is the first line therapy for HTN?

Back 529

beta blockers

Front 530

What are some cardioselective B-Blockers?

Back 530

atenolol, metoprolol, esmolol, and betaxol

Front 531

What are some non-selective B-blockers?

Back 531

nadolol, pindolol, propranolol

Front 532

Can beta blockers be used with co-existing MI and angina?

Back 532

yes

Front 533

What is the MOA of B-blockers?

Back 533

dec HR, dec force of contraction, dec CO, dec BP, dec renin release from kidney and cause vasodilation

Front 534

What B-blocker can enter the CNS?

Back 534

propranolol (may cause depression)

Front 535

What are some side effects of b-blockers?

Back 535

CNS effects: depression, fatigue, insomnia, and hallucination AND others: hyperkalemia, bradycardia, rebound phenomenon

Front 536

When are B-blockers contraindicated?

Back 536

asthma, diabetes, pheochromocytoma

Front 537

What drugs can B-blockers interact with and what is the response?

Back 537

NSAIDs (less hypotensive actions), K sparing (hyperkalemia), and varapamil/diltiazem (bradycardia/AV block)

Front 538

How do you avoid rebound from B-blockers?

Back 538

taper dose instead of abruptly stopping

Front 539

What B-blocker is less lipophilic and has less CNS side effects?

Back 539

atenolol

Front 540

What B-blocker is used in pts undergoing surgery and HTN emergencies?

Back 540

esmolol

Front 541

What b-blocker is indicated in chronic HTN and HTN emergencies but may cause orthostatic hypotension?

Back 541

labetalol

Front 542

What B-blocker has anti-oxidant properties?

Back 542

carvedilol

Front 543

What is the 2nd line of defense against HTN?

Back 543

alpha-adrenergic blockers

Front 544

What is the MOA of A-blockers?

Back 544

inhibits sympathetic activation of A receptors on vascular smooth muscles (dec vascular tone & peripheral resistance)

Front 545

What are 3 selective A-blockers?

Back 545

prazosin, terazosin, doxazosin

Front 546

What is a non-selective A-blocker?

Back 546

phenoxybenzamine

Front 547

What are some side effects of A-blockers?

Back 547

reflex activation of SNS (inc tachycardia, inc force of contraction, inc O2 demand, and inc NE levels), no protection against ventricular arrhythmias, and less useful in pts w/ ischemic dz, activation of RAAS (fluid retention), first dose syncope, and orthostatic hypotension

Front 548

What are some centrally acting drugs?

Back 548

clonidine (prototype), methyldopa, guanabenz, and guanfacine

Front 549

What is the MOA of clonidine?

Back 549

activation of auto A-adrenergic and non-adrenergic I2 receptors

Front 550

What is teh MOA of methyldopa?

Back 550

converted to an active metabolite methylnorepinephrine

Front 551

What is the MOA of centrally acting drugs?

Back 551

dec symp outflow from brain stem to heart, blood vessels, and other tissues (dec PVR, dec HR, dec in CO)

Front 552

What are clinical uses of centrally acting drugs?

Back 552

HTN (methyldopa can be used in preg), clonidine (HF, alcohol w/drawal, diagnosis of pheochromocytoma)

Front 553

What are adverse effects of centrally acting drugs?

Back 553

sedation, dry mouth, other CNS effects, sever rebound HTN, tolerance, water retention, immunological rxn

Front 554

What are interactions with centrally acting drugs?

Back 554

TCAs can block antiHTN effects, EtOH or CNS depressants inc sedative effects

Front 555

What are 2 second generation centrally acting drugs?

Back 555

moxonidine and rilmenidine (activate non-adrenergic imidazoline receptors in RVLM)

Front 556

What is good about selective imidazoline receptor agonists?

Back 556

it dec BP but w/ less sedation and dry mouth than clonidine

Front 557

What are effects of A-adrenergic receptor antagonists?

Back 557

dec PVR, inc CO, inc blood vol, dec plasma renin activity, dec LVH, no chg in serum K, dec chol, dec LDL, inc HDL, dec triglycerides

Front 558

What are the effects of B-adrenergic receptor antagonists?

Back 558

dec PVR, dec CO, dec blood vol, dec plasma renin activity, dec LVH, slight in in serum K, inc chol, inc LDL, variable chg in HDL, inc triglycerides

Front 559

What are the effects of the centrally acting drugs?

Back 559

dec PVR, dec CO, inc blood vol (except guanabenz and guanfacine), dec plasma renin activity, dec LVH, no chg in serum K, chol, LDL, HDL, or triglycerides

Front 560

What are 2 adrenergic neuron blockers?

