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Flashcards in T2: ANS, Histamine Deck (205):
1

bactericidal drugs

penicillinscephalosporinsaminoglycosidesvancomycinaztreonamimipenemfluroroquinolonesmetronidazolepolymyxinsquinupristin-dalfopristinbacitracin

2

bacteriostatic drugs

erythromycin (macrolides)clindamycintetracyclinechloramphenicolsulfonamidestrimethoprimnitrofurantoin

3

narrow spectrum

only G+ or G-: isoniazid against mycobacterium

4

extended spectrum

G+, some G- i.e. ampicillin

5

broad spec

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

6

expense of drug administration

IV>IM>oral (cheapest)

7

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

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

8

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

methicillinnafcillinoxacillin

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

ampicillinamoxicillin

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

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

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

aztreonam

12

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

Imipenem + Cilastatin

13

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

Clavulanic acid, Tazobactam

14

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

CefazolinCephalexin

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

CefaclorCefoxitinCefuroximeCefprozil

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

CeftriaxoneCefiximeCefotaximeCeftazidime

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

Cefepime

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

Ceftaroline

19

other drugs that inhibit bacterial cell wall synthesis

vancomycinbacitracin

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drugs that alter cell membrane permeability

Polymyxin BDaptomycin

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drugs that inhibit bacterial protein synthesis: Tetracyclines

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

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drugs that inhibit bacterial protein synthesis: Macrolides

Erythromycin base" Estolate, " Stearate, " Ethylsuccinate, " LactobionateClarithromycinAzithromycinTelithromycin

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drugs that inhibit bacterial protein synthesis: Aminoglycosides

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

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drugs that inhibit bacterial protein synthesis: Misc.

ClindamycinQuinupristin/DalfopristinLinezolid

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act on 50S ribosomal subunit

Cloramphenicol, macrolides, clindamycin, quinupristin/dalfopristin, linezolid

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act on 30S ribosomal subunit

Aminoglycosides, Tetracyclines

27

drugs that act as anti-metabolites: Sulfonamindes

Silver Sulfadiazine (SILVADINE): topicalTrimethoprim-sulfamethoxazole

28

drugs that inhibit nucleic acid synthesis: Fluoroquinolones

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

29

Misc. drugs that act via nucleic acids

MetronidazoleNitrofurantoinRifampin

30

empirical therapy

"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

31

epsilometer (E) test:

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

32

how to monitor antimicrobial activity in vivo

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

33

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

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

34

BBB may prevent..

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

35

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

abx binding to plasma proteins

36

med doses may need to be adjusted for..

renal/hepatic failurenewbornsoral vs. parenteral admin

37

bactericidal or bacteriostatic?

cidal is better, esp. if immunecomp

38

strains of these are resistant to all known drugs

EnterococciPseudomonasEnterobacter

39

bacterial resistance factors

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

40

how microorganisms produce resistance

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

41

resistance mediated by genetic exchange

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

42

conjugation

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

43

transposon

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

44

biochem mechs of drug resistance

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)

45

forms of synergism seen with combo abx tx

-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)

46

synergism

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

47

antagonism

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

48

antagonism exs.

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

49

combo abx tx uses

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)

50

disadv. of combo abx tx

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

51

abx ppx

-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

52

abx ppx approved surgical procedures

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

53

superinfections

new infection appears during chemotx for other infection

54

why do superinfections occur?

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

55

superinfection orgs

enterobacteriaceae, pseudomonas, candida, fungi

56

inc. risk of superinfection w/

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

57

abx misuse

-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!)

