Autonomic NS Flashcards
(82 cards)
1
Q
methyldopa
A
adrenergic
- effects metabolic transformation
- results in displacement of NE by false neurotransmitter
2
Q
cocaine
A
adrenergic
- blocks transport system at the nerve terminal
- results in accumulation of NE at the receptors
3
Q
reserpine
A
adrenergic
- blockade of transport system of storage granule membrane
- results in destruction of NE by mitochondrial MAO and depletion from adrenergic terminals
depletes NE by blocking vesicular transporter (thus there is no NE in membrane vesicles)
- decreases CO, and is the last choice for antihypertensive medication
- not used clinically any longer
4
Q
amphetamine,tyramine
A
- adrenergic
- displaces transmitter from axonal terminal
- sympathomimetic
5
Q
botulinum toxin
A
- prevents release of ACh transmitter
6
Q
muscarine, methacholine
A
mimics muscarinic NT of postsynaptic receptor and works as a cholinomimetic
7
Q
nicotine
A
mimics nicotinic NT and is cholinomimetic
8
Q
anti-ChE agents
A
physostigmine, diisopropyl phosphorofluoridate (DFP) - inhibit the enzymatic breakdown of ACh
9
Q
MAO inhibitors
A
inhibit the breakdown
10
Q
glaucoma treatment
A
muscarinic stimulants cause contraction ofciliary body, facilitating outflow of aqeous humor and reducing intraocular pressure
- thus can be tx w/ direct-acting cholinergic agonists, but more often treated now with topical beta blockers
11
Q
accomodative esotropia
A
young children who are farsighted overcorrect for farsightedness and eyes become corssed
- treated with cholinomimetic agonists
12
Q
contraindications of use of mACHR agonists
A
asthma, hyperthrydoidism, coronary insufficiency, acid-peptic disease
13
Q
tx for xs muscarinic stimulation
A
atropine, for CNS stimulation use diazepam
14
Q
enteral
A
via GI tract: oral, sublingual, rectal
15
Q
parenteral
A
non-oral route
SQ, IM, IV, inhalation, intranasal, intraarticular
16
Q
quaternary salts
A
permanently charged, thus can’t cross BBB
- good tx for myasthenia gravis
- neostigmine, physostigmine
17
Q
Vd
A
plasma = 4 L
EC fluid = 14 L
total body water = 42 L
18
Q
where are bases and acids best absorbed?
A
weak acid is unionized in low pH thus better absorbed in stomach
weak base is unionized at high pH thus better absorbed in intestine
the opposite is true for excretion
19
Q
which drugs are more likely to bind in plasma?
A
weak acids and lipid-soluble drugs
20
Q
catabolic
A
breakdown rxns
21
Q
anabolic
A
build up rxns
22
Q
phase 1 rxns
A
biological inactivation
- catabolic
- made more polar via oxidation, reduction, hydrolysis
- mixed function oxidases (MFO’s) and Cytochrome P450’s (P450 CYP) carry out this process
- enzymes located in lipophilic ER membranes of liver
23
Q
phase 2 rxns
A
- metabolite w/ increased water solubility and molecular weight
- conjugation reactions
- anabolic
- polar molecules
- occurs in liver
24
Q
CYPs
A
CYP3A4 is most abundant
- use molecular O2 and NADPH to carry out oxidation of substrates
25
pseudocholinesterase
- metabolizes succinylcholine.
