Drugs and poisons

Drugs and poisons

23

D r u g s are c h e m i c a l s u b s t a n c e s that affect y o u r b o d y . T h e y are e i t h e r a d m i n i s t e r e d internally o r a p p l i e d e x t e r n a l l y for p u r p o s e s o f m e d i c a l d i a g n o s i s , p r e v e n t i n g o r c u r i n g d i s e a s e , treating s y m p t o m s , o r birth c o n t r o l . T h e d r u g s u s e d in a health c e n t e r are c a l l e d e t h i c a l d r u g s ; t h e y r e q u i r e a p r e s c r i p t i o n . O t h e r s , that c a n b e b o u g h t " o v e r t h e c o u n t e r " w i t h o u t p r e s c r i p t i o n , are k n o w n as p r o prietary d r u g s . W i t h certain n o t a b l e e x c e p t i o n s , t h e latter c a t e g o r y o f d r u g s , w h i c h i n c l u d e s s u c h p r e p a r a t i o n s as m o u t h w a s h e s a n d c o l d r e m e d i e s , has r e l a t i v e l y little m e d i c a l i m p o r t a n c e . M a n y d r u g s h a v e a l r e a d y b e e n

men-

t i o n e d , as s u m m a r i z e d in T a b l e 2 3 - 1 ; t h o s e in this c h a p t e r are t h e m o s t i m p o r tant d r u g s , w h i c h h a v e far-reaching effects in t h e b o d y .

23.1

The action of drugs M o s t drugs act b y stimulating or d e p r e s s i n g certain activities in t h e c e l l , r e placing a deficient substance, killing or w e a k e n i n g a foreign organism, or c a u s i n g irritation. I n m a n y c a s e s , t h e a c t i o n o f a d r u g results f r o m its i n f l u e n c e on e n z y m e s , on cell m e m b r a n e s , or on other " r e c e p t o r s , " m o l e c u l e s with w h i c h t h e d r u g interacts. After a d r u g is a d m i n i s t e r e d , t h e first e v e n t that takes p l a c e is a b s o r p t i o n , its transfer to t h e b l o o d . T h e n it is d i s t r i b u t e d to v a r i o u s parts o f t h e b o d y , d e p e n d i n g on the size and solubility properties o f the drug m o l e c u l e . Drugs may undergo a process called biotransformation, a chemical change catalyzed b y e n z y m e s , c o m m o n l y in t h e l i v e r . F i n a l l y , the d r u g is e x c r e t e d , g e n e r a l l y b y t h e k i d n e y s into t h e u r i n e . T h e patient's r e s p o n s e to a particular d r u g d e p e n d s o n m a n y factors, i n c l u d i n g a g e , sex, w e i g h t , g e n e t i c m a k e u p , m e a n s a n d t i m e o f a d m i n i s t r a t i o n , e m o t i o n a l state, a n d p r e v i o u s d r u g b a c k g r o u n d ( F i g u r e 2 3 - 1 ) . I n a d d i t i o n , no drug produces

a single

effect—a

d r u g g i v e n to treat a certain c o n d i t i o n c a u s e s

o t h e r c h a n g e s in t h e b o d y , w h i c h m u s t b e taken into a c c o u n t . T h e g u i d i n g 526

T a b le 2 3 - 1

I n d ex to D r u gs in P r e v i o us C h a p t e rs S e c t i o n in text

D r u g class

alkaloid

12.7

cardiac glycoside

13.8

anabolic steroid

21.22

diuretic

22.11

D r u g class

fluoride

15.10

12.8

hypoglycemic

21.20

anticoagulant

22.3

i n o r g a n i c salt

antihistamine

22.2

antilipemic

18.9

antacid antiangina

8.7

S e c t i o n in text

quat radioisotope steroid

3.13 12.4 9.10 21.26

antiseptic

15.9

antitoxin

22.2

sulfa

16.5

birth c o n t r o l

21.24

vaccine

22.2

cancer therapy

16.6

Figure 2 3 - 1 . Administratio n of a d r u g. (Peace Corps p h o to by Paul C o n k l i n. Courtesy of National League for Nurs› ing.)

528 Chapter 2 3 / D r u gs and poisons p r i n c i p l e in p r e s c r i b i n g d r u g s , a n d in fact for all m e d i c a l i n t e r v e n t i o n , is that if n o t h i n g e l s e at least t h e p a t i e n t s h o u l d n o t b e h a r m e d .

23.2

Antibiotics A n t i b i o t i c s are c h e m i c a l s u b s t a n c e s u s e d to treat i n f e c t i o u s d i s e a s e s ; this a p ­ p l i c a t i o n o f d r u g s is r e f e r r e d to as c h e m o t h e r a p y . A n t i b i o t i c s are b a s e d o n a p r i n c i p l e k n o w n as " s e l e c t i v e t o x i c i t y " : t h e y are d e s i g n e d to b e m o r e harmful to t h e i n v a d i n g o r g a n i s m than to t h e patient. T h e i r f u n c t i o n is to e i t h e r kill inhibit

the growth

of a microorganism.

or

A n t i b i o t i c s are g e n e r a l l y p r o d u c e d o r

d e r i v e d f r o m l i v i n g c e l l s b y t h e p r o c e s s o f f e r m e n t a t i o n . ( T h e sulfa d r u g s , d e ­ s c r i b e d in S e c t i o n 16.5, are n o t c o n s i d e r e d a n t i b i o t i c s b e c a u s e t h e y d o n o t c o m e f r o m l i v i n g o r g a n i s m s . ) T h i s class o f c o m p o u n d s is o n e o f t h e m o s t w i d e l y prescribed group of drugs. Bacteria are t h e greatest s i n g l e c a u s e o f d i s e a s e . T h e y are d i v i d e d into t w o m a i n g r o u p s d e p e n d i n g o n t h e i r ability to b e s t a i n e d b y a m e t h o d d e v i s e d b y a D a n i s h p h y s i c i a n n a m e d G r a m . T h o s e b a c t e r i a that c a n b e s t a i n e d are k n o w n as " g r a m - p o s i t i v e " a n d t h o s e that c a n n o t are k n o w n as " g r a m - n e g a t i v e . " T h e s e t w o c l a s s e s o f b a c t e r i a r e s p o n d d i f f e r e n t l y to a n t i b i o t i c s . S o m e d r u g s act o n b a c t e r i a f r o m o n e g r o u p b u t n o t t h e o t h e r . C e r t a i n a n t i b i o t i c s are c a l l e d b r o a d s p e c t r u m b e c a u s e t h e y treat d i s e a s e s c a u s e d b y b o t h t y p e s , as w e l l as some other kinds o f foreign organisms. T h e m o s t p o t e n t antibacterial d r u g s are t h e penicillins

(Figure 23-2). T h e y

are e f f e c t i v e m a i n l y against g r a m - p o s i t i v e b a c t e r i a , s u c h as t h o s e that c a u s e staphylococcus, streptococcus, p n e u m o c o c c u s , m e n i n g o c o c c u s , and g o n o c o c cus infections. T h e y inhibit the synthesis o f bacterial cell walls, causing the c e l l to b u r s t as w a t e r flows i n s i d e . P e n i c i l l i n G , o r b e n z y l p e n i c i l l i n , is t h e m o s t i m p o r t a n t f o r m o f this a n t i b i o t i c . N e w e r d e r i v a t i v e s , w h i c h c o n t a i n g r o u p s o t h e r than t h e b e n z e n e ring, are less p o t e n t b u t o v e r c o m e t h e d i s a d v a n t a g e s o f

C—CH3

(Cj\-CH2—C—NH-CH—CH

0 = C

Ν

?

CH—C—OH

penicillin G (benzyl penicillin) p e n i c i l l i n G — i t s b r e a k d o w n in t h e s t o m a c h a n d p o o r a b s o r p t i o n after oral a d ­ ministration. T h e y i n c l u d e p e n i c i l l i n V ( p h e n o x y m e t h y l p e n i c i l l i n ) , w h i c h is m o r e a c i d s t a b l e , m e t h i c i l l i n ( 2 , 6 - d i m e t h o x y p h e n y l p e n c i l l i n ) , w h i c h is r e s i s ­ tant to t h e p e n i c i l l i n a s e e n z y m e , a n d a m p i c i l l i n ( 6 - a m i n o b e n z y l p e n i c i l l i n ) ,

2 3 . 2 / A n t i b i o t i cs

529

Figure 23-2. A penicillin m o l d. A mutant f o rm of this green m o l d, Penicillin chrysogenum, produces most of t he w o r l d ’s supply of t he antibiotic penicillin. (Courtesy of Pfizer, Inc.)

w h i c h is also e f f e c t i v e against s o m e g r a m - n e g a t i v e b a c t e r i a . A l t h o u g h p e n i c i l lins are a m o n g t h e least t o x i c d r u g s , t h e y c a u s e a l l e r g i c r e a c t i o n s i n a b o u t 5 t o 1 0 % o f t h e adults in t h e U n i t e d S a t e s — t h e m o s t c o m m o n d r u g a l l e r g y . F o r t h e s e p a t i e n t s , t h e a n t i b i o t i c erythromycin similar activity

(it is also

effective

is o f t e n p r e s c r i b e d b e c a u s e o f its

against certain

b a c t e r i a resistant to

penicillin). Tetracyclines

are t h e m o s t w i d e l y u s e d class o f a n t i b i o t i c s , l a r g e l y b e c a u s e

530

C h a p t er 2 3 / D r u gs a nd p o i s o ns

o f their b r o a d s p e c t r u m o f activity. T h e y are e f f e c t i v e against s t r e p t o c o c c u s and

staphylococcus

infections, pneumonia,

gonorrhea,

syphillis,

typhus,

urinary i n f e c t i o n s , a n d a c n e . T h i s g r o u p o f a n t i b i o t i c s i n h i b i t s p r o t e i n s y n t h e ­ sis in the b a c t e r i a at its r i b o s o m e s b y b l o c k i n g t h e b i n d i n g o f t R N A m o l e c u l e s c a r r y i n g a m i n o a c i d s . T h e structure o f t h e p a r e n t m o l e c u l e o f t h e g r o u p , tetra­ c y c l i n e is as f o l l o w s : O H

Ο

I

HCT

C

C H

^ C ^ Η

Ο

I

^ C H ^ C H

3

\

II

O H

I

cr

ic

H C

O H

II

Ο

II

C - C - N H

c

C H 2

2

^ C - O H

^ C H

B M

O H

N ( C H 3)

2

tetracycline D e r i v a t i v e s , s u c h as a u r e o m y c i n ( c h l o r o t e t r a c y c l i n e ) , h a v e similar activity. S i d e effects i n c l u d e gastrointestinal irritation a n d alteration o f t h e n o r m a l m i ­ c r o b i a l p o p u l a t i o n o f t h e i n t e s t i n e , p o s s i b l y r e s u l t i n g in a s e c o n d a r y i n f e c t i o n (superinfection).