Back 560

quanethidine and guanadrel (don't cross BBB)

Front 561

What is the MOA of adrenergic neuron blockers?

Back 561

drugs pump in the vesicles, localize at teh wall of vesicles, and prevents release of neurotransmitters

Front 562

What are clinical uses of adrenergic neuron blockers?

Back 562

HTN emergencies

Front 563

What are side effects of adrenergic neuron blockers?

Back 563

diarrhea, water retention, orthostatic hypotension (b/c symp is blocked), sexual dysfunction

Front 564

What are drug interactions with adrenergic neuron blockers?

Back 564

cocaine, tyramine, TCA (dec hypotensive effects), EtOH (inc hypotensive effects), cold medicine (severe HTN rxn)

Front 565

Do sympatholytic drugs cause water retention?

Back 565

yes most do

Front 566

What does reserpine do?

Back 566

depletes stores of catecholamines and 5HT in CNS and peripheral tissues including the adrenal medulla (1hr after admin and max after 24hrs)

Front 567

What are side effects of reserpine?

Back 567

depression, ulcer, sedation, water retention, and migraine

Front 568

What drugs interact with reserpine?

Back 568

cold medicines

Front 569

What are the 3 primary stimuli to renin secretion?

Back 569

SNS activation of B1-receptors on renal juxtaglomerular cells, dec BP & wall tension in renal afferent arterioles, dec NaCl reabsorption by the renal macula densa

Front 570

How does the RAA normally work?

Back 570

BP dec and renin relase initiates a cascade that returns BP to its normal "set point"

Front 571

Does hyper- or hypotension release renin?

Back 571

HYPOtension

Front 572

Angiotensin II activates ___ and ____ receptors causing inc production of ____ and ______ acid metabolites and dec production of _______.

Back 572

AT1 and AT2, IP3 and arachidonic

Front 573

What receptors also mediate cardiac, renal, and CNS effects?

Back 573

AT1

Front 574

What does ACE also do?

Back 574

catalyzes the inactivation of the endogenous VD bradykinin

Front 575

When are drugs acting on RAAS especially effective?

Back 575

when plasma renin activity is high (ACE-I, ARBs, renin inhibitors, and aldosterone antagonists)

Front 576

What is teh MOA of ACE-I?

Back 576

block formation of the VC angiotensin II and the degradation of teh VD bradykinin (dry cough)

Front 577

What is the hypotensive effect of ACE-I potentiated by?

Back 577

inc renal prostaglandin synthesis

Front 578

What are pharm effects of ACE-I?

Back 578

dec renal Na retention, inc renal K rentention, inc serum K levels (no alteration in lipid profiles)

Front 579

What are 2 indication for ACE-I?

Back 579

mild to severe HTN and pts w/ coexisting HF, MI, or diabetic nephropathy

Front 580

What are adverse effects of ACE-I?

Back 580

fetal and neonatal morbidity and mortality, renal failure in pts w/ bilateral renal artery stenosis, dry cough, pruiritic rash, abnormal taste sensation, angioedema, and neutropenia

Front 581

What are interactions of ACE-I?

Back 581

diruetics augment antiHTN, K sparing and K supplements inc serum K, lithium cmpds inc serum lithium, NSAIDs can block effects of ACE-I

Front 582

What is a good combo with ACE-I?

Back 582

thiazides b/c it augments effects

Front 583

What are 3 classes of ACE-I?

Back 583

sulfhydryl, phosphoryl, and carboxyl derivatives

Front 584

What is a sulfhydryl ACE-I?

Back 584

captopril (short-acting)

Front 585

What is a phosphoryl ACE-I?

Back 585

fosinopril

Front 586

What are some carboxyl derivatives ACE-I?

Back 586

benazepril, enalapril, lisinopril, quinapril, and ramipril

Front 587

Are ACE-I converted to active metabolites?

Back 587

yes except for captopril and lisinopril

Front 588

How are ACE-I admin?

Back 588

orally, but enalaprilat can be IV

Front 589

What happens with PO ACE-I?

Back 589

significant 1st pass hepatic inactivation, bioavailabiltiy 25-75%

Front 590

How do ARBs work?

Back 590

block AT1 receptors in vascualr smooth muscle and adrenal cortex causing vasodilation and dec aldosterone secretion

Front 591

What are some orally effective ARBs?

Back 591

candesartan, irbesartan, losartan, valsartan

Front 592

Why are ARBs good to use?

