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Pharm > T2: ANS, Histamine > Flashcards

T2: ANS, Histamine Flashcards

1
Q

bactericidal drugs

A

penicillinscephalosporinsaminoglycosidesvancomycinaztreonamimipenemfluroroquinolonesmetronidazolepolymyxinsquinupristin-dalfopristinbacitracin

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2
Q

bacteriostatic drugs

A

erythromycin (macrolides)clindamycintetracyclinechloramphenicolsulfonamidestrimethoprimnitrofurantoin

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3
Q

narrow spectrum

A

only G+ or G-: isoniazid against mycobacterium

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4
Q

extended spectrum

A

G+, some G- i.e. ampicillin

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5
Q

broad spec

A

wide variety of G+ and G-: tetracycline, chloramphenicol, imipenem

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6
Q

expense of drug administration

A

IV>IM>oral (cheapest)

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7
Q

drugs that inhibit synthesis of bacterial cell walls: PCN (B-lactam): natural penicillins

A

G, V Potassium, G Procaine, G Benzathine, G Benzathine + Penicillin G Procaine

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8
Q

drugs that inhibit synthesis of bacterial cell walls: PCN (B-lactam): Penicillinase resistant Penicillins (anti-staph)

A

methicillinnafcillinoxacillin

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9
Q

drugs that inhibit synthesis of bacterial cell walls: PCN (B-lactam): ext. spec PNC

A

ampicillinamoxicillin

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10
Q

drugs that inhibit synthesis of bacterial cell walls: PCN (B-lactam): antipseudomonal

A

Ticarcillin + clavulanate potassium (Timentin)Piperacillin + Tazobactam (Zosyn)

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11
Q

drugs that inhibit synthesis of bacterial cell walls: PCN (B-lactam): monobactams

A

aztreonam

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12
Q

drugs that inhibit synthesis of bacterial cell walls: PCN (B-lactam): carbapenems

A

Imipenem + Cilastatin

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13
Q

drugs that inhibit synthesis of bacterial cell walls: PCN (B-lactam): B-lactamase inhibitors

A

Clavulanic acid, Tazobactam

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14
Q

drugs that inhibit synthesis of bacterial cell walls: cephalosporin (B-lactam): 1st gen

A

CefazolinCephalexin

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15
Q

drugs that inhibit synthesis of bacterial cell walls: cephalosporin (B-lactam): 2nd gen

A

CefaclorCefoxitinCefuroximeCefprozil

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16
Q

drugs that inhibit synthesis of bacterial cell walls: cephalosporin (B-lactam): 3rd gen

A

CeftriaxoneCefiximeCefotaximeCeftazidime

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17
Q

drugs that inhibit synthesis of bacterial cell walls: cephalosporin (B-lactam): 4th gen

A

Cefepime

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18
Q

drugs that inhibit synthesis of bacterial cell walls: cephalosporin (B-lactam): 5th gen

A

Ceftaroline

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19
Q

other drugs that inhibit bacterial cell wall synthesis

A

vancomycinbacitracin

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20
Q

drugs that alter cell membrane permeability

A

Polymyxin BDaptomycin

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21
Q

drugs that inhibit bacterial protein synthesis: Tetracyclines

A

short-acting: Tetracycline long-acting: Doxycycline, Minocyclinenew: Tigecycline

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22
Q

drugs that inhibit bacterial protein synthesis: Macrolides

A

Erythromycin base” Estolate, “ Stearate, “ Ethylsuccinate, “ LactobionateClarithromycinAzithromycinTelithromycin

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23
Q

drugs that inhibit bacterial protein synthesis: Aminoglycosides

A

Gentamicin; generic: Garamycin, JenamicinTobramycin; generic: NebcinAmikacin; generic: AmikinStreptomycinNeomycin

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24
Q

drugs that inhibit bacterial protein synthesis: Misc.

A

ClindamycinQuinupristin/DalfopristinLinezolid

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25
Q

act on 50S ribosomal subunit

A

Cloramphenicol, macrolides, clindamycin, quinupristin/dalfopristin, linezolid

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26
Q

act on 30S ribosomal subunit

A

Aminoglycosides, Tetracyclines

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27
Q

drugs that act as anti-metabolites: Sulfonamindes

A

Silver Sulfadiazine (SILVADINE): topicalTrimethoprim-sulfamethoxazole

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28
Q

drugs that inhibit nucleic acid synthesis: Fluoroquinolones

A

Ciprofloxacin (CIPRO)Levofloxacin (LEVAQUIN)Moxifloxacin (AVELOX)

