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Flashcards in Pharm 2 Deck (357):
1

bactericidal drugs

penicillins
cephalosporins
aminoglycosides
vancomycin
aztreonam
imipenem
fluroroquinolones
metronidazole
polymyxins
quinupristin-dalfopristin
bacitracin

2

bacteriostatic drugs

erythromycin (macrolides)
clindamycin
tetracycline
chloramphenicol
sulfonamides
trimethoprim
nitrofurantoin

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)

methicillin
nafcillin
oxacillin

9

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

ampicillin
amoxicillin

10

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

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

11

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

Cefazolin
Cephalexin

15

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

Cefaclor
Cefoxitin
Cefuroxime
Cefprozil

16

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

Ceftriaxone
Cefixime
Cefotaxime
Ceftazidime

17

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

Cefepime

18

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

Ceftaroline

19

other drugs that inhibit bacterial cell wall synthesis

vancomycin
bacitracin

20

drugs that alter cell membrane permeability

Polymyxin B
Daptomycin

21

drugs that inhibit bacterial protein synthesis: Tetracyclines

short-acting: Tetracycline
long-acting: Doxycycline, Minocycline
new: Tigecycline

22

drugs that inhibit bacterial protein synthesis: Macrolides

Erythromycin base
" Estolate, " Stearate, " Ethylsuccinate, " Lactobionate
Clarithromycin
Azithromycin
Telithromycin

23

drugs that inhibit bacterial protein synthesis: Aminoglycosides

Gentamicin; generic: Garamycin, Jenamicin
Tobramycin; generic: Nebcin
Amikacin; generic: Amikin
Streptomycin
Neomycin

24

drugs that inhibit bacterial protein synthesis: Misc.

Clindamycin
Quinupristin/Dalfopristin
Linezolid

25

act on 50S ribosomal subunit

Cloramphenicol, macrolides, clindamycin, quinupristin/dalfopristin, linezolid

26

act on 30S ribosomal subunit

Aminoglycosides, Tetracyclines

27

drugs that act as anti-metabolites: Sulfonamindes

Silver Sulfadiazine (SILVADINE): topical
Trimethoprim-sulfamethoxazole

28

drugs that inhibit nucleic acid synthesis: Fluoroquinolones

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

29

Misc. drugs that act via nucleic acids

Metronidazole
Nitrofurantoin
Rifampin

30

empirical therapy

"best guess" therapy, br. spec/combo abx
guided 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 pathogen
bactericidal 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 failure
newborns
oral vs. parenteral admin

37

bactericidal or bacteriostatic?

cidal is better, esp. if immunecomp

38

strains of these are resistant to all known drugs

Enterococci
Pseudomonas
Enterobacter

39

bacterial resistance factors

indiscrim. use (misuse)
delay in optimal tx
admin of subopt. dose
tx during dormant stage
inability 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. genes
plasmid-->plasmid
plasmid-->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 inf
unknown 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 effects
selection of orgs resis. to >1 abx
possible 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, B
B2: 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: constriction
B2: 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: a1
relaxation: B2 (later on)

79

male sex organs symp

ejaculation: a1

80

male sex organs PS

erection

81

liver, fat cells symp

inc. glucose output: B2
inc. FA output: B1

82

skin pilomotor music and sweat glands symps

contraction: a1
secretion: 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+ channels
or 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

-ACh synthesis
-ACh release
-stim or blockade of postmen. receptors
-inhib. of AChesterase

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 cyclase
a-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

-synth, storage, del of NE
-stim or block of postsyn a1, B1, B2
-stim or block of presyn a2 rec
-inhib of NE reuptake
-inhib of NE metab by MAO

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/eserine
neostigmine (Prostigmin)
pyridostigmine (Mestinon)
rivastigmine (Exelon)
donepezil (Aricept)
carbamate insecticides (Carbaryl)