Back 592

they are as effective as ACE-I but they don't cause the cough, have few adverse effects (dec risk of CV consequences of HTN, no inc in serum glucose, uric acid, or chol, hyperkalemia, neutropenia, and inc serum levels of hepatic aminotransferase enzymes, fetal injury/death

Front 593

What are effects of ACE-I?

Back 593

dec PVR, inc CO, no chg in blood vol, inc plasma renin activity, dec LVH

Front 594

What are the effects of ARBs?

Back 594

dec PVR, inc CO, inc blood vol, inc plasma renin activity, dec LVH

Front 595

What is one renin inhibitor?

Back 595

aliskiren (Tekturna-new oral agent), does not cause cough, or angioedema, may inc risk of colon cancer

Front 596

What are 2 aldosterone antagonists?

Back 596

eplerenone and spironolactone(steroid form)--used in HTN and HF

Front 597

What is an adverse effect of eplerenone?

Back 597

hyperkalemia

Front 598

What are some adverse effects of spironolactone?

Back 598

hyperkalemia, gynecomastia, menstrual irregularities, impotence, hirsutism, deepening of the voice

Front 599

What is a novel class of HTN drugs?

Back 599

endothelin receptor antagonists

Front 600

What is an endothelin receptor antagonist?

Back 600

bosentan: improves endothelial function, inhibition of vascular/cardiac hypertrophy (only indicated in pulm HTN)

Front 601

What group of drugs vasodilates?

Back 601

CCB (invoke compensatory mechanisms more than do drugs that suppress CO, diuretics, and angiotensin inhibitors - often combined w/ other types of drugs)

Front 602

What is the MOA of CCB?

Back 602

blcok Ca ion channels in plasma membranes of SM, relax vascular SM, vasodilates

Front 603

What is the effect on BP of CCB primarily due to?

Back 603

dec PVR with little effect on venous capacitance, cardiac filling pressure, and CO

Front 604

What effect may help dec BP with CCB?

Back 604

natriuretic

Front 605

Does CCB inc or dec serum glucose, lipid, uric acid, or electrolyte levels?

Back 605

neither--no change

Front 606

What are indications for CCB?

Back 606

effective in diabetes, asthma, and when plasma renin activity is low, HTN, angina pectoris, and cardiac arrhythmias

Front 607

What are 2 cardioselective CCBs?

Back 607

diltiazem and verapamil

Front 608

What are most CCBs selective for?

Back 608

vasoselective

Front 609

What are adverse effects of CCBs?

Back 609

verapamil and diltiazem (cause bradycardia, AV block, constipation, gingival hyperplasia) and nifedipine (tachycardia, hyperplasia, inc mortality rate in pts w/ MI--good to pair w/ B-blocker)

Front 610

What are drug interactions of CCB?

Back 610

verapamil/diltiazem inc digoxin, theophylline, carbamazepine levels & dec levels of Li salts and substantial hypotension with quinidine, in serum levels of nifedipine w/ azole antibiotics, cimetidine, grapefruit,

Front 611

What is a contraindication of CCB?

Back 611

hypersensitivity

Front 612

What do NSAIDs do w/ other vasodilators?

Back 612

dec effects of hydralazine and minoxidil

Front 613

What are contraindications for hydralazine?

Back 613

CADs, hypersensitivity, mitral valve disease

Front 614

What are contraindications for minoxidil?

Back 614

MI, pheochromocytoma, hypersensitivity, aortic aneurysm

Front 615

What are contraindications for sodium nitroprusside?

Back 615

reduced cerebral perfusion, allergy

Front 616

What are side effects of vasodilators?

Back 616

alone (reflex tachycardia and fluid retention), w/ hydralazine (lupus-like syndrome), w/ minoxidil (hypertrichmosis)

Front 617

What is the DOC to treat HTN emergencies b/c of short action?

Back 617

sodium nitroprusside

Front 618

What is sodium nitroprusside?

Back 618

prodrug, release NO for vasodilation, rapidly metabolized to cyanide which is converted to thiocyanate in the presence of sulfur (gradual accumulation of toxins)

Front 619

When is sodium nitroprusside contraindicated?

Back 619

cerebral perfusion and allergy

Front 620

What vasodilator can you switch to after 48hrs on sodium nitroprusside?

Back 620

fenoldopam

Front 621

What is fenoldopam?

