Week 7 Random Flashcards

Question

Level loss

Answer 1

In spinal injury all control is lost below the level.

Answer 2

Nerve that comes off the plexus (periferal) = multiple combinations of spinal nerves

Answer 3

2 Preganglionic Postganglionic

Answer 4

Near organ = parasympathetic Near spinal cord = sympathetic

Answer 5

Sympathetic

Answer 6

1st neuron in the CNS brainstem sacral spinal cord S2-4

Answer 7

Only innervates viscera in body cavities, glands in the head, the eye and erectile tissues.

Answer 8

Allows communication with CSN Spinal nerves are inserted with

Answer 9

GSA GVE GVA?

Answer 10

Yes there is (ignore)

Answer 11

A herniated disc is a condition in which the annulus fibrosus (outer portion) of the vertebral disc is torn, enabling the nucleus (inner portion) to herniate or extrude through the fibers.

Answer 12

a region of injured tissue or skin in which blood capillaries have been ruptured; a bruise

Answer 13

Control of vasculature Other: decrease gastric motility / smooth muscle / hair follices

Answer 14

Splanchnic nerve

Answer 15

Branches of spinal branches

Answer 16

NEUROEPITHELIUM (neutral tube) Neuroblast -\> Neruon Astroblast -\> Protoplasmic Astrocyte Astroblast -\> Fibrous Astrocyte Oligodendroblast -\> Oligodendrocyte Neuroepithelium -\> Epithelium of Choroid Plexus Neuroepithelium -\> Ependyma cells

Answer 17

Ganglia (group of neurons outside the CNS) Nucleus (group of neurons within the CNS)

Answer 18

1. **receive** and **integrate** stimuli **from many sources** simultaneously 2. **translate** stimuli **to membrane potential** 3. **propagate** this **membrane potential** 4. **translate** this **electrical message into neurotransmitter** 5. **deliver** neurotransmitter **to target cells**

Answer 19

**Lipofuscin:** golden brown, probably represents old age (found more in older neurons) **Melanin:** a brown black, represents old neurotransmitter? But function not know for sure.

Answer 20

**Perikaryon** (cell body) **Large nucleus** with **owl-eye nucleolus** nissil bodies = rER microtubules / **neurotubules** (24nm) intermediate filaments / neurofilaments (10nm)

Answer 21

Axonal transport

Answer 22

Contains neurofilaments/neurotubules 1. **Axon Hilloc** (**no nissl bodies**) 2. **PInitial Segment** (between axon hillock and myelination; site of action potential **initiation**) 3. Axon Proper

Answer 23

Anterograde transport (kinesin) Retrograde transport (dynein)

Answer 24

Increase surface area (dendritic spines) increased during young age later decreased Lack golgi Synthesize message

Answer 25

Need trophic stimuli (need signal from other cells to survive)

Answer 26

Axosomatic synapse (synapse with body) Axodendritic synapse (on dendrite) Axoaxonic synapse (contacting another axon terminal) Axospinous synapse (ending on dendritic spine)

Answer 27

Multipolar (many dendites; most abundant; pryamidal cells - cerebellum; Purkinje cells - cerebrum) Bipolar (single dendrite opose axon; sensory; retina, olfactory mucosa; inner ear) Pseudounipolar (split axon; no dendrites; DRG and cranial ganglia) Unipolar (short single axon and no dendrite; photoreceptors - rods/cones)

Answer 28

Motor Neurons: excite or inhibit Sensory Neurons Interneurons: chaining neurons; interaction

Answer 29

Cholinergic - acetylcholine / parasympathetic postganglionic Adrenergic - epinephrine / sympathetic postganglionic

Answer 30

Answer 31

Supporting cells in the CNS

Answer 32

**largest glial** cells long branched cytoplasmic processes with vascular end **feet** cover pia mater, blood vessels, and cell bodies specific intermediate filaments = **glial fibrillary acidic protein** **protoplasmic** - in gray matter, **low [GFAP]** **fibrous** - in white mater, **high [GFAP]** **can divide** respond to **injury** by forming **gliosis** (similar to fibrosis)

Answer 33

Tight (BBB)

Answer 34

Most **numerous** **Myelination** in CSN Can **myelinate several** axons **Schmidt-Lanterman cleft**s maintain the membrane forming the mylein

Answer 35

CNS (oligo) | PNS (schawnn) **Neuroepithelium** | **Neural crest** No close association | Close association Oligo provides **multiple** axons | Wrapped around **one** **Inhibit axonal growth** | participate in the **regenration** of injury **astrocyte foot** is present in Node of Ranvier | **Cytoplasm** is trapped in the Node of Ranvier **BOTH INCREASE VELOCITY**

Answer 36

Derived from **monocytes** **Smallest** and **least** numerous **Phagocytic** during injury

Answer 37

Central canal

Answer 38

Line ventricles More than "simple cuboidal epithelium" Connected by macula adherence and zona adherence

Answer 39

2 latteral 3rd and 4th

Answer 40

No basement membrane Long processes go into brain and terminate near blood vessels and hypothalamic cells (neurosecretory). Conntected by tight junctions.