58

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

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

59

B1 adrenergic receptor

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

60

B2 adrenergic receptor

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

61

B3 adrenergic receptor

bladder smooth musc: relaxation

62

a1 adrenergic receptor

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

63

a2 adrenergic receptor

some end organs, @ adrenergic nerve endings and in CNS

64

organs that received both parasym and symp innervation

heart, GI, bladder, eye, etc

65

organs w/ only symp innervation

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

66

reserpine blocks adrenergic system..

produces exaggerated cholinergic response: inc. GI motility, secretions

67

atropine blocks cardiac vagal influence..

cardiac acceleration, reduction of GI motility, secretion

68

eye sympathetics

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

69

gland sympathetics

a, BB2: respiratory secretions

70

heart sympathetics

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

71

BVs sympathetics (mucosa, saliva, skin, splanchnic)

a1, a2: constriction

72

BVs sympathetics (skeletal musc)

a1: constrictionB2: dilation

73

BVs parasyms

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

74

airway symps

relaxation: B2

75

GI symps

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

76

Urinary bladder wall, sphincter, prostate sympathetics

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

77

kidney JG cell symp

inc. renin secretion: B1

78

uterus symp

contraction: a1relaxation: B2 (later on)

79

male sex organs symp

ejaculation: a1

80

male sex organs PS

erection

81

liver, fat cells symp

inc. glucose output: B2inc. FA output: B1

82

skin pilomotor music and sweat glands symps

contraction: a1secretion: muscarinic

83

eye PS

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

84

PS ciliary musc contraction also...

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

85

PS action on lacrimal gland

inc. tear production

86

acetylcholine is formed by action of

choline acetyl transferse (choline + acetate)

87

ACh pathway

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

nicotinic rec. usually coupled to

Na+ channels

89

muscarinic rec may be coupled to

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

90

actions of ACh terminated by

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

91

specific sites where drugs can modify cholinergic system

#NAME?

92

tyrosine-->DOPA-->DA-->NE

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

93

NE acts on postsyn. rec

a1 or B1-->signal transduction pathway-->response

94

Noradrenergic signal transduction pathway

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

95

NE can also act on

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

96

action of NE terminated mostly by

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

97

sites of pharm intervention on Noradrenergic system

#NAME?

98

direct acting muscarinic agonists

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

99

indirect acting drugs: cholinesterase inhibitors -reversible

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

100

indirect acting drugs: cholinesterase inhibitors-irreversible

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

101

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

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

102

Cholinesterase Reactivator

pralidoxime/2-PAM (Protopam)

103

Toxins

botulinum toxin (BOTOX)

104

Muscarinic ANTAGONISTS (anticholinergics)

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

Botulinum toxin (BOTOX) acts by

inhib. syn/rel of ACh

106

M1 rec

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

107

M2 rec

located in heart, some smooth musc

108

M3 rec

glands, smooth musc, BVs

109

ACh stimulated muscarinic rec in what kind of manner

dose/conc. dependent, relatively nonselective

110

Nm vs Nn rec.

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

111

at low/mod doses ACh...at high doses...

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

112

PS heart

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

PS BVs

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

BVs that receive more PS inn.

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

115

PS eye

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

116

PS smooth muscle

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

117

PS glands

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

118

PS airways

bronchoconstriction and inc. respiratory secretions-

119

Muscarinic ANTAGONISTS useful in asthma tx

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

120

PS GI

stimulate GI motility and secretionalso reg by "enteric NS"

121

PS NM junction

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. paralysis*exogenously admin. ACh has little effect on skel. musc. -nicotinic effects can be inhib by ganglionic and NM blockers

122

direct acting muscarinic agonist activity

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

adverse effects of muscarinic stimulation

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

124

major tx uses of muscarinic agonists

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

when muscarinic agonists are contraindicated/used w/ caution

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

126

DO NOT give choinesters..