T a b le 2 3 - 2

C o m m on A n t i b i o t i cs Name ampicillin

Clinical application urinary tract i n f e c t i o n s , s a l m o n e l l a i n f e c t i o n s , bacterial meningitis

bacitracin

skin i n f e c t i o n s ( t o p i c a l u s e o n l y )

cephalosporin

gram-negative bacterial infections

chloramphenicol

typhoid and salmonella infections

erythromycin

p e n i c i l l i n substitute

gentamicin

gram-negative bacteria (sepsis, infected burns,

griseofulvin

fungus infections

p n e u m o n i a ) , urinary i n f e c t i o n s kanamycin

intestinal i n f e c t i o n s , urinary i n f e c t i o n s

penicillin

gonococcus, p n e u m o c o c c u s , streptococcus, m e n i n g o c o c c u s , staphylococcus, and other gram-positive bacteria

polymyxin

g r a m - n e g a t i v e b a c t e r i a in w o u n d s , b u r n s , a n d

streptomycin

t u b e r c u l o s i s , urinary i n f e c t i o n s

tetracycline

broad spectrum

Vancomycin

staphylococcus infections

intestinal i n f e c t i o n s

2 3 . 3 / A s p i r in and analgesics 5 3 1 O t h e r a n t i b i o t i c s a l s o act b y i n h i b i t i n g b a c t e r i a l p r o t e i n s y n t h e s i s . mycin

is o n e e x a m p l e ; it is u s e d p r i n c i p a l l y to treat t u b e r c u l o s i s ( T B ) .

amphenicol,

Strepto­ Chlor­

a n o t h e r s u c h a n t i b i o t i c , is e f f e c t i v e against t y p h o i d a n d o t h e r

salmonella infections, R o c k y M o u n t a i n spotted fever, a n d certain severe in­ f e c t i o n s . Its u s e is l i m i t e d b e c a u s e o f t h e p o s s i b l e s i d e e f f e c t o f aplastic a n e ­ m i a , an o f t e n fatal b l o o d d i s o r d e r c a u s e d b y t h e d r u g ' s a c t i o n o n b o n e m a r r o w . T h e s e a n d o t h e r a n t i b i o t i c s are l i s t e d in T a b l e 2 3 - 2 .

23.3

Aspirin and analgesics A n a n a l g e s i c is a d r u g that r e l i e v e s p a i n . It d o e s n o t i m p a i r t h e patient's c o n ­ s c i o u s n e s s , b u t d e c r e a s e s t h e a w a r e n e s s o f sensitivity to p a i n . Aspirin

is o n e

o f the most w i d e l y u s e d analgesics available without a prescription. A s p i r i n , o r a c e t y l s a l i c y l i c a c i d , is m o s t e f f e c t i v e for m i l d to m o d e r a t e p a i n in h e a d a c h e , neuralgia (pain from a nerve), m u s c l e pain, pain from joints, and

ο

aspirin (acetylsalicylic acid) t o o t h a c h e . It also acts as an a n t i p y r e t i c , l o w e r i n g an e l e v a t e d b o d y t e m p e r a ­ t u r e , a n d as an a n t i i n f l a m m a t o r y a g e n t , r e d u c i n g t h e r e d n e s s , heat, a n d s w e l l i n g that a c c o m p a n y i n f l a m m a t i o n , w h i c h is t h e l o c a l t i s s u e r e s p o n s e to injury. A s p i r i n has m u l t i p l e effects o n t h e b o d y ; its p a i n - r e l i e v i n g a c t i o n p r o b ­ a b l y results f r o m d i l a t i o n o f b l o o d v e s s e l s at t h e site f r o m w h i c h t h e p a i n c o m e s . It m a y also i n h i b i t t h e s y n t h e s i s o f p r o s t a g l a n d i n s ( s e e S e c t i o n 14.1), w h i c h a p p e a r to b e i n v o l v e d in t h e i n f l a m m a t i o n p r o c e s s . I n t h e d i g e s t i v e tract, aspirin is h y d r o l y z e d to acetate a n d s a l i c y l a t e , w h i c h is t h e p h y s i o l o g i c a l l y a c t i v e s p e c i e s . Salicylate c a n b e a d m i n i s t e r e d d i r e c t l y

II c—o-

salicylate ion b u t is t o o irritating. A s p i r i n i t s e l f in a n o r m a l d o s e o f 5 grains (324 m g ) c a u s e s loss o f 2 to 6 m l o f b l o o d f r o m irritation o f t h e m u c o u s m e m b r a n e s o f t h e s t o m -

532

C h a p t er 2 3 / D r u gs a nd p o i s o ns

a c h . In a d d i t i o n , certain i n d i v i d u a l s are a l l e r g i c to a s p i r i n ; t h e i r r e a c t i o n m a y b e asthma or h i v e s (uticaria) in a c u t e f o r m s . Acetaminophen

is t h e m o s t e f f e c t i v e a n d safest aspirin substitute. T h i s c o m O

HO^Q^NH—C—CH

3

acetaminophen p o u n d , h o w e v e r , lacks t h e antiinflammatory a c t i o n o f aspirin. T h e r e l a t e d m o l e c u l e , p h e n a c e t i n (an e t h o x y g r o u p , — O C H 2 C H 3 , r e p l a c e s t h e h y d r o x y l g r o u p ) , has also b e e n u s e d as an a n a l g e s i c . Its u s e , h o w e v e r , c a n c a u s e a hemoglobin disorder, methemoglobinemia, producing anemia.

Phenacetin

m a y also result in h e m o l y t i c a n e m i a , particularly in t h o s e i n d i v i d u a l s w h o g e n e t i c a l l y lack a particular e n z y m e ( g l u c o s e - 6 - p h o s p h a t e d e h y d r o g e n a s e ) , as d o 10 to 1 5 % o f b l a c k s in t h e U n i t e d States. O t h e r c o m p o u n d s are a v a i l a b l e as p a i n r e l i e v e r s o n l y . D a r v o n , p r o p o x y p h e n e , is o n e o f t h e m o s t f r e q u e n t l y p r e s c r i b e d , b u t its e f f e c t i v e n e s s has b e e n questioned.

II

I I

C H 3— C H 2— C — O — C — C H — C H 2— N ( C H 3) 2 CH2

propoxyphene (Darvon) T a b l e 2 3 - 3 lists t h e c o m p o s i t i o n o f c o m m e r c i a l l y a v a i l a b l e a n a l g e s i c s .

23.4

Narcotic analgesics N a r c o t i c a n a l g e s i c s are t h e m o s t p o w e r f u l p a i n r e l i e v i n g d r u g s a v a i l a b l e . F r e q u e n t u s e , h o w e v e r , l e a d s to a state o f d r u g d e p e n d e n c y o r a d d i c t i o n . T h e b o d y o f an a d d i c t e d i n d i v i d u a l adapts to t h e p r e s e n c e o f t h e n a r c o t i c . I f t h e d r u g is n o l o n g e r a d m i n i s t e r e d , p h y s i o l o g i c a l d i s t u r b a n c e s c h a r a c t e r i z e d b y " w i t h d r a w a l s y m p t o m s " take p l a c e . T h e r e f o r e , t h e s e d r u g s are m e d i c a l l y p r e s c r i b e d o n l y in c a s e s o f s e v e r e p a i n , s u c h as that r e s u l t i n g f r o m injury,

2 3 . 4 / N a r c o t ic a n a l g e s i cs T a b le 2 3 - 3

533

C o m p o s i t i on of C o m m e r c i al A n a l g e s i cs Name

Other ingredients

Analgesic ingredient0

Anacin

aspirin (6.17)

caffeine

Bufferin

aspirin (5)

buffer

Cope

aspirin (6.5)

antihistamine, caffeine,

Empirin

p h e n a c e t i n (2.5),

buffer caffeine

aspirin (3.5) Excedrin

a c e t a m i n o p h e n (1.5),

caffeine

salicylamide (2), aspirin (3) Tylenol

a c e t a m i n o p h e n (5)

Vanquish

aspirin ( 3 . 5 ) ,

caffeine, buffer

a c e t a m i n o p h e n (3) Numbers in parentheses indicate the amount, in grams, of analgesic ingredient; 1 grain = 64.8 mg.

a

s u r g e r y , o r a heart attack, w h e n t h e y are taken for r e l a t i v e l y short p e r i o d s o f time. Opium,

the m o s t a b u n d a n t natural s o u r c e o f n a r c o t i c a n a l g e s i c s , c o m e s f r o m

a p o p p y p l a n t ( F i g u r e 2 3 - 3 ) . It c o n t a i n s a m i x t u r e o f a b o u t 2 5 a l k a l o i d s , t h e largest fraction ( a b o u t 1 0 % ) o f w h i c h is m o r p h i n e . P a r e g o r i c , a tincture o f o p i u m , c o n t a i n s m o r p h i n e (0.4 m g / m l ) as its a c t i v e i n g r e d i e n t . Morphine

is

t h e m o s t e f f e c t i v e d r u g against s e v e r e p a i n . It acts b y m o d i f y i n g a w a r e n e s s o f ^ N — C H

3

C H 2/ Η C

HC

/

\

CH H 2C / \ ~ C CHo C H - C H \ \ V \ C—C CH

C=C.

HO

/

\

/

.CH—CH

XT

OH

X

morphine t h e p a i n , r e g a r d l e s s o f its o r i g i n o r i n t e n s i t y . Codeine,

o r m e t h y l m o r p h i n e , is

a l s o f o u n d in o p i u m b u t is a l e s s p o t e n t p a i n k i l l e r . B e c a u s e a d d i c t i o n to c o ­ d e i n e is m u c h less l i k e l y , h o w e v e r , this d r u g is t h e m o s t c o m m o n l y u s e d nar­ c o t i c a n a l g e s i c . (It is also f o u n d in c o u g h p r e p a r a t i o n s b e c a u s e it i n h i b i t s t h e

534

Chapter 2 3 / D r u gs and poisons

Figure 23-3. Opium poppies. (Photo courtesy of U.S. Drug Enforcement Ad› ministration. )

c o u g h c e n t e r o f t h e brain.) H e r o i n , o r d i a c e t y l m o r p h i n e , is n o t p r e s e n t in o p i u m , b u t is m a d e f r o m m o r p h i n e b y a s i m p l e c h e m i c a l p r o c e s s . T h i s n a r c o t i c , w h i c h is o u t l a w e d as a m e d i c a l d r u g , is d e n s e r than m o r p h i n e , m a k i n g it e a s i e r to s m u g g l e a n d to " c u t " o r d i l u t e w i t h a n o t h e r s u b s t a n c e like l a c t o s e b e f o r e s e l l i n g o n t h e street. Meperidine

( D e m e r o l ) is a m a j o r s y n t h e t i c n a r c o t i c a n a l g e s i c . Its p o t e n c y

T / C H 2^

II

C H 3— C H 2— O — C — C

CH2

Ji

H 2C ^ CH2 meperidine (Demerol)

