CAL Effect of drugs on frog’s heart

Following parameters noted

1. Force of contraction

amplitude (N, ↑, ↓)

2. Tone (N, ↑, ↓)

3. Heart rate (bpm)

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)

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

PREDOM

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 ↑

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

Baroreceptor reflex

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

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)

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

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

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.

Indications

• Ocular Indicationsmydriasis (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

• 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 chEinhibitors are given to patients with myasthenia gravis.

2. Reverse the muscarinic effects of cholinesterase inhibitor overdose.

Atropine

Uses (ATROPA)

1. As mydriatic-cycloplegic in refraction error testing, fundoscopy, iridocyclitis

2. Traveller’s diarrhea

3. Rapid onset mushroom poisoning

4. Organophospohorous poisoning

5. Preanaesthetic medication

6. Arrhythmias (brady-arrhythmias)

Propranolol (Uses THAPPAD)

1. Thyrotoxicosis & Tremors

2. HTN & Hypertrophic cardiomyopathy

3. Angina & Acute MI

4. Prophylaxis of migraine

5. Phaeochromocytoma (along with alpha blockers)

6. Anxiety & Arrhythmias

7. Dissecting aortic aneurysm

8. Digitalis toxicity

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

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

Adverse effects of beta blockers (BBC Loses Viewers in Rochedale)• Bradycardia

• Bronchoconstriction

• Claudication

• Lipids (profile altered)

• Vivid dreams & nightmares

• Negative ionotropic action

• Reduced sensitivity to hypoglycemia

Contraindications of Propranolol

• Don’t Prescribe Him Propranolol

1. Diabetes mellitus

2. Pulmonary diseases (Asthma, COPD)

3. Heart block, bradycardia

4. Prinzmetal’s angina

5. Peripheral vascular disease

Review Questions

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-adrenoceptoragonist 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

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 minoxidilis 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

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)

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

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

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

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

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

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)

Q.10. Which of the following is the primary second-messenger process in the contraction of the ciliarymuscle 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)

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

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

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

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

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)

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

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

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

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

Q.20. Which of the following agents does the new drug most closely resemble?

(A) Atenolol

(B) Atropine

(C) Labetalol

(D) Phenoxybenzamine

(E) Propranolol

Thank you