Sunteți pe pagina 1din 131

Nervous

System

Amabelle Mazel Z. Agrabio


Cindy Lou A. Tunguia
1

CNS
Brain and Spinal Cord
Acts as control for regulating physical and mental
processes
Neurons are the brains functional units

The brain is a collection of about 10 billion


interconnected neurons. Each neuron is a
cell that uses biochemical reactions to
receive, process and transmit information.

Neurotransmitters

Chemical substances that carry


messages from one neuron to another
or from a neuron to other body tissues,
such as cardiac or skeletal muscles.

The synapse is a small gap separating


neurons.

Receptors

Proteins embedded in the cell


membranes of neurons.
A neurotransmitter must bind to
receptors to exert an effect on the next
neuron in the chain.

Drugs

affecting
Central Nervous
System Drugs
6

Depressants
Stimulants

Mild CNS depressant: decreased interest in


surroundings, inability to focus.
Moderate CNS depressant: drowsiness or
sleep, decreased perception of heat or cold.
Severe CNS depressant: unconsciousness or
coma, loss of reflexes, respiratory failure
and death.

Mild stimulation: wakefulness, mental


alertness, and decreased fatigue.
Moderate stimulation: hyperactivity,
excessive talking, nervousness, and
insomnia.
Excessive stimulation: confusion, seizures,
and cardiac dysrrhythmias.

Anticonvulsants: help prevent seizures by


suppressing the spread of abnormal
electric impulses from the seizure focus to
other areas of the cerebral cortex
All anticonvulsants are CNS depressants and may
cause ataxia, drowsiness, and hepatotoxicity
Examples:

Phenobarbital (short-acting barbiturate)


Primidone (structurally similar to
phenobarbital)
Diazepam (used IV to treat status
epilepticus)
Clorazepate (adjunct anticonvulsant)
Potassium bromide (adjunct
anticonvulsant)
10

Tranquilizers: used to calm ; reduce


anxiety and aggression
Sedatives: used to quiet excitation;
decrease irritability and excitement
Anti-anxiety drugs: lessen anxiousness,
but do not make drowsy
Examples in these groups:

Phenothiazine derivatives (acepromazine,


chlorpromazine)
Benzodiazepines (diazepam)
Alpha-2 agonists (xylazine, detomidine,
medetomidine)

11

Analgesics: drugs that relieve pain


Analgesics are categorized as non-narcotic
or narcotic
Narcotic analgesics are used for moderate
to severe pain
Narcotic refers to opioid (natural) or opioidlike (synthetic) products

12

Opioids:

Do not produce anesthesia; patients still respond


to sound and sensation
Produce analgesia and sedation, and relieve
anxiety
Side effects: respiratory depression, excitement if
given too rapidly
Produce their effects by the action of opioid
receptors

Mu = found in the brain


Kappa = found in the cerebral cortex
and spinal cord
Sigma = found in the brain
13

Examples of opioids:

Opium
Morphine sulfate
Meperidine
Hydromorphone
Butorphanol
Hydrocodone
Fentanyl
Etorphine
Buprenorphine
Pentazocine

14

Opioid antagonists:
Block the binding of opioids to their receptors
Used to treat respiratory and CNS depression of
opioid use
Examples include naloxone and naltrexone

15

Neuroleptanalgesics:

Combination of an opioid and a tranquilizer or


sedative
Can cause a state of CNS depression and
analgesia and may or may not produce
unconsciousness
Combination products may be prepared by
veterinarian
Examples include acepromazine and morphine;
xylazine and butorphanol

16

17

An effective sedative (anxiolytic) agent


should reduce anxiety and exert a calming
effect with little or no effect on motor or
mental functions.

A hypnotic drug should produce drowsiness


and encourage the onset and maintenance
of a state of sleep that as far as possible
resembles the natural sleep state.

18

Hypnotic effects involve more pronounced


depression of the central nervous system
than sedation, and this can be achieved
with most sedative drugs simply by
increasing the dose.