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29
Q

Misc. drugs that act via nucleic acids

A

MetronidazoleNitrofurantoinRifampin

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30
Q

empirical therapy

A

“best guess” therapy, br. spec/combo abxguided by Gs, site of inf, clinical experience, local hospital antibiogram susc. reports-should be changed to rational therapy (narrow spec) when susc. tests performed and org. ID’d

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31
Q

epsilometer (E) test:

A

also determines MIC, plastic strip containing gradient of known conc. abc placed on agar plate containing pt’s bac. isolate

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32
Q

how to monitor antimicrobial activity in vivo

A

serum inhibitory titer: greatest dilution of pt’s serum that inhibits visible growth of pt’s infecting pathogenbactericidal titer: plate out above no-growth samples onto abx-free plates

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33
Q

min. drug conc. at infected site should be..

A

> = MIC, ideally 2-4x MIC(abscesses must be drained)

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34
Q

BBB may prevent..

A

penetration of drug into CSF-but during infection BBB is diminished (opened up tight junctions of cerebral capillaries)–>inc. penetration

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35
Q

this may prevent abx penetration to site of action (and dec. levels of free drug)

A

abx binding to plasma proteins

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36
Q

med doses may need to be adjusted for..

A

renal/hepatic failurenewbornsoral vs. parenteral admin

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37
Q

bactericidal or bacteriostatic?

A

cidal is better, esp. if immunecomp

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38
Q

strains of these are resistant to all known drugs

A

EnterococciPseudomonasEnterobacter

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39
Q

bacterial resistance factors

A

indiscrim. use (misuse)delay in optimal txadmin of subopt. dosetx during dormant stageinability to reach inf. site (CNS, eye, prostate, abscess) defective funct. status of host defense mech agricult. used of abx in livestock

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40
Q

how microorganisms produce resistance

A

mutation and selection i.e. resistance to:-strep (ribosomal mut.)-quinolone (DNA gyrase)-linezolid (rRNA)-rifampin (RNA polymerase)-M. tuberculosis

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41
Q

resistance mediated by genetic exchange

A

HGT: transformation (PCN res. in pneumo.)transduction (Staph, penicillinase)conjugation

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42
Q

conjugation

A

2 sets of genes transferred: R-determinant (resistance) and resistance transfer factor (RTF)–>ind or combine to for R-factor*can have >1 abx resis. gene!**>50% ppl have int. bac containing R-factors

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43
Q

transposon

A

DNA sequences that can “jump from place to place”, can carry drug resis. genesplasmid–>plasmidplasmid–>chromosome (and vis versa)

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44
Q

biochem mechs of drug resistance

A
  1. dec. perm. of org to drug: porins do not allow in anymore (G-) OR active efflux (tetras)2. inactivation of abx by enzymes: (PCN, Chloramphenicol, Aminoglycosides): B-lactamases (+ and -) acetyl/phosphoryl/adenylate drug (amino glycosides, G-)3. altered drug target site: PBP w/ altered affinity for drug, mut. in FQ target (DNA gyrase)
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45
Q

forms of synergism seen with combo abx tx

A

-block of seq. steps in metabolic pathway (Trimethoprim + Sulfamethosazole–>folic acid)-inhib. enz. inact. of abx (B-lactamase inhibitor)-enhanced abx uptake by bac (aminoglycoside + B-lactam)

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46
Q

synergism

A

4x or greater reduction in MIC or MBC when drug combined

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47
Q

antagonism

A

> 50% MIC of each drug needed to produce inhibition of growth

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48
Q

antagonism exs.

A

bacteriostatic antags. bactericidal (need actively growing org) (PCN + chlortetracycline)induction of enz. inact.: imipenem (induces B-lactamase) + piperacillin (susc. to B-lactamase)

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49
Q

combo abx tx uses

A

mixed bac infunknown specific cause-empirical tx (i.e. pneumonia: macrolides for M. pneumo + ceftriaxone for G-)synergism may be nec. to kill org. (PCN + AMGS better tx for enterococcal endocarditis)may prevent resistances (bismuth salts + amos/tetra/or clarithro + metronidazole for H. pylori)

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50
Q

disadv. of combo abx tx

A

inc. toxic side effectsselection of orgs resis. to >1 abxpossible antag. effect if wrong combo

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51
Q

abx ppx

A

-post-exposure to certain microorgs: gon, syph, anthrax-prevent recurrent dis. in susc. pt: artific. heart valve undergoing dental proc. to prevent bac endocarditis, emphysema pts to prevent chron. bronchitis, frequent UTIs-surgical procedures: 0-2 hrs before, during, 3-4 hrs after-trauma contam wounds

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52
Q

abx ppx approved surgical procedures

A

contam, clean-contam operations, dirty wounds, prosthetic placement, immune comp host (any proc)

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53
Q

superinfections

A

new infection appears during chemotx for other infection

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54
Q

why do superinfections occur?

