Antimuscarinic And Ganglionic Drugs

Front 1

Antimuscarinic Drugs Tertiary amines

Back 1

Atropine M1 M2 M3

Scopolamine M1 M2 M3

Homatropine

Tolterodine M3

Trihexyphenidyl *M1 M2 M3



competitively block muscarinic receptors

Front 2

Antimuscarinic Drugs Quaternary ammonium compounds

Back 2

Glycopyrrolate

Ipratropium

competitively block muscarinic receptors and block ganglionic Nn receptors.

Front 3

Ganglionic stimulant
Drugs

Back 3

Nicotine

Front 4

Ganglionic
blocking Drugs

Back 4

Mecamylamine

hexamethonium

Front 5

ANTIMUSCARINIC DRUGS Mechanism of action

Back 5

competitively block muscarinic receptors

- Atropine and scopolamine block all subgroups M receptors

- Other antimuscarinic have selectivity for a subgroup of M receptors.

- Tertiary antimuscarinic negligible blocking at ganglionic Nn

- Quaternary compounds block muscarinic & Nn ganglionic receptors.

Front 6

ANTIMUSCARINIC DRUGS EFFECTS ON
CNS


atropine and scopolamine

Back 6

1) After intermediate doses:
- Mild central vagal stimulation.
- Fatigue, sedation, drowsiness, dreamless sleep
(more pronounced w/ scopolamine)
- Depression of the vestibular function.
- Reduction of parkinsonian tremor and rigidity.

2) After high doses:
Central stimulation is followed by depression (coma).

Front 7

ANTIMUSCARINIC DRUGS EFFECTS ON
Heart


atropine and scopolamine

Back 7

S-A node:
-decrease HR via blockade M2 presynaptic autoreceptors on postganglionic cholinergic terminals central vagal stimulation)
-tachycardia
-reflex vagal cardiac slowing inhibited

Atria:
-increase automaticity and contractility

A-V node:
increase conduction and automaticity
decrease refractoriness

Ventricles:
minimal direct effects on myocardial cells

Front 8

ANTIMUSCARINIC DRUGS EFFECTS ON
vessels


atropine and scopolamine

Back 8

negligible on circulation
-but vasodilation and hypotension caused by choline esters are readily antagonized

In children even therapeutic doses can cause ‘atropine flush’ = dilatation of cutaneous blood vessels

Front 9

ANTIMUSCARINIC DRUGS EFFECTS ON
gi


atropine and scopolamine

Back 9

- Decreased gastric secretion (PRENZIPINE)

- Decreased tone, amplitude of contractions, peristaltic activity and secretions of intestinal tract.

- Relaxation of the lower esophageal sphincter.

- Mild relaxation of gallbladder and bile ducts.

(since noncholinergic neurons also modulate GI functions the effects of vagal nerve stimulation are less effectively blocked than the effects of exogenous muscarinic stimulants)

Front 10

ANTIMUSCARINIC DRUGS EFFECTS ON
gu


atropine and scopolamine

Back 10

- Relaxation of pelves, calyces and ureters.

- Decreased ureteral peristalsis.

- Relaxation of detrusor muscle (increased capacity of the bladder).

Front 11

ANTIMUSCARINIC DRUGS EFFECTS ON
Respiratory system


atropine and scopolamine

Back 11

- Bronchial smooth muscle relaxation.

- Decreased tracheobronchial secretions.

- Decreased mucociliary clearance (not with ipratropium).

Front 12

ANTIMUSCARINIC DRUGS EFFECTS ON
Eye


atropine and scopolamine

Back 12

- Relaxation sphincter of iris (mydriasis)

- Relaxation ciliary muscle : cycloplegia: accommodation near vision lost hindering outflow aqueous humor through Schlemm’s canal

-atropine given locally mydriatic and cycloplegic effects long-lasting 3+ days

- Decreased secretion lacrimal glands.

