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3.Local anesthetics. Classification. Structure-activity relationships.  Mechanisms of local anesthetic effects. Factors affecting duration and intensitivity of anesthesia. Types of local anesthesia and rational for choosing the drug for different types of anesthesia. Side effects.

Aromatic group (lipophilic) linked to a basic side chain (hydrophilic) by the ester or amide bond.

Clinical classification :

•Local anesthetics for terminal (surface) anesthesia •Anesthesia by direct application on mucous membranes. 

• Infiltration anesthesia : injection of the solution into the tissue to be incised

• Nerve block anesthesia : for peripheral nerves/plexus

• Epidural anesthesia : Injection into the epidural space. Local anesthetic acts on nerve roots.

•Spinal anesthesia : Local anesthetic is injected into the subarachnoid space. 

Chemical classification : 

Esters : inactivated by plasma cholinesterases. Derivatives of benzoic acid – cocaine. Derivatives of paraaminobenzoicacid : Procaine (Novocain), Tetracaine,Benzocaine,Oxybuprocaine (Inocain)


Amides : amide bonds are degraded by N-dealkylation in the liver.E.gLidocaine,Trimecaine,Articaine (Ultracaine D),Mepivacaine (Scandonest),Bupivacaine,Levobupivacaine (chirocaine),Ropivacaine (naropin

Oxybuprocaine– surface type, used in ophthalmology.

Articaine and Mepivacaine – Infiltration and nerve block type, used in dentistry.

Systemic effects of locaanesthetics :

• Antiarrhythmic action – Novocainamide, Lidocaine 

• Psychological dependence – cocaine

• CNS toxicity: depressive effects, excitatory and convulsive effects (high doses)

 • Allergic reactions

Link between chemical structure and activity. The mechanism of anesthetic effect.

Structure – activity relationships.

• R=N – alkaloid weak base with pKa = 8-9 (poor water solubility) 

• R=NH+ – salt (water soluble, is used to prepare liquid injectable formulations) 

• Tissue balance of ionized and non-ionized forms: R=NH+ R=N + H+ 

• Three parts of the molecule: amino group, connecting group and aromatic residue 

• Aromatic part is responsible for lipophilic (hydrophobic) properties, connecting bond – biotransformation speed and amino group – hydrophilic properties Structure-activity relationships 

• Only uncharged form of LA can penetrate lipid membranes 

• The proportion of uncharged LA is governed by pH and the pKa (Henderson-Hasselbach equation): 

B + H = BH+ 

pKa = pH + log BH+ / B 

Log BH+ / B = pKa – pH 

• If pKa=8 and pH=8. 50% of LA charged 

• If pKa=8 and pH=6 99% of LA charged

Mechanism of anesthetic effect : LA interact with receptors on voltage-gated sodium channels. They have affinity to channels at more positive potential (activated and inactivated channel) is much higher. Sequence of sensory switching off: pain, temperature, pressure, motor functions. LA with ester bonds are inactivated by plasma cholinesterases. LA with amide bonds are degraded by N-dealkylation in the liver.

4.Astringents, absorbents, covering drugs and irritants. Classification. Mechanism of action. Indications for use.

Drugs protecting receptors: covering, adsorbing, astringent, softening.

 Drugs producing an excitation of receptors: irritating drugs.

Astringents agents – cause contraction or shrinkage of tissues and dry up secretions.Usually classified into three groups according to their mode of action: (1) those that decrease the blood supply by narrowing the small blood vessels (e.g., epinephrine and cocaine), (2) those that abstract water from the tissue (e.g., glycerol and alcohol), and (3) those that coagulate the superficial tissue layers into a crust (e.g., metallic astringents, such as calamine or alum). Used to reduce swollen mucous membranes that result from inflammations of the nasal, gastrointestinal, and urinary passages, astringents are also often used to dry up excessive secretions and to stop bleeding.

Classification :

Organic substances: Tannium , tannalbuminum.Decoction of chamomile medicinalis , alcohol

Inorganic substances: They are salts of heavy metals. Bismuth subnitrate, Potassium permanganate, zinc sulphate, silver nitrate, minerals are salts of heavy metals

The specific agent Bismuth subgallate, the brand name is “DENO” this agent has antimicrobial property. Deno is active against Helicobacter.pylori.Itcan be prescribed in case of peptic ulcer for two reasons:1, Because it is an astringent and can protect the ulcer from gastric juice and2, This agent can kill H.pylori.Silver nitrate, zinc sulphateare also antiseptic.

Inflammatory disorders: Gastritis, peptic/duodenal ulcers, damaged skin

Potassium permanganate is the drug of choice for gastric lavage.

Side effects: very rare, they are well tolerated, may be discomfort or constipation or nausea.

Adsorbents😛owders which have large active surface, due to this they can absorb poison to the surface of the agent.Active charcoal / magnesium trisilicate.(smecta) smectite diectaedicicum

The main indication is in case of poisoning.Also → GIT disorders, esophagitis, gastritis, any disorder which is associated with hyperacidity.

Side effects:Constipation, diarrhea, intestinal obstruction

Protectants :Substances which form colloidal covering film on the skin and mucous membrane. Due to this prevents stimulation of extra receptors. Protectives also can prevent stimulation of receptors due to formation of colloidal films and protective will act on all mucosal layers.

Separated into two subgroups:1, Organic – mucilagoamili.2.Non-organic –Aluminiumhydroxide.Combined: (almagin) combination of two drugs: Aluminium hydroxide + magnesium hydroxide.Analgin is protective and an absorbent.

Indications: The same as other groups (Astringents, absorbents).Sameside effects.

Irritants:Mechanism of action: This agent stimulate the sensory nerve endings, and decrease inflammation in the site of application.These agents produce arterial dilation, and increase blood supply to the area, these agents decrease pain sensation.Natural agents: Turpentine oil, camphor, menthol.Synthetic preparations: Methyl salicylate, ammonia solution, capsicum.Indication: Malaria, trauma, artritisartrosis

5.Cholinomimetics. Classification. Mechanism of action. Drug effects on different organs and physiological systems. Comparative characteristics of the distinctive drug groups. Indications for use. Side effects. Symptoms of the poisoning. Treatment of the poisoning.

Direct :

Cholinomimeics mimic acetytylcholine on the receptor

Direct-acting : Muscarinic (cholineesters,alkaloids) and nicotinic (ganglionic, NMJ)

MAChRs agonists: choline esters –


Acetylcholine : quaternary nitrogen, poor adsorption, doesn’t penetrate BBB. Decreases heart rate and cardiac output. Decreases BP.



Uses :

Ophtalmic (pupil constriction, miosis, relieve intraocular pressure, glaucoma)

Urinary retention, neurogenic bladder atony (bethanechol)

 Reverse GIT depression, reflux  esophagitis (bethanechol

Diagnostic for belladonna poisoning (methacholine)

Side effects :salivation,lacrimation,urination,diarrhea,vomiting,cardiac slowing (arrest,especiallybethanechol),bronchoconstriction,tremor/CNS-induced convulsions.


Nicotine : tobacco. Metabolized and excreted rapidly. Increases HR, BP, respiratory rate.

AchDMPP : experimental

Lobeline : tobacco

Insecticides & rodenticide

Toxicity – CNS stimulation (convulsions, headache), NMJ paralysis (depolarizing blockade), hypertension, hypotension, cardiac arrhythmias, vomiting, diarrhea, salivation.

Indirect :

They are also called anticholineesterases.They prevent hydrolysis of Ach by antagonizing cholinesterase thus increase Ach concentrations and actions at the cholinergic receptors (both nicotinic and muscarinic). They are similar in structure to Ach so combine with cholinesterase instead of Ach.

Indirect acting : Reversible and irreversible.

Reversibleanticholinesterases :

Edrophonium (short acting )– alcohols. Form weak hydrogen bond with cholinesterase. 

Carbamates (intermediate acting) – physostigmine, neostigmine, pyridostigmine. Carbamates esters. Bind to two sites of cholinesterase enzyme. All polar except physostigmine.

Irreversibleanticholinesterases :

Organophosphates (long acting) – phosphates esters. Very stable covalent bond formed with cholinesterase. Ecothiophateisoflurophate. All phosphates are lipid soluble except ecothiophate which is polar. 

All anticholinesterases have N and M actions. The lipid soluble ones have CNS effects.



 Organophosphates toxicity :

Severe bradycardia, hypotension.


Increased GIT motility, causing cramps and diarrhea.

CNS effects – convulsion, coma and respiratory failure.

Muscle weakness and paralysis.

Treatment of organophosphates toxicity : support respiration, cholinesterase reactivators (oximes), atropine ( to block muscarinic and central actions).

For other indirect cholinomimetics, the poisoning effects are the same as muscarinic poisoning effects (salivation,lacrimation,urination,diaphoresis, gastrointestinal upset, emesis etc) and/or nicotinic poisoning effects (involuntary irregular, violent muscle contractions, then weakness/paralysis) .

Oximes : 

Pralidoxime– cholinesterase reactivator, acts by regenerating cholinesterase enzyme, reactivates recently inhibited enzymes before aging. Use – I.V for organophosphate intoxication.

10.Common anesthetics. Classification. Mechanism of action. Stages and periods of narcosis. Comparative characteristic of individual common anaesthetic groups. The complications in different periods and their relationship with features of local and resorptive effects. Ways of control. Pharmacological basis of combined anesthesia.

They are drugs which affect on the CNS, they cause reversible decrease in all kinds of sensations, with unconsciousness, skeletal muscle relaxation.

Stages of anesthesia:

1. Analgesia: Starts from the beginning of drug administration, and lasts up to unconsciousness; this is loss of pain sensation, breathing, heart rate, skeletal muscle tone are all normal.

2.Excitement:this stage starts from loss of consciousness, to the beginning of regular consciousness, tone of skeletal muscles will be increased, diameter of pupils increased, heart rate will increase, during this stage we can see manifestation of CNS activity.

3, stage of surgical anesthesia:

Has 4 substages, during this stage we have relaxation of skeletal muscles, dilation of pupil, and loss of consciousness.

a, superlight substage:

During this phase we have relaxation of skeletal muscles, eyes become fixed

b, light anesthesia substage:

Diameter of pupil is decreased, and skeletal muscles relaxation, loss of corneal and laryngeal reflexes

c, Deep anesthesia

Manifested by dilation of pupil, light reflex is lost, total relaxation of skeletal muscles.

d, Super deep phase

Manifestations by intercostal paralysis, heart rate increased, dilation of pupil, with no light reflex.

4, stage of medullary paralysis:

Manifestation of this stage is when we stop administration of general anesthetics

This stage is about recovery, increasing in breathing rate, skeletal muscles get back to normal

Classification of general anesthetics.

They are separated into two big groups

1.Inhaled : A. Gases – nitrous oxide, xenon. B – Voltile liquids – Ether, Halothane, Enflurane, Sevoflurane, Isoflurane.

2.Intravenous anesthesia: A. Short acting – propofolketamine.Intermediate duration – barbiturates (thiopental sodium), benzodiazepines (midazolam).Long acting – sodium oxybutirate.

Before operation we should prescribe drugs for premedication means to make the usage of anesthetics safer.Then we will have to use drugs for induction: short acting intravenous anesthetics.Then drugs for basic narcosis.

A good anesthetic should produce 3 important effects: anestheticeffect, analgesiceffect, myorelaxation

What can happen to the patient during operation:1, Respiratory depression: low respiratory rate.2, Cardiovascular: Falling of BP, arrhythmia, delirium, convulsions.3, laryngospasm.4, manifestation of vagal nerve regulation: salivation, respiratory secretions, bradycardia, increase in secretion of HCl, high level of HCl leads to pneumonia

After anesthesia complications :nausea and vomiting.Sedation.Pneumoniaatelectasis.Organ toxicity: liver.Delirium.

Nitrous oxide: It irritates bronchial mucosa, it low anesthetic it can cause anesthesia in high concentration, from 75-90% but this concentration of NO can cause hypoxia,so we mix it with oxygen. This drug is a good analgesic and myorelaxant.SE: Acute MI. Pain.Wecan’t use this drug for more than 6-8 hours.

Ether: highly volatile liquid it is a potent anesthetic, produces good analgesia and causes muscular relaxation, this agent is highly soluble in blood, prolonged induction period (long stage of excitement).Causes salivation, respiratory secretion, recovery period is long, during the postoperative period we have vomiting.This agent has low toxicity.Causes good controlled anesthesia, it is irritant (bronchial mucosa)

Halothane: It is a volatile liquid. It causes potent anesthetic effect, but not good analgesic and skeletal muscle relaxant, due to this we combine it with opioid analgesics, or myorelaxants, this agent is more toxic, causes hepatotoxicity.