Answer 41

Attached by desmosomes

Answer 42

capillary tufts push up ependyma into the brain ventricles made up of **simple cuboidal cells** upon BM responsible for **production and maintenance of CSF **

Answer 43

Allow oligodendrocytes / schwann cells to get nutrients through the “jelly wrap” to the axon that it is myelinating Communication

Answer 44

**Schwann cells** are **capable of mitosis** with the **subsequent production of a basal lamina** and therefor are key to peripheral nerve regeneration. **Astrocytes** produce **gliosis**. **Endoneurium** Is **Not Present** in the CNS. **Oligodendrocytes** Do **Not Proliferate**. In trauma, astrocytes DO proliferate and form scar tissue

Answer 45

Because it is under the pressure

Answer 46

Scalp Skull **Dura mater** Subdural space **Arachnoid membrane** Subarachnoid space **Pia mater** Brain

Answer 47

Layer 1 = molecular Layer 2 = granular Layer 3 = Pyramindal external (small) Layer 5 = Pyramidal internal (large)

Answer 48

1. Molecular layer 2. Purkinje cells 3. Granule cells

Answer 49

Axon wrapped in endoneurium Fassicle wrapped with perineurium Nerve wrapped with epineurium

Answer 50

Wavy Node of Ranvier Schwann cells hug axon Fibroblasts do are not covered by layers

Answer 51

Skin Adrenal medulla

Answer 52

**Somatic **(skeletal muscle) (motor neurons in ventral horn of spinal cord or equivalent area of brainstem) **Autonomic** (cardiac muscle, smooth muscle, glands)

Answer 53

Sensory Neurons Motor Neurons Enteric Nervous System

Answer 54

First Neuron **preganglionic** synapse Second Neuron **postganglionic** synapse **Effector cell**

Answer 55

No Allows for things like systemic verses local responses, or strengthening the intensity of a response.

Answer 56

DRG: no synapse; sensory AG: synapse; motor

Answer 57

Sympathetics often have more systemic effects too because of their association to the adrenal medulla and the principal of divergence.

Answer 58

Cranial nerve III, VII, IX, X S2-4

Answer 59

T1-L2 Lateral horn

Answer 60

chain (paravertebral) ganglia prevertebral/(preaortic) ganglia

Answer 61

To the body wall (T1T4) To the head: travel up in sympathetic chain "superior cervical" (T1T12) To thoracic cavity: from cervical (cardiopulmonary plexus) thoracic ganglia (splanchnic nerves to heart/esophagus) (T1T12) To lumber cavity: The Greater, Lesser and Least thoracic Splanchnics (prevertebral); pass throguh diapghgram "thoracic" (L1L2) To lumber cavity: preaortic ganglia (Celiac, superior mesenteric, aorticorenal, inferior mesenteric) "lumbar" (T1L2) To pelvic cavity: from lumbar by hypogastric nerves (most) others by sacral ganglion "sacral splanchnics" (T8L1) To adrenal gland: traveling on the greater or lesser thoracic splanchnic

Answer 62

Antero-medial

Answer 63

Chromaffin cells

Answer 64

Reflexes Pain

Answer 65

With parasympathetics (reflexes - autonomic, malaise) With sympathetic (reflexes, localizable pain \* often referred)

Answer 66

Referred pain means that pain from an organ is felt in a different part of the body.

Answer 67

Convergence of viscerosensory and somatic sensory fibers on the same dorsal horn cell causes pain to be felt in the skin or muscle.

Answer 68

Brainstem cardiovascular and respiratory centers The hypothalamus The cingulate cortex The amygdala

Answer 69

**Heritable traits** (changes in phenotype) that do **no**t involve **changes** to the underlying **DNA sequence** (changes in genotype).

Answer 70

1. **Cellular differentiation** (Cell fate is maintained by differential methylation of the DNA.) 2. **X-inactivation** (random DNA methylation, XIST RNA binding, and chromatin remodeling during implanation) 3. **Metabolic imprinting** (exposure during pre-natal and neo-natal periods *e.g. grandparents in Europe, agouti mouse*) 4. **Genomic imprinting** (some genes are expressed from only a single copy parent speicifc origin Beckwith-Wiedmann, Prader-Willi, and Angelman)

Answer 71

**In all somatic cells** the **paternal** chromosome (inherited from the father) **can** be **distinguished from** the **maternal chromosome** (inherited from the mother) due to differential **markings**. **Marking** occurs during **gametogenesis**. It is initiated by differential methylation of **specific sites** (imprinting control regions; **ICR**) and **maintained** by **reg**ulatory **RNA** binding and chromatin remodeling. ICRs are methylated on **only one** of the two **chromosomes**. The differential **marking** is **maintained** **in all somatic cells** throughout life, but is **erased** in the **germline cells**, then reestablished during **gametogenesis**.