- succin. deplarizes skeletal mm = relaxant
- individs w/ genetic defect in this enzyme can metabolize it at 50% less
26
slow acetylator phenotype
individs w/ this autosomal recessive trait have decrease in N-acetyltransferase levels in liver
- results in isoniazids, hydralazine (HTN), caffeine and other amines to be metabolized slower and can cause hepatitis (esp. w/ isoniazids, tx of TB)
- problem with Phase I metabolism and responsible of drug induced SLE
27
grapefruit juice effect
irreversibly inhibits intestinal CYP3A4 - decreases oralavailability of many drugs
28
enzyme induction
some P450 substrates can induce the activity and thus increase the rate or reduce the rate of degredation of other drugs
inducers:
- phenobarbital
- ethanol
tobacco smoke
- isoniazids, glucocorticoids
29
potency
- drugs affinity for the receptor
- amount of drug needed to obtain particular effect
- on x axis, represents dose - more potent drugs lie to the left of the LDR
30
intrinsic activity
if the drug can activate the receptor, antagonists have no intrinsic activity though cthey can have efficacy
31
kd
equilibrium dissociation constant - measures affinity for the drug
low kd = high affinity
= concentration at which half the maximal binding occurs
32
ED50, EC50
ED = effective dose to see 50% response (in vivo)
EC = effective concentration to see 50% response (in vitro)
33
efficacy
capacity of drug to produce pharmacologic response
partial agonists/antagonists are less effecacious
34
therapeutic index
LD50/ED50
increased TI usually means safer
35
TD50
toxicity dose
36
first and zero order
- first order kinetics = exponential: rate is dependent on drug concentration. K and t1/2 don't change with drug concentration, but the rate does. the rate is proportional to the concentration of the drug
- zero order: linear, rate is independent of the concentration of the drug and remains steady - usually encountered when mechanism of absorption becomes saturated
- at drug concentrations that exceed saturation of the system zero-order kinetics prevail, in between a mixed order prevails
37
bioavailability
F - fraction of dose that is absorbed and reaches the systemic circulation
= ratio of the area under the curve for IV versus oral administration
38
C0
= initial plasma concentration
hypothetical drug concentration predicted if the distribution had been acheived instantly
where the constant line meets the Y axis
Vd = dose/C0
39
clearance
apparent volume of fluid from which drug is totally removed per unit time
40
G6PD deficiency
G6PD produces NADPH reqd for protecting RBC's against oxid. damage (through the reduction of glutathione)
w/out G6PD protection via NADPH RBCs are susceptible to oxidant drugs like primaquine, cauisng hemolysis
ingestion of fava bean, favism
41
Warfarin therapy (coumadin)
anticoagulant used for prevention of thromboembolism via blocking enzyme Vit K epoxide reductase complext, VKORC1 - results in decreased Vit K factor needed for clotting
Warfarin therapy is dependent upon diet changes in Vit K, meds that interfere, genetic VKORC1 variability, CYP2C9 amounts = all results in individual differences in Warfarin dosage
42
crossover design
consists of pateints receiving each therapy in sequence so that the patients serve as their own controls
43
Phase 0
clinical trial of microdosing to provide early pharmacokinetic data
44
Phase 1
determines whether humans and animals show significantly different responses
small number of healthy volunteers
absorption, half life and metabolism
45
Phase II
test to determine its efficacy
larger group: 100-200 pt
tests efficacy, dosing reqs, toxicities (to test toxicity and pharmacokinetics)
done in clinical centers
drug failure usually occurs here
46
PHase III
large group of patientsto further establish drug safety and efficacy 300-3,000 people
crossover and double blind techniques used here
evaluates overall benefit risk: efficacy and toxicitiy
47
Phase IV
post marketing study w/ purpose of continual monitoring of safety
48
malignant hyperthermia
problem with ryanodine receptor mutations
when inhalation of anesthetics and succinycholine, results in elevation of calcium in the sarcoplasm of muscle causing muscle rigidity, elevation of body temp and rhabdomyolysis
49
organ system effects of cholinergic agonists
Eye: miosis, accomodation
CV: through M2 see vasodilation with minimal doses and resulting tachycardia. With larger doses see bradycardia and decreased conduction along w/ hypotension
GI: M3 mACHR's cause smooth mm. contraction, M2 mACHR's reduce relaxation caused by adrenergic effects
CNS: excitatry mACHR's involved in increased cog. fn, inhibitory mACHRs play role in tremors, hypothermia and analgesia
PNS: nACHR agonist predominates here, results in increased discharge of both PS and Symp (Symp effects on heart, PS on GI)
50
what are two classes of cholinergic agonists?
choline esters: permanencly charged: ACh (Most rapid)> methacholine >carbachol = bethanecol (least rapid)
Alkaloids: uncharged tertiary amines (muscarine, pilocarpine, nocotine)
51
clinical uses of direct acting cholinergic agonists?