Graded dose-dependent depression of


central nervous system function is a
characteristic of sedative-hypnotics.

19

1.
2.

3.

Benzodiazepines: not to lead general


anesthesia, raraly death.
Barbiturates: the older sedativehypnotics, general depression of central
nervous system. With such drugs, an
increase in dose above that needed for
hypnosis may lead to a state of general
anesthesia. At still higher doses, it may
depress respiratory and vasomotor centers
in the medulla, leading to coma and death.
Other classes of drugs: chloral hydrate,
buspirone, et al.
20

The first benzodiazepine,


chlordiazepoxide, was synthesised by
accident in 1961.

21

About 20 are available for clinical use.


They are basically similar in their
pharmacological actions, though some
degree of selectivity has been reported.

22

1. Reduction of anxiety and aggression :


affects the hippocampus and nucleus
amygdalae
2. Sedation and induction of sleep:

(1) the latency of sleep onset is


decreased;
(2) the duration of stage 2 NREM
sleep is increased;
(3) the duration of slow-wave sleep is
decreased.
23

Reasons for their extensive clinical use:


(1) great margin of safety;
(2) little effect on REM sleep;
(3) little hepatic microsomal drugmetabolizing enzymes;
(4) slight physiologic and psychologic
dependence and withdrawal syndrome;
(5) less adverse effects such as
residual drowsiness and incoordination
movement.
24

3. Anticonvulsant and antiseizure

They are highly effective against


chemically induced convulsions
caused by leptazol, bicuculline and
similar drugs but less so against
electrically induced convulsions.
The can enhance GABA-mediated
synaptic systems and inhibit
excitatory transmission.

25

4. Muscle relaxation
relax contracted muscle in joint disease
or muscle spasm.
5. Other effects
lead to temporary amnesia
decrease the dosage of anesthetic;
depress respiratory and cardiovascular
function.

26

Benzodiazepines act very selectively on


GABAA-receptors, which mediate the fast
inhibitory synaptic response produced by
activity in GABA-ergic neurons.

The effect of benzodiazepines is to enhance


the response to GABA, by facilitating the
opening of GABA-activated chloride channels
(an increase in the frequency of channel
opening, but no change in the conductance or
mean open time).

27

Benzodiazepines bind specifically to a


regulatory site on the receptor, distinct from
the GABA binding site, and enhanced receptor
affinity for GABA.

The GABAA-receptors is a ligand-gated ion


channel consisting of a pentameric assembly
of subunits.

28

Well absorbed when given orally;


They bind strongly to plasma protein, and
their high lipid solubility cause many of
them to accumulate gradually in body
fat. Distribution volumes is big.
Metabolic transformation in the
microsomal drug-metabolizing enzyme
systems of the liver, eventually excreted
as glucuronide conjugates in the urine.

29

They vary greatly in duration of action,


and can be roughly divided into

Short-acting compounds:
triazolam, oxazepam(15-30min,
t1/2 2-3 h)
Medium-acting compounds:
estazolam, nitrazepam (40min,
t1/2 5-8 h)
Long-acting compounds:
diazepam, flurazepam(50h)
30

Acute

toxicity:

Benzodiazepines in
acute overdose are considerably less
dangerous than other sedative-hypnotic
drugs. Cause prolonged sleep,without
serious depression of respiration or
cardiovascular. The availability of an
effective antagonist, flumazenil.

31

Side-effects

during
therapeutic use: drowsiness,
confusion, amnesia, impaired
coordination. Main disadvantages are
interaction with alcohol, long-lasting
hangover and the development of
dependence.

Tolerance

and dependence:

induction of hepatic drug-metabolising


enzymes; a change at the receptor level;
32

Classification
(1)Ultra-short-acting barbiturates: act
within seconds, and their duration of
action is 30min. Therapeutic use of
Thiopental: anesthesia
(2)Short-acting barbiturates: have a
duration of action of about 2h. The
principal use of Secobarbital : sleepinducing hypnotics.

