Dr. NTR University of Health Sciences, AP
Second MBBS Examination – February 2022
Pharmacology – Paper I
ESSAY QUESTIONS (2 X 15 = 30 marks)
1. Classify beta-blockers. Write a note on cardiovascular and non-cardiovascular indications of beta-blockers. List the significant adverse effects and drug interactions of beta-blockers. Discuss the management of hypertensive emergency. (3+4+4+4)
Classification of β-blockers
Beta-blocking drugs occupy β-receptors and competitively reduce receptor occupancy by catecholamines and other β-agonists.
a. Non-selective β-blockers = Propranolol, Sotalol, Timolol. These drugs block both β1- and β2-receptors. Propranolol was the first β-blocker used clinically. It is the prototype drug in this group.
b. Non-selective β-blockers with additional α-1 blocking activity = Carvedilol, Labetalol. These drugs are more potent in blocking β than α receptors.
c. β1-selective β-blockers = Atenolol, Bisoprolol, Esmolol, Metoprolol. These drugs show their effects acting predominantly on the SA node, in contrast to the Calcium channel blockers belonging to nondihydropyridine class (Verapamil and Diltiazem) which show their effects acting predominantly on AV node.
d. Other β-blockers
• β-blockers with partial agonistic (intrinsic sympathomimetic) action = Pindolol, Celiprolol. These drugs elicit an agonistic effect but lower than that obtained by a full agonist.
• β-blockers with membrane stabilizing activity = Propranolol, Acebutolol. These drugs inhibit Na+ channel function and impulse conduction in cardiac tissues – contributing to their antiarrhythmic action.
a. Angina pectoris – β-blockers reduce resting and exercise heart rate, reduce oxygen consumption → improve exercise tolerance.
b. Hypertension – β-blockers reduce cardiac output and renin secretion → decrease in peripheral vascular resistance.
c. Myocardial Infarction – β-blockers limit infarct size by reducing oxygen consumption. β-blockers also prevent sudden ventricular fibrillation at the subsequent attack of MI.
d. Supraventricular and ventricular arrhythmias – β-blockers decrease heart rate, atrio-ventricular nodal refractory period and prolong repolarization.
e. Chronic heart failure – β-blockers should not be given to patients with an acute exacerbation of heart failure, as they can worsen the condition. However, β-blockers were shown to reduce mortality and morbidity in patients with chronic stable heart failure and systolic left ventricular dysfunction by decreasing the consequences of excessively activated sympathetic nervous system (i.e increased HR and force of contraction) and by decreasing the renin release and activation of RAAS (which are responsible for vasoconstriction and Na and water retention).
f. Hypertrophic obstructive cardiomyopathy
g. Dissecting aortic aneurysm
a. Glaucoma – β-blockers such as timolol reduce secretion of aqueous humor.
b. Migraine – Propranolol provides a prophylactic effect by reducing the frequency and intensity of migraine headache.
c. Thyrotoxicosis – By decreasing the peripheral conversion of T4 to T3 and by reducing heart rate, propranolol prevents many of the adrenergic symptoms seen in thyroxicosis and the potential for arrhythmias.
d. Anxiety provoking situations
f. Alcohol/ Clonidine withdrawal
g. Esophageal varices and Portal hypertension
a. CVS effects include bradycardia (most common). β-receptor blockade depresses myocardial contractility and excitability. In patients with compensated heart failure, cardiac output is dependent on sympathetic drive. If this stimulus is removed by β-blockade, cardiac decompensation may occur.
b. CNS effects include mild sedation, vivid dreams, and rarely, depression.
c. Respiratory effects – β2-receptor blockade associated with the use of nonselective agents causes worsening of pre-existing asthma and other forms of airway obstruction.
d. Others – Gastrointestinal disturbances, fatigue, cold extremities, erectile dysfunction, increase in triglycerides, decrease in HDL cholesterol.
a. Beta-blockers + Verapamil (calcium channel blocker) leads to severe hypotension, bradycardia, heart failure, and cardiac conduction abnormalities.
b. Beta-blockers + Insulin / Sulfonylureas – β-blockers inhibit gluconeogenesis and mask the symptoms of hypoglycemia due to insulin / sulfonylureas. β1-selective antagonists offer some advantage in these patients, since the rate of recovery from hypoglycemia may be faster compared with that in diabetics receiving nonselective β-adrenoceptor antagonists. There is considerable potential benefit from these drugs in diabetics after a myocardial infarction, so the balance of risk versus benefit must be evaluated in individual patients.