Answer 72

**Increased prevalence** of **AS** and **BWS** in pregnancies conceived by **IVF **(genomic imprinting errors, not new mutations) **Genomic imprinting errors** common in **clones** (mice)

Answer 73

Disorder of growth characterized by **large size for gestational age, large tongue, abdominal wall defects, and predisposition to ****embryonic tumors** (e.g. Wilms tumor, neurofibromas). **two active copies of IGF-2** gene and/or **no active copy of CDKN1C** **IGF-2** expressef from paternally inherited chromosome **CDKN1C** expressef from maternally inherited chromosome Controlled by methylations at DMR1/2 sites 60% cases due to loss of methylation @ DMR2 10% cases due to mutatin @ CDKN1C 20% cases due to paternal uniparental disomy

Answer 74

**PWS:** short stature, hypotonia, small hands and feet, obesity, mild to moderate mental retardation, and hypogonadism. **AS:** severe mental retardation, seizures, and ataxic gait. 70% caused by the same deletion (3-4Mbs) **PWS** region- 5 genes; active only on the paternally derived chromosome. **AS** gene- UBE3A; active only on the maternally derived chromosome. \* maternal nondisjunctions occur more often

Answer 75

methylation-sensitive restriction enzyme analysis

Answer 76

piloerector muscles sweat glands most blood vessels

Answer 77

Adrenal medulla

Answer 78

Rlease "neurotransmitter" epinephrine into blood stream Epinephrine and norepinephrine

Answer 79

**Acetylcholine** all preganglionic neurons para postganglionic neurons muscle "cholinergic" also in CNS **Norepinephrine** symp postganglionic exceptions: sweat glands (ACh) and chromaffin cells (Epi/Nore) "noradrenergic" also in CSN **Epinephrine ** Chromaffin cells also in CSN **Dopamine** postganglionic sympathetic neuroeffector junctions in the kidney "dopaminergic" also in CSN

Answer 80

Cholingergic (Ach) Adrenergic (Epi)

Answer 81

**Nicotinic** (**ligand gated**) Subtypes: **Ganglionic N_N** and **Muscle N_M** **Low** dose **stimulation**; **high** dose **blocking** **Curarae** blocks N_Nand N_M **Muscarinic** Receptors (**GPCR**) Subtypes: M₁-M₅ Odd: Formation of IP3 (+) Ca2+ and DAG =\> PKC Even: K+ channels activation (hyperpolarization) inhibit Adenylyl cyclase (decrease cAMP) **Muscarine** activates **Atropine** blocks

Answer 82

**Alpha** (**IP3-\>Ca++ and DAG activate PKC)** **a₁** receptors (**smooth muscle** & **glandular tissue** | **sm contraction**) **a₂ **receptors (**presynaptic neuron** | **inhibit norepinephrine** release) **Beta** (**+ adenylyl cyclase and + cAMP**) **b₁ **receptors (**heart** | **increase rate** and **contractillity**) **b₂** (**smooth muscle** | **sm relaxation**) **b₃** (**adipocytes** | **lipolysis**)

Answer 83

Divergence and convergence allow for integration of neural input and modulation of end organ responses, as opposed to all-or-none responses, which you see with somatic motor neurons and the neuromuscular junction (NMJ)

Answer 84

Nerve terminal | Varicosities End plate of cell | Distributed across entire plate One muscle receives input from one motor neuron | Signal from multiple postynaptic neurons Quick and all-or-none | Slow and modulatory

Answer 85

excitatory postsynaptic potential inhibitory postsynaptic potential

Answer 86

Salivary glands

Answer 87

Eye: Pupil open; distant focus Heart: Increased rate & force of contraction Blood vessels: Constriction GI: Decreased motility, sphincters constricted Bladder: Bladder wall relaxed, internal sphincter contracted Skeletal Muscle Stimulate glycogenolysis

Answer 88

**SA node** **Sympathetic** activation of **β₁** adrenergic receptors has a **positive** **chronotropic effect** (increases heart rate) **Parasympathetic** activation of **M₂** muscarinic receptors has a **negative** **chronotropic effect** (decreases heart rate) **AV node** **Sympathetic** activation of **β₁** adrenergic receptors has a **positive dromotropic effect** (increases conduction velocity) **Parasympathetic** activation of **M₂** muscarinic receptors has a **negative dromotropic effect** (decreases conduction velocity) **Ventricular muscle** **Sympathetic** activation of **β₁** adrenergic receptors has a **positive inotropic effect** (increases contractility) **Parasympathetic** activation of **M**₂muscarinic receptors **antagonizes** **sympathetic** responses. In the absence of sympathetic tone, parasympathetic activation has little or no effect on the ventricles.