33

Classification
(3)Intermediate-acting barbiturates: have
and effect lasting 3-5h. The principal use
of Amobarbital is as hypnotics.
(4)Long-acting barbiturates: have a
duration of action greater than 6h. Such
as Barbital and Phenobarbital.
Therapeutic uses: hypnotics and
sedative, and antiepileptic agents at low
doses.

34

Barbiturates depress the CNS at


all level in a dose-dependent
fashion. Now it mainly used in
anesthesia and treatment of
epilepsy; use as sedative-hypnotic
agents is no longer recommended.

35

Reasons:
(1) have a narrow therapeutic-to-toxic
dosage range.
(2) suppress REM sleep.
(3) Tolerance develops relatively quickly.
(4) have a high potential for physical
dependence and abuse.
(5) potent inducers of hepatic drugmetabolizing enzymes.
36

(1) Barbiturates share with benzodiazepines


the ability to enhance the action of GABA,
but they bind a different site on the GABAreceptor/chloride channel, and their action
seems to prolong the duration of the
opening of GABA-activated chloride
channels.

37

(2) At high doses, barbiturates can inhibit the


release of the Ca2+-dependent
neurotransmitter.

38

High lipid solubility allows rapid transport


across the blood-brain barrier and results in
a short onset.
Removal from the brain occurs via
redistribution to the other tissues results in
short duration of action.
Barbiturates and their metabolites the
excretion via the renal route. Alkalinization
of the urine expedites the excretion of
barbiturates. Treatment of acute
overdosage: Sodium bicarbonate.

39

Sedative-hypnotic agents
Be used in the emergency treatment of
convulsions as in status epilepticus.
Anesthetic (or be given before
anesthetic)
Combination with antipyretic-analgesic
Treatment of hyperbilirubinemia and
kernicterus in the neonate.

40

After effect: hangover---dizzy, drowsiness,


amnesia, impaired judgment, disorientation.

Tolerance: decreased responsiveness to a


drug following repeated exposure because of
down-regulation of receptors and induction of
hepatic drug-metabolising enzymes.

41

Dependence: including psychologic and


physiologic dependence. Withdrawal
symptoms: excitation, insomnia, tremor,
anxiety, hallucinations and sometimes
convulsions.
Depressant effect on respiration: can
cross the placental barrier during
pregnancy and secrete to breast milk.
Others: Skin eruptions and porphyria

42

Phenothiazines

(Tranquilizers)

Indications
Good sedation for healthy
animals undergoing elective
procedures
Anti-emetic

43

Phenothiazines

Contraindications

Convulsing/epileptic patients, seizure


history or head trauma
Acepromazine may reduce the seizure
threshold
Shock (hypovolemia) and hypothermia
because of peripheral vasodilation that
can lead to hypotension
Depressed patients
Caution with geriatrics and pediatrics;
use a lower dose or consider alternative
agents such as benzodiazepines
Liver or kidney disease
Allergy testing because of antihistamine
effect
44

Phenothiazines

Other effects
Antiarrhythmic effect
May cause excitement rather than
sedation
Personality changes that usually
subside within 48 hours

45

Benzodiazepines (Benzodiazepines)
Indications

Convulsing/epileptic patients
Patients with a history of seizure
CSF taps or myelogram procedures
Minimal cardiovascular or respiratory
depression
Useful in geriatric or pediatric
Ideal for older, depressed or anxious
patients
Works effectively as an induction agent
when used with ketamine
46

Benzodiazepines (Benzodiazepines)
Contraindications

May cause excitement


Does not sedate but has antianxiety
and calming effects
May make more difficult when
inhibitions and anxieties are removed

47

Benzodiazepines (Benzodiazepines)

Valium is in a propylene glycol


solution, is insoluble in water
May precipitate with other drugs
Propylene glycol is irritating and
may sting at the injection site
Does not work well when given via
routes other than IV

48

Benzodiazepines (Benzodiazepines)