Halothane as any other GA can lead to falling BP and to decrease the heart rate, but halothane effects myocardium causes myocardial depression due to reducing intracellular calcium level, causes bradycardia due to decreased conduction in SA-node, increase sensitivity of cardiomyocytes, recovery period: rapid, recovery rare


Short acting:

Ketamine: It causes dissociative anesthesia, profound analgesia, immobility with dissociation.

It stimulates some areas of brain, and supress other areas.This agent doesn’t cause unconciousness. It is most likely “sleep”.It is a bad anesthetic, but a potent analgesic, and no myorelaxation effect.Ketaminecauses analgesic effect by stimulation of opioid receptors. Hypnotic action is due to NMDA receptor blockage. This agent causes sympathomimetic activity, induction and recovery period are rapid. Causes anesthesia for 15 minutes, in post-operative period we can see complications like amnesia, hallucination, nightmare, bronchodilation, recommended for operations on head and neck, for angiography, for short lasting operations.

Propofol: This agent causes anesthesia which lasts 3-5 minutes, ultrashort acting, for diagnostic procedures and short lasting operations, this agent can cause apnea.

Thiopentone sodium:Intermediate acting drug, belonging to barbiturate group, Generally agent enhances inhibitory synapses, this agent manifestations effects of GABA.This drug is lipophilic agent, duration of anesthesia lasts 20-30 minutes, induction is rapid, it is not a potent anesthetic, produces unconsciousness in 15 seconds. we prescribe it only intravenously, not intraarterial, in case of intra arterialcauses intense pain, BP falls immediately after injection, this agent causes hepatotoxicity.

Midazolam:Belongs to benzodiazepine, the duration of action is near 15-20 minutes, causes sedation, amnesia, unconsciousness, not potent analgesic and myorelaxant, doesn’t markedly depress respiration, recovery is rapid and without complications, useful for diagnostic procedures and for induction neurolytic analgesia:

11.Neuroleptics. Chemical classification. Typical and atypical neuroleptics. Pharmacological effects. Mechanism of action. Comparative characteristics of the distinctive drug groups. Clinical use. Side effects.


Phenothiazine derivatives have 3 subfamilies based on primarily side chains: 

  • The least potent: aliphatic derivatives(chloropromazine,triflupromazine,levomepromazine,promazine),piperidinederivatives(thioridazine,mesoridazine,pericyazine,pipotiazine)

  • More potent and more selective –piperazinederivatives(trifluoperazine,fluphenazine,perphenazine)

Thioridazine and Chlorpromazine have effects at muscarinic acetylcholine receptors : dry mouth, blurred vision, urinary retention, constipation.They also have effects at alpha adrenergic receptors, and can cause orthostatic hypotension.

Common side effects include: drowsiness,dizziness,headache,low blood pressure, and blurred vision.

Phenothiazine antipsychotics are medications used to treat schizophrenia and manifestations of psychotic disorders. Some phenothiazine antipsychotics, like prochlorperazine and chlorpromazine, are used for nausea, vomiting, and hiccups. They may work by blocking the action of dopamine in the brain.Phenothiazine antipsychotics are used when patients do not respond to other antipsychotics.

Phenothiazine antipsychotics may cause extra-pyramidal symptoms such as :abnormal muscle contractions,difficulty breathing and swallowing,neck spasms, and movement abnormalities on face, arms, and legs.

They are D2 antagonists.


D2 Activity

5HT2 Activity

Muscarinic Activity

Alpha-1 adrenergic Activity

Antihistamine Activity

Chlorpromazine (Thorazine)






Fluphenazine (Prolixin)






Perphenazine (Trilafon)






Trifluoperazine (Stelazine)






Thioridazine (Mellaril)






Mesoridazine (Serentil) +withdrawn from US market






Adverse effects :


Sedating effects

Anticholinergic effects

Extrapyramidal side effects

Hypotensive effects









Very high

















17.Cardiac glycosides and non-glycoside cardiotonic drugs. Main pharmacological effects and their mechanisms. Symptoms of cardiac glycosides intoxication and their management. Other drug groups to treat heart failure. Hemodynamic basis of their therapeutic effect.   

Cardiac Glycosides – are group of agents with natural origin, with positive inotropic effect, they ↑ force of myocardium contraction, ↑ CO without significant increasing in oxygen consumption.

Molecule of them contain 2 parts: Glycone part and aglycone part(steroidal and non-steroidal) Glycone is sugar part which determine pharmacokinetic characteristics of them. 


Chemical structure:

Polar glycosides – rapidly acting, short duration.(Injections) bad absorbed in GIT. For acute HF.E.gStrophanthinK,strophanthinG,corglyconum.

Non-polar glycosides – Well absorbed in GIT, orally, well bind with plasma proteins – ↑ duration of action, slow acting, can accumulate due to well binding, mainly in fat tissue, only for CHF. E.gDigitoxin

Intermediate polar agents – soluble in lipids and water, intermediate absorption in GIT, duration and action intermediate, injections, for acute HF and tablets for peroral usage for CHF. E.g Digoxin but it can accumulate and can lead to chronic intoxication.E.gCelanidum (lanatoside)

Effects: Separate into cardiac and extracardiac:

-Cardiac: Positive inotropic effect(force of contraction), Due to inhibition of Na-K-ATPase

-Negative chronotropic(bradycardia) – 2 pathways, vagal – these agents can directly inhibit activity of SA-pacemakers due tosensitization of them to acetylcholine, also activate baroreflex of carotid sinus and aortic arch, directly stimulate vagal center. 

Positive tonotropiceffect(tone of myocardium). – Can stop remodeling of myocardium.

In overdose:

Negative dromotropic effect(slow AV conduction) – Due to direct(block directly AV pacemakers, due to vagal influence) and indirect action(influence central stimulation of vagal nerve) side effects: AV-block

side effects: Ventricular extrasystole, ventricular tachycardia, ventricular defibrillation.

Extracardiac influence, ↑ CO without significant oxygen consumption demand, due to ↑ CO → ↑ stroke volume and ↓ venous pressure(↓ venous return, so ↓ remodelling of myocardium), and normalize to make arterial pressure becomes normal, improve coronary blood circulation, any type of circulation(renal(↑ renal perfusion and filtration → weak diuretic effect- ↓ edemas), peripheral through small vessels(↓ cyanosis and edemas), pulmonary(↓ pulmonary edema dyspnea))

Few can cause sedation(Corglyconum)

Can weakly cause vasodilation, not only smooth muscles of vessels but other smooth muscles.

Agents which can penetrate BBB can directly stimulate vomiting center.

Side effects: CVS:Hypokalemia, hypomagnesemia, which ↑ risk of arrhythmia development.

Overdose:AV-block and different types of ventricular tachyarrhythmias.Sinus arrhythmia, weakness of sinoatrial node and due to negative chronotropic effect.Anorexia.Nausea, vomiting, abdominal pain, fatigue, headache, mental confusion, restlessness, disorientation, hyperpnea, psychosis, visual disturbances(abnormal color perception, green and yellow color), gynecomastia.

Toxicity: Digoxin and digitoxin can accumulate → chronic intoxication: signs we can see as abdominal cramps, vomiting, diarrhea, visual disturbances(shadows, green, yellow) different types of arrhythmias, AV-block, bradycardia, ventricular arrhythmias and tachyarrhythmias. worseness of hypokalemia, changes in ECG – ST-interval washed up like.

Treatment of digoxin toxicity: Stop usage of drug.Prescribe drug containing potassium(potassium chloride, pananginum(potassium + magnesium salts).Digoxin antibody(Digibind) – antidote,.Symptomatic treatment – antiarrhythmic agents.

Non – glycoside cardiotonic drugs :

Dobutamine/dopamine produce positive tropic effect, these agents as contrary with cardiac glycosides ↑ oxygen consumption of myocardium.

MoA: Positive inotropic is by stimulation of butamine receptors of cardiomyocytes

Indications: Cardiogenic shock, acute HF, following cardiac surgery, septic shock, acute CV insufficiency, ↓ compensation in case of severe CHF.

Dobutamine not significantly change BP, but this agent has weak vasodilative effect.

Dopamine produce dose dependent effect, in low therapeutic dose it stimulates dopaminergic receptors D1 and D2, → vasodilation of mesenteric and renal arteries, → improve renal circulation, so to improve renal filtration and perfusion, → diuretic and natriuretic effect. In therapeutic dose this drug mainly stimulate beta-adrenergic receptors.In high doses it mainly can stimulate beta, alpha receptors.

Clinical use: Cardiogenic shock inadequate perfusion of vital organs

Adverse effects: Same as dobutamine, cause tachycardia, ↑ AV conductivity, ↑ excitability(can lead to arrhythmias), hypertension(high doses), most important it ↑ oxygen consumption of myocardium.

Levosimendan belongs to non-glycoside non-adrenergic cardiotonics

MoA: Calcium sensitizer, so ↑ sensitivity of heart (troponin-C) to calcium, thus increasing cardiac contractility without the rise of intracellular calcium.

Pharmacological effects: Positive inotropic – binding to cardiac troponin C in calcium dependent manner, and ↑ calcium sensitivity of myocytes.Vasodilatory effect because opening ATP-dependent K channel in vascular smooth muscles and cause smooth muscle relaxation.Cardioprotective due to opening mitochondrial ATP-sensitive-K-channels in cardiomyocytes.

Pharmacokinetics: Haemodynamic effect starts after 24 hours and last up to 9 days, following injection. force of contraction, ↑ preload and afterload.

25.Emergency cardiology drugs (hypertonic crisis, acute coronary syndrome). Justification of choice and application. Features of the action and use of individual drugs.

Loop diuretics (furosemide) – they are highly potent, highly efficient.MOA : ascending loop contains Na – K – 2Cl transporter from lumen to ascending limb cells. Loop diuretics block cotransporter so those ions remain in lumen, excreted along with water. Furosemide receptor is their cotransporter.Itcauses more electrolyte loss.It also has vasodilating effects.

Vasodilators (diazoxide, sodium nitroprusside, nitroglycerine IV).- All vasodilators relax arteriolar smooth muscle to cause vasodilation and a decrease in systemic vascular resistance – sodium nitroprusside also relaxes veins -cellular mechanisms of action include formation of nitric oxide and activation of cyclic GMP (similar to the nitrates) and opening potassium channels.Hydralazine– mechanism of action – through NO and cGMP. Minoxidil – mechanism of action – K+ channelopener.Diazoxide– mechanism of action – K+ channel opener – a vasodilator used for emergencies.Sodium nitroprusside i. mechanism of action – through NO and cGMP ii. adverse effects – hypotension, conversion to thiocyanate and cyanide iii. use – given only IV for emergencies.

Centrally acting agents (clonidine IV).

Ganglionic blockers (pentamine IV) 

Alpha-adrenoblockers (phentolamine, labetalol IV) 

Calcium channelbockers (nifedipine sublingual) – they are myotropic antihypertensive agents. Lowers BP a lot.Coronary arteries tone reduction.

ACEI (captopril sublingual, enaloprilat IV) – Affect RAAS. Inhibit angiotensin-converting enzyme, prevent angiotensinogen I being converted to angiotensinogen II.Cardiovascular effects – Lowering BP, peripheral resistance and afterload – Venous dilatation (decrease of pre-load) – Coronary vessels dilation – Endothelium function amendment – Regress of left ventricular hypertrophy and hyperplasia of smooth muscular cells and vessels intima – Perfusion amelioration in vascular beds of kidney, brain and other organs. Side effects :Hypotension– Dry cough (accumulation of bradykinin) – Hyperkaliemia – Renal failure in bilateral renal artery sclerosis.

Magnesium sulfate

Acute coronary syndrome 


Nitroglycerin – sublingual .Nitrates, like nitroglycerin, dilate blood vessels, which is beneficial against myocardial ischemia in two ways: by increasing blood flow in the coronary arteries and the amount of oxygen that arrives to heart muscle; and by relaxing all blood vessels in the body, thereby reducing the workload that heart needs to produce against them and the oxygen it consumes. The preferred mode of administration is sublingually. By relaxing blood vessels nitrates also reduce blood pressure, which must be carefully monitored; they must not be used if hypotension is present. They must also be avoided in patients who have taken sildenafil or other phosphodiesterase type 5 inhibitors (used for erectile dysfunction) within the previous 24–48 hours, as the combination of the two could cause a serious drop in blood pressure. Intravenous nitrates are useful in patients with hypertension or pulmonary edema.