Back 621

dopamine D1 agonist w/ moderate affinity at alpha2 receptors, rapidly acting, IV to treat HTN emergencies, causes arteriolar VD in systemic vascular beds, dilates afferent and efferent arterioles in kidney (inc renal blood flow), rapidly metabolized, can dec serum K levels

Front 622

What are effects of CCBs?

Back 622

dec PVR, inc CO, no chg in blood vol, inc plasma renin activity, dec LVH, no chg in serum K, chol, LDL, HDL, or triglycerides

Front 623

What are the effects of other vasodilators?

Back 623

dec PVR, inc CO, inc blood vol, inc plasma renin activity, inc LVH, no chg in serum K, chol, LDL, HDL, or triglycerides

Front 624

How do you manage HTN?

Back 624

lifestyle change, drug tx

Front 625

What are some lifestyle modifications for HTN?

Back 625

exercise, weight loss, dec EtOH, low Na diet w/ adequate K, Ca, and Mg

Front 626

What tx is more likely to dec BP to desirable level in timely manner?

Back 626

multiple drug tx

Front 627

What is not a good choice for HTN in women?

Back 627

minoxidil (hair growth)

Front 628

What is not a good choice for HTN in men?

Back 628

Alpha blockers (ED)

Front 629

What is not a good choice for HTN in active patients?

Back 629

B-blockers/diuretics (prevent sweating)

Front 630

What are the most and least preferred drugs for pt older than 65?

Back 630

most: diuretic, ACE-I, CCB

least: centrally acting alpha agonist

Front 631

What are the most and least preferred drugs for pt of African heritage?

Back 631

most: diuretic, CCB

least: B-blocker

Front 632

What are the most and least preferred drugs for pregnant pt?

Back 632

most: methyldopa, labetalol

least: ACE-I, ARB

Front 633

What are the most and least preferred drugs for angina pectoris?

Back 633

most: B-blocker, CCB

least: hydralazine, minoxidil

Front 634

What are the most preferred drugs for MI?

Back 634

most: B-blockers, ACE-I, aldosterone antagonist

Front 635

What are the most and least perferred drugs for CHF?

Back 635

most: ACE-I, ARB

least: B-blocker, CCB, centrally acting drugs

Front 636

What are the most preferred drugs for recurrent stroke prevention?

Back 636

diuretic, ACE-I, ARB

Front 637

What are the most preferred drugs for chronic kidney disease?

Back 637

ACE-I, ARB

Front 638

What are the most preferred drugs for diabetes?

Back 638

diuretic, ACE-I, ARB, B-blocker, CCB

Front 639

What are the most and least preferred drugs for asthma?

Back 639

most: CCB, ACE-I

least: B-blocker

Front 640

What are the most preferred drugs for BPH?

Back 640

A-blocker

Front 641

What are the most preferred drugs for migraines?

Back 641

B-blocker and CCB

Front 642

What are the most preferred drugs for osteoporosis?

Back 642

diuretic

Front 643

What is a HTN emergency?

Back 643

BP > 180/120 w/ target organ dysfunction

Front 644

What is a HTN urgency?

Back 644

severe inc in Bp w/out target organ dysfunction

Front 645

What drugs tend to invoke compensatory mech to a greater extent than others?

Back 645

vasodilators

Front 646

What has been used to manage pheochromocytoma b/c of its long-acting irreversible blockade of alpha receptors?

Back 646

phenooxybenzamine

Front 647

What class of HTN drugs is cardioprotective?

Back 647

B-blockers

Front 648

What is a combined alpha/beta adrenergic receptor antagonist that can cause orthostatic hypotension?

Back 648

labetalol

Front 649

When do ACE-I especially cause fetal problems?

Back 649

2nd and 3rd trimester

Front 650

How do ACE-I reduce the risk of death in pts w/ HF?

Back 650

they dec cardiac afterload, inc CO

Front 651

The dihydropyridines have relatively little effect on ______ tissue at usualy therapeutic levels; however they can evoke ____ ______.

Back 651

cardiac, reflex tachycardia

Front 652

What are the 4 major classes of HTN drugs?

Back 652

diuretics, sympatholytics, angiotensin inhibitors, and vasodilators

Front 653

What are the short and long term effects of thiazides?

Back 653

short: reduce blood vol and CO

long: dec pVR

Front 654

How do sympatholytics primarily reduce BP?

Back 654

by decreasing PVR except for B-blockers

Front 655

How do angiotensin inhibitors work?

Back 655

reduce PVR and aldosterone levels with little effect on blood volume or CO in pts without HF

Front 656

How do vasodilators work?

Back 656

reduce PVR and some provoke reflex tachycardia and fluid retention