Answer 89

**α₁** adrenergic receptors cause vascular **smooth muscle contraction** and constriction of blood vessels. **β₂** adrenergic receptors cause **relaxation of vascular smooth muscle** and dilation of blood vessels.

Answer 90

the face, tongue, genitals and urinary trac

Answer 91

Sympathetic stimulation by preganglionic neurons that synapse directly with chromaffin cells in the adrenal medulla causes the release of epinephrine and norepinephrine into the circulation.

Answer 92

**Sympathetic** activation of **β₂** adrenergic receptors causes **relaxation of bronchial smooth muscle** and **dilation of the airways**. **Parasympathetic** activation of **muscarinic receptors** causes **contraction of bronchial smooth muscle** and constriction of the airways & stimulation of **secretion** of **bronchial glands**

Answer 93

**Sympathetic** activation of **α₁** adrenergic receptors **Contracts** iris **radial** muscles, dilating the pupil (**mydriasis**). **Parasympathetic** activation of **muscarinic** receptors **Contracts** iris **circular** muscles, constricting the pupil (**miosis**)

Answer 94

**Sympathetic** activation of **β₂** adrenergic receptors **Relaxes ciliary** muscles allowing the lens to **focus on far object** **Stimulates ciliary epithelium secretion of aqueous humor** **Parasympathetic** activation of **muscarinic** receptors **Contracts ciliary muscles** Causing the lens to **focus on near objects**. Increasing **outflow** of **aqueous humor** through trabecular meshwork into **canal of Schlemm**

Answer 95

**Sympathetic** activation of **β₂** and **α₂** receptors **decreases motility** and **tone** **α** receptors **contracts sphincters** **Parasympathetic** activation of **muscarinic receptors** **increases** gut **motility and tone** **relaxes sphincters** **stimulates glandular secretion**

Answer 96

**Sympathetic activation** (**promotes filling**) **α** adrenergic receptors **contract** the **internal sphincter muscle** **β** adrenergic receptors **relax the detrusor muscle**

Answer 97

**Sympathetic** activation **α** receptors cause a **weak increase in potassium and water secretion** **β** receptors cause a **weak increase in amylase secretion** Parasympathetic activation of **muscarinic** receptors causes a pronounced **increase in potassium and water secretion**.

Answer 98

Sympathetic activation **α** receptors **contract pilomotor muscles **muscarinic receptor activation by **acetylcholine **released from postganglionic sympathetic fibers **causes** generalized **sweating**

Answer 99

Electrical (heart) and chemical

Answer 100

Presence (at terminal) Release (due to depolarization and Ca2+ dependent) Identity of action (control of posynaptic neuron inh/stim) Removal (mechanism for removal from synaptic cleft)

Answer 101

Evidence that chemical transmission at some neuroeffector synapses (e.g., gut) does not involve either norepinephrine or acetylcholine. Most neurons actually release multiple substances Can act as modulators adenosine 5’-triphosphate (ATP) vasoactive intestinal peptide (VIP) neuropeptide Y (NPY) leutinizing hormone releasing hormone (LHRH) 5-hydroxy tryptamine (5-HT or serotonin) nitric oxide (NO) gamma-amino butyric acid (GABA) substance P •dopamine

Answer 102

1. Synthesis 2. Storage 3. Release 4. Receptor interaction 5. Disposition

Answer 103

ACh is **synthesized** from **Acetyl CoA** and **choline** by the enzyme **choline acetyltransferase** ACh is **transported** into vesicles by the vesicle-associated transporter (**VAT**) ACh is **released** when **Ca2+ influx** into nerve terminal facilitates vesicular fusion by **docking proteins** synaptosome associated proteins (**SNAPs**) vesicle-associated proteins (**VAMPs**) **bind** to **nicotinic** or **muscarinic** receptors on the postsynaptic membrane be **broken** down by acetylcholinesterase (**AChE**) into choline and acetate **Choline** can then be **recycled** by transport back into the presynaptic nerve terminal by the **Na+-dependent** choline transporter (**CHT**)

Answer 104

**VAMPs** (vesicle associated membrane proteins) osynaptobrevin **SNAPs** (synaptosome associated proteins) syntaxin SNAP 25

Answer 105

**synthesis** – **hemicolinium** inhibits the Na+-dependent choline transporter (CHT) **storage** – **vesamicol** inhibits the vesicle-associated transporter (VAT) **release** – **botulinum toxin** blocks exocytosis by modifying vesicle docking proteins: synaptasome associated proteins (SNAPs) vesicle-associated membrane proteins (VAMPs) **disposition** – **neostigmine** inhibits acetycholinesterase