CH3

2 3 . 5 / A n e s t h e t i cs

535

l i e s b e t w e e n that o f m o r p h i n e a n d that o f c o d e i n e . Its e f f e c t is shorter than m o r p h i n e ( a b o u t 2 h o u r s i n s t e a d o f 4 ) , an a d v a n t a g e in short p r o c e d u r e s o r p r e p a r a t i o n for d e l i v e r y . M e p e r i d i n e , an a d d i c t i n g d r u g , is t h e m o s t c o m ­ m o n narcotic abused b y physicians and nurses. Methadone

( s h o w n in S e c t i o n 1 2 . 3 ) , a s y n t h e t i c n a r c o t i c , is n o t u s e d as an

a n a l g e s i c b u t as a substitute for h e r o i n . I n m e t h a d o n e m a i n t e n a n c e p r o g r a m s , h e r o i n a d d i c t s r e c e i v e oral d o s e s o f this d r u g , a l l o w i n g t h e m to f u n c t i o n w i t h o u t h a v i n g to find a " f i x " e a c h d a y . M e t h a d o n e i t s e l f is a d d i c t i n g b u t has l e s s s e v e r e w i t h d r a w a l s y m p t o m s than h e r o i n . H e r o i n w i t h d r a w a l s y m p t o m s m a y i n c l u d e anxiety, p e r s p i r a t i o n , r e s t l e s s n e s s , t r e m o r s , m u s c l e , j o i n t a n d a b ­ dominal pain, fever, and possible convulsions and mental disorders. Metha­ d o n e b l o c k s t h e e f f e c t s o f an i n j e c t i o n o f h e r o i n . O t h e r d r u g s s u c h as N a l o x o n e a n d N a l o r p h i n e are n a r c o t i c a n t a g o n i s t s ; t h e y are u s e d as " a n t i d o t e s " to t e r m i ­ nate t h e effects o f a n a r c o t i c in t h e p a t i e n t ' s s y s t e m .

23.5

Anesthetics L i k e t h e a n a l g e s i c s , a n e s t h e t i c s d e c r e a s e a patient's r e a c t i o n to p a i n . G e n e r a l a n e s t h e t i c s , h o w e v e r , also c a u s e loss o f c o n s c i o u s n e s s , d i m i n i s h e d r e f l e x e s , a n d relaxation o f m u s c l e s in a d d i t i o n to a n a l g e s i a . T h e y act b y d e p r e s s i n g t h e c e n t r a l n e r v o u s s y s t e m , w i t h m i n i m a l e f f e c t o n t h e vital s i g n s . A n e s t h e t i c s are administered during surgery and childbirth. The

anesthetic

ethers

are

described

in

Section

11.5.

Diethyl

ether

(CH3CH2OCH2CH3), w i d e l y u s e d for m a n y y e a r s , is safe a n d e a s y to a d m i n ­ ister, b u t it is e x p l o s i v e a n d has a l o n g r e c o v e r y t i m e a c c o m p a n i e d b y n a u s e a . D i v i n y l e t h e r ( C H 2 = C H — Ο — C H = C H 2 ) is t o x i c to t h e l i v e r a n d k i d n e y ; its u s e is r e s t r i c t e d to b r i e f p r o c e d u r e s . F l u o r o x e n e ( C F 3 C H 2 O C H = C H 2 ) , also e m p l o y e d for short p e r i o d s , is l i m i t e d b y its

flammability.

Methoxyflurane

( C l 2 C H C F 2 O C H 3 ) , a d m i n i s t e r e d for a n a l g e s i a in o b s t e t r i c s a n d m i n o r o p e r a ­ t i o n s , has a s l o w i n d u c t i o n a n d r e c o v e r y p e r i o d . Halogenated

hydrocarbons

also s e r v e as inhalation a n e s t h e t i c s . C h l o r o f o r m

(CHCI3) is rarely u s e d b e c a u s e o f its p o s s i b l e t o x i c i t y to t h e heart a n d l i v e r . T r i c h l o r o e t h y l e n e [ H C ( C 1 ) = C C 1 2] p r o d u c e s r a p i d a n a l g e s i a for d e l i v e r y b u t c a u s e s r a p i d r e s p i r a t i o n a n d affects t h e heart. H a l o t h a n e is t h e m o s t p o p u l a r a n e s t h e t i c . It c a u s e s little respiratory irritation o r p o s t a n e s t h e t i c n a u s e a a n d is F

Η

I

I

F— C—C—Br

I

I

F

CI

halothane

5 3 6 Chapter 2 3 / Drugs and poisons n o t e x p l o s i v e . H a l o t h a n e , h o w e v e r , r e l a x e s m u s c l e s p o o r l y a n d also m a y r e ­ sult in respiratory o r c a r d i a c d e p r e s s i o n . e m p l o y e d as a n e s t h e t i c s i n c l u d e t h e w i d e l y u s e d

Gases

cyclopropane,

w h i c h has a r a p i d i n d u c t i o n p e r i o d a n d little irritation o r aftereffect. Its m a j o r d i s a d v a n t a g e is t h e p o s s i b i l i t y o f e x p l o s i o n . N i t r o u s o x i d e , o r " l a u g h i n g g a s , " N 2 0 , is a d m i n i s t e r e d as a m i x t u r e ( 8 0 % / 2 0 % ) w i t h o x y g e n . T h e gas s e r v e s m a i n l y as an a n a l g e s i c in c o m b i n a t i o n w i t h o t h e r a n e s t h e t i c s . Intravenous

act for v e r y short p e r i o d s o f t i m e . T h i o p e n t a l ( p e n -

anesthetics

tothal) is t h e o n e u s e d m o s t o f t e n . T h e r e l a t e d m o l e c u l e , m e t h o h e x i t a l ( B r e v ital), is m o r e p o t e n t a n d p e r m i t s faster r e c o v e r y . Ο

II

^CH2CH3

CHCH2CH2CH3 /

C

^

HS

N

^

C

V C H Ο

3

w

thiopental Local

anesthetics

b l o c k t h e t r a n s m i s s i o n o f n e r v e i m p u l s e s f r o m t h e site o f

a p p l i c a t i o n w i t h o u t c a u s i n g t h e p a t i e n t to l o s e c o n s c i o u s n e s s . P r o c a i n e ( N o ­ v o c a i n ) , l i d o c a i n e ( X y l o c a i n e ) , a n d b e n z o c a i n e are c o m m o n e x a m p l e s . L o c a l

Ο

C H 2C H 3

Ο

FH* /

H 2N ^ Q y ~ C - 0 ~ C H 2 - C H 2- N C H 2C H 3

^

procaine

(

11

C H 2C H 3

C — C H -8 — :

^ CH3

j

"N

C H 2C H 3 lidocaine

Ο

ΗζΝ-^Ο^-Ο—O-CH2—CH3 benzocaine a n e s t h e t i c s are a p p l i e d e i t h e r t o p i c a l l y o r b y i n j e c t i o n ( s e e F i g u r e 1 2 - 1 ) .

23.6

Sedative-hypnotic s L i k e g e n e r a l a n e s t h e t i c s , t h e s e d a t i v e - h y p n o t i c d r u g s c a n act b y d e p r e s s i n g t h e central n e r v o u s s y s t e m . T h e i r e f f e c t is l o n g e r lasting, h o w e v e r , a n d t h e y c a n b e a d m i n i s t e r e d orally. I n small d o s e s t h e s e d r u g s c a u s e

sedation—a

23.6/Sedative-hypnotic s

537

c a l m i n g e f f e c t . L a r g e r d o s e s result in a state similar to natural s l e e p ( h e n c e t h e n a m e h y p n o t i c ) . Still b i g g e r d o s e s first c a u s e i n t o x i c a t i o n , t h e n a n e s t h e ­ sia, f o l l o w e d finally b y respiratory d e p r e s s i o n a n d d e a t h . C o n t i n u e d a d m i n i s ­ tration l e a d s to p h y s i c a l d e p e n d e n c e a n d w i t h d r a w a l s y m p t o m s i f t h e d r u g is withheld. T h e barbiturates

are an i m p o r t a n t class o f s e d a t i v e - h y p n o t i c d r u g s . T h e

structures o f s e v e r a l e x a m p l e s are as f o l l o w s : Ο Η /

Ο

II

N - C ^

o=c

C H 2C H 3

/

c \

II

Η N"

~

C

o=c

/

\

*

α \

N_c'

/

1

ˇ»

ˇ

phenobarbital

C

H R 3

C H x

3 1

C H 2C H 2C H

1

JC rn H

3

amobarbital

7

Ο Η II N - C

C H 2C H 3

o=c

c \ _ C Η || Ο /

x

C H C H 2C H 2C H 3

I

CH3

pentobarbital T h e y are d i v i d e d i n t o g r o u p s a c c o r d i n g t o t h e l e n g t h o f t h e i r e f f e c t . L o n g a c t i n g b a r b i t u r a t e s , s u c h as p h e n o b a r b i t a l , last for 6 to 12 h o u r s a n d are u s e d to p r o v i d e c o n t i n u a l s e d a t i o n a n d treat a n x i e t y , h y p e r t e n s i o n , a n d e p i l e p s y . I n t e r m e d i a t e - a c t i n g b a r b i t u r a t e s , l i k e a m o b a r b i t a l ( A m y t a l ) , are e f f e c t i v e for 4 to 6 h o u r s ; t h e y are a d m i n i s t e r e d i n c a s e s o f i n s o m n i a . U s e d f o r p r e o p e r a t i v e s e d a t i o n a n d t o treat i n s o m n i a , t h e short-acting b a r b i t u r a t e s , w h i c h i n c l u d e p e n t o b a r b i t a l ( N e m b u t a l ) a n d s e c o b a r b i t a l ( S e c o n a l ) , w e a r o f f after 3 to 4 h o u r s . T h e ultrashort-acting b a r b i t u r a t e s , s u c h as t h i o p e n t a l , are e f f e c t i v e for o n l y m i n u t e s ; as m e n t i o n e d in t h e last s e c t i o n , t h e y s e r v e as i n t r a v e n o u s a n e s ­ t h e t i c s . S i d e e f f e c t s o f t h e barbiturates m a y i n c l u d e a " h a n g o v e r " t h e m o r n i n g after, l i s t l e s s n e s s , d e p r e s s i o n , n a u s e a , a n d e m o t i o n a l d i s t u r b a n c e s . Barbiturates, k n o w n as " d o w n s " o r " g o o f b a l l s , " are w i d e l y a b u s e d . ( P e n ­ tobarbital c a p s u l e s are c a l l e d " y e l l o w j a c k e t s " a n d s e c o b a r b i t a l c a p s u l e s are c a l l e d " r e d d e v i l s " b e c a u s e o f t h e i r c o l o r . ) T h e s e d r u g s are taken in h i g h d o s e s t o c r e a t e e f f e c t s similar to a l c o h o l i n t o x i c a t i o n , w h i c h i n c l u d e e u p h o r i a b u t also s l u g g i s h n e s s a n d i m p a i r m e n t o f m e m o r y , j u d g m e n t , attention s p a n , a n d m o t o r c o o r d i n a t i o n . P h y s i c a l d e p e n d e n c e results

from

above

normal

d o s e s taken d a i l y for s e v e r a l m o n t h s . W i t h d r a w a l f r o m barbiturates is m o r e

H

538

C h a p t er 2 3 / D r u gs a nd p o i s o ns

d a n g e r o u s than w i t h d r a w a l f r o m n a r c o t i c a n a l g e s i c s a n d s h o u l d b e c a r r i e d o u t in a h o s p i t a l . C h l o r a l h y d r a t e [ C l 3C C H ( O H ) 2] is a r a p i d l y acting n o n b a r b i t u r a t e h y p n o t i c . T h i s s u b s t a n c e is k n o w n as " k n o c k o u t d r o p s " a n d a " M i c k e y F i n n " w h e n d i s ­ s o l v e d in a l c o h o l . P a r a l d e h y d e ( s e e S e c t i o n 11.7), a n o t h e r e x a m p l e , is safe b u t irritating a n d has a d i s a g r e e a b l e taste.