100

indirect acting drugs: cholinesterase inhibitors-irreversible

DFP/diisopropylfurophosphate/isoflurophate and echothiophate
organophasphate 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 homatropine
scopolamine and methscopolamine
dicyclomine (Bentyl)
propantheline
glycopyrrolate (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 function
possibly 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: miosis
ciliary 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 secretion
also 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, secretion
dec. HR
dec. BP due to dec. CO and direct vasodilation
contraction of bladder, relax. of ur. sphincters
miosis and dec. IOP
stim 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

muscarine

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 test
tx: pyridostigmine, neostigmine
MG is AI against nicotinic rec. at motor end plate

138

Tensilon Test

admin 2-8 mmg edrophonium; improvement in musc. strength suppors myasthenia gravis dx
if 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 deficit
tetrahydroaminoacridine (Tacrine)* original, but causes liver damage
rivastigmine (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

asthma
bradycardia, hypotension, CAD
peptic ulcer disease
urinary 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

Sarin
potent, 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 CYP3A4
vasodilators (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 fatal
tx: 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 mouth
dry, hot skin
constipation, urine ret.
visual disturbances, blurred vision, photophobia
CNS effects: sedation, confusion, amnesia (elderly)

159

anticholinergics/muscarinic antagonist
CIs/precautions

glaucoma (esp. narrow angle)
prostatic hypertrophy
CV instability
severe ulcerative colitis

160

acute antichol. poisoning

dry, hot skin/ hyperthermia
severe mydriasis, blurring, photophobia
CNS stim: agitation, halluc, seizure-->coma-->death
cessation of GI motility (no bowel sounds)
weak rapid pusle, tachy, arrhyths.

161

tx of acute antichol. poisoning

admin of physostigmine or other cholinesterase inhibitors
benzos for seizure tx
ice 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

-belladonna alkaloid found in nightshade (Atropa belladonna) and jimsonweed, mixture of d, l* -hyoscyamine
(semi-syn. analog), methylbromide salt does NOT penetrate CNS
prototype antimuscarinic

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 agonists
cutaneous vasodil and flushing of skin

166

atropine effects: eye

-mydriasis
-cycloplegia (paralysis of accomm.)
-inc. IOP

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-->retention
tx 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 seizures
mod-high: hallucinogenic

173

atropine tx uses

-preop to red sec (old) and block vagal ref on heart (new)
-cardiac stim post-MI
-antidote for poisoning with cholinesterase inhib/musc. agonists
-to dry resp. sec
-mydriatic and cycloplegic
-antispasmodic for GI: IBS, biliary colic

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 atropine
quarternary 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 tx
quaternary 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)

antimuscarinics
quat. salts admin. by inhalation for asthma and COPD tx
few systemic effects
tiatropium longer duration than ipratropium
aclidium: 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 injury
mediates inflamm. resp/allergic reactions
reg. cell growth/repair
reg. gastric acid sec
NT in CNS
pos. 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 basophils
skin and mucosa of GI and resp tracts
IC 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

-dil of small BVs-->flushing, lowered peripheral resistance, drop in BP
-inc. in cap perm-->leakage of fluid and prot. into extravascular space
-stimulation of peripheral nerve endings-->pain, burning, itching

200

physio effects of histamine: triple response

-red spot (dil. of minute BVs)
-flare (dil. of neighboring arterioles)
-wheal (inc. cap permeability)

201

physio effects of histamine: histamine shock

vasodilation and fluid leakage into EV space-->sig. drop of 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 effectively 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 rec. (blocking these red. stomach acid sec.)

204

physio effects of histamine: cerebral vessels and histamine

-v. sens to histamine!-->intense diation-->pulsatory HA (stretching of sensory nerve endings-histamine cephalgia)
(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

206

H1 receptor

-skin, BVs, heart, airway, CNS
-mediate rapid vasodil., inc. cap perm, irritation of peripheral nerve endings, bronchoconstriction

207

H1 receptor blockers/histamine antagonists

"antihistamines", tx allergies, rhinitis
(actually inverse agonists: red. activity of constitutively act. H1 rec.)