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

127

acetylcholine

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

128

carbachol

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

129

methacholine

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

130

bethanechol (Urecholine)

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

131

pilocarpine (Salagen, Ocusert Pilo)

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

132

cevimeline (Evoxac)

muscarinic agonist, tx for salivary gland dysfunction

133

ascarine

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

cholinesterase inhibitors have similar effects as muscarinic agonists, plus

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

135

toxic effects of cholinesterase inhibitors (cholinergic crisis)

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

tx of acute cholinesterase inhibitor poisoning

-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

major tx uses of cholinesterase inhibitors: myasthenia gravis

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

138

Tensilon Test

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

other (more commonly used) myasthenia gravis dx tests

electromyography (EMG)serology

140

cholinesterase inhibitors: tx of glaucoma

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

cholinesterase inhibitors: tx of Alzheimer's

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

other uses of cholinesterase inhibitors

-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

CI's and precautions in cholinesterase inhibitor use

asthmabradycardia, hypotension, CADpeptic ulcer diseaseurinary or intestinal obstruction

144

reversible cholinesterase inhibitors, quaternary ammonium compounds- cannot enter CNS

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

145

reversible cholinesterase inhibitor, nonquaternary-so able to enter CNS

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

146

Organophosphate insecticides

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

Carbamate insecticides

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

148

DFP/Isoflurophate and Nerve Gases

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

149

Pralidoxime/2-PAM (Protopam)

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

ED drugs

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

ED drug side effects/toxicities

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

152

ED pharmacokinetics

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

ED drug interactions

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

154

botulinium toxin

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

anticholinergic pharm effects

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 doses*quaternary salts do NOT produce CNS effects

156

therapeutic uses of anticholinergics part 1

-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

therapeutic uses of anticholinergics part 2

-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

anticholinergic side effects/toxicities

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

159

anticholinergics/muscarinic antagonist CIs/precautions

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

160

acute antichol. poisoning

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

tx of acute antichol. poisoning

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

162

other drugs with anticholinergic side effects

antihistamines, antipsychotics, antidepressants, etc.

163

atropine (Hyoscyamine) and Homatropine

#NAME?

164

atropine effects: heart

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

165

atropine effects: BVs

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

166

atropine effects: eye

#NAME?

167

atropine effects: GI tract

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

atropine effects: urinary tract

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

169

atropine effects: sweat glands

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

170

atropine effects: salivary glands

inhib. saliva sec. "dry mouth"

171

atropine effects: respiratory tract

dries secretions, bronchodilation

172

atropine effects: CNS

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

173

atropine tx uses

#NAME?

174

at 0.5 mg atropine

some cardiac slowing, mouth dryness, sweating inhib

175

1.0 mg atropine

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

176

2.0 mg atropine

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

177

5.0 mg atropine

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

178

10.0+ mg atropine

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

Scopolamine (hyoscine) and Methscopolamine

-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

Dicyclomine (Bentyl)

nonquart. antimuscarinic-used as intestinal antispasmodic for IBS tx

181

Propantheline (Pro-Banthine)

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

182

Glycopyrrolate (Robinul)

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

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

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

Benztropine (Cogentin)Trihexyphenidyl (Artane)

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

185

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

antimuscarinics, tx of urinary incontinence due to overactive bladder

186

Tropicamide (Midriacyl)

antimuscarinic used to dilate pupil for examination

187

first gen H1 antagonists: v. sedating antihistamines

Promethazine hydrochloride (Phenergan)Hydroxyzine (Vistaril)

188

first gen H1 antagonists: sedating antihistamines

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

189

second gen H1 antagonists: non-sedating antihistamines

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

190

H2 antagonists

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

191

histamine functions

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

192

histamine syn

syn from histidine by histidine decarboxylase

193

histamine metab

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

194

histamine storage

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

histamine release: drug/chem induced

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

196

histamine release may released in response to

cell/tissue damage

197

histamine release: immunologic stimulation

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

198

histamine release: neuronal and endocrine stimulation

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

physio effects of histamine

-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

physio effects of histamine: triple respons

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

201

physio effects of histamine: histamine shock

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

202

physio effects of histamine: bronchial constriction

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

203

physio effects of histamine: stimulation of gastric acid secretion

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

204

physio effects of histamine: cerebral vessels and histamine

-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

physio effects of histamine: direct effects on heart

inc. force of contraction
slowing of AV conduction