23.7

Antianxiety and antipsychoti c drugs C e r t a i n n e w e r d r u g s are u s e d to treat anxiety a n d t e n s i o n , like t h e b a r b i t u ­ rates in l o w d o s e s . Meprobamate

( M i l t o w n , E q u a n i l ) is similar in a c t i o n to

a m o b a r b i t a l . Chlordiazepoxide

( L i b r i u m ) , a m o r e p o p u l a r e x a m p l e , is a

l o n g e r - a c t i n g d r u g . Diazepam

(Valium), o n e o f the m o s t w i d e l y p r e s c r i b e d

O

II

CH3

Ο

I

II

N H 2— C — Ο — C H 2— C — C H 2 — O - C — N H 2 C H 2C H 2C H 3 meprobamate (Miltown, Equanil) C H 3.

:CH

chlordiazepoxide (Librium)

2

diazepam (Valium)

d r u g s , has a similar structure. T h e s e t w o antianxiety agents are n o m o r e e f f e c ­ t i v e than barbiturates as s e d a t i v e s b u t h a v e a h i g h e r m a r g i n o f safety a n d less p o t e n t i a l for a b u s e . T h e y p r o d u c e l e s s s l e e p i n e s s o r i n t e r f e r e n c e w i t h m o t o r activities. M a n y n o n p r e s c r i p t i o n d r u g s ( s u c h as C o m p o z , S l e e p - e z e , N y t o l , a n d S o m i n e x ) are s o l d as s e d a t i v e - h y p n o t i c s . T h e y c o n t a i n a n t i h i s t a m i n e s , aspirin­ l i k e c o m p o u n d s , a n d o t h e r s u b s t a n c e s w h i c h m a y p r o d u c e s o m e s e d a t i o n as s e c o n d a r y e f f e c t s . Little e v i d e n c e , h o w e v e r , s u p p o r t s t h e i r c l a i m s ; t h e s e p r o d u c t s are q u e s t i o n a b l e in terms o f b o t h safety a n d e f f e c t i v e n e s s .

2 3 . 8 / A l c o h ol

539

A n t i p s y c h o t i c a g e n t s are a r e c e n t class o f d r u g s a b l e to r e d u c e t h e m o s t s e ­ v e r e s y m p t o m s in a h i g h p e r c e n t a g e o f p s y c h o t i c p a t i e n t s , t h o s e s u c h as s c h i z o ­ p h r e n i c s w i t h m a j o r p s y c h o l o g i c a l d i s t u r b a n c e s . T h e e f f e c t o f t h e s e d r u g s is v e r y d i f f e r e n t f r o m that o f s e d a t i v e - h y p n o t i c s . C o m p o u n d s l i k e zine

chlorproma-

( T h o r a z i n e ) alter m o o d a n d b e h a v i o r — r e d u c i n g h a l l u c i n a t i o n s a n d i l l u ­

s i o n s , as w e l l as c a l m i n g t h e p a t i e n t . B y a l l e v i a t i n g s e r i o u s s y m p t o m s w i t h o u t Η ^ C ν. HC^ CX

/ s

v.

Η ^C \ CH

« ^ C ^ Η

α 3

^ C ^ CH I Η / ' C H 2— C H 2— C H 2— Ν CH3

chlorpromazine (Thorazine) c a u s i n g l o s s o f c o n s c i o u s n e s s , t h e a n t i p s y c h o t i c d r u g s are r e s p o n s i b l e in part for r e d u c i n g t h e p e r i o d o f h o s p i t a l i z a t i o n for m e n t a l l y ill p a t i e n t s .

23.8

Alcohol E t h y l a l c o h o l o r e t h a n o l ( C H 3 C H 2 O H ) is a central n e r v o u s s y s t e m d e p r e s s a n t u s e d m o r e o f t e n s o c i a l l y than m e d i c a l l y . I n t h e U n i t e d States a b o u t 8 0 % o f t h e m e n a n d 6 7 % o f t h e w o m e n d r i n k at l e a s t o c c a s i o n a l l y ; t h e total c o n s u m p t i o n p e r p e r s o n is a p p r o x i m a t e l y 10 g a l l o n s o f a l c o h o l e a c h y e a r . B u t s o m e p e o p l e d r i n k m o r e than o t h e r s — a b o u t 9 , 0 0 0 , 0 0 0 p e o p l e in this c o u n t r y are e i t h e r c h r o n i c alcohol abusers or a l c o h o l i c s , physically d e p e n d e n t o n the drug. L a r g e q u a n t i t i e s o f a l c o h o l c a u s e i r r e v e r s i b l e d a m a g e to t h e b r a i n , n e r v o u s s y s t e m , a n d heart i n a d d i t i o n t o t h e d i s r u p t i o n o f f a m i l y l i f e a n d j o b . A l c o h o l i c c i r r h o s i s o f t h e l i v e r is t h e fourth l e a d i n g c a u s e o f d e a t h b e t w e e n t h e a g e s o f 2 5 a n d 4 5 in l a r g e U . S . c i t i e s . A l c o h o l is r a p i d l y a b s o r b e d , p a r t i c u l a r l y w h e n t h e s t o m a c h is e m p t y — i n this c a s e , a b s o r p t i o n is n e a r l y c o m p l e t e in an h o u r . It is m e t a b o l i z e d in t h e l i v e r , first b y t h e e n z y m e a l c o h o l d e h y d r o g e n a s e . T h i s r e a c t i o n , t h e c o n v e r ­ s i o n o f e t h a n o l to a c e t a l d e h y d e , is t h e s l o w s t e p in t h e b r e a k d o w n o f a l c o h o l . It is n o t a f f e c t e d b y b l a c k c o f f e e , c o l d air, a c o l d s h o w e r , o r a n y o f t h e tradi­ t i o n a l m e a n s o f " s o b e r i n g u p " s o m e o n e w h o has d r u n k t o o m u c h . T h e a c e t a l ­ d e h y d e is c o n v e r t e d to a c e t a t e a n d t h e n to a c e t y l c o e n z y m e A b e f o r e e n t e r i n g the citric acid c y c l e , p r o d u c i n g 7 kcal/g o f alcohol. T h e b e h a v i o r a l e f f e c t s o f v a r i o u s d o s e s o f a l c o h o l are l i s t e d in T a b l e 2 3 - 4 .

5 4 0 C h a p t er 2 3 / D r u gs a n d p o i s o ns T a b le 2 3 - 4

B e h a v i o r al E f f e c ts of A l c o h ol V o l u m e of 4 0 - 5 0 % ( 8 0 - 1 0 0 proof)

Blood alcohol

alcohol (ounces)

level (g/100 ml)

2 (60)«

0.05

Effect on behavior false s e n s e o f w e l l being, impaired vision, querulous

4(120)

0.10

p o o r reaction time and coordination, confusion

6(180)

0.15

very p o o r reaction time, definite intoxication

8 (240)

0.20

physical and mental

8-14 (240-420)

0.20-0.35

c o n f u s i o n , slurred

12-16 (360-480)

0.30-0.40

stupor

14-18 (420-540)

0.35-0.45

coma

o v e r 18

m o r e than

death

depression speech

(over 540) a

0.45

Numbers in parentheses indicate the volume of alcohol expressed in milliliters.

T h i s c o m p o u n d a l w a y s c a u s e s d e p r e s s i o n o f t h e central n e r v o u s s y s t e m — t h e a p p a r e n t initial s t i m u l a t i o n results f r o m d e p r e s s i o n o f t h e i n h i b i t o r y c e n t e r s o f t h e b r a i n . I n an a v e r a g e p e r s o n , t h e b l o o d a l c o h o l c o n c e n t r a t i o n ( B A C ) m a y r e a c h a b o u t 0 . 1 % 1 h o u r after d r i n k i n g 4 o u n c e s o f 100 p r o o f ( 5 0 % ) a l c o h o l . D r i v i n g w i t h an a l c o h o l l e v e l a b o v e this v a l u e is i l l e g a l in all states b e c a u s e o f t h e greatly i n c r e a s e d c h a n c e o f an a c c i d e n t . T h e b l o o d a l c o h o l l e v e l returns to z e r o after a b o u t 6 h o u r s (2/3 o u n c e o f 5 0 % a l c o h o l is m e t a b o l i z e d e a c h h o u r ) . T h e N a t i o n a l Institute o n A l c o h o l A b u s e a n d A l c o h o l i s m r e c o m m e n d s that y o u d r i n k n o m o r e than IV2 o u n c e s o f a l c o h o l p e r d a y , o n l y w i t h f o o d a n d o n l y in a d i l u t e f o r m . T h i s q u a n t i t y r e p r e s e n t s 3 o u n c e s o f 1 0 0 p r o o f w h i s k e y , o r 12 o u n c e s (one-half o f a bottle) o f w i n e , or three 12-ounce containers o f b e e r (Figure 23-4). A l c o h o l also acts as a d i u r e t i c a n d w i d e n s b l o o d v e s s e l s ; it is s o m e t i m e s u s e d m e d i c a l l y for this p u r p o s e . O t h e r t h e r a p e u t i c u s e s i n c l u d e skin m a s s a g e , reflex stimulation in c a s e s o f c o l l a p s e , p o s t o p e r a t i v e a n a l g e s i a , a n d as a s o l v e n t for d r u g s . A " h a n g o v e r " results in part from m i l d w i t h d r a w a l s y m p t o m s from a l c o h o l , w h i c h m a y i n c l u d e t r e m o r s , f a t i g u e , v e r t i g o , h e a d a c h e , gastritis, a c i d o s i s ,

2 3 . 9 / S t i m u l a n ts

or

or 3 ounces of 100 proof

541

12 ounces (one-half bottle) of wine

three 12-ounce containers of beer

whiskey Figure 23-4. The m a x i m um daily limit of alcohol c o n s u m p t i on (National Council on A l c o h ol Abuse and Alcoholism).

w e a k n e s s , a n d d e h y d r a t i o n . I n t h e c a s e o f an a l c o h o l i c , w i t h d r a w a l is d a n g e r o u s , c a u s i n g d e l u s i o n a n d h a l l u c i n a t i o n s , a c o n d i t i o n k n o w n as d e l e r i u m t r e m e n s ( " D T V ) . D r u g s u s e d t o treat a l c o h o l i c s , l i k e disulfiram ( A n t a b u s e ) , prevent oxidation o f acetaldehyde, causing dizziness, h e a d a c h e , nausea, v o m iting, a n d difficulty in b r e a t h i n g i f a l c o h o l is i n g e s t e d .