Beta Blockers – By reducing sympathetic stimulation of the heart, beta blockers decrease heart rate, blood pressure and cardiac output, and hence heart oxygen consumption. Beta-blockers alleviate ischemic pain, and have also been proved to reduce the size of infarcted heart muscle, the risk of arrhythmias, and the proportion of patients with acute coronary syndrome who actually evolve STEMI. However, they have also been shown to increase the risk of acute heart failure. Their early use is contraindicated if there are signs of congestive heart failure or hypotension, along with other contraindications to beta blockers (slow heart rate, atrioventricular block); in the absence of contraindications beta blocker therapy should begin in the first 24 hours. It may be prudent to prefer oral rather than intravenous forms.


Analgesics – Analgesic agents that are most commonly used are opioids, and especially morphine, which is considered the analgesic of choice in patients with ST elevation. Along with its pain-controlling properties, morphine also reduces the work of breathing, alleviates breathlessness, reduces anxiety and has favorable action on hemodynamic parameters and cardiac oxygen consumption.However, in patients presenting without ST elevation, morphine has been shown to have adverse events potential, and its use is considered acceptable only after inadequate pain relief by medication specific against angina.Non-steroidal anti-inflammatory drugs are contraindicated for both categories of patients.

Anti-platelet drugs :Aspirin – Aspirin inhibits platelet aggregation and formation of blood clots. It is effective across the entire spectrum of acute coronary syndromes, and it actually has been shown to reduce the rate of death in patients with STEMI and in patients presenting without ST elevation. Aspirin is contraindicated in patients with documented allergy or known platelet disorder. Patients who have had gastrointestinal symptoms while on long-term aspirin therapy are usually able to tolerate aspirin in the short term. For patients with true intolerance to aspirin clopidogrel is recommended. Lower doses need days to achieve full antiplatelet effect, therefore a loading dose is necessary for patients who are not already on aspirin.

Anticoagulants in acute coronary syndrome are targeted against the coronary blood clot, as well as towards prevention of thrombotic complications, like formation of blood clots in the ventricles, stroke, pulmonary embolism or deep vein thrombosis.[48] Patients undergoing PCI also need an anticoagulant to prevent catheter thrombosis. Options include unfractionated heparin, enoxaparin (a low molecular weight heparin), fondaparinux (a pentasaccharide antagonist of factor Xa) and bivalirudin (a direct thrombin inhibitor); all the above agents are given parenterally (subcutaneously or intravenously). Unfractionated heparin has the disadvantage of requiring dose adjustment based on a laboratory exam, activated partial thromboplastin time (APTT). In STEMI patients choice depends on the reperfusion strategy used (see below); bivalirudin is used when PCI is employed only, while in the same case fondaparinux is not preferred.[49] Similarly, in Non-STE ACS bivalirudin too is only used when an early invasive strategy is chosen.

39.Diuretics. Classification. Pharmacological characteristic of osmotic and loop diuretics. Mechanism of action. Clinical use. Side effects.

They are the drugs increasing urine secretion. 

Classification :

Chemical and pharmacological classification

Classification based on predominant site of effect


Xantine derivatives 




Proximal tubule

Potent (High ceiling)

Carboanhydrase inhibitors 

Proximal tubule



Loop of Henle (ascending limb) 

Potent (High ceiling) 

Thiazide and thiazide-type

Distal tubule (proximal [diluting] segment)



Distal tubule (end segment) and collecting tube


MOA of osmotic diuretics : They are highly efficient, high ceiling diuretics.

High dose of a chemically neutral substance which is filtered but poorly reabsorbed in the kidneys -> increased total blood volume, hyperhydration -> increased intramedullar blood flow -> decreased medullar osmotic gradient -> increased osmotically active water and electrolyte loss.

There is also increased filtration of hyperosmotic plasma, increased volume of hyperosmotic tubular urine, retention of osmotically active water, increased urine flow rate ,decreased active reabsorption and passive diffusion.

Mannit – distributes in extracellular space, poorly reabsorbed. Urea – Distribution in all sectors. Secondary hyperydration.Glycerol

Indications for osmotic diuretics : cerebral edema, elevated intracranial pressure (prevention and treatment),Acute glaucoma, pre- and post-operative management of intraocular pressure,prevention and treatment of acute renal failure (oliguric phase) in cardiac surgery, in hemolytic post-transfusion reactions, burns, critical states etc.Facilitatingdiureseis in intoxications (+ hemodilution).

They are dangerous in anuric state, acute and chronic blood circulation failure.

Loop diuretics – they are highly potent, highly efficient, high ceiling.Examples :furosemide,bumetanide,ethacrynicacid,pyretanid.

MOA : ascending loop contains Na – K – 2Cl transporter from lumen to ascending limb cells. Loop diuretics block cotransporter so those ions remain in lumen, excreted along with water. Furosemide receptor is their cotransporter.Itcauses more electrolyte loss.

Clinical use : : Acute left ventricular failure, pulmonary edema, hypertonic crisis, acute and chronic renal failure, glaucoma, acute intoxications, cerebral edema, hypercalcemia.

Furosemide has vasodilating effects.

Adverse effects of loop diuretics :Hypochloridemic alkalosis, hypokalemia, hyponatremia,orthostatic reactions, thromboembolic complications,hearing impairment (impairment of hydrodynamics and electrolytes content of cochlear endolympha), potentiation of othotoxic effects of antibiotics, hyperglycemia,decreasedcarbohydrates tolerance.


Targeted action

Diuretic choice


Excretion (mobilization) of the excess of extracellular fluid (positive fluid balance)


Acute heart failure, hypertonic crisis

Hemodynamic unloading, elimination of hypervolemic state 

Highly potent saluretics with rapid onset of action

Arterial hypertension

Elimination of sodiumassociated pathogenetic factors of hypertension

Saluretics effective with long-term use

Acute renal failure (prevention and treatment)

«Washing» kidneys, elimination of nephrotoxins

Highly potent and rapidly acting diuretics


Exogenous and endogenous toxicants excretion

Highly potent and rapidly acting diuretics

Local alterations of hemodynamics (increased intraocular, intracranial pressure)

«Dehydration» effect, fluid «extraction», decreased production of intraocular fluid and cerebrospinal fluid

Highly potent and rapidly acting diuretics

40.Diuretics. Classification. Pharmacological characteristic of thiazide, thiazide-like, potassium sparing drugs and carbonic anhydrase inhibitors. Clinical use. Side effects.

They are the drugs increasing urine secretion. 

Classification :

Chemical and pharmacological classification

Classification based on predominant site of effect


Xantine derivatives 




Proximal tubule

Potent (High ceiling)

Carboanhydrase inhibitors 

Proximal tubule



Loop of Henle (ascending limb) 

Potent (High ceiling) 

Thiazide and thiazide-type

Distal tubule (proximal [diluting] segment)



Distal tubule (end segment) and collecting tube


Loop diuretics – they are highly potent, highly efficient, high ceiling.Examples :furosemide,bumetanide,ethacrynicacid,pyretanid.

MOA : ascending loop contains Na – K – 2Cl transporter from lumen to ascending limb cells. Loop diuretics block cotransporter so those ions remain in lumen, excreted along with water. Furosemide receptor is their cotransporter.Itcauses more electrolyte loss.

Clinical use : : Acute left ventricular failure, pulmonary edema, hypertonic crisis, acute and chronic renal failure, glaucoma, acute intoxications, cerebral edema, hypercalcemia.

Furosemide has vasodilating effects.

Adverse effects of loop diuretics :Hypochloridemic alkalosis, hypokalemia, hyponatremia,orthostatic reactions, thromboembolic complications,hearing impairment (impairment of hydrodynamics and electrolytes content of cochlear endolympha), potentiation of othotoxic effects of antibiotics, hyperglycemia,decreasedcarbohydrates tolerance.

Thiazid and thiazid-like diuretics : hydrochlorothiazide, cyclomethiazidechlorothalidoneclopamine,xipamide,indapamide

Main site of action : proximal segment of distal tubule. 

MOA : Thiazides receptor – Na+/Cl- cotransporter (site of chloride binding).Thiazides slightly inhibit carbonic anhydrase.They decrease Na reabsorption by inhibiting the cotransporter. Effect : increased loss of Na, Cl,K,H,Mg. Decreased loss of Ca. 

Clinical use :

Arterial hypertension : mechanism of action – 1) Decrease total blood volume 2) Decrease Na content in blood vessels wall and decrease total peripheral resistance by decreasing myocytes tone, «edema» and blood vessels wall rigidity 3) decrease of sensitivity of blood vessels to pressor factors; 4) direct vasodilating effect (activation of ATP-sensitive K-channels).

Edema («cardiac», «liver», «renal») 

Other indications: glaucoma, recurrent nephrolithiasis.

Adverse effects :Hypochloridemic alkalosis, hypokalemia, hyponatremia,hyperuricemia, gout exacerbation,hyperglycemia, decreased carbohydrates tolerance,hypercalcemia.

Potassium-sparing diuretics : amiloride, triamterene.

MOA : Amiloride (monovalent cathion) has high affinity to sodium channel of lumenal membrane of the cells of distal nephron segments and blocks potential-independent sodium channels, decreasing transepithelial electrogenic sodium transport.Block of sodium channels causes hyperpolarization of apical (lumenal) membrane and decreases transepithelial potential, which is the «moving power» of the exit of K into the tubular lumen, thus decreasing potassium secretion and loss, I.e. ensures potassium-sparing effect. H+ ,Ca++, Mg++ losses also decrease.

They have weak diuretic action. Usually used in combination with other diuretics

Side effect : hyperkalemia.

Carbonic anhydrase inhibitors.

Examples : acetazolamide, dorsolamide.

CAI inhibit the activity of carbonic anhydrase.Electrolyte changes: increased loss of HCO3 -Na+ and K+ (secondary losses in distal segment of nephron).Impaired acid-alkaline balance: shift of urine pH to alkaline, and plasma pH to acid (metabolic acidosis) values.Self-limitation effect: bicarbonate filtration decreases as acidosis develops.

Clinical use :  Glaucoma: oral, eye drops. Clinical states with increased content of CO2 and bicarbonate in blood (edema in heart and lung failure, pulmonary emphysema, sleep apnoea).

Side effects : hypokalemia, metabolic acidosis, allergic effects, renal failure.

41.The treatment for thrombosis. Classification. Direct and indirect anticoagulants. Mechanism of action. Pharmacological characteristic of individual drug groups. Clinical use. Side effects. Pharmacological antagonists.

Classification : Anticoagulants, Antiplatelet drugs,Fibrinolytics.

Direct acting :

I- Heparin and heparinoids

A. Unfractioned heparin sodium. Heparin is a sulfated glycosaminoglycan found in erlich mast and RES cells. It’s extracted from bovine lung or porcine intestinal mucosa. It’s used unfractioned. It gets rapidly destroyed and not detected in plasma. Mechanism of action : binds to antithrombin III, causing a conformational change that increases its ability to inhibit coagulation factors (e.g thrombin) 1000 times. Side effects : prevents platelet adherence – hemorrhage,thrombocytopenia. Decreased level of LDL. Inhibits enzymes like hyaluronidase, tripsin, histamine, epinephrine and leads to anti-inflammatory action. It must be given parenterally. Clinical use : acute deep vein thrombosis, pulmonary embolism, myocardial infarction.Can also be used as ointment on soft tissue bruise. Pharmacological antagonist : Protamine sulphate. Complex binding with heparin. IV administration.

B. Low molecular fractions of heparin (Nadroparin, EnoxoparinDalteparin)

MOA : Affects factor Xa.Less nonspecific bindging to plasma proteins. Fewer drug interactions, more predictable response, eliminated renally – dosage adjustments must be made in patients with renal insufficiency. Use : to prevent or treat deep vein thrombosis and pulmonary embolism, prevention of ischemic complications associated with unstable angina and non Q-wave MI. Side effects – same as unfractioned heparin but their incidence is much less. Advantages :can be used at home (because administration is subcutaneous), routine monitoring of coagulation times is unnecessary, predictable dose response, better bioavailability, longer half life.

C.Heparinoids : heparoidsulodexid.

Sulodexid : highly purified mixture of glycosaminoglycans composed of low molecular weight heparin and dermatan sulphate. That allows for better oral absorption.It has prolonged half life and reduced effect on global coagulation and bleeding. Due to presence of both glycosaminoglycan fractions, it

allows the antiprotease activities of antithrombin III and heparin cofactor II. Use : prophylaxis and treatment of thromboembolic diseases.