A

doses of abx can inhibit NF growth–>other orgs uninhibited

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55
Q

superinfection orgs

A

enterobacteriaceae, pseudomonas, candida, fungi

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56
Q

inc. risk of superinfection w/

A

brd spec abx, longer course, oral admin over IM/IV

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57
Q

abx misuse

A

-for viral infection (fever 2 wks which could be tb, intra-abd. abscess, inf. endocarditis, Ca-undetermined cause (NOT antipyretics)-improp. dosage -abx has to reach inf. site (get rid of pus and kidney stones)-lack of adeq. bac info: more testing!-improp. duration of tx (finish your abxs!)

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58
Q

receptors at parasympathetic end organs (and symp. sweat glands)

A

muscarinic: M1-5, 2,3*most common

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59
Q

B1 adrenergic receptor

A

heart (inc. force, rate)kidney (mediate renin secr) brain

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60
Q

B2 adrenergic receptor

A

airway, BVs of skel music, pregnant uterus-smooth musc relaxation

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61
Q

B3 adrenergic receptor

A

bladder smooth musc: relaxation

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62
Q

a1 adrenergic receptor

A

most BVs, urinary sphincters, eye-mediate contraction of smooth musc

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63
Q

a2 adrenergic receptor

A

some end organs, @ adrenergic nerve endings and in CNS

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64
Q

organs that received both parasym and symp innervation

A

heart, GI, bladder, eye, etc

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65
Q

organs w/ only symp innervation

A

adrenal medulla, spleen capsule, pilomotor musc, BVs of skin and skeletal muscd

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66
Q

reserpine blocks adrenergic system..

A

produces exaggerated cholinergic response: inc. GI motility, secretions

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67
Q

atropine blocks cardiac vagal influence..

A

cardiac acceleration, reduction of GI motility, secretion

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68
Q

eye sympathetics

A

a1: mydriasis (dilator musc. of iris) B2: inc. aqueous humor

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69
Q

gland sympathetics

A

a, BB2: respiratory secretions

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70
Q

heart sympathetics

A

B1, B2:inc. rate (SA node), contractility (ventricles), automaticity, conduction velocity (SA, AV nodes)

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71
Q

BVs sympathetics (mucosa, saliva, skin, splanchnic)

A

a1, a2: constriction

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72
Q

BVs sympathetics (skeletal musc)

A

a1: constrictionB2: dilation

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73
Q

BVs parasyms

A

no PS inn to most vasc beds, but muscarinic rec are present on endo cells: activation of these receptors: NO-med. vasodilation

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74
Q

airway symps

A

relaxation: B2

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75
Q

GI symps

A

relaxation: a1, a2, B1, B2 dec. motility

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76
Q

Urinary bladder wall, sphincter, prostate sympathetics

A

relaxation: B2, B3 (widens out)contraction: a1 (sphinter)

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77
Q

kidney JG cell symp

A

inc. renin secretion: B1

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78
Q

uterus symp

A

contraction: a1relaxation: B2 (later on)

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79
Q

male sex organs symp

A

ejaculation: a1

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80
Q

male sex organs PS

A

erection

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81
Q

liver, fat cells symp

A

inc. glucose output: B2inc. FA output: B1

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82
Q

skin pilomotor music and sweat glands symps

A

contraction: a1secretion: muscarinic

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83
Q

eye PS

A

miosis (pupillary sphincter musc) accommodation- near vision (ciliary musc.)

84
Q

PS ciliary musc contraction also…

A

inc. pressure on trabecular meshwork–>inc. outflow of AH in canal of Schlemm and dec. intraocular pressure

85
Q

PS action on lacrimal gland

A

inc. tear production

86
Q

acetylcholine is formed by action of

A

choline acetyl transferse (choline + acetate)

87
Q

ACh pathway

A

stored in vesicles–>AP–>inc. IC [CA2+]–>storage vesicle fuses with plasma mem–>ACh rel. into synapse–>acts on postmen. rec–>activates transduction pathway–>response

88
Q

nicotinic rec. usually coupled to

A

Na+ channels

89
Q

muscarinic rec may be coupled to

A

phospholipase C, K+ channelsor act thru G-protein mechanism to inhibit adenylate cyclase

90
Q

actions of ACh terminated by

A

acetycholinesterase (rapid hydrolysis) choline and acetate recycle to ACh by presyn. nerve ending

91
Q

specific sites where drugs can modify cholinergic system

A

NAME?