Other points
Midazolam is water soluble and
readily combines with opioids
(oxymorphone, butorphanol)
Effects are reversed with
flumazenil if adverse effects are
seen

49

2-Agonists

Are derivatives of thiazine


Examples:
Xylazine (Rompun, Anased)
Romifidine
Detomidine (Dormosedan)
Medetomidine (Domitor)

50

2-Agonists

Stimulates the 2adrenoreceptors causing a


decrease in norepinephrine
Indication
Potential side effects limit use
to sedation only, not for
preanesthetic medication

51

2-Agonists

Have some short-lived (16 to 20


minutes) analgesic effects
Will cause vomiting
Xylazine and Detomidine are used
most frequently

52

2-Agonists

Contraindications
Considerable potential for side
effects especially if administered IV
Profound cardiovascular effects
include bradycardia, profound
hypotension, decreased
contractility and stroke volume and
second degree heart block
Contraindicated when concerned
about respiratory function, hepatic
and renal function
53

2-Agonists

Contraindications
Associated with temporary
behavior and personality changes
Reduces pancreatic secretions
causing transient hyperglycemia
(exacerbates dehydration)
Opioids will exacerbate these side
effects

54

Opioids

Commonly used:
Morphine
Oxymorphone (Numorphan)
Butorphanol (Torbugesic, Torbutrol)
Hydromorphone
Meperidine (Demerol, Pethidine)
Fentanyl

55

Opioids

Act by reversible combination with one or more


specific receptors in the brain and spinal column

Also classified according to their


analgesic activity and their addiction
potential
Pure agonists are more effective for
severe pain
In order of decreasing potency they
are:
Fentanyl
Oxymorphone
Buprenorphine
Butorphanol
Meperidine
pentazocine

56

Opioids

Commonly used as an analgesic in


premedication, as an induction
agent or can be used for balanced
anesthesia and post-operative pain
control
Provides some sedation and may
potentiate the action of the
sedative that it is given with
has a synergistic effect
57

Opioids

Commonly used as an analgesic in premedication, as


an induction agent or can be used for balanced
anesthesia and post-operative pain control

Fentanyl, sufentanil and oxymorphone are


often part of a balanced anesthetic
regimen
Fentanyl is available as a transdermal
patch in various sizes for long-term
analgesia
Used as neuroleptanalgesia in
combination wit tranquilizer
Morphine can be injected epidurally or
sub-arachnoidally for regional analgesia

58

Opioids
Fentanyl patches

Takes 8 to 12 hours to reach


effectiveness but will last for several
days
Very few cardiovascular side effects
Does not significantly contribute to
vasodilation or hypotension
Heating pads can increase transdermal
uptake

59

Opioids
Reversible by use of pure antagonists such as
naloxone or nalmefene

Compete with opioids for the specific


receptor sites
Possible to titrate the naloxone dose so
as to remove the side effects yet
maintain analgesia

60

Opioids
Other effects in addition to analgesia

Either stimulate or depress the central


nervous system
Depends on the dose, species and
opioid agent
Excitement occurs if given rapidly IV

61

Opioids

Other effects in addition to analgesia

Cardiopulmonary effects
Bradycardia
Possible hypotension with release of
histamine
Especially if given IV
Morphine and meperidine
Increased muscle contraction in low
doses
Inotropic effect
morphine
62

Opioids
Other effects in addition to analgesia

Respiratory depression is dose dependent


Gastrointestinal effects depend on the
agent
May initially include diarrhea, vomiting
and flatulence
Constipation may occur as a result of
prolonged GI stasis
Addiction

63

Opioids
Contraindications

Previous history of opioid excitement


Morphine has a higher incidence of
producing vomiting so should be
avoided in cases of GI obstruction and
diaphragmatic hernia
Classified as a narcotic in Canada and is a
Schedule II controlled drug in the US

64

Definition

Stimulants

are a substance
which tends to increase
behavioral activity when
administered

65

Two disorders treated with CNS stimulants


are narcolepsy and Attention Deficit
Hyperactivity Disorder
CNS stimulants act by facilitation initiation
and transmission of nerve impulses that
excite other cells.
New drugs act selectively to inhibit reuptake
or norepinephrine in the nervous system.