208

H2 receptor

-GI, heart, brain, various BVs
-mediated gastric acid secretion

209

H2 receptor blockers

-reduce gastric acid sec. (peptic ulcer disease)
-may be used to tx histamine-induced symps of Type 1 immediate hypersensitivity rxns (urticaria)

210

H3 receptors

-CNS
-presyn. autoreceptors to reg rel of histamine as NT (like alpha adrenergic rec?)
-no sp. drugs for clinic use (potentials: sleep/mood disorders, Alzheimer's disease)

211

H4 receptors

-hematopoetic cells
-unclear, inflammation

212

therapeutic uses of histamine

few
dx tests for allergies, asthma, and sensory nerve function

213

structure of antihistaminic drugs: H1

lipophilic ring structure + charged side chain amino group

214

structure of antihistaminic drugs: H2

hydrophilic ring structure + uncharged side chain

215

1st gen H1 antagonists: v. sedating

Promethazine hydrochloride (Phenergan)
Hydroxyzine (Vistaril)

216

1st gen H1 antagonists: sedating

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

217

2nd gen H1 antagonists: non-sedating

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

218

H1 antagonist pharm effects

occupy H1 rec w/out prod/initiating active response (competitive antagonism) OR inverse agonism
-reduce pain, itch, flare, vasodilation, inc. vasc. perm (red), congestion
-DO NOT prevent release of histamine/other inflamm/allerg mediators
-DO NOT reverse anaphylactic bronchospasm

219

uses of H1 antihistamine: allergy tx

hay fever (seasonal) rhinitis
relief of sneezing, wheezing, eye/nose/throat itch, rhinorrhea
certain allergic dermatitis (urticaria) (i.e. diphenhydramine in "anti-itch" topical meds)

220

alone, H1 antihistamines are NOT effective in..

anaphylaxix, angioedema, asthma
*bronchospasm may be life threatening, should be tx w/ epinephrine or other B-agonists, H1 antihist can be adjunct

221

uses of H1 antihistamine: common cold tx

alleviate nasal irritation (burning, itching, "runny nose")
DO NOT alter course of cold

222

uses of H1 antihistamine: antiemetics

(dimenhydrinate, meclinzine): prevent and tx motion sickness/vertigo
(doxylamine): sometimes to tx N/V during pregnancy
-may be more general anti emetics (3 above + hydroxyzine)

223

uses of H1 antihistamines: sedative and sleep aids

-night time cold remedies (Nyquil) and sleep aids
-Hydroxyzine (Atarax: Vistaril): sedatives
-Diphenhydramine, doxylamine: OTC sleep aids

224

uses of H1 antihistamines: antisecretory agents

(diphenhydramine) used in pulmonary medicine (tracheostomy care, etc)

225

uses of H1 antihistamines: Parkinsonism tx

anticholinergic activity (diphenhydramine)

226

side effects/toxicities of H1 antihistamines

anticholinergic: dry mouth, dry/hot skin, constipation, urine retention, loss of visual accomm. etc.
sedation drowsiness, confusion, amnesia, behavioral disturbances occur at common therapeutic doses
*may be more pronounced in elderly
*2nd gen (loratidine, fexofenadine, ceirizine) less CNS effects and sedation

227

more side effects/toxicities of H1 antihistamines

-paradox. CNS stim in some (esp. kids)
-reported teratogenic effects (doxylamine story)
-allergic rxns (topical use)
-lowers seizure threshold
-serious arrhythmias (Astemizole, terfenadine -w/drawn)

228

even more side effects/toxicities of H1 antihistamines

-acute poisoning/OD (kids esp):
symptoms like atropine poisoning: excitation, halluc., ataxia, uncoordination, convulsion, musc tremors, uncontrollagle clonic/tonic jerky motions, fixed dil. pupils, flushed face, fever, coma, cardio-resp collapse and death
tx: symptomatic: cholinesterase inhibitors (physostigmine), anti-seizure, CV meds as needed

229

antihistamine pharmacokinetics: admin

oral*, parenteral, topical
oral:
onset: 15-30 min, pk: 1 hour, duration 3-6 hours
degraded in body, excr. w/in 24 hours
*no cumulative effect if liver/kidneys are functional

230

2nd gen antihistamine pharmkin.

