This presentation deals with the in-depth analysis of various cardiac stimulants & depressants both directly & indirectly acting on frog's heart. Also, includes a nice quiz, a good exercise for the grey cells of the brain at the end of the presentation.
6. Addition of unknown drug (UD) to frog’s heart
↓ ↓
↑ HR, tone, amplitude ↓ HR, tone, amplitude
↓ ↓
UD Cardiac stimulant UD Cardiac depressant
↓ ↓
Ppnl (0.2 ml) inj. foll. By UD Atr (0.2 ml) inj. foll. by UD
↓ ↓ ↓ ↓
No effect ↑ tone No effect ↓ tone
↓ ↓ ↓ ↓
UD - Indir. UD - Directly UD – Indir. UD -Directly
Acting cs acting cs acting cd acting cd
(E,NE, Iso) (CaCl2) (Ach) (KCl)
7. Regulation of the heart
Dominant tone = parasympathetic
Sympathetic
Increases heart rate
and contractility via
beta-1 and 2
(primarily beta-1)
Parasympathetic
Decreases heart
rate and atrial
contractility via M2
14. 1. Ach Cardiac effects ↓ impulse formation in
SAN by ↓ the rate of diastolic depolarization (↓
HR) & ↑ PR interval (Time from SAN to AVN)
2. Atr Cardiac eff. ↑ HR & AV conduction velocity
by blocking the effects of the vagus nerve on sa,av
• Low i.v. atropine paradoxical slowing of HR
(stimulation of the vagal motor nucleus in the brain
stem). After full dose heart rate ↑
15. CVS eff. Of NE, E, Isoprenaline
• NE Activation of α1 receptors (V.c. & ↑ TPR)
Reflex bradycardia if blood pressure increases
sufficiently to activate the baroreceptor reflex
• E ↑ SBP but can ↑ or ↓ DBP
• Isoproterenol Activates β1 and β2 receptors
• Propranolol Blockade of β1 receptors
19. Dopamine
• Low doses (< 2 μg/kg per min) D1 dopaminergic
receptors in renal, mesenteric, and coronary
vascular beds. (vasodilation)
• Moderate dose (2–10 μg/kg per min) β1 recept.
• Higher dose (10 μg/kg per min) α1 receptors
20. Adrenaline
Uses (ABCD)
1. Anaphylactic shock (DOC) 0.5 mg (0.5 ml of 1
in 1000 solution for adult) i.m.
2. Bronchial asthma
3. Cardiac arrest 10 ml of 1:10000 i.v.
4. Control of local bleeding Adr 1 in 10,000
5. During LA combined with Lignocaine (1:50,000 or
1:2,00,000)
21. Acetylcholine
• Choline ester of acetic acid
• Uses
1. During cataract surgery (Miosis) NO topical
2. Diagnostic coronary angiography intracoronary
injection to cause coronary artery spasm
3. Vasospastic angina pectoris, however,
intracoronary injection of acetylcholine can
provoke a localized vasoconstrictive response,
and this helps establish the diagnosis of
vasospastic angina
22. Atropine & Scopolamine (t.a.)
• t1/2 2 hrs (oral route)
• After topical ocular administration, they have
longer-lasting effects because they bind to
pigments in the iris that slowly release the drugs.
• People with darker irises bind more atropine and
experience a more prolonged effect than do people
with lighter irises. The ocular effects gradually
subside over several days.
• “dry as a bone, blind as a bat, red as a beet, and
mad as a hatter.” Atr. toxicity
23. Effects
• Ocular eff. Myd. + cycloplegia
• Cardiac eff. ↑ HR & AV conduction velocity by
blocking the effects of the vagus nerve on SAN,AVN
Low i.v. atropine paradoxical slowing of HR
(stimulation of the vagal motor nucleus in the brain
stem). After full dose heart rate ↑
• Resp. tract eff. bronchial smooth muscle
relaxation and bronchodilation, inhibitors of
secretions in the upper and lower respiratory tract.
24. Indications
• Ocular Indications mydriasis (facilitate peripheral
retina), cycloplegia (refractive errors), iritis and
cyclitis (↓ muscle spasm and pain)
• Cardiac Indications Sinus bradycardia after MI.
AV block to ↑ AV conduction velocity
• Respiratory Tract Indications ↓ salivary and
respiratory secretions & prevent airway obstruction
in patients who are receiving general anaesthetics.
Glycopyrrolate is often used for this purpose today
25. • GIT Indications Relieve intestinal spasms & pain
• UT indications Relieve urinary bladder spasms in
persons with overactive bladder.
