CHOLINOCEPTORACTIVATING & CHOLINESTERASEINHIBITING DRUGS

Question 1

 Mimic acetylcholine

Answer 1

CHOLINOMIMETIC DRUGS

Question 2

TYPE OF CHOLINOMIMETIC DRUGS Classified by

A. Spectrum of action (type of receptor activated)

Answer 2

1. Muscarinic

2. Nicotinic

Question 3

TYPE OF CHOLINOMIMETIC DRUGS Classified by

B. Mechanism of action

Answer 3

1. Direct-acting
 Binding/activate cholinoceptors
2. Indirect-acting
 Inhibiting the hydrolysis of endogenous
ACh

Question 4

CHOLINOMIMETIC DRUGS

 Divided on the basis of their chemical structure
 Directly bind to and activate muscarinic or
nicotinic receptors
 Many have effects on receptors like ACh

Answer 4

A. DIRECT-ACTING CHOLINOMIMETIC DRUGS

Question 5

BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS (2)

Answer 5

1. CHOLINE ESTERS
    Including ACh
2. ALKALOIDS
    Muscarine and nicotine

Question 6

BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS
 4 important choline esters
 Permanently charged quaternary NH 4 group
 Relatively insoluble in lipids

Answer 6

CHOLINE ESTERS

Question 7

BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS
Poorly absorbed
 Poorly distributed in the CNS
 Hydrophilic

Answer 7

CHOLINE ESTERS

Question 8

BASIC PHARMACOLOGY OF THE DIRECT ACTING CHOLINOCEPTOR STIMULANTS
 Hydrolyzed in the GIT
 Differ markedly in their susceptibility to
hydrolysis by cholinesterase

Answer 8

CHOLINE ESTERS

Question 9

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Very rapidly hydrolyzed
 Large amounts must be infused IV to achieve
concentrations high enough to produce
detectable effects

Answer 9

ACETYLCHOLINE

Question 10

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Addition of methyl CH3
 3x more resistant to hydrolysis compared to ACh

Answer 10

METHACHOLINE

Question 11

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Carbamic acid ester derivative of ACh
 More resistant to hydrolysis by cholinesterase
 Longer duration of effect

Answer 11

CARBACHOL and BETANECHOL

Question 12

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANTS

 Addition of beta-methyl group (methacholine and
betanechol reduces the potency of these drugs at
nicotinic receptor sites

Answer 12

CARBACHOL and BETANECHOL

Question 13

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Act mostly with muscarinic receptors
(muscarine, pilocarpine)
 Act with nicotinic receptors
(nicotine, lobeline)

Answer 13

2. ALKALOIDS

Question 14

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Well absorbed from most sites of administration
 Excreted chiefly by the kidneys
 Acidification of urine accelerates clearance of
these amines

Answer 14

2. ALKALOIDS

Question 15

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Liquid
 Sufficiently lipid-soluble to be absorbed across
the skin

Answer 15

NICOTINE

Question 16

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Quaternary amine
 Less completely absorbed from the GIT
 Toxic when ingested
 Eg, in certain mushrooms, it even enters the brain

Answer 16

MUSCARINE

Question 17

BASIC PHARMACOLOGY OF THE DIRECT-ACTING
CHOLINOCEPTOR STIMULANT

 Plant derivative
 Similar to nicotine

Answer 17

LOBELINE

Question 18

ORGAN SYTEM EFFECTS

 Instilled to the conjunctival sac
 Causes contraction of the sphincter muscle
of iris (miosis)
 Causes ciliary muscle contraction
(accommodation)

Answer 18

1. EYE

Question 19

ORGAN SYTEM EFFECTS

 Reduction in peripheral resistance and
changes in heart rate

Answer 19

2. CVS

Question 20

ORGAN SYTEM EFFECTS

 Contraction of the smooth muscles of the
bronchial tree
 Stimulate glands of the tracheobronchial
mucosa to secrete

Answer 20

3. RESPIRATORY SYSTEM

Question 21

ORGAN SYTEM EFFECTS

 Similar to the parasympathetic nervous
system stimulation
 Increase in the secretory and motor activity
of the gut

Answer 21

4. GIT

Question 22

ORGAN SYTEM EFFECTS

 Stimulation of the salivary and gastric glands
 Increase in peristaltic activity
 Relaxation of sphincters

Answer 22

4. GIT

Question 23

ORGAN SYTEM EFFECTS

 Endothelium Derived Relaxing Factor (EDRF)
is released to produce dilation
 Dilation of arteries
 Dilation of veins
 Constriction (high-dose direct effect)

Answer 23

5. BLOOD VESSELS

Question 24

ORGAN SYTEM EFFECTS

 Stimulate the detrussor muscle
 Relax the trigone and sphincter
 Promote voiding

Answer 24

6. GUT

Question 25

ORGAN SYTEM EFFECTS Stimulate the thermoregulatory sweat, lacrimal and nasopharyngeal glands

Answer 25

7. GLANDS

Question 26

CHOLINOMIMETIC DRUGS  Primary effect by inhibiting acetylcholinesterase which hydrolyzes acetylcholine to choline and acetic acid

Answer 26

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

Question 27

CHOLINOMIMETIC DRUGS  Increase endogenous ACh concentration  Stimulates cholinoceptors to evoke increase response

Answer 27

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

Question 28

CHOLINOMIMETIC DRUGS  Parasympathetic effects  Some have direct action at nicotinic receptors