DO NOT cross BBB, do not cause sedation
longer durations of action (about 24 hrs), long 1/2 lives: wk+ to reach steady state

231

antihistamine drug interactions

-potentiates CNS depressants, etOH, barbs, opioids, benzos
-arrhythmias (torsades de pointes) in pts taking terfenadine or astemizole (metab by P450: CYP3A4 to active drug) w/ erythromycin, ketoconazole, or itraconazole
-the antihist. prodrug can block K+ channels in heart, not all prodrug broken down when taken w/ other drugs metabolized by CYP3A4
*both terfenadine (Seldane) and astemizole (Hismanal) w/drawn (Allegra, flexofenadine) is active metab of terfenadine

232

antihistamines can interfere w.

allergy testing, must stop antihistamine 5-7 days before testing

233

antihistamine combo preps

in cold, cough, allergy remedies
-decongestants, analgesics, antitussives, etOH, w/ the antihistamine

234

H2 histamine antagonists summary

comp. antags at H2 rec
tx for peptic ulcer disease

235

H2 histamine antagonists

Cimetidine (Tagamet)* cytP450 metab., anti-androgen
Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid)

236

H2 histamine antagonist pharm effects

-inhib gastric acid secretion (stim. by histamine) in response to:
-vagal stimulation (ACh)
-gastrin secretion (ZES: tumor)
-stress

237

H2 histamine antagonists tx

-duodenal/gastric ulcers
-gastroesophageal reflux
-ZES
-pre-op to lessen aspiration damage
-prevent stress ulcers

238

H2 histamine antagonist adverse rxns

(low: highly selective @ H2 rec)
-HA, dizzy, nausea, myalgia, skin rashes/itching (elderly, renal dysfunction)
-loss of libido, impotence, gynecomastia (chronic high does of Cimetidine-->can tx hirsutism)
-Cimetidine also can cause hematological rxns (cytopenias) and competes w. creatinine for renal secretion (inc. plasma conc. creatinine)

239

H2 antagonist pharmkin

-oral admin-->well absorbed
-1/2 lives about 2-4 hrs
-also injectable: cimetidine, ranitidine, famotidine
-metab by liver (cimetidine can inhib cytP450 and interfere w. metab of other drugs)
-sig. amounts excr unchanged in urine (adj. dose in renal disease pts.)

240

H2 antagonist drug interactions

Cimetidine: inhib hep microsomal drug metab enzymes:
warfarin, phenytoin, theophylline, phenobarbital, benzos, propranolol, nifedepine, digoxin, quinidine, tricyclic antidepressants
(Famotidine and nizatidine do not inhib P450 system, ranitidine has slight effect, not sig.)
-H2 blockers alter gastric pH: alter bioavailability of certain drugs

241

H2 antagonist therapeutic uses

gastric/duodenal ulcers, ZES, stress ulcers, reflux esophagitis, short bowel syndderom, hypersec. states (ZES), preanesthetic meds
*typ. not frontline drugs, PPIs used more commonly
**cimetidine is most widely used, but potential for most side effects/drug interactions

242

CRTZ

-floor of 4th ventricle, area postrema
-vomiting assoc. w. exposure to drugs, metabolic toxins, chemotherapy, radiation, changes in blood chemistry
NTs: DA, 5HT (serotonin) so tx w/ DA/serotonin antagonists
Dopamine antagonists: tx CRTZ induced N/V, NOT motion sickness/vertigo

243

serotonin also

NT action: is released by enterochromafin cells of GI tracts when GI distress (5-HT3 rec blockers prevent N/V)

244

vestibular apparatus and cerebellum

respond to motion (or "perceived" motion)
NTs: ACh and possibly histamine (inhibitors tx)
anticholinergics/antihistamines: tx motion sickness, vertigo NOT other causes of N/V (antihist. have some effect on CRTZ and vomiting center, but less eff. than DA antags)