II – Selective factor Xa inhibitors : apixaban, rivaroxaban, fondaparinux sodium.

Apixaban , rivaroxaban : They are synthetic pentasaccharides. The shortest sequence within heparin that binds to antithrombin III to inactivate factor Xa.Oraladministration.Less potential of hypersensitivity reactions because it’s synthetic, as opposed to unfractioned heparins from bovine or porcine sources.Longerhalf life and needs less monitoring. Less likely to cause heparin-induced thrombocytopenia, but no antidote is available in the case of bleeding complications. Use : prevention of stroke and thromboembolism in atrial fibrillation. Deep vein thrombosis and pulmonary embolism. Unstable angina – to prevent infarction. Dose : one 15-20 mg tablet daily.

Fondaparinux sodium : binds specifically to antithrombin, which then selectively and rapidly inhibits factor Xa, and then thrombin generation and fibrin formation are blocked. Then fondaparinux is further released to act on other antithrombin molecules. Use : subcutaneous once daily to prevent thromboembolism after orthopedic surgery.

III – Direct thrombin inhibitors : dabigatran, bivalirudin.

Dabigatran : MOA – directly binds to the active site of thrombin, inhibiting its effects on fibrinogen. Use : to prevent strokes in people with atrial fibrillation and deep venous thrombosis and pulmonary embolism. In persons who have been treated for 5-10 days with parenteral anticoagulant to prevent DVT and PE in some circumstances. It’s an alternative to warfarin since it can’t be monitored by blood tests for international normalized ratio but it’s similarly effective. Adverse effect : bleeding.

Bivalirudin : a recombinant polypeptide form of the irreversible thrombin inhibitor derived from leeches called hirudin. Bind to active side of thrombin, inhibiting its effects on fibrinogen. IV administration. Use : in patients undergoing angioplasty. Adverse effect : bleeding.

Antithrombine III human : IV administration. Binds to thrombin and inactivates it, inhibits activity of factors IXa,Xa,XIa,XIIa and plasmin. Used in patients with antithrombine deficit.

IV – Ca++ antagonists ( complexones ) : Na hydrocytrate. An acid salt of citric acid. Used as an anticoagulant in donated blood to preserve it.The anticoagulant effect depends on the transfer of calcium in the calcium citrate, which leads to the binding of free calcium ions involved in the formation of thromboplastin and in the transition of prothrombin to thrombin.

Antagonist, in case of overdose of mainly heparin we can use specific antagonist protamine sulphate, which is low molecular protein with high positive charge forms complex with heparin and gets eliminated by kidneys.

Indirect acting :They belong to antithrombotic drugs. They reduce blood coagulability. Effective only in vivo.

I – Coumarinederivatives : warfarin, acenocumarol (syncumar)

Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, XI and X, and interferes with coagulation.

Warfarin inhibits synthesis of IX, X and prothrombin.It has slow onset and long duration of action. Therapeutic effect is delayed for 4-5 days up until all existing factors II,VII, IX and X are depleted from circulation.They are reinstated after a few days after stopping the treatment. It binds extensively and nonspecifically to plasma proteins (up to 99% is bound), so there isn’t much of the the free drug in circulation to exert biologic effects, but coadministration of other highly protein bound drugs may displace it from its binding sites, leading to increased risks of bleeding. Use : long term prophylaxis and treatment of deep vein thrombosis and pulmonary embolism, also prophylactic treatment of patients with atrial fibrillation to prevent mural thrombi, rheumatic heart disease and patients with prosthetic heart valves. It’s also an adjunctive treatment when coronary arteries are occluded. It’s usually the oral anticoagulant of choice.Adverse effects : hemorrhage risk. Teratogenificty,hemorrhagic disorders and abnormal bone formation prohibits warfarin use during pregnancy.

II Phenylindadionederivatives :Phenindion (pheniline)

Vitamin K antagonists block the reducation of Vit K epoxide which is necessary for its action as a cofactor in the synthesis of factors II,YII,IX, X. It prevents the synthesis of prothrombin from descarboxylateprothrombin.It acts similar to warfarin, but it has been associated with hypersensitivity reactions, so it is rarely used and warfarin is preferred

42.The treatment for thrombosis. Classification. Antiplatelet drugs. Mechanism of action. Pharmacological characteristic of individual antiaggregant groups. Indications. Side effects.

Classification : Anticoagulants, Antiplatelet drugs,Fibrinolytics.

Also known as antiaggregants.They are antithrombotic drugs, they prevent blood coagulability.

They are classified by mechanism of action .

Inhibition of cyclooxygenase : acetylsalicylic acid (aspirin).

Alters balance between TXA2 (promoter of aggregation) and PGI2 (inhibitor) in favor of PGI2 by inactivating COX-1, resulting in TXA2 synthesis reduction.Enterosoluble tablets. Use : MI and cerebrovascular accidents, unstable angina, atrial fibrillations, transient ischemic attacks. Adverse effects : gastrointestinal hemorrhage and bronchospam (aspirin asthma), so it limits use in patients with asthma or peptic ulcer disease. Children younger than 12 may develop reyesyndrome : encephalopathy (inflammation,swelling) and liver damage.

Antagonism at ADP receptors : ticlopidine (ticlid), clopidogrel (plavix), ticagrelor (brilinta).

MOA : irreversibly block the ADP receptor on platelets, reducing platelet aggregation. Effects persist for the life of platelet.It’s the main alternative to aspirin for preventing thrombotic events in atherogenic patients with recent MI, strokes, transient ischemic attack, and unstable angina.Adverse effects : increased bleeding risk. Clopidogrel is preferred over ticlopidine because of life-threatening hematologic reactions associated with ticlopidine, including neutropenia/agranulocytosis and thrombocytopenic purpura.Clopidogrel is a prodrug that must be activated by cytochrome P450 ZC19.Genetic polymorphisms in ZC19 or drugs that inhibit its activity can decrease clopidogrel’s efficacy.

GP IIb/IIIa receptors antagonists : monoclonal antibodies – abciximab (reopro). Synthetic peptide – eptifibatid (integrilin)

MOA : abciximab is a monoclonal antibody that targets the glycoprotein IIb/IIIa receptor on platelets. Eptifibatide is a small molecule anntagonist of the same receptor. Activation of this receptor causes fibrinogen and von willebrand factor to bind to platelets, which leads to platelet aggregation. Those drugs prevent fibrinogen from interacting with those platelet glycoprotein receptors, and therefore inhibit platelet aggregation. Use : to manage acute coronary syndromes and prevent acute cardiac ischemia in patients undergoing percutaneous coronary intervention.Adverse effects : bleeding, and hypersensitivity ( to abciximab)

Increase of CAMP : inhibition of phosphodiesterase – dipiridamol (curantil), pentoxyfilline (trental).

Dipiridamol : MOA – prevent breakdown of cAMP within platelets. Increase in intracellular cAMP levels leads to decreased platelet activity. It may also activate adenosine function,stimulateAC,increasecAMP,

cause vasodilation.Also inhibits adenosine uptake by RBC’s, increasing its amount in circulation. Use : adjunct of warfarin to prevent postoperative thromboembolic complications associated with prosthetic cardiac valves or in combination with aspirin to prevent cerebrovascular ischemia. Adverse effects : hypotension and accompanying dizziness, abdominal distress, headache and rash.

Pentoxyfilline : antiplatelet action. Hemorrhagic effects – improves blood deformability,reduces its viscosity, decreases potential for platelet aggregation and thrombus formation. Vasodilation of coronary and pulmonary arteries.

Increase of CAMP : prostaglandins – alprostadil (vasoprostan,alsprostan), iloprost (ventavisilovedin)

Alrpstadil : it’s a synthetic analogue of PgE1. Its actions are wide spectrum : vasodilation, BP decrease, inhibits aggregation, stimulates smooth muscles of GIT and uterus. Use : Intraarterial – for chronic obliterating arteries diseases (limb ischemia). IV – in babies with congenital heart defects to open ductus arteriosus until surgery can be carried out. Intrapenile – to treat erectile dysfunction.

Iloprost : Most strong inhibitor of platelets aggregation. It’s a prostacycline analogue. Affects prostacyclin receptors. Increases activity of adenyl cyclase and concentration of cyclic AMP in the platelets. It’s an active vasodilator. Indications : chronic obliterating and occlusive peripheral arteries disorders.IV infusion after dissolving the concentrate. Adverse effects : nausea, arterial pressure decrease.

Dextrans : polymers of glucose. Change the properties of the platelets membrane and impair their interaction with endothelium.Inhibit the reaction of ADP release and aggregation. Used for prevention and management of thromboembolic complications in surgery, ischemic stroke,thrombophlebites.

43.Fibrinolytics.  Mechanism of action. Comparative characteristic of individuals fibrinolytic groups. Indications. Side effects.

They stimulate fibrinolysis. Aka thrombolytics.

First generation thrombolytics : streptokinase and urokinase.

MOA : streptokinase – a protein synthesised by beta hemolytic streptococci that forms a stable 1:1 complex with plasminogen,altering its conformation to facilitate its conversion to plasmin. Due to its antigenic nature, it gets quickly removed from circulation. Urokinase – an enzyme produced by human kidney cells that directly converts plasminogen to active plasmin.They act on clot-bound and free plasminogens. They dissolve pathologic thrombi and digest fibrin deposits at other body sites. Tend to be hemorrhagic. Streptokinase is now infrequently used due to the advent of tissue plasminogen activators. Clinical use :Treatment of acute events such as evolving transmural MI, PE, DVT, stroke and other arterial thrombosis and embolism.Adverse effects : highly antigenic (can cause hypersensitivity reactions), bleeding.

Second generation thrombolytics : tissue plasminogen activators : alteplase and tenecteplase

Recombinant plasminogen activator (t-PA). t-PA is released by endothelial cells in response to stasis produced by vascular occlusion.MOA : T-PA is colocalized to fibrin. Exogenous t-PA will preferentially activate plasminogen that is in close proximity to fibrin clots, making these drugs somewhat clot specific.In contrast to alteplasetenecteplase may offer an advantage because it is administered as a

bolus rather than a 90-minute infusion. Use : similar to streptokinase and urokinase in acute MI, acute ischemic strokes, and acute PE. But unlike them it doesn’t cause hypersensitivity reactions with recombinant tPA.Adverseeffects : bleeding, threefold higher risk than with heparin.

Third generation thrombolytics : direct fibrinolytics (thrombovasim)

Direct fibrinolytic action (destroy thrombus core – fibrin fibers and filaments).Mechanism different than of plasmin.They are either conjugates of plasminogen activators with monoclonal antibodies against fibrin, platelets, or thrombomodulin; mutants, variants, and hybrids of alteplase and prourokinase (amediplase); or new molecules of animal (vampire bat) or bacterial (Staphylococcus aureus) origin. These variations may lengthen the drug’s half-life, increase resistance to plasma protease inhibitors, or cause more selective binding to fibrin. Compared with the second-generation agent (alteplase), third-generation thrombolytic agents such as monteplasetenecteplasereteplaselanoteplasepamiteplase, and staphylokinase result in a greater angiographic patency rate in patients with acute myocardial infarction, although, thus far, mortality rates have been similar for those few drugs that have been studied in large-scale trials. Bleeding risk, however, may be greater.

46.Drugs affecting P/Ca balance. Vitamin D and its metabolites. Mechanism of action. Comparative characteristic. Indications. Side effects. Drugs contained Ca, P and combined drugs with vitamin D. Clinical use. Side effects.

It’s a drug that affects calcium and phosphorous metabolism.They intensify bone formation and resorption.They increase Ca absorption in small intestine,which facilitates mineralization of the organic matrix of the bony tissue.InducesCalbindin (a calcium binding protein),endocytosis and vesicular transport,andnongenomemechanism.They also reduce renal calcium excretion by increasing tubular reabsorption of calcium and phosphorus.Other effects include stimulation of cell differentiation and modulation of the immune response.

Can be used in osteoporosis. It stimulates proliferation of parathyroid glands cells,synthesis and secretion of PTH,calcuria gets decreased – bone resorption is decreased. Synthesis of bone matrix, growth factors of the bone, restoration of the bone are intensified – bone tissue quality gets improved.Muscularstrength,mobility of joints,tolerance to motion exertion is increased,neuromuscular coordination is improved – risk to fall down is reduced.Therefore, fracture incidence rate is reduced.

MoA: 2 pathways

-Genomic: Interact with intracellular cytoplasmic receptors in target tissues, and formate complex, it penetrates nucleus and bind with DNA fragment, leading to change, activation or suppression transcription, leading to activation or suppression of mRNA, leading to activation of protein synthesis and effects

-Non-genomic: We have receptors in the cell membrane, interaction of vit D with calcium sensitive receptors leads to activation of calcium-channels, leading to calcium entrance into cell, causing biological effect.