Management of Hypertensive emergency
• Systolic BP > 220 or diastolic BP > 120 mm Hg with evidence of active end organ damage is labelled ‘hypertensive emergency’. Emergencies include hypertensive encephalopathy, hypertensive nephropathy, intracranial hemorrhage, aortic dissection, preeclampsia-eclampsia, pulmonary edema, unstable angina, or myocardial infarction.
• Compared to hypertensive urgencies which rarely require emergency therapy, hypertensive emergencies require substantial reduction of blood pressure within 1 hour to avoid the risk of serious morbidity or death.
• Parenteral therapy is indicated in most hypertensive emergencies. The initial goal in hypertensive emergencies is to reduce the pressure by no more than 25% (within minutes to 1 or 2 hours) and then toward a level of 160/100 mm Hg within 2–6 hours.
• Excessive reductions in pressure may precipitate coronary, cerebral, or renal ischemia. To avoid such declines, the use of agents that have a predictable, dose-dependent, transient, and progressive antihypertensive effect is preferable. In most situations, appropriate control of blood pressure is best achieved using combinations of nicardipine or clevidipine plus labetalol or esmolol.
2. Discuss the pathophysiology of Parkinson’s disease and different group of drugs used for its treatment. Discuss the rationale for levodopa carbidopa combination. Write briefly about different strategies to prevent wearing off phenomenon during its treatment. Add a note on drug induced Parkinsonism and its treatment. (6+2+3+4)
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor.
Pathophysiology of Parkinson’s disease
It is caused by a progressive loss of dopamine in the nigrostriatum. The severity of loss of dopamine correlates with the severity of bradykinesia. With the loss of dopamine, the normal inhibitory influence of dopamine on cholinergic neurons in the neostriatum is significantly diminished, resulting in overproduction or a relative overactivity of acetylcholine by the stimulatory neurons. This triggers a chain of abnormal signaling, resulting in loss of the control of muscle movements.
Different group of drugs used for treatment of PD
Drugs in PD act by counteracting deficiency of dopamine in basal ganglia or by blocking muscarinic receptors. None of the available drugs affect the underlying neurodegeneration.
a. Dopamine precursors – Levodopa
b. Catechol-O-methyl transferase inhibitors – Entacapone
c. Dopamine receptor agonists – Pramipexole, Ropinirole, Rotigotine, Bromocriptine
d. Monoamine oxidase-B inhibitors (irreversible) – Selegiline, rasagiline
e. Antiviral drugs – Amantadine (enhance dopamine release)
f. Anticholinergic agents – Trihexyphenidyl
Rationale for levodopa carbidopa combination
Levodopa is often given with a peripheral decarboxylase inhibitor (carbidopa / benserazide) to retard the peripheral breakdown of levodopa, thereby increasing its central delivery and decreasing the dose of levodopa that is required to control symptoms. The combination also lowers the incidence of nausea, vomiting, hypotension, and cardiac irregularities associated with levodopa.
Strategies to prevent wearing off phenomenon
The best results of levodopa treatment are obtained in the first few years of treatment. Levodopa can ameliorate many of the clinical motor features of parkinsonism, particularly effective in relieving bradykinesia. The benefits of levodopa treatment often begin to diminish after about 3 or 4 years of therapy. This could be due to loss of dopaminergic nigrostriatal nerve terminals or some pathologic process directly involving striatal dopamine receptors. However, long-term therapy may lead to a number of problems in management such as the “on-off phenomenon” and “wearing-off phenomenon (end-of-dose akinesia)” due to fluctuating plasma concentration of levodopa. The use of sustained-release preparations of levodopa, or co-administration of COMT inhibitors such as entacapone, may be used to counteract the fluctuations in plasma concentration of levodopa. Apomorphine is sometimes used to control the ‘off effect’ with levodopa.