23.9

Stimulants Stimulants are a class o f d r u g s that i n c r e a s e activity o f t h e central n e r v o u s s y s t e m in a m a n n e r similar to t h e h o r m o n e e p i n e p h r i n e ( a d r e n a l i n e ) . amine

Amphet-

is a t y p i c a l stimulant. It e l e v a t e s t h e m o o d , r e d u c e s f e e l i n g s o f fatigue

a n d h u n g e r , i n c r e a s e s r e a c t i o n t i m e , c o n c e n t r a t i o n , a n d t h e c a p a c i t y to d o

C H 2— C H — N H 2 CH3 amphetamine work. T h e d isomer, dextroamphetamine ( D e x e d r i n e ) , and the racemic mixture o f d a n d I f o r m s , k n o w n as B e n z e d r i n e , are b o t h u s e d m e d i c a l l y , as is t h e m o r e potent methyl derivative, m e t h a m p h e t a m i n e (Methedrine). T h e s e drugs are a d m i n i s t e r e d to treat d e p r e s s i o n , c u r b a p p e t i t e in c a s e s o f o b e s i t y , i m p r o v e p e r f o r m a n c e , a n d treat h y p e r k i n e t i c ( o v e r a c t i v e ) c h i l d r e n . T h e y c r e a t e a state o f d r u g d e p e n d e n c e , particularly w h e n i n j e c t e d d i r e c t l y into t h e b l o o d s t r e a m ( " m a i n l i n i n g " ) . A t y p i c a l " s p e e d

freak"

(Figure 23-5)

c o n t i n u e s i n j e c t i o n o f m e t h a m p h e t a m i n e for 3 to 6 d a y s f o l l o w e d b y 12 to 18 h o u r s o f s l e e p b e f o r e t h e n e x t r o u n d . I n a d d i t i o n to w e i g h t l o s s a n d s u s c e p t i b i l i t y to i n f e c t i o n , this f o r m o f d r u g a b u s e m a y c a u s e an

amphetamine-

542

C h a p t er 2 3 / D r u gs a nd p o i s o ns

Figure 23-5. Injecting " s p e e d ." (WHO photo by E. Mandelmann.)

i n d u c e d p s y c h o s i s w i t h h a l l u c i n a t i o n s a n d d e l u s i o n s as f o u n d in s c h i z o ­ p h r e n i a . C o c a i n e ( " c o k e , " " s n o w , " " c h a r l i e " ) is an a l k a l o i d that also acts as a stimulant a n d has s i d e effects similar to t h o s e o f t h e a m p h e t a m i n e s . Caffeine

is t h e m o s t w i d e l y u s e d n o n m e d i c a l central n e r v o u s s y s t e m s t i m u O H 3C

x

Π

Ν

CH3

V

˝

\

I CH3 caffeine lant. T a b l e 2 3 - 5 lists t h e c a f f e i n e c o n t e n t o f c o m m o n b e v e r a g e s . It is a l s o a v a i l a b l e " o v e r t h e c o u n t e r " in t h e f o r m o f t a b l e t s , s u c h as N o - D o z . A d o s e o f

23.10/Hallucinogens 5 4 3 T a b le 2 3 - 5

C a f f e i ne C o n t e nt of B e v e r a g es Beverage

Caffeine (mg/cup)

c o f f e e (regular)

100-150

c o f f e e (instant)

60-80 2-4

coffee (decaffeinated)

25-7 5

tea

u n d e r 50

cocoa

30-50a

cola a In 12 ounces.

50 t o 200 m g o f c a f f e i n e i n c r e a s e s m e n t a l alertness a n d r e d u c e s d r o w s i n e s s a n d f a t i g u e . M o r e than this a m o u n t c a u s e s n e r v o u s n e s s , irritability, t r e m o r s , a n d h e a d a c h e . H e a v y u s e o f this d r u g m a y l e a d t o a c r a v i n g a n d p h y s i c a l d e ­ pendence.

23.10

Hallucinogens H a l l u c i n o g e n i c a g e n t s , also k n o w n as p s y c h e d e l i c o r p s y c h o t o m i m e t i c a g e n t s , alter t h o u g h t p r o c e s s e s . T h e y affect p e r c e p t i o n o f s p a c e a n d t i m e , m o o d , a n d m e m o r y w i t h o u t d i s t u r b i n g t h e central n e r v o u s s y s t e m . T h e s e s u b s t a n c e s are rarely a d m i n i s t e r e d m e d i c a l l y b u t a u s e r w h o reacts p o o r l y (a " b a d t r i p " ) m a y seek m e d i c a l assistance. Lysergic

L S D o r " a c i d " ( s h o w n in S e c t i o n 12.7 a n d F i g ­

acid diethylamide,

u r e 23-6) is t h e m o s t p o t e n t h a l l u c i n o g e n . E f f e c t s s u c h as m o o d

fluctuation,

i n t e n s e c o l o r p e r c e p t i o n , a n d l o s s o f p e r s o n a l i d e n t i t y o c c u r w i t h oral d o s e s o f less than 0.05 m g . C o m m o n s i d e e f f e c t s i n v o l v e f e e l i n g s o f p a n i c r e s u l t i n g f r o m anxiety. Marijuana

contains

substances

chemically

known

b i n o l s , o n e o f w h i c h h a s t h e f o l l o w i n g structure: C H

O H

3

I

C — C

C = C H

/

\

:

H C -

\

/

C H

2

c

/

/

\ /

\

^ c

C = C H

— C H

H 3C

/

Η

C -

\

Ο

CH3 a tetrahydrocannabinol

as t e t r a h y d r o c a n n a ­

544

C h a p t er 2 3 / D r u gs a nd p o i s o ns

Figure 23-6. LSD. Only a very small a m o u nt of this c o m p o u nd is required to produce a physiological effect. (Photo courtesy of Pharmaceutical Manufacturers Associa› tion.)

T h e s e m o l e c u l e s h a v e effects similar to t h o s e o f the s e d a t i v e - h y p n o t i c s . T h e y p r o d u c e initial e u p h o r i a a n d e n h a n c e d s e n s e p e r c e p t i o n , f o l l o w e d b y a s e d a ­ tive d r e a m l i k e p h a s e . T h e d r u g shortens m e m o r y span a n d distorts t i m e a n d s p a c e . Marijuana, w h i c h has b e e n tried at least o n c e b y 2 5 m i l l i o n p e o p l e in t h e U n i t e d States, creates n o p h y s i c a l d e p e n d e n c e . F i g u r e 2 3 - 7 is a p h o ­ t o g r a p h o f marijuana l e a v e s . M e s c a l i n e is a h a l l u c i n o g e n f o u n d in p e y o t e cactus that is similar in e f f e c t to L S D . A n o t h e r e x a m p l e , p s i l o c y b i n , is p r e s e n t in certain m u s h r o o m s . P o s ­ s i b l e m e d i c a l p r o b l e m s result f r o m the p r e s e n c e o f harmful i m p u r i t i e s in s y n ­ t h e t i c h a l l u c i n o g e n s s o l d o n the " s t r e e t . " Η C H 30

C

C — C H 2C H 2N H 2

C H 3o

c

CH

II

0CH3 mescaline

23.11 / Drugs and the autonomic nervous system 5 4 5

Figure 23-7. Marijuana leaves. (Photo courtesy of U.S. Drug Enforcement Ad› ministration. )

23.11

Drugs and the autonomic nervous system I n a d d i t i o n to a c e n t r a l n e r v o u s s y s t e m , w h i c h p r o d u c e s c o n t r o l l e d r e s p o n s e s to c h a n g e s in y o u r s u r r o u n d i n g s , y o u r b o d y has an a u t o n o m i c n e r v o u s s y s t e m , w h i c h r e g u l a t e s t h e m u s c l e s a n d g l a n d s o f internal o r g a n s . A s d e s c r i b e d in a p r e v i o u s c h a p t e r ( S e c t i o n 1 6 . 7 ) , c h e m i c a l s u b s t a n c e s k n o w n as n e u r o t r a n s mitters are i n v o l v e d in b r i n g i n g " m e s s a g e s " f r o m t h e n e r v o u s s y s t e m to o t h e r c e l l s o f t h e b o d y . T h e n e u r o t r a n s m i t t e r s o f t h e a u t o n o m i c n e r v o u s s y s t e m are norepinephrine, epinephrine, and acetylcholine. D r u g s that p r o d u c e

effects

similar to t h o s e o f e p i n e p h r i n e

or

norepi-

n e p h r i n e are c a l l e d s y m p a t h o m i m e t i c ( a d r e n e r g i c ) d r u g s . T h e p h y s i o l o g i c a l e f f e c t s o f t h e s e t w o c a t e c h o l a m i n e s h a v e b e e n d i s c u s s e d in t h e c h a p t e r o n h o r -

5 4 6 Chapter 2 3 / D r u gs and poisons m o n e s ( S e c t i o n 2 1 . 2 5 ) . A m a j o r c l i n i c a l u s e o f this class o f d r u g s , w h i c h i n ­ cludes phenylephrine (Neo-Synephrine), isoproterenol (Isuprel), and e p h e d r i n e , in a d d i t i o n to e p i n e p h r i n e itself, is to o p e n t h e b r o n c h i a l p a s s a g e s in a p e r s o n w i t h asthma a n d to r e l i e v e nasal c o n g e s t i o n ( b y a c t i n g as a v a s o c o n ­ strictor). D r u g s that b l o c k t h e e f f e c t o f t h e s e a m i n e s are k n o w n as s y m p a t h o p l e g i c drugs or adrenergic b l o c k i n g agents. HO

\

HO—C

c-

/

Η -C

HO

\

Η C - C C—CH—CH,—NH-CH

HC

C - C H —CH2— NH—CH3

/

\

\

I

c= =c Η Η

Η

OH

3

OH

Η

phenylephrine

epinephrine H

O \

Η C - C

CH3

HO—C

C — C H — C H 2-

\

/

C = C Η Η

HC

NH—CH

I

I

OH

CH3

/

Η Η C—C

\ C -CH—CH—NH-CH \ / C = C OH CH3 Η Η

3

ephedrine

isoproterenol

P a r a s y m p a t h o m i m e t i c ( c h o l i n e r g i c ) d r u g s h a v e e f f e c t s similar to t h o s e o f a c e t y l c h o l i n e . S o m e m e m b e r s o f this c l a s s , s u c h as p h y s o s t i g m i n e , p r o d u c e Ο

CH3

II

I

C H 3— C — O — C H 2— C H 2— N +— C H 3 CH3 acetylcholine their e f f e c t b y i n h i b i t i n g t h e e n z y m e a c e t y l c h o l i n e s t e r a s e , w h i c h inactivates a c e t y l c h o l i n e . T h e s e d r u g s are u s e d to treat t h e e y e d i s o r d e r g l a u c o m a a n d Ο CH3

II

Η

NH—C—Ο—C

^c

HC.