92
Q

tyrosine–>DOPA–>DA–>NE

A
  1. tyrosine hydroxylase* 2. DOPA decarboxylase 3. Dopamine B-hydroxylase
93
Q

NE acts on postsyn. rec

A

a1 or B1–>signal transduction pathway–>response

94
Q

Noradrenergic signal transduction pathway

A

typ. involve G-prot. coupled rec. B-rec: coupled to adenylate cyclasea-rec: coupled to pholspholipases or ion channels

95
Q

NE can also act on

A

a2 rec on presynaptic nerve ending: feedback inhibition on NE release

96
Q

action of NE terminated mostly by

A

rapid reuptake into presyn. nerve ending, med. by high affinity transport pump–>broken down by MAO or requestered in storage vesicles

97
Q

sites of pharm intervention on Noradrenergic system

A

NAME?

98
Q

direct acting muscarinic agonists

A

acetycholine (Miochol-E)carbachol (Isopto Carbachol)methacholine (Provocholine)bethanechol (Urecholine)pilocarpine (Salagen/Ocusert Pilo)cevimeline (Evoxac)

99
Q

indirect acting drugs: cholinesterase inhibitors -reversible

A

edrophonium (Tensilon)physostigmine/eserineneostigmine (Prostigmin)pyridostigmine (Mestinon)rivastigmine (Exelon)donepezil (Aricept)carbamate insecticides (Carbaryl)

100
Q

indirect acting drugs: cholinesterase inhibitors-irreversible

A

DFP/diisopropylfurophosphate/isoflurophate and echothiophateorganophasphate insecticides (Parathion, Malathion)nerve gases in chem warfare (Sarin, soman, Tabun, Vx)

101
Q

indirect acting drugs: cGMP phosphodiesterase (PDE-5) inhibitors

A

sildenafil (Viagra)vardenafil (Levitra)tadalafil (Cialis)

102
Q

Cholinesterase Reactivator

A

pralidoxime/2-PAM (Protopam)

103
Q

Toxins

A

botulinum toxin (BOTOX)

104
Q

Muscarinic ANTAGONISTS (anticholinergics)

A

atropine (hyoscyamine) and homatropinescopolamine and methscopolaminedicyclomine (Bentyl)propanthelineglycopyrrolate (Robinul)ipratropium (Atrovent)tiatropium (Spiriva)benztropine (Cogentin)trihexyphenidyl (Artane)tolterodine (Detrol)oxybutynin (Ditropan)solifenacin (VESIcare)tropicamide (Mydriacyl)

105
Q

Botulinum toxin (BOTOX) acts by

A

inhib. syn/rel of ACh

106
Q

M1 rec

A

in symp. gang and myenteric plexus, unclear functionpossibly stomach: med gastric acid sec

107
Q

M2 rec

A

located in heart, some smooth musc

108
Q

M3 rec

A

glands, smooth musc, BVs

109
Q

ACh stimulated muscarinic rec in what kind of manner

A

dose/conc. dependent, relatively nonselective

110
Q

Nm vs Nn rec.

A

Nm rec. located on sk. music at NM junc, Nn rec. located in autonom ganglia and adrenal medulla

111
Q

at low/mod doses ACh…at high doses…

A

-stim both types nicotinic receptor-desensitizes rec at high conc.–>gang. blockade, muscle paralysis(in contrast to muscarinic: no desensitization, just plateau)

112
Q

PS heart

A

atria, SA node, AV node, minor to ventricles-dec. HR by slowing firing of SA nodal pacemaker cells and slowing AV conduction-only min. effects on ventricular contractility and automaticity

113
Q

PS BVs

A

not inn. by PS, but endothelial cells in most BVs do contain muscarinic rec., stim. by ACh or muscarinic agonists–>NO (cGMP) med vasodilation–>dec. in BP-enhanced by cholinesterase inhibs like edrophonium, blocked by muscarinic antagonists such as atropine

114
Q

BVs that receive more PS inn.

A

corpus cavernosum, some cerebral, coronary, skeletal musc. BVs

115
Q

PS eye

A

pupillary constrictor muscles: miosisciliary muscle: accommodation-lowered IOP (outflow of AH)

116
Q

PS smooth muscle

A

bladder, stomach, sm. intestine, bowel, etc.-typ. stim. contraction of sm. musc to increase motility

117
Q

PS glands

A

salivary, lacrimal, mucosa of GI, airway, etc.-stimulate secretions (muscarinic ANTAGONISTS have drying effect)

118
Q

PS airways

A

bronchoconstriction and inc. respiratory secretions-

119
Q

Muscarinic ANTAGONISTS useful in asthma tx

A

ipratropium (Atrovent) tiatropium (Spiriva)(muscarinic agonist or cholinesterase inhibs. can aggravate asthma)