Drug induced Parkinsonism and its treatment
Drug-induced parkinsonism is mainly due to dopamine receptor blockers such as antipsychotics (haloperidol), metoclopramide etc. The syndrome usually develops within 3 months of their continuous usage. Symmetric tremors are most commonly seen in this condition. After the culprit drug withdrawl, it takes several weeks to reduce the tremors. If treatment is necessary, antimuscarinic agents such as trihexyphenidyl are preferred.
SHORT ANSWER QUESTIONS (10 x 5 = 50 marks)
3. Discuss the clinical significance of plasma protein binding.
• After administration, many drugs at therapeutic concentrations exist mainly in bound form in our body. The fraction of drug that is unbound and pharmacologically active in plasma can be less than 1%, the remainder being associated with plasma protein. Even the small differences in protein binding can have significant effects on free drug concentration and drug effect.
• The most important plasma protein in relation to drug binding is albumin, which binds many acidic drugs such as warfarin, NSAIDs, sulfonamides etc and a smaller number of basic drugs such as atropine. Other plasma proteins include β-globulin and an acid glycoprotein. They bind to basic drugs such as quinidine, lidocaine, and propranolol.
• The amount of a drug that is bound to protein depends on three factors:
a. the concentration of free drug
b. its affinity for the binding sites
c. the concentration of protein
• Plasma albumin binds many different drugs, so competition can occur between them. If two drugs (A and B) compete this way, administration of drug B can reduce the protein binding, and hence increase the free plasma concentration, of drug A. To do this, drug B needs to occupy a significant fraction of the binding sites.
• At therapeutic plasma concentrations, most drugs occupy only a small fraction of the available sites on plasma proteins. However, drugs such as NSAIDs, antiepileptics, warfarin, sulfonamides occupy about 50% of the binding sites at therapeutic concentrations. This can cause harmful effects by displacing other drugs.
• Example – Displacement of bilirubin from albumin by highly plasma protein binding drugs in jaundiced premature neonates results in crossing of unbound bilirubin through immature blood–brain barrier and cause kernicterus (staining of the basal ganglia by bilirubin). This causes a distressing and permanent disturbance of movement known as choreoathetosis, characterised by involuntary writhing and twisting movements in the child.
• However in adults, it should be remembered that when the amount of unbound drug in plasma increases, the metabolism and rate of elimination also increases, and after four half-lives the unbound concentration will return to its previous steady-state value.
4. Write about the parenteral routes of drug administration.
Parenteral refers to administration by injection which takes the drug directly into the tissue fluid or blood without having to cross the enteral mucosa. Gastric irritation and vomiting are not provoked. Parenteral routes can be employed even in unconscious, uncooperative or vomiting patient.
Important parenteral routes include –
a. Subcutaneous (s.c.)
The drug is injected in the loose subcutaneous tissue which is richly supplied by nerves but has poor vascular access.
Advantages – Self injection is possible (e.g. insulin by diabetics). Depot preparations containing hormones and contraceptives can be injected for prolonged action.
Disadvantages – Only small volumes can be injected. Irritant drugs cannot be injected. Absorption is slower than intramuscular. This route should be avoided in shock patients who are vasoconstricted—absorption will be delayed.
b. Intramuscular (i.m.)
The drug is injected into large skeletal muscles such as deltoid, triceps, gluteus maximus, rectus femoris, etc. which are highly vascular but has limited sensory nerve supply.
Advantages – Mild irritants can be injected, less painful. Absorption of drugs in aqueous solution is faster.
Disadvantages – Self injection is not possible as deep penetration is needed. Depot preparations (oily solutions, aqueous suspensions) can be injected by this route. I.M injections should be avoided in anticoagulant treated patients, because it can produce local haematoma.
c. Intravenous (i.v.)
