Pharmacology of Sedative Drugs

8/8/2019 Pharmacology of Sedative Drugs

1/55

Pharmacology ofConscious Sedation

Drugs

Wael Galal; M.D.Anesthesia Consultant

KFH Al-Baha


2/55

The Ideal Sedating Agent


3/55

The Ideal Sedating Agent

Predictable onset of

action

Lack of cumulativeeffects

Promote rapid recovery

Minimal side-effects

Residual analgesia

Short duration of action

Patient safety

Reversible

No residual depression

Painless administration


4/55

Classification

Benzodiapezin

es: Midazolam

Diazepam

IV

Anesthetics: Ketamine

Propofol

Benzodiapezines:

Midazolam

(Dormicum)

Diazepam

(Valium)

Opioids:

-Fentanyl

-Morphine

-Meperidine

(Demerol)

IV Anesthetics:

Thiopentone

(Pentohal)

Ketamine

Propofol

ALL THOSE 3-GROUPS DRUGS ARE APPROVED FOR

CONSCIOUS SEDATION BUT AT DIFFERENT SERVICE LOCALION LEVELS


5/55

Discussion Questions

Medications approved for conscious

sedation at KFH include the following:

1. Fentanyl, meperidine, midazolam

2. Phenobarbital, morphine, diazepam

3. Pentothal, magnesium sulfate, propofol4. 1 and 2 only


6/55

Drug Choice forConscious

Sedation

This depends on the requirement of:

Amnesia Midazolam

Analgesia Opiates / Ketamine

Relaxation IV anesthetics/NotKetamine

Consciousness Avoid anesthetics


7/55

ALL SEDATIVES

Can Do the Following:

Cause Upper Airway Obstruction

Produce Respiratory Depression

Blunt Ventilatory Response to CO2 (main ventilatory drive) and

Oxygen.


8/55


9/55


10/55

How This Presentation Goes? Sedation drugs follow two lists(Adult/Pediatric).

Each Drug has a Dosage instruction to

follow, initial bolus increments STOPwhen a maximum recommended dose is

reached.

Care with age, excretory organ

dysfunction and debilitation dosage by

1/3-1/2.

GENERAL RULES


11/55

Specific precautions (Mostly patients with

CNS dep., Resp. disorders and CVD).

REMEMBER: our target is Moderate

Sedation. Dose-to-effect titration is yourtool.

Sedating agents potentiate the effects of

one another (Synergism).


12/55

The Conscious Sedation Sheets

(Adults/Pediatric)Distributed to All Wards

THIS SESSION WILL SIMPLIFY & EXPLAIN


13/55

Drugs Used for Adult Sedation


14/55

DRUG Adult Dose ONSET SPECIAL

CONSIDERATION

S

REVERSAL

AGENT

PRECAUTIONS

CONTRAINDICATIONS

& SIDE EFFECTS

MIDAZOLAM

(Dormicum)

Anxiolytic

Sedative

Amnesic

Anti-convulsant

Initial dose:

1mg.

elderly/debilitated2.5mg. healthy

adult

Initial dose should

not exceed 2.5mgm.

Usual max:

Average adult60years: 3.5 mg within

30 min.

IV Dose rate: 1mg.

over 1 min. Wait 2

min. after each

increment to fully

evaluate effects.

Maintain level with

25% of initial IVdose.

Onset: 1 -5 min.

Peak: 10-15 min.

Duration: 60-90

min.

Metabolized: liver

Excreted: kidney

Recovery is dose

dependent, usually1-2 hrs.

Reduce dose by 1/3 to

1/2 when used with

other CNS depressingdrugs or in the elderly

or debilitated.

Manufacturer

recommends not

more than 1.5 mgm

over at least two

minutes in patients

with decreased

pulmonary reserves.

FLUMAZENIL

(Anexate)P- Elderly/debilitated

C- Hypersensitivity, acutenarrow angle glaucoma

S- CNS / Resp. depression- Hypotension

- Agitation

- N/V, hiccups

DIAZEPAM

(Valium)

Sedative

Anxiolytic

Anti-convulsant

Initial dose: 2mg.