Answer 106

* *agonists** * *ACh** – nicotinic (N) and muscarinic (M) receptors * *nicotine** – nicotinic receptors * *bethanacol** – muscarinic receptors * *antagonists** * *trimethaphan** – neuronal nicotinic receptors (NN) * *d-tubocurarine** – muscle nicotinic receptors (NM) * *atropine** – muscarinic receptors

Answer 107

**Tyrosine** is taken up into the presynaptic nerve terminal by a **Na+**-**dependent** amino acid **transporter** (A) where it is then **converted** to **DOPA** by the rate limiting enzyme tyrosine hydroxylase. **DOPA** is then **converted** to **dopamine** by the enzyme **DOPA decarboxylase** (also called dopamine decarboxylase). **Dopamine** is then **transported** into vesicles by the vesicular monoamine transporter (**VMAT**). The predominant adrenergic **neurotransmitter** released **depends** on what **enzymes** are present in the vesicles. In the **presynaptic** nerve terminal of most postganglionic adrenergic neurons in the ANS, **dopamine** is **converted** to **norepinephrine** by dopamine **beta-hydroxylase**. In **chromaffin cells**, **norepinephrine** is **converted** to **epinephrine** by phenylethenolamine **N-methyltransferase** (**PNMT**). **Once released** into the synaptic cleft, norepinephrine (**NE**) can either **bind** to pre or postsynaptic adrenergic receptors be **taken up** by the **presynaptic** nerve terminal or **other cells** (extraneuronal) **diffuse** out of the cleft * *Neurotransmitter** taken up by the presynaptic nerve terminal can be * *Transported** back into **vesicles** by the **VMAT**, or * *Metabolized** by monoamine oxidase (**MOA**) **Neurotransmitter** taken up **extraneuronally** can be **metabolized** by **MAO** and **COMT** **Neurotransmitter** not taken up is **metabolized** primarily by **COMT** found in the **liver**

Answer 108

**synthesis** – **α-methyltyrosine** inhibits tyrosine hydroxylase **storage** – **reserpine** inhibits the vesicular monoamine transporter (VMAT) * *release** – **bretylium**, **guanethadine**, and **clonidine** * *bretylium inhibits** the nerve **a**ction **p**otential **preventing Ca2+** influx * *guanethadine** is taken up into nerves by the NET. It then gets concentrated **in** the synaptic **vesicles**, **displacing** endogenous sympathetic **neurotransmitters**. * *clonidine** inhibits catecholamine release by activating **α2** receptors on the presynaptic nerve terminal. **disposition** * *entacapone inhibits** catechol-O-methyl transferase (**COMT**) * *pargyline inhibits** monoamine oxidase (**MAO**) * *cocaine** and **amphetamines inhibit** neuronal reuptake by the norepinephrine transporter (**NET**)

Answer 109

**α agonists** -oxymetazoline – α1 and α2 receptors -phenylephrine – α1 receptors -clonidine – α2 receptors - **α antagonists** -phentolamine – α1 and α2 receptors prazosin – α1 receptors yohimbine – α2 receptors - **β agonists** isoproterenol – β1 and β2 receptors dobutamine - β1 receptors terbutaline – β2 receptors - **β antagonists** propranolol – β1 and β2 receptors metoprolol – β1 receptors

Answer 110

**Class of compounds** that include the **endogenous neurotransmitters** and **hormones released by adrenergic neurons** in the sympathetic nervous system. **Catechol** (benzene ring with hydroxyls at the 3 (meta) and 4 (para) positions) and **ethylamine**

Answer 111

Exogenous compounds that imitate the functional responses produced by endogenous catecholamines

Answer 112

exogenous compounds that block the functional responses to endogenous catecholamines or sympathomimetics

Answer 113

Type of **receptor** Type of **tissue** The **signaling pathway** activated by receptor Are the effects **direct** and/or **indirect**

Answer 114

[Gq] a1: (+) PLC = sm contraction [Gi/o] a2: (-) Ca++ = inhibit neurotranmitter AND (-) AC = inhibit sm contract [Gs] b: (+) AC =\> cardiac contractility, sm relaxation, glycogenolysis [Gs] D1/5 (+) cAMP =\> sm relxation

Answer 115

* *blood vessels** * *eye** (iris radial muscle) * *bladder** (sphincter muscle) * *skin** (piloerector muscles)

Answer 116

Some vascular smooth muscle (-) AC =\> Vasoconstriction Central and peripheral presynaptic nerve terminal (+) Gi/o inhibition of presynaptic Ca++ channels =\> inhibition of neurotransmitter release

Answer 117

heart Gs (+chronotropic, +dromotrophic, +inotropic, +lusitropic) kidney Gs (+renin secretion from JG-cells)