Answer 28

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

Question 29

CHOLINOMIMETIC DRUGS  Chief difference of the group are chemical and pharmacokinetics  3 chemical groups

Answer 29

B. INDIRECT-ACTING CHOLINOMIMETIC DRUGS

Question 30

BASIC PHARMACOLOGY 0F INDIRECT-ACTING CHOLINOMIMETICS  Quaternary NH4 group  2 to10 minutes  Reversible

Answer 30

1. SIMPLE ALCOHOLS

Question 31

BASIC PHARMACOLOGY 0F INDIRECT-ACTING CHOLINOMIMETICS  Quaternary or tertiary NH4 group  30 minutes to 6 hours  Reversible

Answer 31

2. CARBAMIC ACID ESTERS OF ALCOHOL

Question 32

BASIC PHARMACOLOGY 0F INDIRECT-ACTING CHOLINOMIMETICS  Highly lipid soluble  Very long duration  Irreversible

Answer 32

3. ORGANIC DERIVATIVES OF PHOSPHORIC | ACID

Question 33

BASIC PHARMACOLOGY 0F INDIRECT-ACTING CHOLINOMIMETICS  Echothiophate -Retains the very long duration of other organophosphates -More stable in aqueous solution

Answer 33

3. ORGANIC DERIVATIVES OF PHOSPHORIC | ACID

Question 34

ORGANIC DERIVATIVES OF PHOSPHORIC ACID  Used as insecticides

Answer 34

 Parathion and malathion (thiophosphates)

Question 35

 Primary action is to amplify the actions of endogenous Ach  Effects are similar, but not always identical, to the effects of direct-acting cholinomimetics

Answer 35

ORGAN SYSTEM EFFECTS

Question 36

ORGAN SYSTEM EFFECTS |  Most prominent effects

Answer 36

 CVS  GIT  Eye  Skeletal muscle neuromuscular junction

Question 37

CLINICAL PHARMACOLOGY OF CHOLINOMIMETICS ``` Pilocarpine Echothiophate (long-acting effect) ```

Answer 37

1. EYE

Question 38

CLINICAL PHARMACOLOGY OF CHOLINOMIMETICS POSTOPERATIVE ILEUS URINARY RETENTION POST OP

Answer 38

2. GIT and GUT

Question 39

2. GIT and GUT Clinical disorders that involve depression of smooth muscle activity without obstruction Betanechol

Answer 39

CLINICAL PHARMACOLOGY OF | CHOLINOMIMETICS

Question 40

NEUROMUSCULAR JUNCTION  Disease affecting the skeletal muscles neuromuscular junction  Autoimmune process

Answer 40

MYASTHENIA GRAVIS

Question 41

``` NEUROMUSCULAR JUNCTION   Production of antibodies that decrease the functional nicotinic receptors at the postjunctional end plates  Cholinesterase inhibitors are used for therapy ```

Answer 41

MYASTHENIA GRAVIS

Question 42

MYASTHENIA GRAVIS | diagnostic test

Answer 42

 Edrophonium

Question 43

MYASTHENIA GRAVIS long term therapy

Answer 43

 Neostigmine, pyridostigmine

Question 44

CLINICAL PHARMACOLOGY OF CHOLINOMIMETICS  SUPRAVENTRICULAR TACHYCARDIA  Treated by short-acting cholinesterase inhibitor (edrophonium)  Replaced by newer drugs (calcium channel blockers)

Answer 44

4. HEART

Question 45

5. ANTIMUSCARINIC DRUG INTOXICATION  Lethal in children  Causes prolonged severe behavioral disturbances and arrhythmias in adults

Answer 45

ATROPINE INTOXICATION

Question 46

5. ANTIMUSCARINIC DRUG INTOXICATION  Causes severe muscarinic blockade  Physostigmine Antidote to atropine poisoning

Answer 46

ATROPINE INTOXICATION

Question 47

``` CNS  ALZHEIMER’S DISEASE  With anticholinesterase activity  With cholinomimetic action  Used for therapy ```

Answer 47

Tacrine

Question 48

TOXICITY | A. DIRECT-ACTING MUSCARINIC STIMULANTS

Answer 48

```  Nausea and vomiting  Diarrhea  Salivation  Sweating  Cutaneous vasodilatation  Bronchial constriction  Excitation  Lacrimation ```

Question 49

A. DIRECT-ACTING MUSCARINIC STIMULANTS | BLOCKED BY

Answer 49

atropine

Question 50

DIRECT-ACTING NICOTINIC STIMULANTS |  40 mg or 1 drop of pure liquid is fatal 2 cigarettes  Central stimulant action

Answer 50

ACUTE TOXICITY

Question 51

DIRECT-ACTING NICOTINIC STIMULANTS ```  Convulsion  Coma  Respiratory arrest or paralysis  Hypertension  Arrhythmia ```

Answer 51

ACUTE TOXICITY

Question 52

DIRECT-ACTING NICOTINIC STIMULANTS  Treatment is symptom directed  Atropine  Anticonvulsants

Answer 52

ACUTE TOXICITY

Question 53

DIRECT-ACTING NICOTINIC STIMULANTS  Smoking

Answer 53

CHRONIC TOXICITY

Question 54

RISK OF chronic toxicity increased when

Answer 54

Vascular disease  Peptic ulcers  60 % carcinogenic

Question 55

C. CHOLINESTERASE INHIBITORS Major source of intoxication is pesticid Organophosphates Treated with large doses of atropine

Answer 55

ACUTE TOXICITY