Usual Maximum:

10-20mg. within 30

mins.

Elderly 5-15 mgm.

over 30 mins.

IV Dose Rate: 2mg.

over 3-5 min. Wait5-10 minutes to

Onset: 1-5min.

Peak: 2 min.

Duration: 15-60

min.

Metabolized: liver

Administer into large

vein

Inject close to IV site

If additives in IV

solution, flush tubing

before and after

administration.

FLUMAZENIL

(Anexate)P- Elderly/debilitated

C- Hypersensitivity-Narrow angle glaucoma

- Psychosis

S- CNS / resp. depression- N/V

- Hypotension


15/55


16/55

Thiopental

(Pentothal)

General anaesthetic

agent

Initial dose:

50 - 100 mg

Usual maximum:3mg/kg

Incremental and

maximum doses are

reduced to 1/3- 1/2 in the

elderly.

Onset: 1- 2 min

Peak: 4-8 min

Duration of Action:

10 - 30 min

Metabolized: liver

Excreted: kidney

Reduce dose to 1/3 to 1/2

when given with other

CNS depressing drugs or

in the elderly or

debilitated.

- S- Hypotension, myocardial depression,

CNS and respiratory depression, nausea,

vomiting, diarrhea, laryngospasm

C- Respiratory conditions

Porphyrias

P- Inactive, debilitated, and elderly may

be more susceptible to adverse effects.

Increased toxicity with other CNS

depressants

KETAMINE

(Ketalar)

General anaesthetic

agent

Initial dose:

0.2 - 1.0 mg/kg

Usual maximum:

2mg/kg.

Onset: 30 sec. IV

3-4 min. IM

Duration: 5-10 min.

IV

12-25 min.

IM

Full Recovery: 30-120

min

Initial IV dose over 60

sec.

(rapid administration

may cause respiratory

depression)

Antisecretory agent such as

atropine (.01mgm/kg) or

scopalamine given prior

Barbituates and Ketamine

should not be injected using

the same syringe.

Not recommended outside

the OR.

- S- Nystagmus,resp. depression,

hypersalivation, laryngospasm, non-

purposeful movements, emesis,

HR,B/P, ICP

- Emergence reaction

- Unpleasant dreams/hallucinations

(most common in females>age 10)

C- Hx CV disease or hypertension

- Active pulmonary infection or disease

- Head injury

- Glaucoma or acute globe injury

- Psychosis

- Conditions with intracranial

hypertension

- Seizure or CNS disorders

- Hx of airway instability, tracheal

surgery or stenosis

Propofol

(Diprivan)

General anaesthetic

agent

Anti-emetic

Anti-convulsant

Initial dose:

10 - 20mg incremental

doses every 5 minutes as

needed

Usual Maximum:

100mg.

Give slow IV push to

avoid hypotension.

Onset: 30 sec

Duration of Action:

10 - 15 min

Reduce dose by 1/3 to 1/2

when given with other CNS

depressing drugs or in the

elderly or debilitated.

Restricted to monitored

ICU/ED patients and/or use

by anesthesia personnel

- S- Respiratory depression,

- HR,B/P

P- Hx CV disease or hypotension


- Concomitant use with narcotics


surgery or stenosis


17/55

Drugs Used for Pediatric Sedation


18/55

DRUG Pediatric Dose ONSET SPECIAL

CONSIDERATIONS

REVERSAL

AGENT

PRECAUTIONS

CONTRAINDICATIONS

& SIDE EFFECTS

MIDAZOLAM

(Dormicum)

Anxiolytic

Sedative

Amnesic

Anti-convulsant

No manufacturer

published

recommendations

Onset: 1 -5 min.

Peak: 10-15 min.

Duration: 60-90

min.

Metabolized:

liver

Excreted: kidney

Recovery is dose

dependent, usually

1-2 hrs.


1/2 when used with

other CNS depressing

drugs or in the

debilitated.

Manufacturer

recommends not more

than 1.5 mgm over at

least two minutes in

patients with decreased

pulmonary reserves.