Answer 118

Cardiac muscle (Gs) =\> (+) HR and contracitility Smooth muscle (vascular, airway, gastrointestinal, bladder (detruser), uterus) =\> Relax smooth muscle Liver =\> Increase glycogenolysis

Answer 119

adipose tissue (Gs) =\> lipolysis

Answer 120

vascular smooth muscle Gs smooth muscle relaxation

Answer 121

central nervous system Gi (-) AC CNS control of motor movement and regulation of prolactin secretion

Answer 122

**Direct** (acting compounds produce their effects by **directly activating** adrenergic **receptors**. Endogenous catecholamines belong to this class) **Indirect** (acting compounds produce their effects by **increasing** the availability of **endogenous catecholamines**. This can be achieved by: inhibiting reuptake, stimuating release, inhibiting metabolism) **Mixed** (both)

Answer 123

Direct acting sympathomimetics will have substitutions on at least 2 of the following 3 positions: the **meta** position on the benzene ring, the **para** position on the benzene ring, or the **beta** carbon of the **ethylamine** side chain, and it must be a **hydroxyl**. Large substitutions on the terminal nitrogen tend to **promote** β **adrenergic receptor activity**. Small substitutions tend to promote **α adrenergic receptor activity** **Hyroxyl substitutions** on the **3** and **5** positions of the benzene ring tend to enhance **β2** adrenergic receptor selectivity.

Answer 124

**Indirect** acting sympathomimetics will have no or only **1** substitution at either the meta or para postion of the benzene ring **or** the **beta**-**carbon** of the **ethylamine** side chain. Both D and L might be active. (e.g. Amphetamine+) b carbon increase CNS effects COMT not metabolize if either 3 or 4 hydroxyl is missing

Answer 125

**Imadazolines** are a class of **sympathomimetics** that contain an imidazole moiety. Many of these compounds are **potent α agonists** used as **vasoconstrictors** in topical over the counter nasal and **ophthalmic** preparations. OTC

Answer 126

a1\>a2 b1\>\>b2 - **therpeutic use** (limited) hypotension (shock) - **cardivascular responses** (a1/b1): (+) heart contractility b1; (-) reflex rate (+) vasocontrction a1; (+) s&d pressure - **smooth muscle** (a1) not much effect on airway, gut, uterus not many receptors; (+) radial muscle in iris mydriasis; (+) bladder sphincter contraction

Answer 127

a1=a2 b1=b2 - **therapeutic use:** bronchospasm, anaphylatic shock, cardiac arrest, open angle glaucoma, local anesthetic (adjunct) - **cardiovasuclar resposnes** (b1/b2) low dose similar to isorpoterenol (b1b2) high dose similar to norepinephrine (a1/b1) - **smooth muscle** (a1 and b2 effects) airways = significant dialation (b2) gut = transient decrease in motility (b2) bladder = relaxation of detrusor muscle (b2) contraction of sphincter muscle (a1) uterus relaxation (b2)

Answer 128

D1-5 \> b \> a - **therapeutic use** = cardiogenic short; heart failure - **cardivascular resposnes** (D1/5, b1, and a1 effects) D1/5 activation increasing blood floow and urin production intermediate doses activate b1 receptors icnrease CO high dose activation a1 casuing vasoconstriction and increasing BP - **central effects** controlling motor movememnt in basal ganglia; inhibits prolactin secretion in the anterior pituitary

Answer 129

β1=β2=β3 - **therapeutic use** = bradycardia (heart block, cardiac arrest), bronchospasms - **cardiovascular responses** (β1 and β2 effects) increase in cardiac output due to increased heart rate and contractility (β1) vasodilation of most vascular beds (β2) increase in systolic and pulse pressure, decrease in diastolic pressure, slight decrease in MAP other **smooth muscle** responses (β2 effects) airways – significant dilation gut – transient decrease in motility bladder – relaxation of detrusor muscle (promotes filling) uterus – relaxation

Answer 130

b1\>b2 **therapeutic uses** – cardiogenic shock, acute heart failure **mechanism of action** (+) dobutamine – selective activation of β1 receptorsa a1 antagonist (-) dobutamine – α1 agonist **pharmacologic responses** •increased cardiac output (β1) primarily through an increase in contractility •increase in systolic and pulse pressure (little change in diastolic pressure) increase in MAP

Answer 131

**mechanism of action** – selective activation of β2 receptors **pharmacologic responses** – smooth muscle relaxation, especially **airwaysotherapeutic uses** – obstructive airway diseases, acute bronchospasms, preterm labor

Answer 132

* *mechanism of action** – selective activation of α receptors (α1 and α2) * *pharmacologic responses** – smooth muscle contraction, especially vascularo **therapeutic uses** – nasal decongestant