Front 13

ANTIMUSCARINIC DRUGS EFFECTS ON
skin


atropine and scopolamine

Back 13

- Decreased secretion of sweat glands =raise body temperature

Infants and children are particularly prone to ‘atropine fever’

Front 14

ANTIMUSCARINIC DRUGS EFFECT

Back 14

decrease/opposite/inhibition of
DUMB BELS

Front 15

Tertiary amines distribute

Back 15

all tissues.

Front 16

Quaternary derivative distribute

Back 16

dont enter the CNS

Front 17

ANTIMUSCARINIC DRUGS
side effects

Back 17

when atropine is used to treat diarrhea, -side effec tachycardia

when atropine is used to counteract sinus bradycardia
-side effect constipation

Front 18

Acute poisoning of Atropine

Back 18

therapeutic index good in adults, but 5 mg can be lethal for children.

S&S due to: peripheral & central muscarinic receptor blockade
-with rapid long last effects

death, due to respiratory failure, circulatory collapse and coma.

Diagnosis via IM injection of physostigmine for confirmation = + If signs of muscarinic activation do not occur

treatment is symptomatic include:
a) Maintenance of vital signs
b) Alleviation of convulsion with diazepam
c) Temperature control with ice bags and alcohol sponges.

Front 19

POISONING BY ANTIMUSCARINIC DRUGS



OPPOSITE DUMBELLS

Back 19

Eye
-Mydriasis (iris obliterated),
-blurring of near vision,
-dryness of conjunctiva.

Respiratory system
-Difficulty speaking,
-dyspnea,
-respiratory depression.

Skin
Dry, hot, red

GI systems
Dryness of mouth / thirst;
-difficulty swallowing;
absence bowel sounds;
-paralytic ileus.

Urinary system
Difficulty in micturition.

Cardiovascular system
-Tachycardia, palpitations,
arrhythmias.

CNS
Fatigue, ataxia, headache, restlessness, hallucinations, delirium, generalized convulsions, coma.

Front 20

CONTRAINDICATIONS AND PRECAUTIONS
OF ANTIMUSCARINIC DRUGS

Back 20

- Glaucoma
- Prostatic hypertrophy
- Urinary tract obstruction
- Gastrointestinal tract obstruction
- Adynamic ileus
- Gastric ulcer
- Severe infectious diarrhea
- Reflux esophagitis
- Ulcerative colitis, Crohn’ disease (toxic megacolon can ensue)
- Tachyarrhythmias
- Coronary artery disease, cardiac failure
- Hyperthyroidism
- Children
- Elderly

Front 21

Prevention of motion sickness

Back 21

scopolamine

Front 22

treat Parkinson’s disease

Back 22

Triexyphenidyl

Front 23

counteracts the parasympathomimetic effects of neostigmine in myasthenic patients

Back 23

antimuscarinic drugs: Atropine

Front 24

tx for Poisoning by AchE inhibitors

Back 24

atropine

Front 25

THERAPEUTIC USES OF ANTIMUSCARINIC DRUGS for EYe

Back 25

- funduscopic examination (mydriasis)

-measurements of refractive errors (cycloplegia)

- Iritis, iridocyclitis, choroiditis (prevents adhesion formation)

Front 26

THERAPEUTIC USES OF ANTIMUSCARINIC DRUGS FOR
GI

Back 26

- Irritable bowel syndrome
(when diarrhea prevalent symptom)

- Abdominal colic, biliary colic.

- Diarrhea (from mild dysentery, traveler’s disease, diverticulitis, or drug induced)

- Sialorrhea
(due to heavy-metal poisoning or parkinsonism).

Front 27

ANTIMUSCARINIC DRUGS USED TO TREAT.... IN GU

Back 27

- Renal colic

-enuresis = involuntary urination

- Urge incontinence
(reduce urinary frequency)

Front 28

Tx of Bronchial asthma and COPD

Back 28

ipratropium
doesnt decrease bronchial secretions and mucociliary clearance)

Front 29

THERAPEUTIC USES OF ANTIMUSCARINIC DRUGS ON
Cardiovascular

Back 29

- Cardiopulmonary resuscitation
(when vagal hyperactivity is cause of cardiac arrest)

- Sinus or nodal bradycardia
(due to myocardial infarction, hyperactive carotid sinus reflex, etc.)