FLUMAZENIL

(Anexate)P- Debilitated

C- Hypersensitivity, acute

narrow angle glaucoma

S- CNS / Resp. depression- Hypotension

- Agitation

- N/V, hiccups

DIAZEPAM

(Valium)

Sedative

AnxiolyticAnti-convulsant

No manufacturer

published

recommendations

Clinician info:

>30 days of age

0.25mg/KG over 3min. Can repeat in

15-30 min. until total

of 0.75mg/Kg

Onset: 1-5min.

Peak: 2 min.

Duration: 15-60

min.

Metabolized:

liverExcreted: kidney

Administer into large

vein

Inject close to IV site

If additives in IVsolution, flush tubing

before and after

administration.

Never IM

FLUMAZENIL

(Anexate)P- Debilitated

C- Hypersensitivity- Narrow angle glaucoma

- Psychosis

S- CNS /resp. depression- N/V

- Hypotension

-Dizziness


19/55

Fentanyl

Analgesia

Sedative

No manufacturer

published

recommendations

Onset: 1-2 min.

Peak: 3-5 min.

Duration: 30-60

min.

Metabolized: liver

Excreted: kidney


1/3

when used with other

CNS depressing drugs

or in the debilitated.

Muscle rigidity from

high doses may prevent

adequate chest wall

expansion andrespirations. This is

reversed with

neuromuscular blockers

but patient must be

artificially ventilated.

Naloxone

(Narcan)P- Debilitated- Bradyarrhythmias

- Head injury

- Resp. disease

C-Hpersensitivity

S- CNS/resp. depression- Hypotension

- Muscle rigidity

- Bradycardia

- N/V

- Puritus

-Seizures

Morphine

Analgesia

Sedative

0.05-0.1mg/kg slowly Onset: 1 min.

Peak: 15 min.

Duration: 2-4 hrs.

Metabolized: liver

Excreted: kidney


1/2 when given with


drugs or in the

debilitated.

Naloxone

(Narcan)

P- Debilitated

-Respiratory conditions

-- Seizure disorders

-Head injury

-C- Hypersensitivity

-Biliary colic

-S- CNS/resp. depression

- Hypotension

- N/V

-Dizziness

Pethedine(Demerol)

Analgesia

Sedative

1-2 mg/kg slowly Onset: 1 min.

Peak: 5-7 min.

Duration: 2-4 hr.

Metabolized: liver

Excreted: kidney


1/2 when given with


drugs or in the

debilitated.

Naloxone

(Narcan)P- Debilitated- SVT

- Seizure disorders

- Respiratory conditions

C- Hypersensitivity- MAO inhibitors past 14 days

S- CNS/resp. depression

- Hypotension

- N/V


20/55

Thiopental

(Pentothal)

General anaesthetic

agent

Initial dose:

50 - 100 mg

Usual maximum:3mg/kg

Incremental and

maximum doses are

reduced to 1/3- 1/2 in the

elderly.

Onset: 1- 2 min

Peak: 4-8 min

Duration of Action:

10 - 30 min

Metabolized: liver

Excreted: kidney

Reduce dose to 1/3 to 1/2

when given with other

CNS depressing drugs or

in the inactive or

debilitated.


the OR.

- S- Hypotension, myocardial depression,

CNS and respiratory depression, nausea,

vomiting, diarrhea, laryngospasm

C- Respiratory conditions

Porphyrias

KETAMINE

(Ketalar)

General anaesthetic

agent

Initial dose:

0.2 - 1.0 mg/kg

Usual maximum:

2mg/kg.

Onset:

30 sec. IV

3-4 min. IM

Duration:

5-10 min. IV

12-25 min. IM

Full Recovery: 30-120

minInitial IV dose over 60

sec.

(rapid administration

may cause respiratory

depression)

Antisecretory agent such as

atropine (.01mgm/kg) or

scopalamine given prior

Barbituates and Ketamine

should not be injected using

the same syringe.


the OR.