245

cerebral cortex and limbic system:

vomiting ref. activated by emotional state (can be consciously suppressed): anxiolytic agents

246

efferent component of reflex

output from vomiting center-->salivary glands, stomach, sm. intestine, diaphragm, abd. mm

247

anticholinergic agents for nausea

Scopolamine
-acts on vestibular system, tx/prevents vertigo/motion sickness
-gen. effects on CRTZ, not as effective as DA, 5-HT untags
-Transderm Scop preperation

248

Scopolamine side effects/toxicity

-antichol. effects: dry mouth, constip, urinary retention, loss of accomm.
-sedation, confusion, amnesia

249

antihistamine for N/V effects

-primarily on vestibular, some have weak effects on CRTZ or vomiting center (cyclizine, doxylamine, meclizine, promethazine, hydroxyzine) (b/c of antichol. activity?)
-tx for motion sickness/vertigo
-some for gen. antiemetic (cyclizine, meclizine, promethazine, hydroxyzine)

250

antihistamine side effects/toxicity

antichol. effects, sedation, teratogen effects?

251

antihistamines for N/V

dimenhydrinate (Dramamine)
meclizine (Bonine, Antivert)
promethazine (Phenergan)
diphenhydramine (Benadryl)
doxylamine (Bendectine: teratogen? no-->now Diclegis)

252

Dopamine (D2) antagonists action

acts on CRTZ, tx:
postop nausea, cytotoxic drugs, radiation sickness, toxins

253

DA (D2) antagonist side effects/toxicity

parkinsonism (blocks striatum), post. hypotension, anticholinergic effects, sedation, lethargy, psychomotor slowing (antipsychotics), possible teratogen

254

D2 antagonists for N/V

prochlorperazine (Compazine) -phenothiazine
metoclopramide (Reglan)


255

metoclopramide (Reglan) for N/V

DA antag in CRTZ but also acts on enteric nerves to inc. GI/lower eso. sphincter tone and motility
tx: N/V from chemo, postop, toxin-induced, radiation
tx: gastric stasis, GERD, possible aspiration of vomitus

256

metoclopramide (Reglan) side effects

sedation, extrapyramidal motor problems: parkinsonism and acute dystonia

257

5-HT3 antagonists (serotonin) for N/V

ondansetron (Zofran)
granisetron (Kytril)
dolasetron (Anzmet)

258

5-HT3 antagonist actions

tx: N/V from chemo, postop; effective in about 80% pts
-depress CRTZ and inhib serotonin mediated afferent input from GI tract
-may be given orally/IV, metab by hepatic microsomal enzymes (drug interactions)
-adverse effects: HA, constipation

259

cannabinoids for N/V

dronabinol (Marinol): d-9-THC (marijuana)
-oral oil capsule
tx for N/V in chemo (back-up drug), prevent wasting "kekexia" in AIDS pts.
*smoking may be more effective than oral, bypass liver and produces combustion products

260

cannabinoid side effects

sedation, confusion, disorientation, loss of control, alt. sensations, paranoia, psychotic rxns (not tol. well in some esp. elderly)

261

corticosteroids for N/V

dexamethasone, prednisone, methylprednisolone
-adj. antiemetics in chemo regimens

262

P/neurokinin rec (NK1) antagonist for N/V

aprepitant (Emend)
tx: N/V from chemo, v. expensive, not 1st line

263

pyridoxine (vit B6) and doxylamine

Bendectine: terotogen scare in 80's-->unfounded-->now Diclegis (2013) for N/V during pregnancy

264

amphetamine

-some benefits in preventing motion sickness, can counteract sedative effects of other drugs
-not typ. used: CNS effects, abuse potential

265

other antiemetics

-phosphorylated carb. solutions (Emetrol), cola syrups
-antimicrobial agents
-antianxiety drugs: benzos for N/V from fear, anxiety
-ginger

266

antiemetics for motion sickness/vertigo

antihistamines, anticholinergics

267

antiemetics for postop

DA or 5-HT3 antagonists

268

antiemetics for radiation sickness

DA antagonists

269

antiemetics for drug-induced vomiting

DA / 5-HT3 antagonists, cannabinoids

270

antiemetics for pregnancy

try to avoid drugs, diet modification
pyridoxine +/- doxylamine-->antihistamine-->DA antagonist (avoid 5-HT3 antagonists)

271

cough reflex controlled by....
receives input from..
responds to..

cough control center
input from pharynx, larynx, airway, lungs
stretch (distension), presence of particulate matter, chem. irritation

272

afferent impulses from receptors sent to cough control center via

glossopharyngeal and vagus nn.

