1 General Anesthetics Pharmacology 604 Katherine L. Nicholson, D.V.M., Ph.D. Dept. Pharmacology/Toxicology [email protected]History of Anesthesia General Anesthesia - Characteristics • Definition (G&G) - “Reversible depression of CNS function resulting in loss of response to and perception of all external stimuli.” - Produce reversible "sleep" - Produce analgesia - Suppress reflexes - Produce muscle relaxation - Produce Amnesia - Do not suppress respiratory and cardiovascular function - Inexpensive and easy to administer Balanced Anesthesia • Ideal general anesthetic does not exist. • Combinations of drugs to accomplish what one anesthetic can not do alone. • Agents used for balanced anesthesia are- – Hypnotics – Neuromuscular blocking agents – Analgesics COMBINATION OF DRUGS CAN LOWER DOSES OF EACH DRUG TO PRODUCE THE SAME OR GREATER EFFECT ON PATIENT Four Stages of Anesthesia • Stage I - analgesia • Stage II - delirium • Stage III - surgical anesthesia • Stage IV - respiratory paralysis Types of General Anesthetics Extremely diverse group of chemicals which produce a similar endpoint • Inhalant or volatile • Injectable (intravenous)
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1
General Anesthetics
P h a r m a c o l o g y 6 0 4
K a t h e r i n e L . N i c h o l s o n , D . V . M . , P h. D .
D e p t . P h a r m a c o l o g y / T o x i c o l o g y
k l n i c h o l @h s c . vcu . edu
History of Anesthes ia
General Anesthesia -
Characterist ics• D e f i n i t i o n ( G & G ) - “ R e v e r s i b l e d e p r e s s i o n o f C N S
func t i on r e su l t i ng i n l o s s o f r e sponse t o and pe r cep t i on o f
a l l ex te rna l s t imul i . ”
- P r o d u c e r e v e r s i b l e " s l e e p "
- P r o d u c e a n a l g e s i a
- S u p p r e s s r e f l e x e s
- P r o d u c e m u s c l e r e l a x a t i o n
- P r o d u c e A m n e s i a
- D o n o t s u p p r e s s r e s p i r a t o r y a n d c a r d i o v a s c u l a r
f u n c t i o n
- I n e x p e n s i v e a n d e a s y t o a d m i n i s t e r
Balanced Anesthesia
• I d e a l g e n e r a l a n e s t h e t i c d o e s n o t e x i s t .
• C o m b i n a t i o n s o f d r u g s t o a c c o m p l i s h w h a t o n e
a n e s t h e t i c c a n n o t d o a l o n e .
• A g e n t s u s e d f o r b a l a n c e d a n e s t h e s i a a r e -
– H y p n o t i c s
– N e u r o m u s c u l a r b l o c k i n g a g e n t s
– A n a l g e s i c s
C O M B I N A T I O N O F D R U G S C A N L O W E R D O S E S O F
E A C H D R U G T O P R O D U C E T H E S A M E O R G R E A T E R
• Sex• PaCO2 between range of 14-95 mmHg• Metabolic alkalosis
• PaO2 between range of 38-500 mmHg• Hypertension• Potassium
Solubility & Pharmacokinetics
• S o l u b i l i t y e x p r e s s e d a s p a r t i t i o n c o e f f i c i e n t s
( a r a t io o f the concen t ra t ion o f the agen t in two phases a t
e q u i l i b r i u m )
• B l o o d : g a s p a r t i t i o n c o e f f i c i e n t
– S o l u b i l i t y i n b l o o d
– ma in f ac to r t ha t de t e rmines t he r a t e o f i nduc t i on and
r e c o v e r y
• O i l : g a s p a r t i t i o n c o e f f i c i e n t
– fa t so lub i l i ty
– d e t e r m i n e s t h e p o t e n c y o f a n a n e s t h e t i c ( a s w e l l a s k i n e t i c s )
Induction and Recovery
• T h e l o w e r t h e b l o o d : g a s p a r t i t i o n c o e f f i c i e n t t h e f a s t e r t h e
i n d u c t i o n a n d r e c o v e r y
– T h e l o w e r t h e s o l u b i l i t y i n b l o o d , t h e f a s t e r t h e p r o c e s s o f e q u i l i b r a t i o n
– L e s s d r u g h a s t o b e t r a n s f e r r e d v i a t h e l u n g s t o t h e b l o o d i n o rde r t o ach ieve a g iven pa r t i a l p re s su re
– A s i n g l e l u n g f u l o f a i r c o n t a i n i n g a l o w-so lub i l i ty agen t wi l l b r i n g t h e p a r t i a l p r e s s u r e i n t h e b l o o d c l o s e r t o t h a t o f t h e insp i red a i r
• R e c o v e r y i s t h e s a m e
L o w s o l u b i l i t y i n b l o o d = f a s t i n d u c t i o n a n d r e c o v e r y
H i g h s o l u b i l i t y i n b l o o d = s l o w e r i n d u c t i o n a n d r e c o v e r y