- S- Nystagmus,resp. depression,

hypersalivation, laryngospasm, non-

purposeful movements, emesis,

HR,B/P, ICP

- Emergence reaction

- Unpleasant dreams/hallucinations

(most common in females>age 10)

C- Hx CV disease or hypertension

- Active pulmonary infection or disease- Head injury

- Glaucoma or acute globe injury

- Psychosis

- Conditions with intracranial

hypertension

- Seizure or CNS disorders


surgery or stenosis

Propofol

(Diprivan)

General anaesthetic

agent

Anti-emetic

Anti-convulsant

Initial dose:

10 - 20mg incrementaldoses every 5 minutes as

needed

Usual Maximum:

100mg.

Give slow IV push to

avoid hypotension.

Onset: 30 sec

Duration of Action:

10 - 15 min

Reduce dose by 1/3 to 1/2

when given with other CNS

depressing drugs or in the

inactive or debilitated.

Restricted to monitored

ICU/ED patients and/or use

by anesthesia personnel

- S- Respiratory depression,

-

HR,B/P

P- Hx CV disease or hypotension


- Concomitant use with narcotics


surgery or stenosis


21/55

Reversal Agents for Drugs used for Adult and Pediatric Sedation

DRUG

ACTION

&ONSET

ADMINISTRATION

GUIDELINES(In Adults)

PEDIATRIC DOSING SPECIAL

CONSIDERATIONS

PRECAUTIONS

CONTRAINDICATIONSSIDE EFFECTS

NALOXONE

(Narcan)Reversal of

narcotics

Onset: 1-2 min.

0.4mg. 2mg. IV

May repeat as needed in

2-3 min. intervals PRN

0.01mg/kg every 2-3 min.

May repeat as needed.

If does not produce desired

outcome a subsequent dose

of 0.1mg/kg may be

administered.

Alternate infusion at

0.4mg/hour

Can precipitate VT/VF in

patients with CV disease

or receiving potentially

cardiotoxic drugs.

P - Cardiovascular disease

C- Hypersensitivity

- Narcotic dependency

S- N/V, sweating- Tachycardia, hypertension

- Pulmonary edema

FLUMAZENIL

(Anexate)Reversal of

benzodiazepine

induced

sedation

Onset: 1-2 min.

Peak effect: 6-10

min.

High Risk people may

be necessary to

increase interval

between doses to over

one minute.

Initial dose:

0.2mgm. IV over 15 sec.

Wait 45 sec, additional

0.2mg. doses at one

minute intervals until

maximum of 4 additional

doses have been given.

Maximum cumulative

dose is 1.0 mg.

Repeat above in 20 min. if

needed

No more than 3 mg. in

one hour.

No manufacturer published

recommendations

Can precipitate seizures in

those with seizures

controlled by

benzodiazepines, with

tricyclic depression

overdose & with high risk

for seizures.

P - Resedation, monitor for

resedation, respiratory

depression for up to 120 min.

Resedation least likely in low

dose sedation,

(eg < 10mg Versed)

C- Hypersensitivity

- Tricyclic antidepressant

overdose

- Benzodiazepine dependency

S - Visual disturbances,

diaphoresis, seizures,

arrhythmias


22/55


23/55

Adult Sedation

Midazolam (Dormicum):

A Benzodiazepine.

Initial Dose: 1 - 2.5 mg (max. 2.5 mg).

Maximum: 3.5 - 5 mg in 30 min.

How to administer: Evaluate Your Patient first insert & secure IV Give The Initial Dose Slowly Wait 2 min to evaluate effects

Give Incremental Dosing in order to maintain sedation level with

of the initial dose DO NOT EXCEED MAX DOSE.

Onset: 1 -5 min - Peak: 10-15 min - Duration: 60-90 min.

Recovery is dose dependent, usually 1-2 hrs.


24/55

Pediatric Patients Less Than 6 Monthsof Age No manufacturer publishedrecommendations

Pediatric Patients 6 Months to 5 Yearsof Age: 0.05 to 0.1 mg/kg

Pediatric Patients 6 to 12 Years of Age:0.025 to 0.05 mg/kg

Pediatric Sedation Midazolam


25/55

Elderly

Debilitated

Respiratory Disorders

CNS / Resp. depression

Hypotension

Agitation

N/V

Hiccups

Hypersensitivity

Acute narrow angle glaucoma


26/55

Adult Sedation

Diazepam (Valium):

A Benzodiazepine.