CH3 x

C

-C

£

physostigmine

CH2

CH Ν

H

CH2

—

I

CH3

N

X

I

CH3

t h e m u s c l e d i s e a s e m y a s t h e n i a gravis. A l t h o u g h n o t u s e d m e d i c a l l y , n i c o t i n e , f o u n d in t o b a c c o l e a v e s , p r o d u c e s stimulatory effects l i k e a c e t y l c h o l i n e .

2 3 . 1 2 / P o i s o ns 5 4 7

A

CH2

/ O H

^CH2

HC^

C

Ν

ι

ii

ι

HC

CH

CH2

CH3

nicotine C o m p o u n d s that b l o c k s o m e o f t h e e f f e c t s o f a c e t y l c h o l i n e are k n o w n as p a r a s y m p a t h o l y t i c ( a n t i c h o l i n e r g i c ) d r u g s . A t r o p i n e , an a l k a l o i d f r o m t h e b e l ­ l a d o n n a s h r u b , is o n e e x a m p l e . It is u s e d as a p r e a n e s t h e t i c m e d i c a t i o n to p r e H Η C—C

Η C \ // \ II H/ \ ^ C H HC C — C H — C — O — C H 3C — Ν I \ / I \ / ^ C H C = C C H 2O H C Η Η H2 Η atropine vent obstruction

H2 C

Ο

2

2

o f the airway b y r e d u c i n g secretions. Atropine

relaxes

s m o o t h m u s c l e , s u c h as in t h e b l a d d e r a n d ureter, a n d s u p p r e s s e s s e c r e t i o n in c a s e s o f p e p t i c u l c e r . S c o p o l a m i n e is a d r u g similar in structure a n d e f f e c t to a t r o p i n e , d e c r e a s i n g t h e activity o f s m o o t h m u s c l e a n d g l a n d s that p r o d u c e e x ­ ternal s e c r e t i o n s .

23.12

Poisons M o s t s u b s t a n c e s t a k e n in e x c e s s c a n act as p o i s o n s , c a u s i n g injury or d e a t h . O f c o u r s e , t h e m o s t d a n g e r o u s s u b s t a n c e s are t h o s e that are h a r m f u l in small a m o u n t s . O f t h e o v e r 1 m i l l i o n c a s e s o f p o i s o n i n g e a c h y e a r in t h e U n i t e d States, the

largest

cause

is medicine

designed

for

internal

use.

Most poi­

s o n i n g s are a c c i d e n t a l a n d i n v o l v e s u c h d r u g s as aspirin, b a r b i t u r a t e s , a n d a n ­ tianxiety a g e n t s . T h e e f f e c t s p r o d u c e d b y o v e r d o s e s o f t h e t y p e s o f d r u g s d e ­ s c r i b e d i n this c h a p t e r are l i s t e d i n T a b l e 2 3 - 6 . C h i l d r e n u n d e r 5 years o l d make u p about one-third o f the accidental poisonings (Figure 23-8). P o i s o n s c a n result in d a m a g e b y l o c a l irritation b u t c a u s e t h e m o s t s e r i o u s ef­ fects internally w h e n c a r r i e d b y t h e b l o o d . T h e y c a n d e s t r o y t h e tissues o f an o r g a n , inactivate e n z y m e s , c o m b i n e w i t h c e l l c o m p o n e n t s , o r c a u s e r e l e a s e o f h a r m f u l s u b s t a n c e s . B e c a u s e t h e y are o r g a n s o f e x c r e t i o n , t h e k i d n e y s are e s ­ p e c i a l l y v u l n e r a b l e to t o x i c a g e n t s . T h e l i v e r is t h e site o f d e t o x i f i c a t i o n , t h e a t t e m p t to c h e m i c a l l y c o n v e r t p o i s o n s i n t o less t o x i c m o l e c u l e s . S o m e p o i s o n s h a v e a c u t e e f f e c t s — t h e i r p r e s e n c e is d e t e c t e d shortly after exposure, requiring i m m e d i a t e assistance. Others have c h r o n i c effects, w h i c h

548 T a b le 2 3 - 6

C h a p t er 2 3 / D r u gs a nd p o i s o ns

E f f e c ts of D r ug P o i s o n i ng Class o f d r u g

Effects

anesthetic

respiratory d e p r e s s i o n

antibiotic

d e p e n d s on specific drug

aspirin a n d salicylates

fever, convulsions, acidosis,

narcotic analgesics

respiratory d e p r e s s i o n , c o m a

sedative-hypnotics and

anesthesia, circulatory shock,

stupor

respiratory d e p r e s s i o n

antianxiety d r u g s

hypertension, toxic psychosis

stimulants

POISOn ALERT Poisons are the number one danger in house› holds. Join Pinky and write for free informa› tion and emer› gency telephone numbers to call for assistance, write the Master Poison

Figure 23-8. A warning on the dangers of p o i s o n. (Courtesy of Children’s Memorial Hospital, Ne› braska.)

Information Center at Chlldrens Memorial Hospital, Omaha, 68105.

d e v e l o p after l o n g - t e r m e x p o s u r e to l o w c o n c e n t r a t i o n s o f t h e p o i s o n . I n e i t h e r c a s e , t h e m a i n c o n c e r n is r e m o v i n g t h e s o u r c e o f t h e p o i s o n

and

k e e p i n g t h e p a t i e n t a l i v e . F e w p o i s o n s h a v e s p e c i f i c a n t i d o t e s that c a n b e a d m i n i s t e r e d to c o u n t e r t h e e f f e c t s .

23.13

Environmental pollutants M a n y t o x i c s u b s t a n c e s are r e l e a s e d into t h e e n v i r o n m e n t e i t h e r b y a c c i d e n t o r as w a s t e p r o d u c t s . S o m e o f t h e s e , t h e air p o l l u t a n t s , h a v e a l r e a d y b e e n briefly m e n t i o n e d ( S e c t i o n 5.13). Carbon

monoxide,

C O , t h e m a j o r p o l l u t a n t , is p r o -

d u c e d b y i n c o m p l e t e c o m b u s t i o n o f g a s o l i n e in a u t o m o b i l e e n g i n e s . 2C + Q2

> 2CO

2 3 . 1 3 / E n v i r o n m e n t al p o l l u t a n ts

549

Its t o x i c e f f e c t results f r o m t h e f o r m a t i o n o f c a r b o x y h e m o g l o b i n , w h i c h p r e ­ vents o x y g e n from reaching the tissues and causes death b y asphyxiation. T h e n o r m a l " b a c k g r o u n d " b l o o d l e v e l is 0 . 5 % ; h i g h e r c o n c e n t r a t i o n s p r o d u c e t h e f o l l o w i n g e f f e c t s : 1 to 2 % — s o m e b e h a v i o r a l c h a n g e s ; 2 to 5 % — c e n t r a l n e r v o u s s y s t e m e f f e c t s ; 5 to 1 0 % — c a r d i a c a n d p u l m o n a r y e f f e c t s ; 10 to 8 0 % — h e a d ­ a c h e , f a t i g u e , d r o w s i n e s s , c o m a , respiratory failure, a n d d e a t h . A " m o d e r a t e " c i g a r e t t e s m o k e r ( o n e p a c k p e r d a y ) i n h a l e s e n o u g h c a r b o n m o n o x i d e to r e a c h a b l o o d level of about 5%. Nitrogen

oxides,

l a r g e l y nitric o x i d e , N O , a n d s o m e n i t r o g e n d i o x i d e , N 0 2 ,

are f o r m e d d u r i n g h i g h - t e m p e r a t u r e c o m b u s t i o n o f g a s o l i n e , c o a l , a n d gas: N2 + 0

» 2NO

2

2NO + Oz Hydrocarbons,

> 2N02

o f w h i c h t h e m o s t a b u n d a n t is m e t h a n e , are r e l e a s e d into t h e

a t m o s p h e r e f r o m t h e g a s o l i n e in a u t o m o b i l e s . T h e y p r o d u c e o t h e r p o l l u t a n t s , s u c h as p e r o x y a c e t y l nitrates ( P A N ) , b y r e a c t i o n s i n l i g h t k n o w n as p h o t o c h e m ­ ical o x i d a t i o n . O z o n e , 0 3 , f o r m a t i o n is also r e l a t e d to t h e p r e s e n c e o f h y d r o O

II C H 3— C — O — O — N 0

2

a p e r o x y a c e t y l nitrate (PAN) c a r b o n s ; h i g h c o n c e n t r a t i o n s o f this gas (9 p p m ) result in s e v e r e p u l m o n a r y e d e m a ( p r e s e n c e o f fluid in t h e l u n g s ) . P h o t o c h e m i c a l s m o g ( " s m o k e - f o g " ) , w h i c h c a u s e s e y e irritation a n d interferes w i t h n o r m a l r e s p i r a t i o n , is f o r m e d t h r o u g h t h e i n t e r a c t i o n o f h y d r o c a r b o n s a n d n i t r o g e n d i o x i d e ; it c o n t a i n s 0 3 , C O , P A N , a n d o r g a n i c c o m p o u n d s s u c h as a l d e h y d e s a n d k e t o n e s . oxides,

Sulfur

l a r g e l y sulfur d i o x i d e , S 0 2 , w i t h s o m e sulfur t r i o x i d e , S 0 3 , result f r o m

c o a l a n d f u e l o i l c o m b u s t i o n , as w e l l as f r o m v o l c a n o e s :

s + o 2 —> so 2 2S02 + 0

2

> 2S03

T h e s e p o l l u t a n t s irritate t h e respiratory s y s t e m a n d c a n c a u s e c o n s t r i c t i o n o f t h e air p a t h w a y s . T h e y are m o s t d a n g e r o u s to t h o s e p e o p l e , s u c h as t h e e l ­ d e r l y , w h o m a y suffer f r o m c h r o n i c respiratory o r c a r d i o v a s c u l a r d i s e a s e . S o l i d s , k n o w n as particulates,

c o n s i s t o f v e r y small p a r t i c l e s ( 0 . 0 0 0 2 to 5 0 0

μηι in d i a m e t e r ) , w h i c h are p r o d u c e d b y c o a l c o m b u s t i o n , industrial p r o ­ c e s s e s , a n d forest fires. T h e y m a y c o n s i s t o f c a r b o n a n d t h e o x i d e s o f m a n y e l e m e n t s , i n c l u d i n g F e 2 0 3 ( F e 3 0 4 ) , S i 0 2 , A 1 20 3, K 2 0 , P 2 O s , C a O , M g O , T i O z , a n d N a 2 0 . T h e p e n e t r a t i n g ability o f t h e s e particles d e p e n d s o n their s i z e ; t h o s e s m a l l e r than 0.5 μτη in d i a m e t e r m a y r e a c h t h e a l v e o l i . O t h e r s o l i d s , s u c h as a s b e s t o s f i b e r s , are r e l e a s e d i n t o t h e air f r o m b u i l d i n g insulation a n d

5 5 0 Chapter 2 3 / D r u gs and poisons fireproofing materials. T h e p r e s e n c e o f this m i n e r a l in t h e l u n g s m a y l e a d to a s b e s t o s i s , a respiratory d i s e a s e , a n d l u n g c a n c e r . S i l i c o s i s , a p u l m o n a r y d i s e a s e , is c a u s e d b y t h e a c c u m u l a t i o n o f particles o f s i l i c o n d i o x i d e , S i 0 2 , f o u n d in sand a n d r o c k s . C o a l d u s t p r o d u c e s t h e m i n e r ' s " b l a c k l u n g " d i s e a s e ( F i g ure 2 3 - 9 ) . T h e inhalation o f b e r y l l i u m salts m a y result in b e r y l l i o s i s , an a c u t e pneumonia, or chronic lung disease.