Answer 133

**omechanism of action** – selective activation of α1 receptors **pharmacologic responses** – smooth muscle contractionotherapeutic uses – vasopressor, nasal decongestant, mydriatic **other α1 selective agonists** – midodrine, methoxamine, metaraminol

Answer 134

**mechanism of action** – selective activation of α2 receptors **pharmacologic responses** – reduced sympathetic tone (central effect), inhibits NE release **therapeutic uses** – hypertension, reducing sympathetic responses associated with withdrawal, analgesic adjuvant **other α2 selective agonists** – α-methyldopa, guanfacine, guanabenz, dexmedetomidine

Answer 135

**mechanism of action** – indirectly acting sympathomimetic; stimulates the release of neurotransmitters (central and peripheral **pharmacologic responses** •increased cardiac output •vasoconstriction - increases systolic, diastolic, and mean arterial pressure •contraction of urinary bladder sphincter •CNS stimulation **therapeutic uses** – narcolepsy, attention deficit hyperactivity disorder (ADHD), appetite suppression, enuresis, incontinence **toxicity** •CNS effects - restlessness, dizziness, tremor, irritability, anxiety, delirium, paranoia, hallucinations cardiovascular effects – severe hypertension,

Answer 136

**mechanism of action** – mixed acting sympathomimetic: stimulates release of NE, also causes direct activation of α and β receptors **pharmacologic responses** – vasoconstriction, positive inotropy, bronchodilation, CNS stimulationo **therapeutic uses** – bronchodilator, nasal decongestant, mydriatic, narcolepsy

Answer 137

**mechanism of action** •blocks catecholamine metabolism by inhibiting monoamine oxidase (MAO) **therapeutic uses** •depression •Parkinson’s disease **pharmacologic responses** •enhance neurotransmission at catecholaminergic synapses

Answer 138

Lipid-water partition coefficient size of the molecule concentration gradient pH active vs. passive transport paracellular transport

Answer 139

Paracellular tranport Facilitated diffusion Diffusion Drug transporters

Answer 140

**ATP-binding cassette (ABC) transporters** Active tranport; 49 genes in seven families ABCA-ABCG P-glycoprotein; CFTR **Solute carrier trasnporters (SLC)** Facilitated transporters and ion-coupled secondary active transporters; 300 different proteins Serotonin transporter (SERT); dopamine transporter (DAT)

Answer 141

is the process of a body delivering blood to a capillary bed

Answer 142

Active/inactitve Oxidations/Hydrolytic/Conjugative

Answer 143

fluoxetine (Prozac®) P-glycoprotein cyclosporine A inhibits OATP transporters, which is at the same time a substrate of CYP3A4

Answer 144

Phase 1 "oxygenases" Phase 2 "transferases" Other "dehydrogenases"

Answer 145

57 genes, 18 families, 43 subfamilies families 1,2,3 are responsible for drug metabolism Rates of metabolism are slow Overlapping specificity Competition leads to ADR SNPs present CYP3A4/5 family with most enzymes

Answer 146

CYP2D6 CYP = cytochrome P450 2 = genetic family D = genetic sub-family 6 = specific gene **genetical not functional**

Answer 147

CYP1A2 CYP3A CYP2C9 CYP2C19 CYP2D6

Answer 148

Potent inhibitor of intestinal cytochrome CYP3A4 Can lead to increase in bioavailability in serum drug levels

Answer 149

Carbamazepine Rifampin Rifabutin St. John’s wor It is a medicinal herb with antidepressantproperties and potential antibacterial and anti-inflammatory properties. Neurotransmitter re-uptake inhibition Involving 5-HT, dopamine, oradrenaline And possibly GABA and glutamate.

Answer 150

In GI tract and liver Metabolism of: –Most calcium channel blockers –Most benzodiazepines –Most HIV protease inhibitors –Most HMG-CoA-reductase inhibitors –Cyclosporine –Most non-sedating antihistamines –Cisapride

Answer 151

Ketoconazole Itraconazole Fluconazole Ritonavir Cimetidine Clarithromycin Erythromycin Troleandomycin Grapefruit juice

Answer 152

Absent in 7% caucasians, 1-2% non-caucasians Metabolize: codeine, b-blockers, tricyclic antidepressants Inhibited by: Fluoxetine (Prozac), Haloperidol, Paroxetine (Paxil), Quinidine

Answer 153

Absent in 1% caucasians and african americans Metabolism: NSAID (including COX-2), S-warfarin, phenytoin Inhibites: Fluconazole

Answer 154

Absent in 20-30% asians, and 3-5% caucasians Primary metabolism of: –Diazepam –Phenytoin –Omeprazole Inhibited by: –Omeprazole –Isoniazid –Ketoconazole

Answer 155

Induced by smoking tabaco •Catalyzes primary metabolism of: –Theophylline –Imipramine –Propranolol –Clozapine •Inhibited by: –Many fluoroquinolone antibiotics –Fluvoxamine –Cimetidine

Answer 156

Liver disease Renal disease Cardiac disease (hepatic blood flow) Acute myocardial infarction? Acute viral infection? Hypothyroidism or hyperthyroidism?