Initial Dose: 2 mg (max. 2.5 mg).

Maximum: 10-20 mg in 30 min (1/2 this dose in theelderly).

How to administer: Evaluate Your Patient first insert &

secure IV Give The Initial Dose Slowly Wait 5-10

min to evaluate effects Give Incremental Doses inorder to maintain sedation level with of the initial dose

DO NOT EXCEED MAX DOSE.

Onset: 1-5 min - Peak: 20 min - Duration: 15-60 min.


27/55


recommendations

> 1 month of age: 0.25 mg/kg over 3 min;

Can repeat in 15-30 min until total of

0.75mg/kg (MAX DOSE)

Pediatric Sedation Diazepam


28/55

Elderly

Debilitated



Hypotension N/V

Dizziness

Hypersensitivity

Acute narrow angle glaucoma

Psychosis


29/55

Potency

Midazolam > Diazepam = 1:4

Diazepam is a more cumulative drug, it

has a long half life (30 hrs). Midazolam

t =1-2hrs; less cumulative.


30/55


Midazolam (Dormicum) is:

1. Approximately four times as potent asdiazepam, a respiratory depressant

2. Usually given in 0.5 - 2 mg. increments

3. Reversed by flumazenil4. All of the above


31/55

Adult Sedation

Fentanyl:

A Potent Opioid.

Initial Dose: 25-50 g.

Maximum: 100-250 g in 30 min.


secure IV Give The Initial Dose Slowly Wait 5 min to

evaluate effects Give Incremental Dosing in order to

maintain sedation level with - of the initial dose DO

NOT EXCEED MAX DOSE.

Onset: 1-2 min - Peak: 3-5 min - Duration: 30-60

min.

Recovery is dose dependent, usually 1 hr.


32/55


recommendations

We try 0.25-1 g/kg/dose.

Pediatric Sedation Fentanyl


33/55

Elderly

Debilitated


Bradyarrhythmias

Head injury


Hypotension, bradycardia N/V, pruritus, seizures

Muscle rigidity

Hypersensitivity


34/55

Adult Sedation

Morphine: An Opioid.

Initial Dose: 2.5-10 mg.

Maximum: 10 mg in 30 min.




maintain sedation level with - of the initial dose DO

NOT EXCEED MAX DOSE.

Onset: 1 min - Peak: 15 min - Duration: 2-4 hrs.


35/55

0.05 - 0.1 mg/kg slowly

Pediatric Sedation Morphine


36/55

Elderly

Debilitated


Seizure disorders

Head injury


Hypotension

N/V, pruritus

Dizziness

Hypersensitivity

Biliary colic


37/55

Adult Sedation

Meperidine,P

ethidine (Demerol): An Opioid.

Initial Dose: 25-50 mg.

Maximum: 100 mg in 30 min.




maintain sedation level with - of the initial dose

DO NOT EXCEED MAX DOSE.

Onset: 1 min - Peak: 5-7 min - Duration: 2-4 hrs.


38/55

1 - 2 mg/kg slowly

Pediatric Sedation Demerol


39/55

Elderly

Debilitated


Seizure disorders

SVT

CNS depression

Resp. depression

Hypersensitivity

MAO inhibitors

Hypotension

N/V


40/55


41/55


Fentanyl is:

1. Capable of causing chest wall rigidity with

inability to ventilate if administered too rapidlyand in large doses; known to causehypotension if administered to a hypovolemicpatient

2. A potent respiratory depressant (100 times aspotent as morphine)

3. Usually administered in 250 500 ug.increments

4. 1 and 2 only


42/55

Meperidine (Demerol) is:

1. One-tenth as potent as morphine; maycause nausea, vomiting, hypotension,dizziness, and urinary retention

2. The narcotic of choice for sedating apatient. with a history of depression whotakes MAO inhibitors

3. Usually administered in 50 mg.increments

4. 1 and 3 only


43/55

Special Considerations


44/55

Administration of IV anesthetic agents for

conscious sedation is not recommendedoutside the ICU & OR

Also, sedative drugs are not

recommended in infants < 6 month of age,

ASA III & IV patients outside the OR & ICU.