1. glaucoma (miosis causes contraction of ciliary body, causing outflow of vitreous humor)
2. acccommodative esotropia
3. GI/GU disorders: Bethanecol for increased GI motility, Pilocarpine/cevimeline for Sjogrens and increased secretions
52
contraindications of mACHR agonists
asthma, hyperthyroidism, coronary insufficiency, acid-peptic disease
53
Nicotinic toxicity
seen in insecticides, results in skeletal mm and plate depolarization leading to resp. paralysis, hypertension and cardiac arrythmias
54
three types of indirect-acting cholinergic agonists
"cholinesterase inhibitors"
1. alcohols: alcohol group + quaternary ammonium ion (charged) - binding is noncovalent and reversible, and short lived (edrophonium)
2. carbamic acid esters (carbamates): quaternary ammonium groups (pos. charged or neutral) - binding to AChE is noncovalent and reversible, and lasts 1-6 hours (ex. pysostigmine, neostigmine, pyridostigmine, carbaryl)
pyrid and neo = charged
physo= uncharged
3. organophosphates: charge neutral and highly lipid soluble - binding is covalent and irreversible and can last 100 hours (ex. insecticides, nerve gases). Regeneration of ACHE is reqd in order to reestablish termination of ACh signaling at NMJ
* After initial binding, the enzyme complex may undergo aging, and the complex is even more stable and difficult to break
55
organ effects of AChE inhibitors?
Quaternary AChE inibitors are absorbed poorly from GI tract and excluded from CNS - work preferentially at the NMJ and have less effect at autonomic sites
Organophosphates and tertiary AChE inhibitors act at peripheral and central sites and may be sequestered fro a long time
1. stimulate mACHRs at autonomic effector organs
2. stimulate all autonomic ganglia and nACHR's resulting in paralysis
3. stimulate cholinergic receptor sites in CNS with occasional depression
56
myasthenia gravis
therapeutic doses of AChE inhibitors prolong intensity oif ACh and can be used to treat MG
57
therapeutic uses of AChE inhibitors?
diseases of eye (glaucoma, accomodative esotropia),
GI And urinary tracts (postoperative atony, neurogenic bladder),
the NMJ (myasthenia gravis, curare-induced nm paralysis) - reverse surgical paralysis
Atrial arrhythmias
CNS: dementia and alzhemiers
58
cholinergic antagonists
antinicotinic = influence at NMJ and ganglia
mACHR blockers block PS discharge
ex. atropine: tertiary amine exerts effects on eye or CNS - antagonizes mACHR's
59
organ effects of cholinergic antagonists?
CNS: treat tremor assoc with parkinsons, decreased drowsiness and motion sickness
EYE: unopposed mydriasis, useful for opthamologic exams, reduced lacrimal secretion
CV: prevent CV effects of direct muscarinics: high doses of atropine cause tachycardia and blockade of vagal slowing
Resp: bronchodilation and reduced secretion
GI: decreased salivary secretion, decreased gastric emptyping, treatment for urinary incontinence, decreased sweating
60
clinical uses of cholinergic antagonists?