• CNS Indications A transdermal formulation of
scopolamine can be used to prevent motion
sickness (blocking Ach neurotransmission from the
vestibular apparatus to the vomiting center in the
brain stem). Also, PD.
• Other Indications
1. Prevent muscarinic side effects when chE
inhibitors are given to patients with myasthenia
gravis.
2. Reverse the muscarinic effects of cholinesterase
inhibitor overdose.
28. MUSCARINIC effects (OP poisoning)
M Miosis
U Urination
S Secretions ↑ (salivation, lacrimation, sweating)
C Cardiac contraction & conduction slows
A Abdominal cramps
R Redn. In i.o.t. esp. in glaucoma
I ↑ GI motility
N NO dependent vasodilatation
I Inc. secretion from GIT & tracheobronchial tract
C Constriction of tracheobronchial tract
29. Adverse effects of Atropine
(DHATURA)
1. Dry mouth, difficulty in swallowing & speaking
2. Hot dry skin & hypotension
3. Accommodation paralysis (blurring of near vision)
4. Tachycardia
5. Urinary retention & fecal retention (constipation)
6. Respiratory depression
7. Ataxia & acute congestive glaucoma may
precipitate
33. Q.1. 1. A 3-year-old child has swallowed the contents
of 2 bottles of a nasal decongestant whose primary
ingredient is a potent, selective α-adrenoceptor
agonist drug. Which of the following is a sign of α-
receptor activation that may occur in this patient?
(A) Bronchodilation
(B) Cardiac acceleration (tachycardia)
(C) Pupillary dilation (mydriasis)
(D) Renin release from the kidneys
(E) Vasodilation of the splanchnic vessels
34. Q.2. Ms Green is a 60-year-old woman with poorly
controlled hypertension of 170/110 mm Hg. She is to
receive minoxidil. The active metabolite of minoxidil
is a powerful arteriolar vasodilator that does not act
on autonomic receptors. Which of the following
effects will be observed if no other drugs are used?
(A) Tachycardia and increased cardiac contractility
(B) Tachycardia and decreased cardiac output
(C) Decreased mean arterial pressure and decreased
cardiac contractility
(D) Decreased mean arterial pressure and increased
salt and water excretion by the kidney
(E) No change in mean arterial pressure and
decreased cardiac contractility
35.
36. Q.3. Full activation of the sympathetic nervous
system, as in the fight-or-flight reaction, may occur
during maximal exercise. Which of the following
effects is likely to occur?
(A) Bronchoconstriction
(B) Increased intestinal motility
(C) Decreased renal blood flow
(D) Miosis
(E) Decreased heart rate (bradycardia)
37. Q.4. Nicotinic receptor sites do not include which
one of the following sites?
(A) Bronchial smooth muscle
(B) Adrenal medullary cells
(C) Parasympathetic ganglia
(D) Skeletal muscle end plates
(E) Sympathetic ganglia
38. Q.5. Which one of the following is the
neurotransmitter agent normally released in the
sinoatrial node of the heart in response to a blood
pressure increase?
(A) Acetylcholine
(B) Dopamine
(C) Epinephrine
(D) Glutamate
(E) Norepinephrine
39.
40. Q.6. A 30-year-old woman undergoes abdominal
surgery. In spite of minimal tissue damage, complete
ileus (absence of bowel motility) follows, and she
complains of severe bloating. She also finds it
difficult to urinate. Mild cholinomimetic stimulation
with bethanechol or neostigmine is often effective in
relieving these complications of surgery. Neostigmine
and bethanechol in moderate doses have
significantly different effects on which one of the
following?
(A) Gastric secretion
(B) Neuromuscular end plate
(C) Salivary glands
(D) Sweat glands
(E) Ureteral tone
41. Q.7. Ms Brown has been treated for myasthenia
gravis for several years. She reports to the
emergency department complaining of recent onset
of weakness of her hands, diplopia, and difficulty
swallowing. She may be suffering from a change in
response to her myasthenia therapy, that is, a
cholinergic or a myasthenic crisis. Which of the
following is the best drug for distinguishing between
myasthenic crisis (insufficient therapy) and
cholinergic crisis (excessive therapy)?