273

efferent component of cough reflex

epiglottis, pharynx, larynx, lungs, diaphragm, mm. of thorax/abdomen
-cough mech can be activated and suppressed (to some extent) consciously

274

rationale for antitussive therapy

-remove cause of irritant
-inc. airway sec. to mobilize irritants (expectorant)
-desens. peripheral rec.
-act on CNS component

275

antitussives that act on cough control center: opioids

codeine, hydrocodone, etc.
-prob. most effective, given at lower doses than for pain
-side effects: sedation, lightheaded, confusion, nausea, dizzy, constipation, abuse, physical dependence

276

antitussives that act on cough control center: non-opioids

dextromethorphan (syn. analog of levorphanol)
-effective as codeine for mild-mod cough, not as eff. for severe cough
-block NMDA rec
side effects: mild; sedation, dizzy confusion
-no analgesic effects, lower abuse potential

277

non-opioid antitussives

dextromethorphan:
Benylin DM, Pertussin, Vicks Formula 44, etc. OTC
*may be abused in higher doses (kids, i.e. cough syrup)

278

agents that act on airway receptors

benzonatate (Tessalon):
-local anesthetic, desens. airway receptors
-some effect on CCC, capsule for oral use
-side effects: mild: constipation, nasal cong., nausea, drowsiness, rashes
menthol (in many preps)

279

antitussives: expectorants

guaifenesin: questionable efficacy
mild irritants in GI tract-->activates reflex-->inc. mucus production in airway

280

antitussives: mucolytic agents

acetylcysteine (Mucomyst) (nebulization)
disrupts disulfide linkages-->inc. mucus viscosity, breaks mucus plugs-->easier to mobilize, humidifies air

281

antitussives: mucolytic agents tx

postop, tracheotomy care, sever bronchitis, emphysema
*antidote in Tylenol (acetaminophen) poisoning (Acetadote)

282

antitussives: antihistamines

diphenhydramine, promethazine, etc (in many cough/cold remedies)
-antag effects of histamine-->dec. irritation/constriction of airway-->also sedation and weak effects on CCC

283

antitussives: bronchodilators

dec. airway resistance (asthma)

284

antitussives: demulcents

"syrupy" materials that exert coating and soothing action (cough preps)

285

should cough be tx?

-cough is useful if productive
-tx in pts w/ hernias, CV probs, postop/trauma

286

mild-mod cough tx

dextromethorphan

287

severe cough tx

codeine (or other opioid)

288

if overly productive cough, consider a prep with

antihistamine

289

antitussives may be combo of

antihistamines, expectorants, decongestants, acetaminophen, etOH

290

direct acting sympathomimetics (adr. rec agonists): mixed, nonselective agonists

epinephrine (adrenalin, EpiPen, Auvi-Q)
NE (Levophed)
Isoproterenol (Isuprel)
DA (Intropin)

291

selective B1 agonists

dobutamine (Dobutrex)

292

selective B2 agonists

albuterol (Proventil)
Metaproterenol
Pirbuterol (Maxair)
Salmeterol (Serevent)
Terbutaline

293

selective B3 agonists

Mirabegron (Myrbetriq)
Solabegron

294

selective a1 agonists

phenylephrine
midodrine (ProAmantine)

295

indirect-acting sympathomimetics (next exam?)

cocaine
pseudoephedrine (Sudafed) ephedrine
amphetamine and methamphetamine
methylphenidate (Ritalin)