120
Q

PS GI

A

stimulate GI motility and secretionalso reg by “enteric NS”

121
Q

PS NM junction

A

ACh released by motor neurons can act on nicotinic rec. at motor end plate to cause musc. contraction receptors are DESENSITIZED if excess ACh (i.e. high dose cholinesterase inhib.)–>musc. paralysisexogenously admin. ACh has little effect on skel. musc. -nicotinic effects can be inhib by ganglionic and NM blockers

122
Q

direct acting muscarinic agonist activity

A

inc. GI motility, secretiondec. HRdec. BP due to dec. CO and direct vasodilationcontraction of bladder, relax. of ur. sphinctersmiosis and dec. IOPstim of secretions

123
Q

adverse effects of muscarinic stimulation

A

hypotension, bradycardia, chronchoconstriction, diarrhea, cramping, urinary incontinence, excessive sweating, salivation

124
Q

major tx uses of muscarinic agonists

A

promote GI motility (bethanechol)tx urinary retention (bethanechol)tx of glaucoma (pilocarpine, acetylcholine, carbachol)tx of sal. gland dysfunc (pilocarpine, cevimeline)pulmonary function testing in asthma (methacholine)- dangerous dx test

125
Q

when muscarinic agonists are contraindicated/used w/ caution

A

asthma, bradycardia, hypotension, vasomotor instability, CAD, peptic ulcer disease, hyperthyroidism, weakened smooth musc of bladder/GI, urinary/intestinal obstruction

126
Q

DO NOT give choinesters..

A

IV or IM, but rather subQ, orally, topically(eye)

127
Q

acetylcholine

A

limited, tx for glaucoma–>rapidly hydrolyzed by pseudocholinesterase in plasma

128
Q

carbachol

A

analog of ACh, resistant to hydrolysis-stim both muscarinic and nicotinic-topically for glaucoma

129
Q

methacholine

A

ACh analog, stim muscarinic (little nicotinic effect)used in asthma pulmonary function testing

130
Q

bethanechol (Urecholine)

A

ACh analog, resis to hydrolysis, direct muscarinic agonist (little nicotinic effect)stim. GI motility and tx for urinary retention

131
Q

pilocarpine (Salagen, Ocusert Pilo)

A

muscarinic agonist, tx for glaucoma and xerostomia (dry mouth) due to poor salivary secretion

132
Q

cevimeline (Evoxac)

A

muscarinic agonist, tx for salivary gland dysfunction

133
Q

ascarine

A

natural in mushrooms (Inocybe and Clitocybe)-salivation, lacrimation, nausea, extreme GI hypermotility, bronchospasm, bradycardia, hypotension, shock-can be tx with high dose atropine (1-2 mg IM every 30 min)

134
Q

cholinesterase inhibitors have similar effects as muscarinic agonists, plus

A

stimulation of skeletal muscle–>paralysis of skeletal muscles @ toxic doses

135
Q

toxic effects of cholinesterase inhibitors (cholinergic crisis)

A

i.e. organophosphate insecticide/nerve gase poisoning-SLUDGE (salivation, lacrimation, urination, defection, GI distress, emesis)-skel musc fasciculations–>paralysis-bradycardia, hypotension, shock-severe miosis-CNS stimulation and seizures–>coma-chronic exposure to some–>demyelination of axons and various neuropathies

136
Q

tx of acute cholinesterase inhibitor poisoning

A

-administer high doses atropine (2-4 mg IV initially) followed by 2 mg IM every 10 min until symptoms disappear to block muscarinic receptors -admin pralidoxime to reactivate enzyme (effective w/ organophosphates only)-provide additional symptomatic tx as needed (i.e. diazepam for seizures)

137
Q

major tx uses of cholinesterase inhibitors: myasthenia gravis

A

dx: endrophonium testtx: pyridostigmine, neostigmineMG is AI against nicotinic rec. at motor end plate

138
Q

Tensilon Test

A

admin 2-8 mmg edrophonium; improvement in musc. strength suppors myasthenia gravis dxif musc. wkns worsens: indicative of musc. wkns from exc. doses other cholinesterase inhibitors (cholinergic crisis)- 5 min duration of action

139
Q

other (more commonly used) myasthenia gravis dx tests

A

electromyography (EMG)serology

140
Q

cholinesterase inhibitors: tx of glaucoma

A

cholinergic agonists (acetylcholine, carbachol, pilocarpine)cholinesterase inhibitors (echothiophate)again..these contract ciliary musc–>put tension on trabecular meshwork–>inc. outflow of AH through canal of Schlemm