45/55


Medications approved for conscioussedation include the following:

1. Fentanyl, meperidine, midazolam

2. Phenobarbital, morphine, diazepam

3. Pentothal, magnesium sulfate, propofol

4. 1 and 2 only


46/55

ONE MORE AGENT TO GO in

Pediatric C.S.

CHLORAL HYDRATE

The Gold Standard of the 50s for

Immobility, Non-painful ConsciousSedation

i.e. The Radiology Suite


47/55

Disadvantages

High failure rate (30%)

Paradoxical excitement

CNS depression: when it works it produces one thing

only Unconsciousness and Sleep

Irritant to skin and mucous membrane

Unpleasant taste, N/V

Hypotension, Resp. depression


48/55

CHLORAL HYDRATE

Dosage: 30-100 mg/kg PO (better) or PR

(less reliable)

Maximum: 1.5 2 gm

Give with anti-emetic


49/55

Alert: Excessive Sedation!!


50/55

Reversal Agents for Drugs used for Adult and Pediatric Sedation

DRUG

ACTION

&ONSET

ADMINISTRATIO

N GUIDELINES(In Adults)

PEDIATRIC DOSING SPECIAL

CONSIDERATIONS

PRECAUTIONS

CONTRAINDICATIONSSIDE EFFECTS

NALOXONE

(Narcan)Reversal of

narcotics

Onset: 1-2 min.

0.4mg. 2mg. IV

May repeat as needed in

2-3 min. intervals PRN

0.01mg/kg every 2-3 min.

May repeat as needed.

If does not produce desired

outcome a subsequent dose

of 0.1mg/kg may be

administered.

Alternate infusion at

0.4mg/hour

Can precipitate VT/VF in

patients with CV disease

or receiving potentially

cardiotoxic drugs.

P - Cardiovascular disease

C- Hypersensitivity

- Narcotic dependency

S- N/V, sweating- Tachycardia, hypertension

- Pulmonary edema

FLUMAZENIL

(Anexate)Reversal of

benzodiazepine

induced

sedation

Onset: 1-2 min.

Peak effect: 6-10 min.

High Risk people may

be necessary to increase

interval between doses

to over one minute.

Initial dose:

0.2mg IV over 15 sec.

Wait 45 sec, additional

0.2mg. doses at one

minute intervals until

maximum of 4

additional doses have

been given.

Maximum cumulative

dose is 1.0 mg.

Repeat above in 20 min.

if needed

No more than 3 mg. in

one hour.


recommendations

Can precipitate seizures

in those with seizures

controlled by

benzodiazepines, with

tricyclic depression

overdose & with high risk

for seizures.

P - Resedation, monitor for

resedation, respiratory

depression for up to 120 min.

Resedation least likely in low

dose sedation,

(eg < 10mg Versed)

C- Hypersensitivity

- Seizure disorders

- Tricyclic antidepressant

overdose

- Benzodiazepine dependency

S - Visual disturbances,

diaphoresis, seizures,

arrhythmias


51/55


Naloxone is the proper reversal agents

for the following drugs, except:

1. Fentanyl

2. Midazolam

3. Meperidine (Demerol)4. Morphine


52/55

The following should be considered when

administering naloxone:

1. The dose may need to be repeated because the

duration of action of naloxone may be shorter

than that of the narcotic being reversed

2. Acute narcotic reversal may cause pain, nausea,

vomiting, hypertension and CHF

3. Desired effects are alertness and adequate

ventilation without discomfort; naloxone should betitrated to effect in 0.1 mg increments to avoid

serious side effects

4. All of the above


53/55

Flumazenil:

1. Is a specific reversal agent for

benzodiazepines?

2. May cause seizures in benzodiazepines

dependent patients

3. Should be titrated in effect in 0.2 mg.

increments

4. All of the above


54/55


55/55

Documents

Pharmacology of Sedative Drugs