Classification :

Vitamin D preparations :

Vitamin D3,cholecalciferol– solution for oral administration/intra muscular (depending on the trade name) e.gvigantol is for oral, Vitamin D3 can be for IM.

Vitamin D2,Ergocalciferol– can be for oral administration.

Both D3 and D2 go to our body with meal, but D3 can be synthesized in melanocytes of skin.

Vitamin D analogues :

1alpha-OH-D3 – alphacalidol– capsules, can be for oral use.

1,25-(OH)2-D3 – Calcitriol– capsules

Combined preparations :

Cholecalciferol + – alendronate + calciumcarbonate

Alphacalcidol + – calciumcarbonate

Tevabon– alendronate

DHT (dihydrotachisterol) – modified form of vit D2. Renal hydroxylation not required so active after nephrectomy.Indicated in hypoparathyridism.

Clinical use :rickets and osteomalaciahypoparathyroidism,osteoporosis,renal osteodystrophy in CRF.

Adverse effects :Hypercalcaemia and hypercalceuriaNausea,vomiting,anorexia,drymouth,discomfort in epigastric area. Weakness, apathy,fatigue,diziness,drowsiness. Tachycardia. Rash,Itching.

More rarely :hyperphosphatemia,thirst,dehydration,risk of calcinosis in soft tissues.

Drug interactions : Cardiac glycosides – risk of arrhythmia. Thiazides – risk of hypercalcaemia.

47.Drugs affecting P/Ca balance. Classifications. Hormonal drugs and their analogs (thyroid, parathyroid and female sex steroids). Bisphosphonates. Pharmacokinetic features. Mechanism of action. Side effects.

Classification due to process which the drugs affect

-Bone formation :calcium preparation (enhance formation),Vit D and its metabolites,PTH,Anabolic steroids – decrease,Growth hormone – decrease,GCC – decrease,Fluoride preparations – increase

-Bone resorption :Calcium preparation – decrease,Vit D and its metabolites,PTH,Calcitonin – decrease it,Estrogens – decrease bone resorption,Bisphosphonates – decrease,Thiazides – decrease,Anabolic steroids – decrease,GCC – increase.

PTH – consist of 84 amino acids, the precursor is pro-PTH which contain 115 amino acids, and pro-PTH activity is lower when compared to PTH.

Drugs: PTH (preotact) – human PTH identical to natural polypeptide, recombinant technology, temporary increase of PTH concentration following subcutaneous injection, stimulation of osteogenesis by direct action, at low dose concentration stimulate osteoblasts, and non-direct action, so PTH facilitate intestine and renal absorption and reabsorption of calcium.

We can give it for menopausal osteoporosis in women with high risk of fractures.

Teriparatide – recombinant fragment of human PTH, the mechanism same as PTH(directly interact with receptors on target tissue)

Directly stimulate osteoblasts leads to increased bone formation and any does doesn’t affect osteoclasts.

Indication: For menopausal osteoporosis in women, and primary osteoporosis in men caused by hypogonadism.

DIhydrotachysterol – which is modified form of vit D2, product of it so this agent is metabolized down to calcitriol in intestine and bone, active after nephrectomy because renal hydroxylation is not required.

This agent improve absorption of calcium and phosphor in GIT, and increase excretion of phosphorous by the kidney.

Is ib-450 times less active than D2, according to the anti ricketts action, due to this we don’t prescribe it for that.

But in higher dose it’s more active and require mobilization of bone minerals.

Indications: Hypoparathyroidism and tetani

This agent is prepared in drages, dose from 0,5-1,5 mg.

Paricalcitol(Vit D metabolite with lactonic acid) is also anti parathyroid agent, so same indication, but this agent got higher MoA: activate calcium sensitive receptors in parathyroid gland, and also this agent activatevit D sensitive receptors in parathyroid gland. Decrease release of PTH.

Calcitonin: Decrease bone resorption due to inhibition of the osteoplast activity and decrease production and activity of osteoblasts.

Increased calcium level in serum will be decreased, not lower than norm.

In the beginning of the course of treatment increase calcium and phosphorous excretion in the urine, and reduces intensity of painful syndrome in osteopenia and osteolysis.

2 drugs: neoclassic(synthetic, solution for injections, spray) calco(tonocalci)(solution and spray for inhalation)

We have spray because bioavailability is 3-50%, maximum conc in blood after inhalation we will see after 1 hour.

50% of parenteral forms, subcutaneous or IM.

Dose dependent dose on the concentration after administration from 100-400 IU, half life 40-50 minutes.

Indication: Osteoporosis


Paget disease – osteodystrophy

Painful syndrome in osteopenia or osteolysis

Sex-hormone preparations: Estrogens

Decrease resorption due to intensification of the inhibiting effect of RANKL and OPG, so affect osteoblast but not too much, mainly decrease activity of osteoplasts.

So inhibiting effect of osteoblasts on osteplasts due to effecting RANKL and OPG.

Directly inhibit activity of osteoplasts.

Activity increase of 1-alpha hydroxylase in the kidney


Rarely used for osteoporosis, only in postmenopausal osteoporosis, very rarely.


Classification, 3 gen

-1st:Etidronic acid, clodronate

-2nd: Pamidronate, alendronate


Pyrophosphate and bisphosphonates have high affinity to calcium phosphate and bind with it on crystal structure of the bone, they reduce production, delay aggregation and slow down solution of crystals of calcium-phosphate.

Pharmacokinetics: Are chemically inert and very slowly metabolized, bioavailability is 1-10%, intake with meal iron compounds worsen absorption. Bone tissue absorbs from 20-80% of the drug, and they can accumulate for a long time, half life in plasma 0,5-1 h, in the bones concentration after long lasting administration 3-20 months and sometimes up to 10 years.

Slow administration in dissolved form leads to risk of intravascular aggregation due to binding of calcium, and that leads to acute hypocalcemia, so IV not good.

Mainly decrease bone resorption.

MoA: Directly inhibit osteoplasts, after entering the bony tissue cells with bisphosphonates, and also have direct effect on osteoblasts, so production increase ?74:56? and differentiation inhibition.

Pharmacotherapeutic effects: Suspend bone mass loss in various form of osteoporosis

Increase density of bone tissue mass

Reduce fracture incidence rate

Addition to the existing drugs to treat osteoporosis.

Indications: Osteoporosis, postmenopausal, for alternative or combined with estrogens steroids.

Osteolysis and hypercalcemia in bone tumor and metastasis

Hypervitaminosis D


Paget disease


Dentistry – topically as paste

Side effects: Disorders of GIT up to ulceration and oesophagitis.(alendronate?78:09?)

Etidronate increase risk of fractures due to reduction of bone calcification, due to this administered in cycles, so with time for rest.

48.Drugs to prevent and treat hypothyroidism. Metabolism effects. Clinical use. Antithyroid drugs. Classification. Mechanism of action. Clinical use. Side effects.

Drugs for hypothyroidism – preparations of thyroid hormones

L-thyroxine (levothyroxine, euthyrox) (T4),Liothyroxin 9T3),Thyreotom(T4 and T3).Often administered with potassium iodide.

MOA : Free T4 and T3 enter the cell by active transport.Within the cell, T4 is converted to T3 .T3 enters the nucleus → binds to a specific T3 receptor protein →↑formation of RNA and protein synthesis.Large numbers of TR are found in the most hormone-responsive tissues (pituitary, liver, kidney, heart, skeletal muscle, lung, and intestine).Few receptor sites occur in hormone-unresponsive tissues (spleen, testes).Brain lacks an anabolic response to T3 , contains an intermediate number of receptors.Affinity of receptor site for T4 is about 10 times lower than T3.

Choice :synthethic levothyroxine because of its stability, content uniformity, low cost, lack of allergenic foreign protein, easy laboratory measurement of serum levels, and long half-life (7 days) → once-daily administration.

Liothyronine: greater hormone activity and consequent greater risk of cardiotoxicity, best used for short-term suppression of TSH. 

Thyroid PreparationsT3: its shorter half-life (24 hours), which requires multiple daily doses; its higher cost; and the greater difficulty of monitoring its adequacy of replacement by conventional laboratory tests. 

Animal origin : 

Dessicated thyroid

Side effects : nervousness, heart palpitations, tremors, weight loss,heat intolerance.

Side effects: All clinical manifestations of hyperthyroidism

Anti Hyperthyroidism

-Hormone synthesis inhibitors -Agents which ↓ activity of peroxidase, (→ ↓ synthesis of T3 and T4)

Derivatives of thioamides :Timazol,propylthiouracil.

-Inhibitors of T3 and T4 release, and deiodination of T4 :Lithium carbonate

-Inhibitors of TSH, TTH :Diodthiazine,Iodidesodium,iodide potassium

-Drugs which prevent iodide absorption by thyroid gland :Glonol

-Destruction of thyroid follicles :Radioactive iodine 131, 132

-Agents for symptomatic treatment :Betablockers,Sympatholytics,Glucocorticoids..

Side effects: Nephrotoxicity,Hepatotoxicity – cholestatic jaundice, ↑ level of liver transaminases.,Dyspepsia,Allergic reaction, skin rash.Most dangerous: Immunosuppression, manifested by anemia, agranulocytosis, thrombocytopenia..Arthralgia – pain in joints.Hypothyroidism.Goiter

T3, T4 release inhibitors – MoA: Inhibit proteolysis of thyroglobulin, and release of T3 and T4. Also inhibit D-aladinase so ↓ deiodination of T3 and T4.Side effects: Tremor,Sleepin,Nausea, vomiting, diarrhea,Skeletal Muscle weakness,Polyuria,Hypothyroidism

Potassium-iodine –MoA: ↓ release and synthesis of Thyroliberin and Thyrotropic hormone, → ↓ synthesis of T3 and T4, → inhibition thyroglobulin proteolysis and release of T3 and T4. Also can ↓ the size of thyroid gland and ↓ the vascularization of it.Sideeffects:hypersalivation, lacrimation, rhinitis, bronchitis, skin rash, and fever.Thyrotoxicosis.

Radioactive iodine – MoA: Cause destruction of thyroid gland follicles.Side effects: Hypothyroidism,Incase of overdose can cause radiation sickness.This agent we mainly use for diagnostics.

Indication: All these agents for hyperthyroidism, thyrotoxicosis.

49.Insulin and human insulin analog preparations. Classification. Effect on metabolism. Comparative characteristics of individual drug groups. Clinical use. Side effects.

Classification : rapidly acting: begin to work within 5 to 15 minutes and are active for 3 to 4 hours (  insulin analogues aspart, lispro, and glulisine).Shortacting:  begins working within 30 minutes and is active about 5 to 8 hours (such as regular insulin-human soluble insulin).Intermediateacting:begins working in 1 to 3 hours and is active for 16 to 24 hours(such as NPH insulin-isophane insulin), longer-actingbegins working within 1 to 2 hours and continues to be active for 24 hours(such as insulinglargine), ultra long ( degludec) Mono component insulin( High-purity insulin) , Combination insulin products( Includes a combination of either fast-acting or short-acting insulin with a longer acting insulin – The beginning of action we will see like rapid insulin, ex insulin aspart start acting after 5 min, but duration will be like insulin isophan12-14 hours)

Indication : Diabetes mellitus type 1(For basic treatment of diabetes mellitus, so to control the level of glucose, in this case we will use intermediate, long acting and super long acting insulins. Also we have to prescribe insulin to decrease prandial hyperglycemia(high level of glucose caused by meal).Corrective treatment, to correct high level of glucose quickly, here we will choose rapid and short acting insulins), diabetes mellitus type 2, gestational diabetes, and complications of diabetes such as diabeticketoacidosis and hyperosmolar hyperglycemic states

Side effect: Hypoglycemia.Allergicreaction.Insulinresistance.Cancause hypoglycemia until glycemic coma.Weight gain, increased mass of body.Allergicreaction,Insulinresistance,Lipodystrophy.

The route of administration commonly is subcutaneous injection, (to relieve emergency type we will give IV injections) mainly aesthetic problem, but to prevent this we can change the places of insulin injections.

54.Glucocorticoids. Classification. Therapeutic effects. Mechanisms of action. Clinical use. Side effects.

Feedback control : Corticotropin-releasing hormone –>  adrenocorticotropic hormone –> cortisol

Cortisol : the primary glucocorticoid. It’s the stress hormone. Uses glucogenesis to break down muscle and fat into glucose. Necessary to maintain critical processes in times of stress. Controls inflammation reactions. Metabolised in the liver by reduction and conjugation.