(A) Atropine
(B) Edrophonium
(C) Physostigmine
(D) Pralidoxime
(E) Pyridostigmine
42. Q.8. A crop duster pilot has been accidentally
exposed to a high concentration of a highly toxic
agricultural organophosphate insecticide. If
untreated, the cause of death from such exposure
would probably be
(A) Cardiac arrhythmia
(B) Gastrointestinal bleeding
(C) Heart failure
(D) Hypotension
(E) Respiratory failure
43. Q.9. Actions and clinical uses of muscarinic
cholinoceptor agonists include which one of the
following?
(A) Bronchodilation (asthma)
(B) Improved aqueous humor drainage (glaucoma)
(C) Decreased gastrointestinal motility (diarrhea)
(D) Decreased neuromuscular transmission and
relaxation of skeletal muscle (during surgical
anesthesia)
(E) Increased sweating (fever)
44. Q.10. Which of the following is the primary second-
messenger process in the contraction of the ciliary
muscle when focusing on near objects?
(A) cAMP (cyclic adenosine monophosphate)
(B) DAG (diacylglycerol)
(C) Depolarizing influx of sodium ions via a channel
(D) IP3 (inositol 1,4,5-trisphosphate)
(E) NO (nitric oxide)
45. Q.11. Probable signs of atropine overdose include
which one of the following?
(A) Gastrointestinal smooth muscle cramping
(B) Increased heart rate
(C) Increased gastric secretion
(D) Pupillary constriction
(E) Urinary frequency
46. Q.12. Accepted therapeutic indications for the use of
antimuscarinic drugs include all of the following
except
(A) Atrial fibrillation
(B) Motion sickness
(C) Parkinson’s disease
(D) Postoperative bladder spasm
(E) To antidote parathion poisoning
47. Q.13. A 7-year-old boy with a previous history of bee
sting allergy is brought to the emergency department
after being stung by 3 bees. If this child has signs of
anaphylaxis, what is the treatment of choice?
(A) Diphenhydramine (an antihistamine)
(B) Ephedrine
(C) Epinephrine
(D) Methylprednisolone (a corticosteroid)
(E) Phenylephrine
48. Q.14. A 65-year-old woman with long-standing
diabetes mellitus is admitted to the ward from the
emergency department, and you wish to examine
her retinas for possible changes. Which of the
following drugs is a good choice when pupillary
dilation—but not cycloplegia—is desired?
(A) Isoproterenol
(B) Norepinephrine
(C) Phenylephrine
(D) Pilocarpine
(E) Tropicamide
49. Q.15.An anesthetized dog is prepared for recording
blood pressure and heart rate in a study of a new
blocking drug. Results show that the new drug
prevents the tachycardia evoked by isoproterenol?
Which of the following standard agents does the
new drug most resemble?
(A) Atropine
(B) Hexamethonium
(C) Phentolamine (an α blocker)
(D) Physostigmine
(E) Propranolol (a β blocker)
50. Q.16. Your new 10-year-old patient has asthma, and
you decide to treat her with a β2 agonist. In
considering the possible drug effects in this patient,
you would note that β2 stimulants frequently cause
(A) Direct stimulation of renin release
(B) Hypoglycemia
(C) Increased cGMP (cyclic guanine monophosphate)
in mast cells
(D) Skeletal muscle tremor
(E) Vasodilation in the skin
51. Q.17. A patient is to receive epinephrine. She has
previously received an adrenoceptor-blocking agent.
Which of the following effects of epinephrine would
be blocked by phentolamine but not by metoprolol?
(A) Cardiac stimulation
(B) Increase of cAMP in fat
(C) Mydriasis
(D) Relaxation of bronchial smooth muscle
(E) Relaxation of the uterus
52. Q.18. When given to a patient, phentolamine blocks
which one of the following?
(A) Bradycardia induced by phenylephrine
(B) Bronchodilation induced by epinephrine
(C) Increased cardiac contractile force induced by
norepinephrine
(D) Miosis induced by acetylcholine
(E) Vasodilation induced by isoproterenol
53. Q.19. A 56-year-old man has hypertension and an
enlarged prostate, which biopsy shows to be benign
prostatic hyperplasia. He complains of urinary
retention. Which of the following drugs would be the
most appropriate initial therapy?
(A) Albuterol
(B) Atenolol
(C) Metoprolol
(D) Prazosin
(E) Timolol
54.
55. Q.20. Which of the following agents does the new
drug most closely resemble?
(A) Atenolol
(B) Atropine
(C) Labetalol
(D) Phenoxybenzamine
(E) Propranolol
3 chambered 2 atria + 1 ventricle SVC & IVC open into sinus venosus
Venous blood : Sinus venosus RA Ventricle
Arterial blood : LA Ventricle
Ventricle pumps mixed blood Aorta
Aorta has spiral valve that directs arterial blood to body & venous blood to lungs through pulm. Art.