66

Signs and symptoms:


1- Elevate Mood
2- Increase Motor Activity
3- Increase Alertness
4- Decrease need for Sleep
In case of overdose lead to convulsion and
death.

67

- They can be divided based on their site of


action:

1.Cerebral stimulants (amphetamines)

2.Medullary stimulants (picrotoxin)

3.Spinal stimulants (strychnine)

68

Analeptics (CNS stimulants) Reversal of


anaesthesia-induced respiratory depression
Anorexiants Thought to suppress the appetite
control centre in the brain
ADHDStimulate the areas in the brain
responsible for mental alertness and
attentiveness
NarcolepsyIncrease mental alertness
Migraine headaches
Caffeine, co-administered with other drugs,
used to treat headaches
69

Wide range, dose related


Tend to speed up body systems
Common adverse effects include:

Palpitations, tachycardia, hypertension, angina,


dysrhythmias, nervousness, restlessness, anxiety,
insomnia, nausea, vomiting, diarrhea, increased
urinary frequency

70

MOAs :
Block the reuptake of norepinephrine
and dopamine into the presynaptic neuron
and increase the release of these
monoamines into the extraneuronal space.

- Clinical use:
1. Narcolepsy.
2. Attention-deficit hyperactivity disorder

71

Adverse effects:
- Cardiovascular: Hypertension
- Endocrine metabolic: Weight loss
- Gastrointestinal: Abdominal pain , Loss
of appetite, Xerostomia
- Neurologic: Headache , Insomnia
- Psychiatric: Feeling nervous

72

After injecting, the mice with amphetamine


you well notice:
- Hair erection
- Licking, gnawing.
- Stereotype
- Sniffing

73

MOA:
Non-competitive antagonist of GABA
receptors.
After injecting the mice with picrotoxin you
wellnotice:
- Clonic convulsion characterized by :
1. Asymmetric
2. Intermittent
3. Spontaneous
4. Coordinated

74

MOA:
Competitive antagonist of the glycin
receptors.

After injecting the mice with Strychinine


you well
notice:
- Tonic convulsion characterized by :
1. Symmetric
2. Reflex in origin
3. Continuous
4. Uncoordinated.

75

Methylphenidate
Brand Name: Ritalin
Classification Therapeutic: CNS stimulant
Action: Produces CNS and respiratory
stimulation with weak sympathomimetic
activity.
Therapeutic Effects: Increased attention
span in ADHD. Increased motor activity,
mental alertness, and diminished fatigue
in narcoleptic patients.

76

Drug
List
carbamazepine (Epitol, Tegretol)
clonazepam (Klonopin)
diazepam (Valium)
divalproex (Depakote)
ethosuximide (Zarontin)
Fosphyenytoin (Cerebyx)
gabapentin (Neurontin)

77

Drug
List
lamotrigine (Lamictal)
levetiracetam (Keppra)
lorazepam (Ativan)
oxcarbazepine (Trileptal)
phenobarbital (Luminal Sodium)
phenytoin (Dilantin)

78

Drug
List
primidone (Mysoline)
topiramate (Topamax)
valproic acid (Depakene)
zonisamide (Zonegran)

79

Drug
List
amantadine (Symmetrel)
benztropine (Cogentin)
bromocriptine (Parlodel)
entacapone (Comtan)
levodopa (Dopar)
levodopa-carbidopa (Sinemet)

80

Drug
List
levodopa-carbidopa-entacapone (Stalevo)
pergolide (Permax)
pramipexole (Mirapex)
ropinirole (ReQuip)
selegiline (Eldepryl)
tolcapone (Tasmar)