Effects : 

On protein– increases catabolism, decreases anabolism. Decreases utilization of amino acids.Reduces protein formation. Occurs everywhere except liver. Increases levels of amino acids in blood,they get transported more rapidly to liver, glucogenesis. Can cause osteoporosis.

On lipids – increases lipolysis. Mobilizes fatty acids and glycerol from adipose tissue. Used for glucogenesis. Causes redistribution of fat – fat in trunk areas and face. 

Carbs– increased blood glucose levels from amino acids and lipids. Increases enzymes in liver responsible for glucogenesis.

Electrolytes – aldosterone – like effect. Decreases Calcium ion absorption from intestine, increases its excretion from kidney,increases uric acid secretion.

Theyhave antinflammatory effect e.g by the inhibitory protein 1kb. Also inhibits neutrophil and macrophage function, inhibition of platelet activation factor, inhibition of nitric oxide reductase. Inhibits production of leukotrienes and prostaglandins by decreasing activity of the phospholipase A2 enzyme of the arachidonic acid pathway. Inhibits leukocyte adhesion. Blocks mast cell degranulation. Reduces eosinophil count. Blocks interleukin 2 production. Inhibits protein synthesis (decreases production of cytokines and inflammatory mediators). Decreases histamine release.Use : asthma, inflammatory bowe diseases. Immunosuppressant – autoimmune diseases e.g SLE .Also to prevent transplant rejection.Can also help treat cancers of white blood cells e.g leukemia, lymphoma.

Can also be used in adrenal insufficiency.

Cortisol deficiency – primary hypofunction and secondary.

Short acting preparations : cortisol, cortisone. T1/2 12h

Intermediate acting : prednisone, prednisolone,methylprednisolone,triamcinolone. T1/2 = 12-36h

Long acting :dexamethasone,betamethasone,paramethasone. T1/2>36h

Classification: -Natural 12 hours) Cortisone Hydrocortisone 

Synthetic –Non-halonized( 24 – 32 hours ) Prednisone,Prednisolone,Methylprednisolone

Halonized( 36 – 72 hours ) Triamcinolone,Dexamethasone,Flumethasone,Fluocinolone,Fluticasone,Beclamethazone,Betamethasone ,Budesonide,Momethazone.

Halonized is GCC with halogen(iodine, chloride, fluoride) → ↑ ability to penetrate cell membrane, → higher potency than non-halonized and natural, but side effects are more common, and have better clinical manifestation. Also → ↑ duration of action.

Adverse effects : hyperglycemia, high BP, truncal obesity, moon facies, abdonmialstriaeimmunosuppression,osteoporosis. Iatrogenic cushing’ssundromeOsteoporosis,myopathy. Behavioral toxicity : euphoria, psychomotor reactions, suicidal tendency.

60.Biosynthetic and semisynthetic penicillin. Classification. Mechanism of action. Spectrum of antimicrobial activity. Side effects. Comparative characteristic of drugs. 
Clinical use. Side effects.

Classification :

Natural penicillins (benzylpenicillin – sodium and potassium salts,phenoxymethylpenicillin,benzatinpenicillin). Small range of action. Sensitive to:Not producing beta-lactamase strains of Gram-positive and Gram-negative cocci – streptococci (beta-hemolytic and anaerobic strains), pneumococci, menigococcigonococci.Diphtheria pathogens (Corinebacteriumdiphteriae), syphilis ,most anaerobes (Clostridia spp., Peptostreptococcus spp., Fusobacterium spp., excluding Bacteroides fragilis).Low-sensitivity to:Gram-negative bacteria.

Benzylpenicillin – parenteral.Broken down by gastric juice.Contraindication of potassium salts in patients with chronic renal failure, cardial conduction disorders,hyperkaliemia.It’s eliminated by kidneys.Half life is short, it must be taken every 4 hours. In renal failure half life increases up to 30 hours.It is the drug of choice in treatment of a coccal (streptococcal, pneumococcal, meningococcal) infection.

Phenoxymethylpenicillin. acid-resistant (taken per os).Bioavailability is 60% since food decreases it.Spectrum is similar to that of benzylpenicillin.No high blood concentrations of the drug are reached. Intake of 0,5 g of phenoxymethylpenicillin per os is approximately equal to administration of 300 thousand U of benzylpenicillin by intramuscular route.Used in out-patient practice in treatment of mild infections of upper respiratory tract (tonsillitis, pharyngitis), and streptococcal anginas.

Benzatinpenicillin– prolonged form of penicillin.Administered by intramuscular route and slowly absorbed. Does not reach high blood concentrations, but is retained in the body for up to 4 weeks.Used in syphilis, gonorrhea, prevention of rheumatism and recurrent erysipelas.

The number of resistant pneumococci to penicillines is growing; resistant forms of gonococci are common.Formation of resistance is possible (beta-lactamases, modification of PBPs, efflux)

Semisynthetic penicillins.

Isoxazolilpenicillines (penicillinase stable ,antistaphylococcal): Methicillin and Oxacillin. Penicillinase-resistant, antistaphylococcalpenicillines.Acyl side-chain protects beta-lactam bond in molecule from destruction of staphylococci by beta-lactamases. Methicillin – high toxicity, forbidden for clinical use but used to define staphylococcal sensitivity.Oxacillin – spectrum is similar to that of natural penicillin, but yields the latter in activity by more than 20 times in regard to other coccal microorganisms. Used to treat infections, caused by penicillinase producing strains of staphylococci that are especially often occurs in hospitals (infections of skin, soft tissues, bones, joints, endocarditis, cerebral). Well absorbed when taken per os and by intramuscular route. Food significantly lowers absorption. Eliminated from the body with bile and urine. Can be used in renal failure because no delay in drug elimination is observed.

Aminopenicillinesampicillin,amoxicillin. Affect pathogens that are sensitive to natural penicillines plus enetrococci (!), some Gram negative bacteria (colon bacillus, Proteus, Salmonellae, Shigellae, hemophilic bacteria.Non-sensitive are pseudomonal bacillus, indole-positive strains of Proteus, KlebsiellaeSerracia, beta-lactamase producing strains of Gram-positive and Gram-negative cocci, destroying penicillin.Indications: community-acquired infections of the respiratory tract, infections of the urinary tract, infections of the CNS. Amoxicillin is more preferable than enteral formulations of ampicillin in the out-patient practice to treat infections of ENT-organs (sinusitis, otitis media), lower respiratory tract, urinary tract (cystitis, pyelonephritis, bacteriuria), eradication of Helicobacter pylori. Drug resistance to aminopenicillines has increased and in this case they must be used with inhibitors of beta lactamases (ampicillin+sulbactam or amoxicillin + clavulanic acid).

Carboxypenicillines (antipseudomonade): carbenicillin, ticracillin.

Ureidopenicillines (antipseudomonade): azlocillin, mezlocillin, piperacillin.

,inhibitors of beta lactamases, inhibitor-protected penicillins.

Side effects :

Allergic reactions,diarrhea,rashes.

61.Beta-lactam antibiotics. Classification. Cephalosporins. Mechanism of action. Spectrum of antimicrobial activity. Spectrum of cephalosporin I-V antimicrobial activity. Clinical effects. Side effects. Carbapenems and monobactams. Drugs. Features of antimicrobial spectrum. Indications.

Includes penicillins, cephalosporins, carbapenems and monobactams.


First generation : Parenteral – cefazolin,cefalotin, oral – cephalexin,cefadroxil

Second generation : parenteral – cefuroxime, cefamandol,cefoxitine. Oral – cefuroxime axetil,cefaclor.

Third generation : parenteral – cefotaxime, cephodisim,ceftriaxone,ceftadisime,cefoperazone. Oral – cefixime, ceftibuphen.

Fourth generation : cefpirome. Cefepime.

I GENERATION (CS-I): Active mostly against Gram (+) cocci (staphylococcus

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, pneumococcus, pyogenic streptococcus) and some Gram (-) bacteria (E. coli and hemophilic bacilli, Proteus) .Destroyed by beta-lactamases of Gram (-) bacteria. Do not affect enterococci, pseudomonal bacillus, anaerobes, intracellular microorganisms

II GENERATION (CS-II):As in CS-I generation + Gram (-) bacteria, producing beta-lactamases.Cefoxitin affects anaerobes

III GENERATION (CS-III):Wider range of action on Gram (-) flora, than that of cephalosporins of II generation .Though, their effect on Gram (+) flora is less effective (especially on staphylococci). Cefoperazone and ceftasidime affect pseudomonalbacillus .All drugs slightly affect enterococci

SULBACTAM/CEFOPERAZONE (Sulperazone) – has increased activity for pseudomonal bacillus and a number of other pathogens, producing beta-lactamases of extended range

IV GENERATION (CS-IV):I generation + III generation


Like CS-IV they readily penetrate through porins and reach high concentrations in the periplasmic space, providing the safety of the bactericidal effect.High affinity to several types of PBP, with which other beta-lactam antibiotics have a weaker interaction. It allows increasing efficiency of the drugs regarding the most resistant pathogens, including those resistant to cephalosporins.Have wider spectrum of antimicrobial activity among all beta-lactams. Optimal drugs for empirical monotherapy of severe hospital infections, including pathogens resistant to CS and fluoroquinolones.

They inckude : imipenem, meropenem,tienam.

Imipenem : Wide spectrum, powerful bactericide, resistant to beta-lactamase of Gram (-) bacteria, affect Pseudomonas aeruginosa, Serratia, Enterobacter, that are resistant to most beta-lactams.Broken down in the kidneys by dehydropeptidase-1 and used with its inhibitor – cilastanin in ratio of 1:1.

Imipenem/cilastatin (tienam) : Combination of impinem and dehydropeptidase I-cilastatin inhibitor, having pharmacokinetic properties similar to that of impinem, provides elimination of up to 70% of impinem in active form and significant improvement of its efficiency.

Meropenem : It is close to imipenem but is more resistant to renal dehydropeptidase and can be administered without cilastatin.It is less active regarding gram-positive cocci but more active for gram-negative pathogens.It is most active from all antipseudomonal antibiotics regarding P.aeruginosa and other unfermentingpathogens.It is resistant to renal dehydropeptidase, does not require combination with cilastatin.It is best tolerated, has lower nephrotoxicity, causes no seizures (can be used in meningitises).

Monobactams : Synthetic beta-lactams with monocyclic lactam system and high bactericidal activity. Resistant to beta lactamases.

Aztreonam (azactam) : Highly efficient against pseudomonal bacillus (Affect hospital strains that are resistant to aminoglycosides, penicillines , CS-III) and enterobacteria,but broken down by beta-lactamases of gram-positive and anaerobic pathogens (staphylococci, streptococci, pneumococci, bacteroids), most strains resistant to the drug.

Distributed well in the body, entering most organs, tissues and media. In inflammation of the arachnoid membranes it crosses the blood-brain barrier rather well. As most beta-lactam antibiotics the drug has not long half life time (1.5–2 h) and it is rather intensively eliminated by the kidneys and does not undergo hepatic metabolism.

It is used in severe bacterial infections caused by Gram (-) pathogens:Infections of the urinary tract,infections of the lower respiratory tract and ENT-organs,infections of the abdominal cavity and small pelvis organs,infections of the skin, soft tissues, bones and joints,antibiotic prevention of surgical infections.It is administered by intravenous route 1–2 g each 6–8 h.

62.Macrolides and azalides. Classification. Spectrum and mechanism of action. Indications. Side effects.

Macrolides and Azalides-

Chemical characteristics- these agents contain macrolide lactone ring, and this is the main functional structure.

Classification- we can classify macrolides according to atoms (members)-

*macrolides having 14 atoms (members): they are divided into- Natural: erythromycin

Semisynthetic: clarithromycin,


*macrolides having 15 atoms (members): azithromycin (15 membered AZALIDE)

*macrolides having 16 atoms (members): spiramycindrosomycin

MOA- macrolides bind to 50S subunit of the ribosome, and thus inhibiting protein synthesis in bacteria.

ToA– bacteriostatic

SOA- macrolides have wide SOA, but these agents are more potent against G(+) bacteria, but they also effective against others, including- G(+/-) cocci and bacilli, and also they are effective against Helicobacter pylori.

For treatment of helicobacter pylori (causing peptic ulcer) we use combination of drugs, the treatment can include 3 drugs or 4 drugs, for example-

=>3 drugs: amoxicillin + clarithromycin + omeprazole (to decrease acidity in stomach)

=>4 drugs: amoxicillin + clarithromycin + omeprazole + DE-NOL

(DE-NOL : bismuth subcitrate. This drug belongs to non-organic astrogens, this agent is included in the treatment of peptic ulcer because this agent has antimicrobial activity against helicobacter pylori.)