1. PD- Parkinson disease, reduce tremor
2. Motion sickness
3. Anesthesia: blocks vagal reflexes induced by surgical manipulations
4. opthalamic disorders uveitisis and iritis along with mydriasis for surgeries
5. respiratory disorders: treat asthma and COPD
6. CV: acts against reflex vagal discharge
7. GI: traveller's diarrhea
8. Urinary disorders: oxygutynin, darifenacin, solifenacin, tolterodine
9. cholinergic poisoning: insecticides, wild mushrooms, chemical warfare
61
adverse effects of mACHR antagonists
high concentration of atropine blocks all PS- dry, blind, red, mad, hot
overdoses treated w/ cholinesterase inhibitors
62
contraindications of mAChR antagonists?
glaucoma, prostatic hyperplasia, acid-peptic disease
63
alpha1 adrenergic effects?
constriction of blood vessels, mydriasis, smooth mm. contraction, glycogenolysis in the liver
64
glycogenolysis in liver
alpha1 and beta2 (thus for nonspecific beta blockers, must be careful when giving to diabetic patients)
65
Beta1 effects?
increased chronotropic, increased inotropic, renin release
66
Beta2 effects?
smoooth mm. relaxation, glycogenolysis in liver, insulin release
67
Beta3 effects?
lipolysis
68
epi, NE, Iso compared
alpha1: epi>NE>>>iso
beta2: iso>epi>>>NE (epi has greater affinity for beta2, so at low doses it results in vasodilation)
beta1: iso>epi=NE
69
clinical use for epi?
1. bronchial asthma in children (B2)
2. anaphylactic shock: bronchodilation, decreased edema, decreased spread of ag, alleviation of hypotension (efficacy is on a1 and B2)
3. glaucoma - lowers intraoc pressure through unknown mechanism
4. infiltration with local anesthetics
5. topical hemostatic
70
adverse effects of epi?
BP: cerebral hemorrhage
CV: arrhythmias
CNS: fear, anxiety, h/a
71
contraindications of epi?
HTN,
shock w/ compromised bloodflow to organs
hyperthyroidism- increased incidence of arryhthmias
angina pectoris: increased work and demand on heart
asthamatics w/ degenerative heart disease
72
what does blocking alpha2 do?
results in enhnaced release of NE from symp. nn. this often causes tachycardia at the heart when it is due to a nonspecific alphablocker.
73
tyramine
found in beer, red wine, cheese
- normally rapidly degraded by MAO in GI tract and liver
- Patients taking MAO inhibitor have high levels
- Tyr displaces NE from nerve terminal --> hyptertensive crisis, MI, stroke
74
Cocaine
blocks reuptake of NE
75
Ephedrine
mixed acting agonist
direct B receptor agonist, indirectly releases NE
- no substrate for COMT or MAO Thus is long lasting
- use: pressor agent, bronchospasm, nasal decongestant
76
clonidine**
- alpha2 agonist
- centrally acting hypotensive agent that works at the brainstem
- decreses symp outflow and regulates NT release
- clinical use: hypertension and off-label uses
- third line tx to HTN
- b/c it can block symp outflow it is used offlabel for help from narcotic withdrawal
77
methyldopa
- False neurotransmitter concept
- Converted to methyl-NE
stored in vesicles instead of NE
- released & acts as a centrally acting a2-agonist
- compare with clonidine
- Considered a drug of choice for treating hypertension in pregnant females
78
why alpha 1 selective blocker?
don't block alpha 2, thus reflex tachycardia is less prevalent
used to treat HTN, and BPH
79
why use beta blockers?
angina pectoris - reduce CO and work
HTN: decreases CO And produces slow decrease in peripheral resistance due to blockade of renin
migraine headaches
arrhythmias
pheochromocytoma
panic attacks
CHF
80
uses of NE and epi?
```
cardiac arrest
adjunct to local anesthetic
hypotension
anaphylaxis (epi only)
asthma (epi only)
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81
two types of treatment for glaucoma?
beta blockers to decrease formation of fluid by ciliary epithelial cells
muscarinic agonist to improve drainage
82
Dumbbells
```
Diarrhoea
Urination
Miosis/muscle weakness
Bronchorrhea
Bradycardia
Emesis
Lacrimation
Salivation/sweating
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