- A-V block
(due to increased vagal tone)

- Preoperative use
(to block cardiovagal reflexes)

Front 30

GANGLIONIC STIMULATING
DRUGS

Back 30

- Nicotine

- Tetramethylammonium

- Carbachol

- Cholinesterase inhibitors

- Succinylcholine

Front 31

GANGLIONIC BLOCKING
DRUGS

Back 31

- Hexamethonium

- Mecamylamine

- Glycopyrrolate

- Ipratropium

- Tubocurarine

Front 32

NICOTINE Mechanism of action doses

Back 32

1. Low/intermediate doses activate nicotinic receptors at:
a) autonomic ganglia
(ganglionic stimulation is the main action)
b) neuromuscular junction
c) some presynaptic nerve terminals
d) adrenal medulla
e) central nervous system

2 Large doses depolarization blockade (the prolonged depolarization of the postjunctional membrane hinders neuronal transmission).

Front 33

NICOTINE Mechanism of action

Back 33

- Nicotine also stimulates most sensory receptors, including:
a) mechanoreceptors of mesentery, tongue, stomach, lung and skin.
b) chemoreceptors of carotid and aortic bodies.
c) thermal receptors of skin and tongue.
d) pain receptors.

Front 34

Effects of nicotine on cns

Back 34

- Stimulation Renshaw cells (interneurons ventral horn)

- Stimulation (low dose) or depression (high dose) of reticular formation

- Direct and reflex stimulation respiratory & vasomotor centers

- Reflex stimulation emetic center

- Direct stimulation of chemoreceptor trigger zone

- Stimulation of ADH secretion

- Sedative-anxiolytic activity (higher doses)


- Generalized stimulation of cerebrospinal axis (toxic doses) which leads to hyperreflexia, tremors and convulsions

Front 35

NICOTINE EFFECTS ON
Cardiovascular system

Back 35

- Increased cardiac output and heart rate (heart efficiency is diminished)

- Constriction of skin and splanchnic vessels

- Dilation of muscular vessels

- Increased blood pressure

toxic doses:
- Cardiovascular collapse

Front 36

NICOTINE EFFECTS ON
gi

Back 36

- Anorexia, nausea and vomiting

- Stimulation of peristalsis and secretions

After toxic doses:
- Paralytic ileus

Front 37

NICOTINE EFFECTS ON
Respiratory system

Back 37

- Stimulation of respiration
(by central action and stimulation of chemoreceptors of the carotid and aortic bodies)

- Bronchoconstriction

-increased bronchial secretions

toxic doses:
- Apnea
(due to central depression and block of diaphragm & intercostal muscles).

Front 38

NICOTINE EFFECTS ON
GU

Back 38

- Decreased diuresis
(due to ADH release).

- Contraction detrusor muscle.

- Relaxation trigone and internal sphincter of urethra.

Front 39

NICOTINE EFFECTS ON
Other systems

Back 39

- Stimulation of sweat glands

- Miosis
(due to activation Nn receptors ciliary ganglion)

- Induction of mixed function oxidases
(rate of metabolism of many drugs is increased)

- Increased platelet aggregation and blood coagulability

chronic use
- Loss of body weight
- Increased hand tremors


toxic doses
- Paralysis of skeletal muscle

Front 40

Nicotine tolerance and dependence

Back 40

-Nausea, vomiting, dizziness,headache

-dysphoria

-effects due to peripheral ganglionic stimulation undergo tachyphylaxis

- This rapid tolerance is lost overnight

- Tolerance to other effects is less pronounced

- Nicotine can cause bot psychological and physical dependence.

Front 41

ACUTE NICOTINE POISONING

Back 41

-Onset S & S is rapid.

Initial symptoms include:
- Salivation
- Nausea and vomiting
- Abdominal pain, diarrhea, loss of urine and feces
- Cold sweat
- Tachypnea
- Tachycardia
- Disturbed hearing and vision
- Headache, dizziness, mental confusion
- Marked weakness

The symptoms then progress to:
- Faintness and prostration
- Falling of blood pressure
- Weak, irregular and rapid pulse
- Difficulty in breathing
- Tremors, convulsions

Death may result within few minutes from respiratory failure.