The drug is injected into one of the superficial veins. The drug reaches directly into the blood stream and effects are produced immediately.
Advantages – Extremely helpful in emergency situations as drugs can be given as a bolus or infused slowly over hours. Bioavailability is 100%. Titration of the dose with the response is possible. Highly irritant drugs can be injected but if extravasation occurs, they can cause thrombophlebitis of the injected vein and necrosis of adjoining tissues.
Disadvantages – Only aqueous solutions are to be injected i.v. Aqueous suspensions or depot preparations can cause embolism. Can result in air embolism.
d. Intradermal injection
The drug is injected into the skin raising a bleb.
Examples – Administration of BCG vaccine, Penicillin sensitivity testing
General disadvantages of all parenteral routes
• Drug preparations have to be sterilized
• Injectables are costlier than oral drugs.
• Injection technique is invasive and often painful
• Assistance of another person is mostly needed.
5. Discuss briefly about the Pharmacovigilance program of India.
Adverse Drug Reaction is one of the leading causes of morbidity and mortality worldwide. In developing countries, the cost of management of adverse reactions in the general population is very high and under-recognized. It is, therefore necessary to evaluate the safety of medicines.
Pharmacovigilance is the ‘science and activities relating to the detection, assessment, under-standing and prevention of adverse effects or any other drug related problems.’ Pharmaco-vigilance generates evidence-based information on safety of medicines. It also promotes rational use of medicines.
In India, pharmacovigilance programme was launched in July 2010 by Ministry of Health & Family Welfare. Indian Pharmacopoeia Commission, Ghaziabad is the National Coordination Centre for Pharmacovigilance Programme of India. The mission of PvPI is to safeguard the health of Indian population by ensuring that the benefits of use of medicine outweigh the risks associated with its use.
Healthcare Professionals or Patients or Consumers may report ADRs (known/unknown, serious/ non-serious, frequent/rare) using ADR Reporting Form and submit to ADR monitoring centers or directly to National Coordination Centre, PvPI via e-mail or mobile app. These reports are processed for causality assessment and communicated to WHO Uppsala Monitoring Center, Sweden through a software called VigiFlow. The information generated by pharmacovigilance is communicated to central drug regulatory agency CDSCO, India for appropriate regulatory actions.
The regulatory actions include ‘drug alerts’, or changes in the labelling of medicines indicating restrictions in use or statuary warnings, precautions, or even withdrawal of the drug from the market.
6. A farmer presented to the emergency department with signs and symptoms suggestive of organophosphorus poisoning. How will you manage this case. Give justification for the drugs to be used.
Organophosphates such as parathion, malathion, etc inhibit the enzyme acetylcholinesterase resulting an increase in acetylcholine activity at nicotinic and muscarinic receptors and in the peripheral and central nervous system. This results in abdominal cramps, diarrhea, vomiting, excessive salivation, sweating, lacrimation, miosis, wheezing and bronchorrhea, seizures, and skeletal muscle weakness. Initial tachycardia is usually followed by bradycardia.
Managing OP poisoning
Emergency and Supportive Measures
• Gut decontamination must be considered if the organophosphate was recently ingested. This is done by aspiration of the liquid using a nasogastric tube followed by administration of activated charcoal.
• Extreme care should be taken by the healthcare providers to avoid skin contact as most of the organophosphates are often formulated with an aromatic hydrocarbon solvent such as xylene and are well absorbed through intact skin. Wearing of gloves and waterproof aprons will minimise the contact risk.
• Atropine is an anticholinergic agent. Blocks muscarinic receptors – effective for treatment of salivation, bronchial hypersecretion, wheezing, abdominal cramping, and sweating. However, it does not interact with nicotinic receptors at autonomic ganglia and at the neuromuscular junction and has no direct effect on muscle weakness.