296

NE and E released from

adrenal medulla (E>NE)
pheochromocytoma cells (NE>=E)

297

pheochromocytomas tx w.

metyrosine: sp. tyrosine hydroxylase inhibitor

298

extrasynaptic receptors

a2, B2
activated pref. by circulating NE > NE from nerve endings

299

intrasynaptic receptors

a1, B1
activated by NE from nerve endings, would need ^^^ conc. circ. NE to be stimulated
more intra>extrasynptic receptors
(narrow syn. space, reuptake pump)

300

inactivation of NE or E

MAO-->deaminated metabolites
COMT-->O-methylated metabolites
Vanillylmandelic acid (VMA) is a deaminated AND o-methylated metabolite

301

high urine levels of these are dx for pheochromocytoma

metanephrines and/or VMA

302

pts on these meds will experience more intense effects of symp. drugs

MAO inhibitors

303

these vessels typ. do not become highly constricted during sympathetic activity (a rec. agonist admin)

coronary and cerebral vasc. smooth muscle
(fewer in #, receive less symp. neural traffic, powerful authoreg. capabilities)

304

dopamine receptors are present here to mediate vasodilation

renal and other splanchnic (gut) beds

305

normal resting symp. nerve activity is

10-20% of max
-maintains BP, body temp
(i.e. spinal anesthesia-->drop in art. pressure-->restored w/ NE
can be altered by brain centers receiving info from sens. afferent neurons from baroreceptors and thermoreceptors

306

baroreceptors

in carotid arteries and aortic arch
sense small changes in mean BP-->changes ANS outflow from CNS vasomotor centers to the vessels (symp) and heart (symp + PS) to correct BP changes

307

inc in SNA to lower body vv imp. to..

prevent venous pooling during orthostasis, helps maintain art. perfusion pressure

308

thermoreceptors

brain, skin, etc.
-redistrib. SNA to surface + core vessels in response to temp changes
-also: brain tells adrenomedulla-->rel. more E to inc. glucose output (hep. cells) and FFA output for thermogenesis (also triggered by exercise and hypoglycemia)-->HR will inc.

309

abnormally excessive symp. NE response to cold stress can lead to

Raynaud's disease

310

epinephrine stimulates

ALL receptors nearly alike: a1, a2, B1, B2

311

low IV rates of E stimulate

extrasynaptic rec (a2, B2): dec. in diastolic and increase systolic, PP, and HR (MAP unchanged)

312

higher IV rates of E stimulate

intrasynp. rec as well (a1, B1 as well as a2, B2): inc. PP, inc. diastolic and systolic, inc. MAP

313

E used in circulatory shock

tx bronchospasm and circ. collapse from anaphylactic shock
-high systemic dose, multi. rec stim: bronchial B2, vascular a, cardiac ventricular B

314

low, local E used to tx

asthma: bronchial B2
cardiac arrest: high systemic (cardiac B, vascular a) accomp. CPR, e-stim

315

high, systemic E used to tx

cardiac arrest: (cardiac B, vascular a) accomp. CPR, e-stim

316

E also tx bradycardia

high doses for A-V block (AV node B and/or purkinje fiber B) until pacemaker insertion
low doses for non-A-V block bradycardias, so MAP is not increased (SA node B2)

317

E can also be mixed w.

local anesthetics; prolongs action at local inj. sites, min. syst. toxicity and local bleeding
*high local conc. to stim. all vascular a rec.

318

NE stimulates these rec

a1, a2, B1 (not B2)

319

both low and high doses of NE..

increase all pressures

320

NE reflexively

DECREASES HR

321

most uses of NE due to effects on

vascular a rec.