81

Drug
List
azathioprine (Imuran)
cyclophosphamide (Cytoxan)
edrophonium (Enlon, Reversol)
neostigmine (Prostigmin)
pyridostigmine (Mestinon)

82

Drug
List
atomoxetine (Strattera)
clonidine (Catapres, Catapres-TTS)
desipramine (Norpramin)
dexmethylphenidate (Focalin), C-II
dextroamphetamine-amphetamine
(Adderall), C-II

83

Drug
List
imipramine (Tofranil)
methylphenidate (Concerta, Metadate,
Ritalin, Ritalin-SR), C-II
nortriptyline (Aventyl, Pamelor)
pemoline (Cylert), C-IV

84

Drug
List

riluzole (Rilutek)

85

Drug
List
baclofen (Lioresal)
glatiramer acetate (Copaxone)
interferon beta-1a (Avonex, Rebif)
interferon beta-1b (Betaseron)
mitoxantrone (Novantrone)
tizanidine (Zanaflex)

86

Drug
List
donepezil (Aricept)
galantamine (Reminyl)
ginkgo
memantine (Namenda)
rivastigmine (Exelon)
tacrine (Cognex)

87

Drugs

affecting
Peripheral
Nervous System
Drugs
88

Sympathetic:
(Adrenergic)
Activators

Sympthomimetics
Agonists

Blockers

Sympatholytic
Antagonists

Receptors

Alpha 1 & 2
Beta 1 & 2
Dopamine

Parasympathetic
(Cholinergic)
Activators

Parasympathomimetics
Agonists

Blockers

Anticholinergics
Antimuscarinics
Parasympatholytics
Antagonists

Receptors

Muscarinic
Nicotinic N & M
89

Muscarinic agonists: no agents


Muscarinic antagonists (anticholinergics): 7
agents
Ganglionic blockers: no agents
Neuromuscular blockers: no agents
Cholinesterase inhibitors: neostigmine,
physostigmine (difference and use)

90

Neostigmine (Prostigmine)
(anticholinesterase) prototype

Primarily used to treat Myasthenia


Gravis

Pyridostimine (Mestinon)

Myasthenia Gravis

Donepezil (Aricept)

Works in the CNS to inhibit


synthesis of Acetylcholinesterase
Used to treat Alzheimers disease

91

Direct acting Cholinergic drugs

Directly stimulates the nerve


ending to secrete
acetylcholine
Bethanechol (Urecholine)
Used to treat urinary
retention
92

Limited uses:
Urinary retention
Increase GI peristalsis
Glaucoma, eye surgery

Adverse effects
Bradycardia, hypotension
Excess saliva, cramps, diarrhea
Urinary (contra: bladder obstruction &surgery)
Asthma exacerbation

93

Sources
Muscarinic agonists
Cholinesterase inhibitors
Mushrooms

Symptoms
Profuse salivation, tearing, bronchospasm,
diarrhea, bradycardia, hypotension

Treatment: atropine

94

Anticholinergics
Agents to know forever

Atropine: strongest, general use


Oxybutinin (Ditropan): overactive bladder
Tolerodine (Detrol): overactive bladder
Scopolamine: sedation, motion sickness
Ipratropium, Tiotropium: lungs
Dicyclomine (Bentyl): IBS, diarrhea

95

Mechanism: blocks muscarinic receptors by


competing with Acetylcholine
high doses will block nicotinic as well

Route: PO, topically (eye), injection

96

Pharmacologic
effects:
heart rate
secretions (GI, tear,
salivary)
smooth muscle
(peristalsis, urination)
Dilate eye (mydriasis)
CNS excitability

Therapeutic Uses
Preanesthesia (make
sure heart doesnt stop)
Eye surgery: (dilate
eye)
Bradycardia: heart
rate
Intestinal hypertonicity,
hypermotility (slows GI
tract)
Muscarinic Agonist
Poisoning (antidote)

97

Xerostomia (Dry Mouth)


Blurred vision, photophobia
Elevation of IOP
Urinary retention
Constipation
Anhidrosis (no sweat)
Tachycardia
Asthma: secretions too thick and crusty
Dementia