Pharmacokinetics characteristics- these agents, macrolides, are well absorbed in GIT, so they have high Bioavailability. These agents accumulate in human body especially in- liver, lungs (parenchymal organs), and this accumulation in these organs leads to specific effect, which is called- post antibacterial effect, this means that upon accumulation of the antibiotic in these organs, this leads to increased concentration of drug in these organs, and so this leads to prolongation of the antimicrobial action of macrolides. Carbapenems have the same effect.

(so any drug which has good bioavailability and can be stored in parenchymal organs, produces – post antibacterial or post antibiotic effect, this means that when we stop the usage of the drug, the antimicrobial effect will continue)

Another factor which explains why we will see post-antibacterial effect is- due to half-life of drug, for example- erythromycin: half-life is about 2 hours, while azithromycin: has very long half-life about 96 hours. And so because of long half-life, this leads to long post antibacterial effect.

Which drug from macrolides have the most potent antibacterial effect?Azithromycin, but some authors say that: spiramycin

#one more specific action of macrolides and azalides-

These agents also are agonists (can stimulate) for specific type of receptors, and these receptors are: motilin receptors, these receptors regulate peristalsis of intestine in human body, and macrolides are agonists for motilin receptors. (motilin is the ligand for motilin receptors)

*the most potent agonist for motilin receptors is- erythromycin. Second potent is- azithromycin

So these agents (macrolides), beside potent antimicrobial activity, produce or can increase intestinal peristalsis. Motilin can also increase the release of pepsinogen and also can stimulate beta-cells of pancreas to release insulin.

-indications of macrolides- *peptic ulcer

*macrolides are alternative group in case of hypersensitivity to penicillins and cephalosporins, this means that we can prescribe them for- respiratory tract infections, urinary tract infection, GIT infection, skin infection and others.

*azithromycin: due to long half-life of this drug, we can give this agent only for 3 days course of treatment. (in general is for- 1-2 weeks in case of acute infection)

-toxicity and SE-

*macrolides and azalides are well-tolerated, so they are not toxic agents.

*macrolides and azalides can cause-hypersensitivity (allergic reactions)



another specific side effect: these agents are contraindicated, so we don’t prescribe these agents together with antiarrhythmics because these agents (macrolides) prolong QT-interval in ECG, and also antiarrhythmic drugs prolong QT-interval.

Weak hepatotoxicity: manifests by cholestatic jaundice

Weak nephrotoxicity

Which drugs we can give during pregnancy? (according to toxicity)

We can prescribe- penicillins (not toxic agents), cephalosporins and macrolides.

Macrolide is first line of choice for pregnant woman.

63.Aminoglycosides. Classification. Spectrum and mechanism of drugs. Side effects.

Aminoglycosides :

First generation : neomycin sulphate (mixture of sulphates of neomycins A,B,C. Kanamycin.

Second generation : gentamicin sulphate, tobramycin, sisomycinsulphate.

Third generation :amicacinesulphate, netilmicin.

Mechanism of action : penetrate inside a microbial cell by passive diffusion and active transport (more) that occurs only in aerobic conditions. That is why they are inactive against anaerobes. Passive diffusion increases when the cell wall synthesis is disordered, which explains synergism with beta-lactams. They break the process of translation, protein synthesis of a microbial cell on the initial stages. Binding site – 30S subunit of ribosomes. Consequence of amino acids inclusion is broken – unusual non-vital protein.

Spectrum: wide. Bactericides. Effect is increased by agents that break the cell wall synthesis

Sensitive: Gram (+) aerobes and part of Gram (+) pathogens. Enterobacteria (E. coli, Proteus spp., Klebsiella spp., Enterobacter spp., Serratia spp.). Mycobacteria tuberculosis (streptomycin, kanamycin, amicacin).Non-sensitive to anaerobes (bacteroids, clostridia).

Resistance: Pathogens produce enzymes (amicacin was created as non-sensitive substrate for resistance enzymes).Penetration failure (it is overcome by combined administration with penicillin and vancomycin).

I generation: Aminoglycosides of I generation are not implemented practically due to marked oto– and nephrotoxicity. Moreover, they do not affect such actual pathogens as pseudomonal bacillus, Acinetobacter.Streptomycin and kanamycin can be used as anti-tuberculosis drugs in combination with other tuberculostatics.

Difference between second and first generation :

Higher activity against the Enterobacteriacеae family, including (theoretically) against pseudomonal bacillus, against staphylococci. Also do not have effect on streptococci (including pneumococci, beta-hemolytic streptococcus etc.) and anaerobes. Unlike the I generation they do not affect mycobacteria of tuberculosis. Significantly less toxic.

Side effects : Ototoxicity (neomycin, amicacin) and vestibulotoxicity (streptomycin, gentamicin).For a long-term therapy netimycin is preferable.Do not combine with other ototoxic drugs (for example, loop diuretics) .Nephrotoxicity.Neuromuscular blockade : Inhibition of calcium uptake by nerve endings and release of acetylcholine.Detected in myasthenia and in combination with muscle relaxants and general anesthetics.

64.Tetracyclines, glycylcyclines and chloramphenicols. Spectrum and mechanism of drugs. Indications. Side effects.


For Tetracycline:

Natural:Tetracycline,Chlortetracycline,Oxytetracycline.(notusenow). Synthetic:Doxycycline,Methacycline,Minocycline

Spectrum:Broad-spectrum.Forrickettsia,Various G+,G-(+ more effective than -). Chlamydia,  MycoplasmaSpirochaeta.

Mechanism of action: Tetracyclines enter the microorganisms in part by passive diffusion and in part by active transport.Once inside the cell,they bind 30s ribosome of bacteria,blocking the binding of aminoacyl-tRNA to the acceptor site lead to inhibit peptide growth and protein synthesis.

Indications: Rickettsia infection:Rocky Mountain Fever,Typhoidfever.Chlamydiaeinfection:Chlamydialpneumonia,.Trachoma.First choice Doxycycline.

Mycoplasma infection:Mycoplasmalpneumonia,also first choice Doxycycline.Spirochetalinfection:Relapsing Fever(caused by Borrelia Recurrentis),FC:same.Bacterialinfection:Before used for Cholera.Nowcan used for some skin infections such as Rosacea.Tigecycline is approved for treatment of skin and skin-structure infections which caused by methicillin-resistance Staphylococcus aureus.And intra-abdominal infections caused by Escherichia Coli, and acquired bacterial pneumonia.

Side effects:Gastrointestinaleffects:Nausea,Vomiting and Diarrhea.Bone Structures and Teeth:When Tetracycline is given to pregnant woman,itcan be deposited in the fetal teeth,leading to fluorescence,discoloration and enamel dysphasia.it also can be deposited in bone lead to deformity or growth inhibition.These effects also can influence children who are younger than 8 years old.OtherToxicities:impair hepatic function and toxicity of kidney.


MOA : the same as tetracyclines.It has wide SOA. Same indications as tetracyclines.Tigecycline is used against MRSA, but not active against pseudomonas aeruginosa,so tigecycline is used in case if the bacteria have resistance to tetracyclines


1.chloramphenicol (levomycetin)

2.DL-chloramphenicol (sentomycin)

Chloramphenicols are not useful agents because they are highly toxic, these agents stand for third line of choice.

MOA :Chloramphenicols bind to 50S subunit of ribosomes, and this will inhibit the ribosomes, thus decreasing the synthesis of proteins in MOs.They are bacteriostaticantibiotics.The same spectrum as tetracyclines.

Indication : also the same as tetracyclines. But if we have to choose between tetracycline and chloramphenicol for typhus, then we will choose- chloramphenicols.

Chloramphenicol also can be as ointment. Also used for skin infections.

SE :Chloramphenicols are highly toxic agents, and this is because very often cause hematotoxicity which manifests by bone marrow suppression, resulting in- thrombocytopenia, agranulocytosis, leukopenia, anemia etc. also teratogenic side effect. And also gray-baby syndrome, so it is contraindicated for newborns. Gray-baby because this agent results in cyanosis and respiratory problems, asphyxia, problems with cardiovascular system.

Tetracyclines and chloramphenicol have one more side effect- teratogenic, due to this they can cause problems in fetus. So these agents are contraindicated for pregnant women.

65.Lincosamides and cyclic (polymyxins, bacitracin, gramicidin). Spectrum and mechanism of drugs. Indications. Side effects.

Lincosamides are a class of antibiotics which include lincomycin, clindamycin.

Spectrum:Broad-spectrum.They mainly against G+,G- anaerobes,but aerobes also.

Mechanism of action: Lincosamides prevent bacteria replicating by interfering with the synthesis of proteins. They bind to the 23s portion of the 50S subunit of bacterial ribosomes and cause premature dissociation of the peptidyl-tRNA from the ribosome.

Clindamycin is a derivative of lincomycin and it is more potent and less toxic than lincomycin.

Indications:Clindamycin is used primarily to treat anaerobic infections caused by susceptible anaerobic bacteria, including dental infections, and infections of the respiratory tract, skin, and soft tissue, and peritonitis. In people with hypersensitivity to penicillins, clindamycin may be used to treat infections caused by susceptible aerobic bacteria, as well. It is also used to treat bone and joint infections, particularly those caused by Staphylococcus aureus.Clindamycin sometimes in combination with an aminoglycoside or cephalosporin,is used to treat penetrating wounds of the abdomen and the gut.Infections originating in the female genital tract,eg,septicabortion,pelvicabscesses,or pelvic inflammatory diseases.and lung abscess.

Side effects:Common side effects are diarrhea,nausea,and skin rashes.Impaired liver function and neutropenia sometimes occur.

Bacitracin is a complex labile polypeptide produced by Bacillus subtilis. It inhibits peptidoglycan synthesis during the second step of bacterial cell wall synthesis by interfering with the activity of phosphorylase and is bactericidal.

Bacitracin has activity against gram-positive bacteria and is often combined with antibiotics that have gram-negative spectrum of activity (such as polymyxin B, neomycin, or both). Bacitracin is not absorbed orally; systemic usage is associated with the development of nephrotoxicity in addition to pain, induration, and petechiae at the site of injection. As a result, bacitracin is most commonly applied topically in ointments.


The polymyxin antibiotic colistin E is used for the treatment of serious Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.

Gramicidin is particularly effective against gram-positive bacteria. Because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. Gramicidin D binds to and inserts itself into bacterial membranes (with a strong preference to gram-positive cell membranes). This results in membrane disruption and permeabilization

66.Fluoroquinolones. Classification. Comparative characteristic of different generations. Clinical use. Side effects.

Classification: there are 4 gens:

1st gen is quinolones: nalidixic acid, pipemidic acid, oxolinic acid

2nd gen is fluoroquinolones: ciprofloxacin, norfloxacin, ofloxacin

3rd gen: levofloxacin, sparfloxacin

4th gen: moxifloxacin, gatifloxacingemifloxacin

MOA-the mechanism is different for G(-) and G(+) bacteria.ForG(-) bacteria: these agents inhibit activity of DNA-gyrase.ForG(+) bacteria: these agents inhibit the activity of- topoisomerase-4.Bactericidal.


1st gen (quinolones): it has narrow SOA, it is used against (which bacteria)- G(-) bacteria

2nd gen (fluoroquinolones): it has kinda wide-SOA , it is used against: G(+) and some G(-) and aerobes and some atypical bacteria. So starting from second gen, we can give fluoroquinolones for tuberculosis for example (atypical bacterial infection).

3rd gen: it has wide SOA, it is highly active and used against- G(+), and G(-). Especially used against: streptococcus pneumonia (pneumococci), and staphylococci.

4th gen: it has wide SOA, it is used against- G(+), G(-), and anaerobes (so the same SOA as 3rd gen, but plus (+) anaerobes)

=>so activity against G(-) bacteria is the same for any gen, while activity against G(+) bacteria widens from 2nd to 4th gen.

SE and toxicity – dyspepsia: fluoroquinolones can cause dyspeptic reactions like- vomiting, discomfort in stomach, pain in abdomen, nausea etc.allergicreactions.Central nervous system side effect- sleeplessness, headache, dizziness.Photodermatoses (or photosensitivity reactions, skin reactions).Cardio-toxicity- these are arrhythmogenicagents.Myalgia (pain in muscles)- especially in old patients.Arthralgia (pain in joints)- especially in old patients

67.Sulfonamides. Classification. Spectrum and mechanism of drugs. Comparative characteristic. Clinical use. Side effects and their prevention.