141
Q

cholinesterase inhibitors: tx of Alzheimer’s

A

loss of cholinergic neurons (Nucleus basal is of Meynert)–>raise ACh levels and reverse deficittetrahydroaminoacridine (Tacrine)* original, but causes liver damagerivastigmine (Exelon)donepezil (Aricept)galantamine (Reminyl)

142
Q

other uses of cholinesterase inhibitors

A

-tx of poisoning by atropine/other antimuscarinic drugs: physostigmine-reversal of NM blockade by nondepol. NM blockers: neostigmine, pyridostigmine-tx of atony of bladder or GI tract (i.e.: urine retention, paralytic ileus, etc)-pyridostigmine used by military to protect against nerve gas: ““pre-exposure antidotal enhancement”

143
Q

CI’s and precautions in cholinesterase inhibitor use

A

asthmabradycardia, hypotension, CADpeptic ulcer diseaseurinary or intestinal obstruction

144
Q

reversible cholinesterase inhibitors, quaternary ammonium compounds- cannot enter CNS

A

edrophonium (Tensilon), neostigmine (Prostigmin) pyridostigmine (Mestinon)

145
Q

reversible cholinesterase inhibitor, nonquaternary-so able to enter CNS

A

physostigmine/eserine (Antilirium)tx for atropine/other antimuscarinic agent poisoning(fallen into disfavor, esp. with tricyclic antidep. OD)

146
Q

Organophosphate insecticides

A

parathion, malathion–>need to be oxidized to active metabolites (paroxone and malaoxone) happens faster in insects, cannot detoxify(but can still cause toxicity in humans)-can be absorbed thru skin-S&S typical of cholinesterase inhibs.-tx poisoning w. atropine, pralidoxime (& other sympt. support)

147
Q

Carbamate insecticides

A

carbaryl-absorbed less thru skin-tx poisoning w/ atropine, pralidoxime is NOT useful in tx of carbamate insecticides!

148
Q

DFP/Isoflurophate and Nerve Gases

A

Sarinpotent, toxic, irreversible cholinesterase inhibitors-S&S typ. for cholinesterase inhibs.-tx poisoning w/ atropine and pralidoxime-DFP/Isoflurophate: glaucoma tx

149
Q

Pralidoxime/2-PAM (Protopam)

A

cholinesterase reactivator! binds phosphate grp that inhib. enzyme thereby regenerating enzyme-antidote for orgphos poisoning w/in 2 hours of exposure-does not work with carbamate insecticides

150
Q

ED drugs

A

Sildenafil (Viagra)Vardenafil (Levitra)Tadalafil (Cialis)-NO activates guanylcyclase in vasc. sm musc to produce cGMP–>vasodilation–>erection-drug inhibits cGMP phosphodiesterase type 5 (PDE-5) which breaks down cGMP

151
Q

ED drug side effects/toxicities

A

-general vasodilation–>hypotension–>reflex inc. in HR (problem for men w/ CV disease)-visual distrubances: blue/green discrim. probs-auditory disturbances

152
Q

ED pharmacokinetics

A

oral admin, sildenafil and vardenafil onset: 30 min, pk plasma levels about 1 hr, duration 4 hrs tadalafil longer 1/2 life, onset 45 min, and duration about 36 hrs-metabolized by CYP3A4: potential for drug interactions-dosage adj. for renal/hepatic disease pts

153
Q

ED drug interactions

A

erythromycin, ketaconazole, cimetidine, others metabolized by CYP3A4vasodilators (nitrates, Ca2+ channel blockers, a1 blockers)sympathomimetics

154
Q

botulinium toxin

A

produced by Clostridium botulinium-rel. of ACh from nerve endings–>affects both autonomic nerve endings (antichol. effects) and NM junction (paralysis)-death from diaphragmatic paralysis, 0.5-1.0 ug dose may be fataltx: sympt. support (resp) + abx to toxin-med uses: optham. disorders, wrinkles (BOTOX), dystonia, exc. sweating, over-active bladder

155
Q

anticholinergic pharm effects

A

competitive antagonists at muscarinic receptors-drying of secretions-dec. tone and motil. of GI tract-relax. of bladder and urine retention-bronchodilation-mydriasis w/ cycloplegia (loss of accomm.) and inc. in IOP-inc. HR (atropine may cause initial slight bradycardia)-CNS: sedation and amnesia at low doses; excitation and seizures at toxic dosesquaternary salts do NOT produce CNS effects