98

Dry as a bone
Red as a beat
Hot as a hare
Blind as a bat
Mad as a hatter

**Must determine whether psychosis is real or


anticholinergic

Treatment:
Minimize absorption
Cholinesterase inhibitor

99

Competitive antagonists

Compete with ACh


Inhibit nerve transmission

Sites of action

All systems except musculoskeletal

10
0

EXAMPLES

Bentyl (dicyclomine HCL)

Antispasmotic used to decrease


intestinal cramping in IBS
Atropine (Prototype)

Acetylcholine antagonist
Antidysrhythmic
Antispasmotic
Antisecretory

10
1

USES

Dry oral secretions


Increase heart rate
Treat urethral colic
Decrease GI motility
Parkinsons disease
Decrease upper respiratory secretions

10
2

OXYBUTYNIN (DITROPAN)
Synthetic antimuscarinic
INCREASES BLADDER CAPACITY
DECREASES FREQUENCY OF VOIDING

TOLTERODINE (DETROL, DETROL LA)


Synthetic antimuscarinic
DELAYS THE URGE TO VOID
INHIBITS BLADDER CONTRACTIONS

10
3

Dose
dependent
Low dose

Glands: sweat,
salivary, bronchial
Heart
Eye
Bladder
Intestine motility
Lung

High dose

Stomach

10
4

Drugs with anti-muscarinic (anticholinergic)


side effects effects

Antihistamines
Phenothiazine antipsychotics
Tricyclic antidepressants
Furosemide (Lasix)

10
5

Increase Acetylcholine at all receptors!


Reversible (must know these agents)

Neostigmine: myasthenia gravis


Physostigmine: anti-cholinergic antidote

Irreversible (do not need to know for test)


Used as insecticides
Developed in WW2 as nerve gas
One is used for glaucoma (just trivia for you
attorney types)

10
6

Etiology: Antibodies against Nicotinic-M


receptors
Clinical manifestations: fatigue, muscular
weakness, dyspnea
Treatment
Cholinesterase inhibitors
Side effects: can cause accumulation of
acetylcholine and nicotinic-M and muscarinic
receptors

10
7

Treatment
Side effects cont
Muscarinic effects
Neuromuscular blockade (toxicity)

10
8

Neuromuscular Blockers
Paralyze muscle

Use to intubate so they dont fight


Agents

Nondepolarizing: tubocurarine, et al.


Depolarizing: succinylcholine
Uses
Surgery
Mechanical Ventilation, ET intubation
Adjunct to ECT

10
9

Phenylephrine and Pseudoephedrine


Epinephrine, Norepi, Dopamine,
Dobutamine
All lung beta-2 agonists
Alpha blockers: terazosin, phentolamine
Beta blockers: propanolol, metoprolol,
atenolol, carvedilol
Indirect antagonists: Clonidine

11
0

Catecholamines:
Broken down by MAO
and COMT in liver and
intestine
Parenteral only
Cannot be given orally,
short half-life
Colorless solutions; color
is sign of oxidation
Natural catecholamines:
epi, norepi, dopamine
Synthetic: dobutamine
(others we dont need to
know)

Non-catecholamines
Can be given PO
Last longer in body

11
1

Noncatecholamines
Phenylephrine: (alpha1) nasal congestion,
inotropic support (rare now)
Pseudoephedrine (all alpha and beta):
Nasal congestion
Can be used to make amphetamines

11
2

-1

-2

-1

-2

Epinephrine

Dopamine

Dobutamine
Norepinephrine

dopa

+
+

11
3

Therapeutic effects
Vasoconstriction
BP (intensive care, last resort)
Hemostasis
local anesthesia absorption

Nasal decongestion
Mydriasis

Adverse effects
Hypertension
Necrosis
Bradycardia
11
4

Therapeutic Uses
Cardiac arrest (make heart beat again)
Heart Failure: inotropic support
Shock: inotropic and chronotropic support
A-V heart block (speed conductivity)