Front 42

Effect of ganglionic blockade

Back 42

Heart : Tachycardia

Arterioles: Vasodilation, orthostatic hypotension

Veins: Vasodilation; venous pooling; decreased cardiac output

Iris: Mydriasis

Ciliary muscle: Cycloplegia

GI tract: Decreased motility & tone (constipation, gas accumulation)

Urinary bladder: Urinary retention

Exocrine gland: Reduced secretion

Sweat glands: Reduced secretion (anhydrosis)

Sex organs(Male): Impaired erection, ejaculation

Front 43

GANGLIONIC BLOCKING DRUGS
Mechanism of action

Hexamethonium
Mecamylamine

Back 43

-Competitive blockade of nicotinic receptors (Nn) in:
a) autonomic ganglia

b) adrenal medulla

c) presynaptic nerve terminals

d) central nervous system (mecamylamine)

Front 44

Mecamylamine treats?

Back 44

neurological diseases

Tourette's syndrome.


proposed recently for the therapy of nicotine and coke dependence

Front 45

GANGLIONIC BLOCKING DRUGS
Pharmacokinetics

Back 45

Hexamethonium
-quaternary ammonium
-negligible oral absorption and access to the CNS



Mecamylamine
-secondary amine
- oral route and enters the brain

Front 46

ATROPINE:

Back 46

PHARMACOLOGICAL ACTIONS : Atropine blocks M
CNS : CNS stimulant action .
High doses causes restlessness, hallucinations and disorientati

Front 47

ATROPINE:
CVS :

Back 47

tachycardia --- due to blockade of M2 receptors
It facilitates AV conduction
No marked effect on the BP

Front 48

ATROPINE:
EYE

Back 48

Atropine causes mydriasis and cycloplegia (paralysis of accommodation) by blocking M3 receptors
Vision is fixed for far objects

Front 49

ATROPINE : SMOOTH MUSCLES

Back 49

All smooth muscles that receive parasympathetic innervations are relaxed by atropine.

GIT – Peristalsis is inhibited - Constipation

Bronchus – dilatation

Urinary bladder – retention of urine

Front 50

ATROPINE :
GLANDS

Back 50

decreases secretions of salivary, lacrimal glands, acid in stomach.

Body temp increase.

mild local anesthetic effect on cornea.

Front 51

Adverse effects of atropine :

Back 51

Blurred vision, Confusion, Mydriasis, Constipation, urinary retention, tachycardia.

May precipitate glaucoma or urinary retention.

Front 52

Nonselective
alpha agonists effects on glaucoma

Back 52

-Epinephrine
-Dipivefrin
-Decreased aqueous humor production due to vasoconstriction via alpha-2 activation

-Increased aqueous humor outflow

Front 53

Nonselective
alpha agonists

Back 53

-Epinephrine
-Dipivefrin

-Decreased aqueous humor production due to vasoconstriction via alpha-2 activation

-Increased aqueous humor outflow

Front 54

Selective
alpha-2 agonists tx for glaucoma

Back 54

-Apraclonidine

-Decreased aqueous humor production

(due to activation of alpha-2 on ciliary processes

Front 55

Selective
alpha-2 agonists tx for gluacoma

Back 55

-Apraclonidine

-Decreased production aqueous humor

(via activation alpha-2 on ciliary processes)

Front 56

Beta-blockers tx for glaucoma

Back 56

-Timolol
-Betaxolol

-Decreased aqueous humor production

due to blockade of beta-2 on ciliary processes

Front 57

Diuretics tx for gluacoma

Back 57

-Acetazolamide
-Dorzolamide

-Decreased aqueous humor production

due to lack of HCO3-

Front 58

how is Mannitol used to tx glaucoma

Back 58

-Increased aqueous humor outflow

via increased osmotic pressure of plasma

Front 59

Prostaglandin
analogs tx for glaucoma

Back 59

-Latanoprost

Increased aqueous humor outflow

through the uveoscleral route