Figure 23-9. A lung taken f r om a patient suffering f r om " b l a ck l u n g" disease. (EPA Documerica photo by Leroy Woodson.)

Heavy

metals,

those with high atomic weights, may b e systematic poisons,

affecting n u m e r o u s o r g a n s , as s h o w n in T a b l e 2 3 - 7 . M e r c u r y , for e x a m p l e , acts b y b i n d i n g strongly to s u l f u r - c o n t a i n i n g g r o u p s in t h e b o d y , i n h i b i t i n g e n z y m e a c t i o n a n d c a u s i n g c e l l u l a r d a m a g e . T h e v a p o r o f this l i q u i d m e t a l c a n pass f r o m the l u n g s i n t o t h e b l o o d , l e a d i n g to d a m a g e o f t h e b r a i n a n d central n e r v o u s s y s t e m . I n o r g a n i c m e r c u r y salts affect t h e l i v e r a n d k i d n e y t i s s u e ; o r g a n i c m e r c u r y c o m p o u n d s , t h e alkyl m e r c u r i a l s , p o s e a greater h a z a r d b e c a u s e t h e y a c c u m u l a t e in b r a i n tissue a n d are n o t r e a d i l y e l i m i n a t e d . L e a d c a n b i n d to sulfur a t o m s like m e r c u r y b u t c a n also gather in t h e s k e l e t o n l i k e c a l c i u m . B e c a u s e o f its f o r m e r u s e in w a l l paints, i n g e s t i o n o f l e a d is c o m m o n in o l d e r b u i l d i n g s , w h e r e c h i l d r e n m a y eat p i e c e s o f p e e l i n g paint. (Its u s e is

23.13/Environmental pollutants 5 5 1 T a b le 2 3 - 7

H e a v y - M e t al P o i s o ns Symptoms Metal

Sources

Acute poisoning

pesticides,

arsenic (As)

gastrointestinal

metal industry

disturbances

Chronic poisoning skin p i g m e n t a t i o n , edema, kidney and liver damage

antimony

alloys, batteries,

(Sb)

ceramics

nausea, hepatitis

anemia, weight l o s s , skin diseases

cadmium

metal industry

fever, chest

industry

dermatitis

(Cd)

respiratory a n d

pain

chromium

kidney disease gastrointestinal,

(Cr)

liver and kidney damage, cancer

lead (Pb) mercury (Hg)

flaking

paint

abdominal

(auto e m i s s i o n s ) fish,

shellfish,

antiseptics

anemia, cramps,

p a i n , irritability gastrointestinal disturbances

" l e a d l i n e , " palsy kidney and central n e r v o u s system damage

selenium (Se)

paper, coal,

gastrointestinal

petroleum

disturbances

kidney and liver disease

n o w restricted to t h e o u t s i d e s o f b u i l d i n g s . ) F i g u r e 2 3 - 1 0 s h o w s w o r k e r s in a l e a d f o u n d r y w e a r i n g s p e c i a l f a c e m a s k s to p r o t e c t t h e m f r o m t h e m e t a l f u m e s . C e r t a i n m o l e c u l e s [ s u c h as d i m e r c a p r o l , p e n i c i l l a m i n e , a n d e t h y l e n e d i a m i n e t e t r a a c e t i c a c i d ( E D T A ) ] b i n d s t r o n g l y to h e a v y m e t a l s a n d are u s e d to r e m o v e t h e m f r o m t h e b o d y . M a n y o r g a n i c pesticides,

s u b s t a n c e s u s e d to d e s t r o y b i o l o g i c a l p e s t s , are

t o x i c . T h e m o s t c o m m o n t y p e s are o r g a n o c h l o r i n e c o m p o u n d s ( D D T , m e t h o x y c h l o r , a l d r i n , d i e l d r i n , l i n d a n e ) , organophosphorous c o m p o u n d s

(parathion,

m a l a t h i o n ) , a n d c a r b a m a t e c o m p o u n d s (carbaryl, b a y g o n ) ; e x a m p l e s are s h o w n in F i g u r e 2 3 - 1 1 ( p . 5 5 3 ) . T h e organophosphorous a n d c a r b a m a t e p e s t i c i d e s d e a c t i v a t e t h e e n z y m e a c e t y l c h o l i n e s t e r a s e , c a u s i n g a c e t y l c h o l i n e to c o n t i n u e to trigger n e r v e i m p u l s e s , w h i c h results in t r e m o r s , c o n v u l s i o n s , a n d d e a t h . O r g a n o c h l o r i n e p e s t i c i d e s d i s s o l v e in t h e fatty m e m b r a n e s u r r o u n d i n g t h e n e r v e fibers, i n t e r f e r i n g w i t h t h e transport o f s o d i u m a n d p o t a s s i u m i o n s a n d c a u s i n g effects similar to t h o s e o f t h e t w o o t h e r t y p e s o f p e s t i c i d e s . Industrial a n d h o u s e h o l d s o l v e n t s are also p o t e n t i a l p o i s o n s . T h e s e i n c l u d e products

of petroleum

distillation

(kerosene,

gasoline), aromatic

hydro-

carbons ( b e n z e n e ) , and halogenated hydrocarbons (carbon tetrachloride). R e -

5 5 2 Chapter 2 3 / D r u gs and poisons

Figure 23-10.

Workers in a lead foundry. (WHO photo.)

c e n t l y , p o l y c h o r i n a t e d b i p h e n y l s ( P C B ' s ) , h a v e b e e n a d d e d to t h e list o f e n v i ­ r o n m e n t a l p o i s o n s . T h e s e c o m p o u n d s affect l i v e r tissue a n d e n z y m e s y s t e m s . Cl

\

HC

/

Cl

c

/

Η - C

\

C== c

Η

\

c-

/

- C

/

Η C -

Cl

-c

\

CH

/ c = =c

\

Η

\

Cl

a polychlorinated biphenyl (PCB) S e v e r a l t y p e s o f " p o l l u t a n t s " m a y b e c a r c i n o g e n s , c a n c e r - c a u s i n g a g e n t s , as s h o w n in T a b l e 2 3 - 8 ( p . 5 5 4 ) . A w i d e variety o f c o m p o u n d s h a v i n g v e r y differ­ e n t c h e m i c a l structures c a n act as c a r c i n o g e n s . A r o m a t i c b e n z y p y r e n e f o r m s w h e n m e a t s are c h a r c o a l - b r o i l e d . N i t r o s a m i n e s are b e l i e v e d t o f o r m t h r o u g h c h e m i c a l r e a c t i o n s in t h e s t o m a c h b e t w e e n nitrites ( u s e d as m e a t p r e s e r v a ­ t i v e s ) a n d a m i n e s f r o m y o u r d i e t . V i n y l c h l o r i d e is t h e b a s i s for t h e c o m m o n plastic material p o l y v i n y l c h l o r i d e ( P V C ) . N o t e that naturally o c c u r r i n g s u b -

2 3 . 1 3 / E n v i r o n m e n t al pollutants 5 5 3 organochlorine CI

CI

Η I H / C \ H / C \ / C \ C \ C-Cl O . I H 2 C I C 1 2C II X C / C /JC-Cl

\

Η

.CI -H

c - -CI

CI'

I

Η

/

/

Η

CI dieldrin

\

CI

lindane

organophosphorus S C H 3C H 2O x f

H

h

C ^

C ^

Ο / - . u r» 3 C H 30 |

P - O --C C H 3C H 20

C ^ C H

C H aO

7

C

P—S—CH—CH2

C—N02

/

, O/ C H 2 C H 3

^

/

X > C H 2C H 3

H

parathion

malathion

carbamate

Η Η C = C

Ο

II

Η

—C—NH—CH, CH

HC

I

I

CH

HC Η

Η carbaryl

Figure 23-11.

Examples of insecticides.

HC

/

Ο

\

^

II

C—O—C—NH—CH3 //

c-c, Η

\

Q

CH3 XC

H

I CH3 baygon

s t a n c e s l i k e aflatoxins from f u n g u s c a n a l s o s e v e as c a r c i n o g e n s . A large n u m b e r o f c a n c e r s a p p e a r to b e t r i g g e r e d in s o m e w a y b y c h e m i c a l s u b s t a n c e s in t h e environment. M a n y h a r m f u l p o l l u t a n t s are difficult t o trace b e c a u s e o f t h e l o n g w a i t i n g p e r i o d , u p to 2 0 t o 3 0 y e a r s , b e f o r e t h e e f f e c t s , s u c h as a t y p e o f c a n c e r , b e ­ c o m e n o t i c e a b l e . H e a l t h w o r k e r s k n o w n as e p i d e m i o l o g i s t s m u s t c o m p a r e t h e

T a b le 2 3 - 8

C a r c i n o g e ns Class

Example

p o l y n u c l e a r aromatic

Η

hydrocarbon Η

Η

HC

C

I

II

CH

v c" v I c

Gx

HC

I

I CH

CH

HC

v

c

Η benzpyrene

(L

aromatic amine HC

/ C . C

/ N H

2

C

I

I

CH

HC

c Η 2-naphthylamine

chlorinated hydro­

C H 2= C H C 1

carbon

vinyl chloride

N-nitroso c o m p o u n d

( C H 3) 2N - N = 0 dimethylnitrosamine

inorganic substance

n i c k e l (Ni)

natural p r o d u c t

Ο

II

Ο

HC-

II

HC

ο

.c

CH2

Η

cO ^ o ^ C ^ O C H a Η

aflatoxin Β alkylating a g e n t

CH2

C H 2C 1 — C H 2— S — C H 2— C H 2C 1 bis(2-chloroethyl)sulfide (mustard gas)

S u m m a ry

555

d i s t r i b u t i o n o f d i s e a s e w i t h i n s p e c i f i c p o p u l a t i o n s to i d e n t i f y p o s s i b l e c a u s e s in t h e e n v i r o n m e n t .