NO valves & NO conducting tissue !!
Start with 0.1 ml. If sufficient response is not there, increase dose to 0.2 ml
The increased systolic pressure results partly from an increased heart rate and cardiac output. The effect on diastolic pressure depends on the relative stimulation of α1- and β2-adrenoceptors. which mediate vasoconstriction and vasodilation, respectively. Lower doses of epinephrine produce greater stimulation of β2-receptors than α1-receptors, especially in the vascular beds of skeletal muscle, thereby causing vasodilation and decreasing diastolic blood pressure. Higher doses produce
more vasoconstriction throughout the body and can increase both diastolic and systolic pressure. And produces vasodilation and cardiac stimulation. It usually
lowers the diastolic and mean arterial pressure, but it can increase the systolic pressure by increasing the heart rate and contractility. Its potent chronotropic effect can cause tachycardia and cardiac arrhythmias. For this reason, an alternative drug (e.g., dobutamine) is usually administered to increase cardiac output in cases of heart failure. Dobutamine selectively increases myocardial contractility and stroke volume while producing a smaller increase in heart rate.
reduces sympathetic stimulation of the heart, causing a negative chronotropic, inotropic, and dromotropic effect. Because the β-blockers reduce cardiac output and blood pressure (see Fig. 9-2), they can be used to treat arterial hypertension
The baroreceptor reflx. A, Increased arterial pressure activates stretch receptors in the aortic arch and carotid sinus. B, Receptor activation initiates afferent impulses to the brain stem vasomotor center (VMC). C, Via solitary tract fiers, the VMC activates the vagal motor nucleus, which increases vagal (parasympathetic) outflw and slows the heart. At the same time, the VMC reduces stimulation of spinal intermediolateral neurons that activate sympathetic preganglionic fiers, and this decreases sympathetic stimulation of the heart and blood vessels. By this mechanism, drugs that increase blood pressure produce reflex bradycardia. Drugs that reduce blood pressure attenuate this response and cause reflex tachycardia.
Vasomotor reversal of Dale. Comparison of the cardiovascular effects of four catecholamines when a low dose of each drug is given by intravenous infusion. Arrows
indicate when the infusion was started and stopped. The blood pressure recordings show systolic, diastolic, and mean arterial pressure. Peripheral resistance
is expressed on an arbitrary scale, ranging from 0 to 4 units. The reflex mechanism, adrenoceptors (α1, β1, and β2), or dopamine (D1) receptors responsible
for changes in the heart rate and peripheral resistance are illustrated. Norepinephrine increases peripheral resistance and blood pressure, and this leads to
reflex bradycardia. Epinephrine increases heart rate while reducing peripheral resistance, and the mean arterial blood pressure increases slightly. Isoproterenol
increases heart rate but significantly lowers peripheral resistance, and the mean arterial pressure declines. Dopamine increases heart rate (and increases
cardiac output) while lowering vascular resistance, and the mean arterial pressure increases.
Vasomotor reversal of Dale
The heart is innervated by vagal and sympathetic fibers. The right vagus nerve primarily innervates the SA node, whereas the left vagus innervates the AV node; however, there can be significant overlap in the anatomical distribution. Atrial muscle is also innervated by vagal efferents, whereas the ventricular myocardium is only sparsely innervated by vagal efferents. Sympathetic efferent nerves are present throughout the atria (especially in the SA node) and ventricles, including the conduction system of the heart.
Sympathetic stimulation of the heart increases heart rate (positive chronotropy), inotropy and conduction velocity (positive dromotropy), whereas parasympathetic stimulation of the heart has opposite effects. Sympathetic and parasympathetic effects on heart function are mediated by beta-adrenoceptors and muscarinic receptors, respectively.
The solution also can be used in other types of ophthalmic surgery that require rapid and complete miosis. Topical ocular administration of acetylcholine is not effective, because acetylcholine is hydrolyzed by corneal cholinesterase before it can penetrate to the iris and ciliary muscle.
E. Respiratory failure, from neuromuscular paralysis or CNS depression, is the most important cause of acute deaths in cholinesterase inhibitor toxicity. The answer is E.
Tremor is a common β2 effect. Blood vessels in the skin have almost exclusively α (vasoconstrictor) receptors. Stimulation of renin release is a β1 effect. Beta2 agonists cause hyperglycemia. The answer is D.