Answer 157

Altering pH to keep or remove compound from serum

Answer 158

The **fraction** of the admnistered dose that reaches the systemic circulation Higher absorption =\> (+) Bioavailability F = AUC_router/AUC_IV=AUC_P.O./Dose

Answer 159

PK: What your body does to the drug (change in [c] as the drug moves in a body) PD: What tyhe drug does to your body

Answer 160

Are Underneath the Curve

Answer 161

Vd=Total Mass Absorbed / Cplasma

Answer 162

exogenous compounds that imitate functional responses associated with parasympathetic stimulation

Answer 163

exogenous compounds that imitate functional responses produced by acetylcholine (ACh) at cholinergic receptors

Answer 164

compounds that block cholinergic transmission at involving muscarinic receptors (antimuscarinics), neuronal nicotinic receptors (ganglionic blockers) or the neuromuscular junction (neuromuscular blockers).

Answer 165

the type of cholinergic receptor involved the type of cell and/or tissue involvedo the signaling pathway activated by that receptoro whether or not the effects or direct or indirect

Answer 166

Muscle Ligand gated 4 different subunits Muscle contraction

Answer 167

Parasympathetic ganglia, adrenal medulla, CNS ligand gated composed of alpha and beta isofrom neuronal excitation

Answer 168

Gq sm (vessels, airways, eye, gut, bladder) / contraction endothelial cells (blood vessels) / relax blood vessels exocrine gland (salivary, sweat, airway, gut) / stimulate secretion CNS

Answer 169

Gi aCyclase / K+ channels cardiac muscle (M2) -chrono -dromo -iso CNS (M4)

Answer 170

Direct/Indirect

Answer 171

**Akaloids** **Choline Esters** Methyl substitution on β carbon (orange) of methacholine and bethanecol - reduces potency at nicotinic receptors - limits hydrolysis by cholinesterases The carbamic acid ester group (green) of carbachol and bethanecol limits hydrolysis by cholinesterases.

Answer 172

Indirect acting cholinomimetics work by inhibiting cholinesterase breakdown of endogenous ACh. **Acetylcholinesterase (AChE) – “true cholinesterase”** AChE contains two important sites at catalytic center Anionic site – interacts electrostatically with charged nitrogen and methyl groups of ACh Esteratic or esteric site – serine that combines via hydroxyl group with electrophilic carboxyl residue of the acetyl group of ACh Steps: Binding of ACh to anionic site Cleavage of ACh at the ester linkage releasing choline Reaction with water yielding acetic acid **Butyrylcholinesterase (BuChE) – “pseucocholinesterase”**

Answer 173

Two types: Interfering with anionic site, or Interfering with esteratic site Effects: Low levels – increase skeletal muscle activity (fasciculations) High levels – neuromuscular blockade Increased ganglionic transmission Complex cardiovascular responses CNS effects

Answer 174

**Mono- or bis-quaternary amines** – edrophonium **Carbamates** – neostigmine, physostigmine **Organophosphates**: * echothiophate – used clinically * parathion, malathion, diazinon used as insecticides * Form “irreversible” covalent bond with the esteratic site of cholinesterases * Pralidoxime or 2-PAM (2-pyridine aldoxime methyl chloride) can be used to “regenerate” cholinesterase. Used to treat organophosphate poisoning * Cholinesterase interaction with organophosphates can undergo “aging”, preventing reversal by 2-PAM.

Answer 175

**therapeutic use** •postoperative and neurogenic ileus •postoperative urinary retention • **effects** – causes smooth muscle contraction (GI and urinary tract) o **mechanisms of action –** •muscarinic agonist – activates M1 and M3 receptors •negligible effect at nicotinic receptors

Answer 176

**therapeutic use** •Glaucoma •Sjögren’s syndrome, xerostomia **effects** •contracts sphincter and ciliary muscles of the eye facilitating aqueous humor outflow (glaucoma) •stimulates salivary gland and tear duct secretions (Sjögren’s) **mechanisms of action** – muscarinic agonist (primarily M3 receptor)

Answer 177

**therapeutic use** •medical – smoking cessation •non-medical – smoking, insecticides **effects** •activates NN receptors in central nervous system •activates NN receptors on postganglionic sympathetic and parasympathetic neurons •activates NM receptors at the neuromuscular junction **mechanisms of action** – agonist at NM and NN receptors

Answer 178

**therapeutic use** •treatment of myasthenia gravis •postoperative and neurogenic ileus •postoperative and neurogenic urinary retention **effects** •generalized parasympathetic stimulation **mechanisms of action** – reversible cholinesterase inhibitor