SUMMARY D r u g s are c h e m i c a l s u b s t a n c e s that affect y o u r b o d y . T h e y are u s e d for m e d i cal d i a g n o s i s , p r e v e n t i n g o r c u r i n g d i s e a s e , treating s y m p t o m s , o r birth c o n trol. M o s t d r u g s act b y s t i m u l a t i n g o r d e p r e s s i n g certain activities in t h e c e l l , k i l l i n g o r w e a k e n i n g a f o r e i g n o r g a n i s m , o r c a u s i n g irritation. A n t i b i o t i c s are c h e m i c a l s u b s t a n c e s u s e d to treat i n f e c t i o u s d i s e a s e , an a p p l i c a t i o n k n o w n as c h e m o t h e r a p y . T h e y are p r o d u c e d f r o m l i v i n g c e l l s a n d act b y k i l l i n g o r i n h i b i t i n g t h e g r o w t h o f a m i c r o o r g a n i s m . P e n i c i l l i n s are t h e m o s t p o t e n t antibacterial d r u g s ; t h e y i n h i b i t c e l l w a l l s y n t h e s i s in g r a m p o s i t i v e b a c t e r i a . T e t r a c y c l i n e s , a w i d e l y u s e d class o f a n t i b i o t i c s , h a v e a b r o a d s p e c t r u m o f activity. A n a l g e s i c s r e l i e v e p a i n b y d e c r e a s i n g t h e p a t i e n t ' s s e n s i t i v i t y w i t h o u t loss o f c o n s c i o u s n e s s . A s p i r i n , a c e t y l s a l i c y l i c a c i d , is a n o n p r e s c r i p t i o n a n a l g e s i c e f f e c t i v e against m i l d to m o d e r a t e p a i n in h e a d a c h e , n e u r a l g i a , m u s c l e p a i n , j o i n t p a i n , a n d t o o t h a c h e . It also acts as an a n t i p y r e t i c ( l o w e r i n g f e v e r ) a n d as an antiinflammatory a g e n t . A c e t a m i n o p h e n is t h e m o s t e f f e c t i v e a n d safest asp i r i n substitute. N a r c o t i c a n a l g e s i c s are t h e m o s t p o w e r f u l p a i n - r e l i e v i n g d r u g s a v a i l a b l e . F r e q u e n t u s e , h o w e v e r , l e a d s t o a state o f d r u g d e p e n d e n c e , o r a d d i c t i o n , c h a r a c t e r i z e d b y w i t h d r a w a l s y m p t o m s if t h e d r u g is d i s c o n t i n u e d . T h e y are m e d i c a l l y p r e s c r i b e d o n l y in c a s e s o f s e v e r e p a i n for r e l a t i v e l y short p e r i o d s o f t i m e . M o r p h i n e , an a l k a l o i d f r o m o p i u m p o p p y , is t h e m o s t e f f e c t i v e narc o t i c a n a l g e s i c . M e p e r i d i n e ( D e m e r o l ) is a s y n t h e t i c n a r c o t i c a n a l g e s i c s o m e times abused b y physicians and nurses. G e n e r a l a n e s t h e t i c s d e c r e a s e r e a c t i o n to p a i n as w e l l as c a u s i n g loss o f c o n s c i o u s n e s s , d i m i n i s h e d r e f l e x e s , a n d m u s c l e relaxation. A n e s t h e t i c i n c l u d e diethyl ether, divinyl ether,

fluoroxene,

ethers

and methoxyflurane. Chloro-

f o r m , t r i c h l o r o e t h y l e n e , a n d p o p u l a r h a l o t h a n e also s e r v e as i n h a l a t i o n a n e s t h e t i c s . G a s e s e m p l o y e d are c y c l o p r o p a n e a n d nitrous o x i d e , o r " l a u g h i n g g a s . " I n t r a v e n o u s a n e s t h e t i c s l i k e t h i o p e n t a l last for o n l y short p e r i o d s . L o c a l a n e s t h e t i c s s u c h as p r o c a i n e act o n l y at t h e site o f a p p l i c a t i o n . S e d a t i v e - h y p n o t i c s d e p r e s s t h e c e n t r a l n e r v o u s s y s t e m . T h e y are u s e d to c a u s e s e d a t i o n , a c a l m i n g e f f e c t , o r in larger d o s e s to p r o d u c e a state similar to natural s l e e p . Barbiturates, a m a j o r class o f s e d a t i v e - h y p n o t i c s , i n c l u d e l o n g a c t i n g p h e n o b a r b i t a l , i n t e r m e d i a t e - a c t i n g a m o b a r b i t a l , a n d short-acting p e n tobarbital and secobarbital. N e w e r antianxiety d r u g s i n c l u d e m e p r o b a m a t e , c h l o r d i a z e p o x i d e , a n d d i a z e p a m . T h e latter t w o , s o l d as L i b r i u m a n d V a l i u m , r e s p e c t i v e l y , h a v e a

556

C h a p t er 2 3 / D r u gs a nd p o i s o ns

h i g h e r safety m a r g i n a n d less p o t e n t i a l for a b u s e than barbiturates. A n t i p s y c h o t i c d r u g s , s u c h as c h l o r p r o m a z i n e , r e d u c e the m o s t s e v e r e s y m p t o m s , s u c h as h a l l u c i n a t i o n s a n d i l l u s i o n s , in a h i g h p e r c e n t a g e o f p s y c h o t i c patients l i k e schizophrenics. E t h y l a l c o h o l , o r e t h a n o l , is a central n e r v o u s s y s t e m d e p r e s s a n t u s e d m o r e s o c i a l l y than m e d i c a l l y . C o n t i n u e d u s e in large q u a n t i t i e s p r o d u c e s i r r e v e r s i b l e b r a i n , n e r v o u s s y s t e m , a n d heart d a m a g e as w e l l as c i r r h o s i s o f t h e l i v e r . Stimulants i n c r e a s e t h e activity o f t h e central n e r v o u s s y s t e m . A m p h e t a m i n e , a t y p i c a l e x a m p l e , e l e v a t e s t h e m o o d , r e d u c e s f e e l i n g s o f fatigue a n d h u n g e r , a n d i n c r e a s e s r e a c t i o n t i m e , c o n c e n t r a t i o n , a n d t h e c a p a c i t y to d o w o r k . C a f f e i n e is t h e m o s t w i d e l y u s e d n o n m e d i c a l stimulant. H a l l u c i n o g e n s , k n o w n as p s y c h e d e l i c o r p s y c h o t o m i m e t i c a g e n t s , alter p e r c e p t i o n o f s p a c e a n d t i m e , m o o d , a n d m e m o r y w i t h o u t d i s t u r b i n g t h e central n e r v o u s s y s t e m . L y s e r g i c a c i d d i e t h y l a m i d e , L S D , is t h e m o s t p o t e n t h a l l u cinogen. D r u g s that p r o d u c e

effects

similar to t h o s e o f e p i n e p h r i n e

or

norepi-

n e p h r i n e , neurotransmitters o f t h e a u t o n o m i c n e r v o u s s y s t e m , are c a l l e d sympathomimetic

drugs; examples

are p h e n y l e p h r i n e

and

isoproterenol.

P a r a s y m p a t h o m i m e t i c d r u g s , l i k e p h y s o s t i g m i n e , are similar in a c t i o n to a c e t y l c h o l i n e . P a r a s y m p a t h o l y t i c d r u g s , s u c h as a t r o p i n e , b l o c k t h e effects o f acetylcholine. M o s t s u b s t a n c e s t a k e n in e x c e s s c a n act as p o i s o n s , c a u s i n g injury o r d e a t h . T h e largest c a u s e is m e d i c i n e d e s i g n e d for internal u s e , s u c h as aspirin, b a r b i turates, o r antianxiety a g e n t s . P o i s o n s act b y d e s t r o y i n g t i s s u e , inactivating e n z y m e s , c o m b i n i n g with cell c o m p o n e n t s , or causing release o f harmful s u b stances. M a n y t y p e s o f t o x i c s u b s t a n c e s are r e l e a s e d into t h e e n v i r o n m e n t . T h e s e i n c l u d e g a s e s , h e a v y m e t a l s , p e s t i c i d e s , industrial a n d h o u s e h o l d s o l v e n t s , a n d particulates. S o m e p o l l u t a n t s c a u s e i m m e d i a t e o r a c u t e e f f e c t s ; others result in c h r o n i c d i s e a s e s , d e v e l o p i n g o v e r m a n y years f r o m l o w e x p o s u r e s . C o m p o u n d s o f w i d e l y v a r y i n g structure, s u c h as a r o m a t i c h y d r o c a r b o n s , n i t r o s o c o m p o u n d s , a n d i n o r g a n i c s u b s t a n c e s , c a n act as c a r c i n o g e n s , c a n c e r - c a u s i n g agents.

Exercises 1. (Intro.) What is a drug? What are the general uses of drugs? 2. (23.1) In what ways do drugs act? 3. (23.1) What series of events takes place in the b o d y after a drug is administered? 4. (23.1) What factors determine a patient's response to a drug? 5. (23.2) Define antibiotic, chemotherapy, selective toxicity. 6. (23.2) Describe the advantages and disadvantages of the penicillins.

E x e r c i s es

557

7. (23.2) Why are tetracyclines known as "broad spectrum ,, antibiotics? 8. (23.3) What is an analgesic? 9. (23.3) Draw the structure and write the chemical name of aspirin. Describe its functions in the b o d y . 10. (23.4) H o w d o narcotic analgesics differ from aspirin? 11. (23.4) Describe the uses of two natural and two synthetic narcotics. 12. (23.5) H o w does a general anesthetic differ from a local anesthetic? 13. (23.5) Give an example o f each of the following types of anesthetic and state its properties: ether, halogenated hydrocarbon, gas, intravenous anesthetic, local anesthetic. 14. (23.6) H o w is a sedative-hypnotic different from an anesthetic? 15. (23.6) What are the different categories o f barbiturates and their uses? 16. (23.7) Describe h o w the newer antianxiety drugs differ from barbiturates. 17. (23.7) What are the functions of antipsychotic drugs? 18. (23.8) Summarize the physiological and behavioral effects of ethyl alcohol. 19. (23.9) Describe the activity of a stimulant such as amphetamine. 20. (23.10) What are the effects o f a hallucinogen? 21. (23.11) Define sympathomimetic drug, parasympathomimetic drug, parasympatholytic drug. Give one example o f each type. 22. (23.12) What kinds o f substances can act as poisons? What are the most common poisons? 23. (23.12) Describe the types o f effects a poison can have on the body. 24. (23.13) Give an example of each o f the following types of environmental pollutant: gas, heavy metal, insecticide, solvent, dust. 25. (23.13) What is the difference between an acute effect and a chronic effect of a pollutant?