Dose: 2 mg given intravenously, and if bronchial secretions and wheezing not decreased after 5 minutes, repeated boluses in rapidly escalating doses (eg, doubling the dose each time) have to be administered.
b. Pralidoxime (2-PAM)
• Pralidoxime is a cholinesterase reactivator. When 2-PAM, is administered, the positively charged quaternary nitrogen on 2-PAM is attracted to the anionic site of cholinesterase and reacts with the phosphorus atom of organophosphate compound that was attached to the esteratic site of cholinesterase. The oxime-phosphonate bond so formed diffuses away leaving the cholinesterase enzyme
Dose: 1–2 g intravenously as a loading dose followed by a continuous infusion (200–500 mg/h, titrated to clinical response.
• Treatment with PAM should be started as early as possible (within few hours), because of formation of a permanent bond with cholinesterase by some organophosphate compounds that cannot be reversed by oximes. This happens in a process called “aging.”
• Pralidoxime causes more marked reactivation of skeletal muscle cholinesterase than at autonomic sites and not at all in the CNS (does not penetrate into brain).
7. Describe the uses and adverse effects of Thiazide diuretics.
Thiazide diuretics are a group of diuretics that increase the rate of urine formation by acting on the distal tubule of nephron.
Drugs include – Hydrochlorothiazide and related drugs such as Chlortalidone and Indapamide
Mechanism of action – Thiazides bind to the Cl– site of the distal tubular Na+/Cl- co-transport system and inhibits its action. This causes natriuresis with loss of sodium and chloride ions in the urine.
Absorption – well absorbed orally.
Distribution – have larger volumes of distribution
Metabolism – undergo little hepatic metabolism
Excretion – excreted in the urine, mainly by tubular secretion.
Indications – Hypertension, Mild heart failure, Severe resistant oedema, Prevent recurrent stone formation in idiopathic hypercalciuria by increasing Ca2+ reabsorption, Nephrogenic diabetes insipidus
Adverse effects – Hypokalemia, Hyponatremia, Metabolic lkalosis, Hyperglycemia, Hyperlipidemia, Hyperuricemia, Allergic reactions
• Hypokalaemia due to thiazide diuretics enhances digoxin toxicity (in CHF) and reduces sulfonylurea action (in diabetes).
• Antihypertensive action of thiazides is diminished by NSAIDs by inhibiting PG synthesis in the kidney.
• Thiazide diuretics reduces uricosuric action of probenecid in gout.
8. Add a note on different dose of aspirin and its therapeutic uses.
Aspirin (acetylsalicylic acid) is the oldest non-steroidal anti-inflammatory drug (NSAID). It acts by irreversibly inactivating cyclo-oxygenase (COX-) 1 and COX-2. By inhibiting COX enzymes, aspirin shows anti-inflammatory, analgesic, antipyretic and antiplatelet properties.
Aspirin is available in doses ranging from 75mg to 1500mg.
• Lower doses produces antiplatelet activity.
• Higher doses produces anti-inflammatory activity.
While inhibition of platelet function is a feature of most NSAIDs, the effect of aspirin is longer lasting. This is because it irreversibly acetylates COX enzymes. COX enzymes are replaced in most cells, but not in platelets. Platelets lack nucleus and hence they can’t synthesize new COX enzymes. Platelets remain inactivated for their lifetime (approximately 10 days). Since a proportion of platelets are replaced each day from the bone marrow, platelet inhibition by aspirin gradually reduces.
Doses of 75–325 mg once daily are often used to decrease the incidence of
• Transient ischemic attacks
• Unstable angina
• Coronary artery thrombosis with myocardial infarction (MI)
• Thrombosis after coronary artery bypass grafting (CABG)
• Additionally some studies suggest that long-term use of aspirin at low dosage is associated with a lower incidence of colon cancer.
At antiplatelet doses, aspirin’s main adverse effects include gastric upset (intolerance) and gastric and duodenal ulcers. Hepatotoxicity, asthma, rashes, GI bleeding, and renal toxicity occur rarely. With larger doses, aspirin causes dizziness, deafness and tinnitus (‘salicylism’), compensatory respiratory alkalosis.