322

NE used in

shock: i.e. cardiogenic and neurogenic: stim cardiac B1 and/or vascular a rec
and early septic shock: esp. when shock persist after fluid replacement (vasc. a)

323

NE supports BP during

spinal anethesia

324

NE could be used w.

anesthetics (like E) (this use discontinued)

325

Isoproterenol stimulates these rec

B1, B2 (NOT a)

326

both low and high doses Iso..

dec. diastolic and MAP
inc. PP and HR

327

Iso was rec. removed from use as

a bronchodilator, but longer action than epi

328

Iso tx this when other tx fail

bradyarrhythmias (cardiac B)

329

Iso used as

"pharmacologic provocation" med. alternative to tilt-table test to dx unexplained syncope (vasovagal) (cardiac ventricular B)

330

diastolic pressure reflects

total peripheral resistance

331

mean pressure is

a rough average of sys and dias pressure

332

control of HR may be affected by barorec. as well as

direct stimulation of rec in SA node

333

pulse pressure reflects

left ventricular cardiac contractility

334

systolic pressure =

diastolic + pulse pressure

335

Dopamine (DA) stimulates

DA receptors>B1>a1

336

low doses DA stimulates

DA rec in splanchnic regions like GI and renal art. smooth muscle: inc. blood flow here

337

intermediate doses DA stim

B1 rec: cardiac contractility and rate (as well as DA)

338

high doses DA stim

a1 rec: may blunt effects of DA on splanchnic/kidney art. sm musc. (constricts)-->stim of all other vasc. a1-->rise in MAP due to increase in TPR

339

DA used in shock

cardiogenic and neurogenic (B1 +/- a1)
early or late septic shock

340

DA also used in..

CHF (w/ other tx failure) (cardiac B1 +/- renal D)
-controversial

341

DA for bradycardia

in pts. unrespon. to other tx
-desirable to stim. B1 not a1 so inc. HR w/out inc. MAP(would cause reflex bradycardia)

342

selective B1 agonist

Dobutamine (+a1 agonist or a1 antag + B1 agonist)
-inc. cardiac contractility, rate-->inc. CO, PP
(not much inc. in diastolic and MAP)

343

Doputamine used for

CHF
shock (cardiogen, late phase septic) (only B1)

344

IMPORTANT use of Doputamine

stimulate the heart during emergence from heart surgery

345

selective B2 agonists used as

bronchodilators ("rescue" inhalers) for COPD, asthma
post-exercise-induced bronchospasms
(oral, IV, inhaled)

346

terbutaline (B2 agonist) used to manage

premature labor: B2-mediated uterine relaxation (not. rec. for prolonged use, risk of CV effects)

347

selective B3 agonists

Mirabegron and Solabegron
tx for over-active bladder, relaxes detrusor sm. musc (relax to keep urine in)

348

tx anaphylactic shock w/

epinephrine 1st: high systemic dose

349

cardiogenic shock usually caused by

sig. loss of left ventricular musc. contractile function (post-acute MI)
-->dec. CO, resistance may inc., pressures still fall

350

tx cardiogenic shock w/

NE, DA, and/or dobutamine (support circulation)
-B just for heart or a to support diastolic pressure btw contractions

351

tx neurogenic shock w/

NE, DA, phenylephrine
(heart, BVs, or both?)

352

septic shock typ. involves

G- bacteria, endotoxins

353

2 phases of septic shock

warm phase, cold phase

354

warm phase of septic shock

dec. syst. resistance-->massive systemic dilation-->art. pressure falls
tx: NE and/or vasoconstrictor (a1-stim) dose of DA (or phenylephrine)

355

cold phase of septic shock

1-2 days later
myocardial depression-->low CO-->low art pressure
vasc. resistance may go up (high SNA)
tx: DA (not high vasc. a1-stim level), dobutamine to reverse low CO

356

late phase septic shock

involves inadeq. perf. of vital vasc. beds
mesenteric/renal circ. compromise
tx: low dose DA (acts on D rec) can improve flow to those regions (vasodil)

357

effects of HIGH IV epinephrine infusion

all pressures go up, enough a1, a2 constriction to overcome B2 vasodilation (in contrast to low epi dose, diastolic goes down due to vasc B2 rec not opposed enough by a rec-vasoconstriction)
-inc. in pulse pressure: left ventr. B1 rec. are stim. along w/ B2 rec.

Decks in Micro Class (61):