156
Q

therapeutic uses of anticholinergics part 1

A

-GI disorders-urine incontinence-opth: mydriatic agents (*do NOT use in pts w/ glaucoma!)-anesthesiology to reduce vagal tone on heart and dry secretions; also to prevent muscarinic side effects when cholinesterase inhibs used to reverse effects of NM blockers-antidote for poisoning with cholinesterase inhibs. or muscarinic agonists (some mushroom poisoning)

157
Q

therapeutic uses of anticholinergics part 2

A

-prevent motion sickness (Scopolamine)-Parkinson’s (benztropine, trihexyphenidyle, diphenhydramine)-dental proc. to inhib salivation (atropine, glycopyrrolate)-cardiac stim in emergencies (atropine)-asthma and COPD (ipratropium, tiatropium)-pulmonary med to dry resp secretions

158
Q

anticholinergic side effects/toxicities

A

dry mouthdry, hot skinconstipation, urine ret.visual disturbances, blurred vision, photophobiaCNS effects: sedation, confusion, amnesia (elderly)

159
Q

anticholinergics/muscarinic antagonist CIs/precautions

A

glaucoma (esp. narrow angle)prostatic hypertrophyCV instabilitysevere ulcerative colitis

160
Q

acute antichol. poisoning

A

dry, hot skin/ hyperthermiasevere mydriasis, blurring, photophobiaCNS stim: agitation, halluc, seizure–>coma–>deathcessation of GI motility (no bowel sounds)weak rapid pusle, tachy, arrhyths.

161
Q

tx of acute antichol. poisoning

A

admin of physostigmine or other cholinesterase inhibitorsbenzos for seizure txice baths to cool down, keep pt in dark, quiet area

162
Q

other drugs with anticholinergic side effects

A

antihistamines, antipsychotics, antidepressants, etc.

163
Q

atropine (Hyoscyamine) and Homatropine

A

NAME?

164
Q

atropine effects: heart

A

tachycardia w/ slight inc. CO (may have transient bradycardia)tx for MI w/ inc. vagal tone: low CO and dec. BP

165
Q

atropine effects: BVs

A

can reverse hypotensive actions of acetylcholine/other muscarinic agonistscutaneous vasodil and flushing of skin

166
Q

atropine effects: eye

A

NAME?

167
Q

atropine effects: GI tract

A

inhib. motility and tone (antispasmodic action for IBS)need high dose to dec. acid sec, so H2-histamine blockers (cimetidine, ranitidine, nizatidine, famotidine, or PPIs) used for peptic ulcers instead

168
Q

atropine effects: urinary tract

A

relaxes bladder body and contracts sphincter–>retentiontx incontinence, CI in prostatic hypertrophy

169
Q

atropine effects: sweat glands

A

blocks muscarinic rec.–>inhib sweating–>rise in body temp *children extra sensitive

170
Q

atropine effects: salivary glands

A

inhib. saliva sec. “dry mouth”

171
Q

atropine effects: respiratory tract

A

dries secretions, bronchodilation

172
Q

atropine effects: CNS

A

depressant (low doses) and stimulation (hight doses): agitation and seizuresmod-high: hallucinogenic

173
Q

atropine tx uses

A

NAME?

174
Q

at 0.5 mg atropine

A

some cardiac slowing, mouth dryness, sweating inhib

175
Q

1.0 mg atropine

A

def dry mouth, thirst, heart accel. (slowing 1st), mild pupil dilation

176
Q

2.0 mg atropine

A

rapid HR, marked dry mouth, dil. pupils, blurred near vision

177
Q

5.0 mg atropine

A

all above + diff speaking/swallowing, restless, fatigue, HA, dry, hot skin, diff mictur., red intestinal peristalsis

178
Q

10.0+ mg atropine

A

all above + more marked, pulse rapid/wk, iris almost obliterated, vision v. blurred, skin flushed, hot dry, scarlet, ataxia, restless, excitement, hallucinations, delirium, coma

179
Q

Scopolamine (hyoscine) and Methscopolamine

A

-plant Hyoscyamus niger (henbane), chem sim to atropinequarternary analog, does NOT cross BBB-sim to atropine but more of CNS depressant (sed/amn) than atropine-oral and patch form (Transderm Scop) for pref of motion-sickness, vertigo

180
Q

Dicyclomine (Bentyl)

A

nonquart. antimuscarinic-used as intestinal antispasmodic for IBS tx

181
Q

Propantheline (Pro-Banthine)

A

antimuscarinic-antispasmodid, IBS txquaternary comp. w/ few CNS effects

182
Q

Glycopyrrolate (Robinul)

A

quart. antimuscarinic (no CNS effects)-used in anesthesiology as prep med to dry resp. sec and inhib vagal reflexes-also used as gen purpose antimuscarinic