9. Discuss the role of steroids in asthma.
Asthma is an inflammatory condition in which there is recurrent reversible airways obstruction in response to irritant stimuli. The clinical features of asthma are recurrent episodes of shortness of breath, chest tightness, and wheezing, often associated with coughing.
An asthmatic attack often consists of two phases: an immediate and a late (or delayed) phase.
• Immediate phase occurs rapidly and is mainly caused by spasm of the bronchial smooth muscle. Drugs that are helpful in this phase are “relievers” or bronchodilators – which include sympathomimetics, anticholinergics, methylxanthines.
• Late phase or delayed response is a progressing inflammatory reaction. Drugs that are helpful in this phase are “controllers” or anti-inflammatory agents – which include corticosteroids.
Glucocorticoids act as anti-inflammatory agents by reducing the transcription of gene for IL-2 leading to
• inhibition of clonal proliferation of Th cells.
• decrease formation of cytokines that recruit and activate eosinophils and are responsible for promoting the production of IgE and the expression of IgE receptors.
Glucocorticoids also inhibit the generation of the vasodilators PGE2 and PGI2, by inhibiting induction of COX-2.
Glucocorticoids should be considered for
• Patients who require regular bronchodilators mainly long acting drugs such as salmeterol. Usually combined with low-dose inhaled steroids such as beclometasone.
• More severely affected patients. They are treated with high-potency inhaled drugs such as fluticasone.
• Patients with acute exacerbations of asthma. They may require iv hydrocortisone and oral prednisolone.
Inhaled steroids are highly polar, only a small fraction of the dose is systemically absorbed. They can be administered via nebulizers, ‘spacer’ devices, metered-dose inhalers or as dry powders.
A ‘rescue course’ of oral prednisolone may be needed at any stage of severity if the clinical condition is deteriorating rapidly.
10. Write the role of statins as cholesterol lowering agent.
Coronary heart disease (CHD) is the leading cause of death worldwide. CHD is correlated with elevated levels of low-density lipoprotein cholesterol (LDL-C; “bad” cholesterol) and triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C; “good cholesterol”).
Lifestyle changes, such as diet, exercise, and weight reduction, can lead to modest decreases in LDL-C and increases in HDL-C. However, most patients are unable to achieve significant LDL-C reductions with lifestyle modifications alone, and drug therapy may be required.
Treatment with statins is the primary treatment option for hypercholesterolemia.
Drugs include – Atorvastatin, Rosuvastatin, Simvastatin
Mechanism of action – Statins inhibit HMG-CoA reductase, which is the rate-limiting enzyme in the formation of cholesterol. Cholesterol synthesis in the liver is reduced, with a compensatory increase in hepatic LDL receptors → increased clearance of LDL-C from the blood → thereby decreasing oxidative stress and vascular inflammation with increased stability of atherosclerotic lesions.
• Absorption – well absorbed orally.
• Distribution – distributes well, binds to plasma proteins
• Metabolism – undergo high first-pass extraction by the liver using CYP450, therefore the major effect is on the liver.
• Excretion – excreted mainly in the bile and to some extent in the urine
• Statins are indicated in patients with hypercholesterolemia. Significant reduction of new coronary events and atherothrombotic stroke has been observed. Statins are useful alone or with resins, niacin, or ezetimibe in reducing levels of LDL. Because cholesterol synthesis occurs predominantly at night, statins are usually given in the evening.
• All of the statins reduce LDL-C up to 30% with the starting doses. Statins can reduce cholesterol level by 50% or more at the highest doses. There are also modest increases in HDL levels, substantial decreases in triglyceride levels, and marked reductions in high-sensitivity C-reactive protein levels.
• The effect on circulating lipids is observable within 2 weeks of treatment; the maximum effect requires up to 6 weeks of drug therapy.
Adverse effects, drug interactions and contraindications
• Statins, like all cholesterol lowering agents, may increase serum aminotransferase levels but rarely cause true hepatitis, and even more rarely cause acute liver failure. Statins are no longer considered contraindicated in patients with liver disease.