Adverse effects
HR
Angina pectoris

dysrhythmia

11
5

Therapeutic use
Asthma: bronchodilate
Preterm labor: stop contraction

Adverse effects
Hyperglycemia
Tremor

11
6

Therapeutic uses:
absorption of local
anesthetics
Control superficial
bleeding
BP
Mydriasis
AV block, V. fib,
Asystole
Status Asthmaticus
Anaphylactic shock
Reduce nasal
congestion

Adverse events

Hypertensive crisis
Dysrythmias
Angina pectoris
Necrosis
Hyperglycemia

11
7

Absorption
Inhalation: minimal
Injection

Preparations
SC, IM, IV, Intracardiac, intraspinal, inhalation,
Lidocaine with epi
No fingers, nose, penis, and toes

Inactivation: MAO and COMT in liver

11
8

Interactions
MAO inhibitors (why oh why?)
Alpha-adrenergic blocking agents
Beta-adrenergic blocking agents

11
9

Receptor: dopamine, alpha1, (beta1 higher


doses)
Therapeutic Uses
Shock:
HR and contractility
Maintain renal artery perfusion

Heart failure: same as above


ARF: low dose (may not be effective)

Adverse Effects
Dysrhythmias, angina pectoris

12
0

Short acting
Albuterol
Levalbuterol

Long acting
Salmeterol
Formoterol

12
1

Dobutamine (beta1) uses


Shock (inotropic support)
Stress Echoes

Terbutaline: (beta2) uses


Stop preterm labor contractions

12
2

Receptor: alpha 1 & 2, beta1


Therapeutic uses

Hypotensive state
Cardiac arrest (last resort)

Brand: Levophed (Leave em dead!)

12
3

Can be quite selective for receptors

12
4

Therapeutic uses
Hypertension
BPH
Reverse toxicity of
epinephrine
Pheochromocytoma
(what is it?)
Raynauds disease

Adverse effects
Orthostatic
hypotension
Reflex tachycardia
Nasal Congestion
Inhibition of
ejaculation
Na+ & H2O retention

12
5

Prazosin - HTN
Doxazosin HTN, BPH
Terazosin HTN, BPH
Tamsulosin BPH
Phentolamine Pheochromocytoma, tissue
necrosis

12
6

Therapeutic Uses
MI
HF
Angina Pectoris
Dysrhythmias
HTN
Other

Hyperthyroid
Migraine
Stage Fright
Pheochromocytoma
Glaucoma

Adverse Effects (1)


HR
CO
AV heart block
Precipitate HF
Rebound cardiac
excitation

Adverse Effects (2)


Bronchoconstriction
Inhibition of
glycogenolysis

12
7

Beta1, Beta2

Propanolol*
Nadolol
Pindolol

Labetalol
Carvedilol*

Selective
Metoprolol*
Atenolol*
Bisoprolol

Beta1,beta2,
alpha1

Used for HF
Metoprolol*
Carvedilol*

* Means must know


12
8

Clonidine
activates alpha-2 receptors in CNS
norepinephrine release
Uses
Hypertension
Pain relief in cancer (epdidural use only)

Adverse effects
Drowsiness, dry mouth, rebound HTN, bradycardia

Preparations
Oral: at least twice a day
Transdermal: seven days

12
9

Reserpine
Suppresses NE synthesis and promotes MAOmediated destruction
Crosses BBB
Effects
Hypotension

Adverse effects
Depression, sedation, apathy
Bradycardia, hypotension

Guanethidine: similar but fewer CNS effect

13
0

Methyldopa, Methyldopate
Similar to clonidine, but are taken up in brain
stem neurons and converted to active alpha2
agonist
Use: HTN
Adverse effects
10 20% Positive Coombs test (5%) will go on to
have hemolytic anemia
Hepatotoxicity
Drowsiness, dry mouth, hypotension, etc.

13
1

S-ar putea să vă placă și