183
Q

Ipratropium (Atrovent)Tiatropium (Spiriva)aclidinium (Tudorza)

A

antimuscarinicsquat. salts admin. by inhalation for asthma and COPD txfew systemic effectstiatropium longer duration than ipratropiumaclidium: new drug approved for COPD (long acting in lungs, broken down by esterases in plasma: few systemic effects)

184
Q

Benztropine (Cogentin)Trihexyphenidyl (Artane)

A

centrally acting antimuscarinics used in Parkinson’s/drug-ind. Parkinsonism tx

185
Q

Tolterodine (Detrol)Oxbutynin (Ditropan)Solifenacin (VESIcare)

A

antimuscarinics, tx of urinary incontinence due to overactive bladder

186
Q

Tropicamide (Midriacyl)

A

antimuscarinic used to dilate pupil for examination

187
Q

first gen H1 antagonists: v. sedating antihistamines

A

Promethazine hydrochloride (Phenergan)Hydroxyzine (Vistaril)

188
Q

first gen H1 antagonists: sedating antihistamines

A

Diphenhydramine (Benadryl)Dimenhydrinate (Dramamine)Doxylamine (Unisom)Chorpheniramine maleate (Chlor-Trimeton)Meclizine (Bonine, Antivert)

189
Q

second gen H1 antagonists: non-sedating antihistamines

A

Loratadine (Claritin, Alavert)/Desloratidine (Clarinex)Certirizine (Zyrtec) and Levocetirizine (Xyzal)Fexofenadine (Allegra)

190
Q

H2 antagonists

A

Cimetidine (Tagamet)Ranitidine (Zantac)Famotidine (Pepcid)Nizatidine (Axid)

191
Q

histamine functions

A

mediates phys. resp to tissue/cell injurymediates inflamm. resp/allergic reactionsreg. cell growth/repairreg. gastric acid secNT in CNSpos. reg. of cardiac functions

192
Q

histamine syn

A

syn from histidine by histidine decarboxylase

193
Q

histamine metab

A

involved N-methylation–>oxidation to N-methylimidazole acetic acid

194
Q

histamine storage

A

mast cells and basophilsskin and mucosa of GI and resp tractsIC histamine stored in granules, loosely bound to proteoglycans like heparin sulfate or chondroitin sulfate

195
Q

histamine release: drug/chem induced

A

-displaced by amine drugs (morphine, tubocurarine, B-blockers)-compound 48/80-toxins and venoms

196
Q

histamine release may released in response to

A

cell/tissue damage

197
Q

histamine release: immunologic stimulation

A

mast cells sensitized w/ IgE Abs–>rel. histamine when exposed to approp. allergen-other autocoids syn or del: PGs, LKTs, kinins (bradykinin)

198
Q

histamine release: neuronal and endocrine stimulation

A

gastric mucosa: rel in resp to neuronal (vagal)/endocrine stim (gastrin)-neuronal med. by ACh -the histamine binds to H2 rec on parietal cells–>HCl sec–>permissive effect, allows gastrin and acetyl choline to directly stim. acid secretion(H2 rec ANTAGONISTS are effective in red. sec of gastric acid in response to histamine, vagal stim, ACh, or gastrin)

199
Q

physio effects of histamine

A
  • dilation of sm. BVs–>flushing, lowered peri. resis., dec. BP
  • inc. cap perm–>leakage of fluid and protein into extravascular space
  • stim of peripheral nerve ending: pain, burning, itching
200
Q

physio effects of histamine: triple respons

A
  • red spot, local (dilation of minute BVs)
  • flare (dil. or neighboring arterioles)
  • wheal (inc. cap perm)
201
Q

physio effects of histamine: histamine shock

A

vasodilation and fluid leakage into EV space–>sig. drop in BP (resembles traumatic, septic, or hemorrhagic shock)

202
Q

physio effects of histamine: bronchial constriction

A

asthmatic and anaphylactic bronchospasm
-not completely dep on histamine, so not effec. antag by antihistamines alone (use sympathomimetic drugs, methylaxanthines)

203
Q

physio effects of histamine: stimulation of gastric acid secretion

A

in response to stress, vagal stim, gastrin and cholinergic agonists
-mediated by H2 receptors (blocking these red. stomach acid sec.)

204
Q

physio effects of histamine: cerebral vessels and histamine

A

-v. sens. to histamine!–>intense dilation–>pulsatory HA (stretching of sensory nerve endings-histamine cephalalgia)
(attempt to antag H1 and H2 rec, little success)

205
Q

physio effects of histamine: direct effects on heart

A

inc. force of contraction

slowing of AV conduction

Pharm (45 decks)

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