• About 0.1% of patients taking a statin drug alone develop myopathy, concomitant administration of other drugs (especially those that inhibit CYP450 enzymes – macrolide antibiotics, azole antifungals, and protease inhibitors) increases the risk.
• Statins are absolutely contraindicated during pregnancy because of their ability to inhibit essential lipid metabolism in the developing fetus.
11. Enumerate the obstetrics and gynecological uses of prostaglandin analogues.
Cyclooxygenases are the enzymes that catalyze prostaglandin and thromboxane biosynthesis from arachidonic acid. Two unique COX isozymes have been found:
• Cyclooxygenase-1 (COX-1) – expressed in most tissues of the body and generates prostanoids for “housekeeping” functions, such as gastric epithelial cytoprotection.
• Cyclooxygenase-2 (COX-2) – major source of prostanoids in inflammation, especially prostaglandin E2 and prostaglandin I2 which markedly enhance edema formation and leukocyte infiltration in the inflamed area.
PGF2α and low concentrations of PGE2 causes uterine muscle contraction. PGF2α together with oxytocin, is essential for the onset of parturition. PGI2 and high concentrations of PGE2 cause uterine muscle relaxation. PGI2 production leads to maturation of uterine smooth muscle cell prior to labor.
Obstetrics and Gynecological uses of prostaglandin analogues
Dinoprostone – Synthetic preparation of PGE2, administered vaginally (as gel or as a controlled-release insert) for
• inducing abortion in the second trimester of pregnancy
• missed abortion
• benign hydatidiform mole
• ripening of the cervix for induction of labor in patients at or near term.
Misoprostol – Synthetic analog of PGE1.
• Usually combined with antiprogestins (eg, mifepristone) to produce early abortion.
• Oral administration is recommended.
Carboprost – Synthetic analog of PGF2α.
• Used to induce second trimester abortions and to control postpartum hemorrhage.
• Administered as intramuscular injection.
Common adverse effects of the prostaglandins include nausea, vomiting, and diarrhea. PGF2α is a bronchoconstrictor and should be used with caution in women with asthma.
12. After injecting succinylcholine IV to have muscle relaxation during a surgical procedure, a patient developed prolonged apnea. What could be the probable cause?. What is the management for the above condition?.
Succinylcholine (SCh) is a depolarizing skeletal muscle relaxant. SCh very closely resemble acetylcholine (ACh) in that it is made up of two joined ACh molecules. Because of the resemblance of ACh, succinylcholine not only stimulates nicotinic cholinergic receptors at the neuromuscular junction, it stimulates all ACh receptors. The actions of succinylcholine are therefore very complex.
At the neuromuscular junction, succinylcholine reacts with the nicotinic receptor to open the channel and cause depolarization of the motor end plate. Unlike ACh, sccinylcholine is not metabolized by acetylcholinesterase, and its concentration in the synaptic cleft does not fall as rapidly, resulting in a prolonged depolarization of the muscle end-plate leading to flaccid paralysis of skeletal muscle (phase I block). With prolonged exposure to succinylcholine, the initial end plate depolarization decreases and the membrane becomes repolarized. Despite this repolarization, the membrane cannot easily be depolarized again because it is desensitized (phase II block).
Because depolarizing muscle relaxants are not metabolized by acetylcholinesterase, they diffuse away from the neuromuscular junction and are hydrolyzed in the plasma and liver by another enzyme, pseudocholinesterase or butyrylcholinesterase into succinylmonocholine. However, in persons with genetically determined deficiency in pseudocholinesterase – succinylcholine is metabolized slowly resulting in prolonged respiratory paralysis – Succinylcholine Apnea.
Management of Succinylcholine Apnea
• Mechanical ventilation support under continuous sedation is the mainstay of treatment until respiratory muscle paralysis spontaneously resolves. Recovery eventually occurs as a result of passive diffusion of succinylcholine away from the neuromuscular junction.