4 Groups-

1.drugs with resorptive action: classified according duration of action.

*Short acting (6-8 hours)- etoxazole, sulfadiazine, urosulfan

*long acting (18-24 hours)- sulfadimethoxinesulfamonomethoxine

*ultra-long acting (over 48 hours)- sulfalenesulfatonum

2.drugs acting on GIT (poor absorbed sulfonamides): phthalylsulfathiazole (phthalazole), sulgin

3.combined preparations: A.combined with 5-aminosalicylic acid: sulfasalazine .B.combined with trimethoprim: co-trimoxazole (biseptol, Bactrim)

4.locally acting (topically) sulfonamides: Sulfanilamide (streptocide).Sulfathiazole silver -(ointment).Sulfadiazine silver -(ointment).Sulfacetamide (sulfacyl-sodium)- (eye-drop).Ingalipt (aerosol or spray)

Right now sulfonamides are not used, because we have antibiotics, and also because sulfonamides are highly toxic agents. Just topically acting (locally) sulfonamides are useful.

MOA :These agents inhibit the synthesis of FA. The synthesis of FA starts from para aminobenzoic acid (paba).Paba —-(folate synthase)———-> dihydropteroic acid ———————> dihydrofolic acid ——-(folate reductase)———> tetrahydrofolic acid

So sulfonamides are chemically similar to natural PABA, due to this the MOA is competitive antagonism with PABA, so MOs to synthesize new molecular of PABA, they will use sulfonamides, and this will lead to inhibition activity of- folate synthase. So sulfonamides are competitive antagonists for PABA, and this inhibits folate synthase and this leads to stop and blockage first step of FA synthesize.It’sbacteriostatic

Combination with trimethoprim- It’s: sulfamethoxazole + trimethoprim (this combination is called- co-trimoxazole).MOA:sulfamethoxazole will produce the same MOA as sulfonamides (which is mentioned above), while trimethoprim inhibit the activity of enzyme: folate reductase. So this leads to inhibit second step of FA synthesize, so inhibits the conversion of dihydrofolic acid to tetrahydrofolic acid. So co-trimoxazole has two mechanisms of actions, it blocks both steps of FA synthesize, and this leads to bactericidal effect. 

SOA :Sulfonamides have wide SOA, they are used against: G(+), G(-), and also against ACTINOMYCETES, and against PROTOZOA, including: PLASMODIUM MALARIA, and other PLASMODIUM SPP.

Co-trimoxazole: this combination has wider SOA than sulfonamides, and this is due to additional trimethoprim, because trimethoprim alone as mono-drug also has antimicrobial activity.

Toxicity : sulfonamides are highly toxic agents and also co-trimoxazole is highly toxic.

SEofsulfonamides-nephrotoxicity,neurotoxicity,hepatotoxicity,allergic reaction,dyspepsia,dysbacteriosis,hematotoxicity,hypovitaminosis,sulfonamides cause bone marrow suppression: which manifests by- anemia, thrombocytopenia, leukopenia etc.

Pharmacokinetics characteristics-

Resorptive sulfonamides are well-absorbed, but other sulfonamide drugs are badly absorbed, so badly absorbed agents can accumulate in the intestine, that’s why these poorly absorbed subgroups of sulfonamides are drugs from first line of choice for GIT infection. While resorptive are used for systemic infections.

These agents are metabolized in the liver, and after metabolism it will produce: acetylic metabolites, some of these acetylic metabolites can cause- crystalluria, and these acetylic metabolites which can cause crystalluria are-cristallin. And this is cause nephrotoxicity.

Nephrotoxicity:These agents are metabolized in the liver, and after metabolism it will produce: acetylic metabolites, some of these acetylic metabolites can cause- crystalluria, and these acetylic metabolites which can cause crystalluria are-cristallin.

Another characteristics of these agents-toxicity-As we know FA takes place in synthesis of vitamins in human body, and also synthesize of DNA and also takes place in synthesis of new hematological cells.So due to this, these agents can block the synthesis of FA in MOs and also in human cells, and this can lead to toxicity.

We should not combine sulfonamides with PABA of local anesthetics, these are: procaine, benzocaine, novocaine. And this is because sulfonamide will compete with local anesthetics for PABA.

Sulfonamides also can cause hypovitaminosis of: vitamin b12, vitamin B and vitamin C. deficiency of these vitamins leads to- folic deficiency anemia and B12 deficiency anemia

68.Antibacterial drugs: nonfluor quinolone derivatives, derivatives of oxiquinolone, nitrofuran and quinoxaline. Mechanism of action. Clinical use. Side effects.

Non-fluorinated quinolone derivates: Cinoxacin, Nalidixic acid ,Pipemidic acid ,Piromidic acid, Rosoxacin

Cinoxacin : spectrum of activity: Gram-negative aerobes:Enterobacter species, Escherichia coli, Klebsiella species, Proteus mirabilis, Proteus vulgaris. Enterococcus species, Pseudomonas species, and Staphylococcus species are resistant. Indication use: Urinary tract infections side effect: gastrointestinal system and the central nervous system.nausea, vomiting, diarrhea, headache, dizziness, nervousness, and insomnia drug interaction : deflazacort, dexamethasone ,betamethasone :tendinitis and tendon rupture

Nalidixic acid: spectrum: Aeromonashydrophila, Clostridium and Haemophilus are generally susceptible to nalidixic acid, while other bacteria such as Bifidobacteria, Lactobacillus, Pseudomonas and Staphylococcus are resistant indication use:For the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species. Side effect: rash, itchy skin, blurred or double vision, halos around lights, changes in color vision, nausea, vomiting, and diarrhea. Nalidixic acid may also cause convulsions and hyperglycaemia, photosensitivity reactions, and sometimes haemolyticanaemia, thrombocytopenia or leukopenia.

Nitrofuran :Furazolidone,Nifurfoline,Nifuroxazide,Nifurquinazol,Nifurtoinol,Nifurzide,Nitrofural (also known as nitrofurazone),Nitrofurantoin,Ranbezolid

Nitrofurantoin: mechanism of action:The drug works by damaging bacterial DNA, since its reduced form is highly reactive.

Spectrum :Most Gram-positive bacteria and negative bacteria have inhibitory or bactericidal effect, but not sensitive with Pseudomonas aeruginosa and Proteus species

Indication for use: For Escherichia coli, enterococci, staphylococcal-induced urinary tract infections e.g Pyelonephritis, cystitis, prostatitis etc

Side effect: most common side effects with nitrofurantoin are nausea, headache, and less common include diarrhea, dyspepsia, abdominal pain, constipation, emesis, dizziness, drowsiness, fever, acute pulmonary hypersensitivity reaction

No drug interaction

Furazalidone : indication use: treat diarrhoea and enteritis caused by bacteria or protozoan infections Mechanism of action :work by crosslinking of DNA

Other is same with nitrofurantoin.

Quinoxaline derivatives: Echinomycin is a peptide antibiotic. It intercalates into DNA at two specific sites, thereby blocking the binding of hypoxia inducible factor 1 alpha.

69.Antifungal agents. Classification. The management of candidiasis. Clinical use. Side effects.

Classification :1.antibiotic: polyenes( amphotericin B, nystatin) non-polyenes( griseofulvin)

2. azole: imidazole( ketoconazole, miconazole, clotrimazole, bifonazole,) triazole (itraconazole, fluconazole, voriconazole)

3.allylamine( naftifine, terbinafine)


polyenes: amphottericin B: Indication use: Intravenous infusion is used to treat deep fungal infections. For fungal meningitis, also need intrathecal injection. Oral use only for intestinal infections. Topical application to the skin, nails, mucosal fungal infections

Side effect: high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea, drowsiness, and generalized weakness. hypokalemia and hypomagnesemia ,Liver and kidney dysfunction

Spectrum :Antibacterial activity to all fungi, Cryptococcus neoformans, Candida albicansBlastomyces, Histoplasma capsulatum, spores filament bacteria have a strong antibacterial effect

Mechanism action:Binds to ergosterol in the cell membrane, altering membrane permeability, extravasation of small molecules and electrolytes, leading to fungal death or cessation of growth

nystatin: Indication use: skin ,mucosal fungal infection side effect:Temporary nausea, vomiting, loss of appetite, diarrhea

Non-polyenes: griseofulvin indication use: only for dermatophytosis.forcases with nail, hair, or large body surface involvement side effect : allergic reactions, nausea, diarrhea, headache, trouble sleeping, and feeling tired, rash,Leukopenia Mechanism action:The drug binds to tubulin, interfering with microtubule function, thus inhibiting mitosis.It binds to keratin in keratin precursor cells and makes them resistant to fungal infections.

Spectrum :EpidermophytonPachysin, and genus Mucor

Azole: imidazole: ketoconazole :indicationuse:Deep, subcutaneous and superficial fungal infections side effect: Nausea, vomiting, rash, dizziness, drowsiness, photophobia, occasional liver toxicity, very few endocrine abnormalities

Miconazole : indication use: Vaginal, skin, nail fungal infections No obviously side effect(Skin and mucous membrane is not easy to absorb)

Bifonazole: indication use:Dermatophytes infection side effect:Contact dermatitis, one-time slight reddening of the skin, burning, peeling, cracking

Triazole : itraconazole: indication use: Deep, subcutaneous and superficial fungal infections ,and for rare fungi infection such as histoplasmosis and blastomycosis infections

Side effect: Gastrointestinal reactions, headache, dizziness, hypokalemia, hypertension, edema, pruritus

Mechanism action: Interfere with ergosterol synthesis, damage cell membranes, increase permeability, inhibit fungal growth, or kill fungi

Allylamine : terbinafine : indication use: Onychomycosis and other superficial fungal infections

Side effect: Gastrointestinal reactions Mechanism action: inhibits ergosterol synthesis by inhibiting squalene epoxidase,change cell membrane permeability, causing fungal cell lysis

Spectrum : Aspergillus, Fusarium and other filamentous fungi have antibacterial activity

pyrimidine :flucytosine: indication use:serious infections caused by susceptible strains of Candida or Cryptococcus neoformans. Side effect:Nausea, vomiting, diarrhea, rashes, fever, elevated transaminases, jaundice, thrombocytopenia, elevated urinary nitrogen

Septum :Cryptococcus, Candida and coloration mold

Mechanism :converted into the cytostatic fluorouracil , disturbing the building of certain essential proteins.

72.Antiviral effects. Classification. Antiherpetic and anti-flu agents. Mechanisms of action. Clinical use. Side effects.


Antiretroviral agents: NRITs: zidovudine ,didanosine, stavudine, zalcitadine,

NNRTIs: nevirapine , efavirenz, delavirdine

Protease inhibitors: saquinavir, indinavir, atazanavir, atazanavir

Antiinflunza agents: amantadine, oseltamivir, rimantadine

Antiherpes agents: aciclovir , valacyclovir, idoxuridine

Aciclovir : indication of use: HSV infection, topical treatment of herpes keratitis, herpes simplex, herpes zoster. Oral or injection, herpes simplex encephalitis, genital herpes, herpes simplex infection for immunodeficiency patients

Mechanism: Inhibition of the virus DNA polymerase, blocking viral DNA synthesis

Side effect :Gastrointestinal disorders, headache, rash. Intravenous injection: phlebitis, reversible renal dysfunction

valacyclovir : indication of use: Primary or recurrent genital herpes, zoster herpes and frequent genital herpes mechanism:Inhibition of the virus DNA polymerase, blocking viral DNA synthesis

Side effect:Nausea, diarrhea, headache

idoxuridine : indication of use: Eye or cutaneous herpesvirus infections, vaccinia virus infections, acute epidemic herpetic keratitis mechanism:Competitive inhibition of thymidylate synthase, DNA synthesis blocked

Side effect: Common side effects of the eye drops include irritation, blurred vision and photophobia.[5] Corneal clouding and damage of the corneal epithelium may also occur

Antiinflunza agents: rimantadine, oseltamivir,amantadine

rimantadine: indication use: Prevention of influenza A virus infection Mechanism : preventing the uncoating of the virus’s protective shells, which are the envelope and capsid,and block transfer of viral nucleic acids to host cells side effect : gastrointestinal and central nervous system adverseeffects:nausea,upset stomach, nervousness, tiredness ,lightheadedness, trouble sleeping ,difficulty concentrating oseltamivir: indication use: prevention and treatment of influenza caused by influenza A and B viruses 

Mechanism :competitive inhibitor of influenza´s neuraminidase enzyme side effect: nausea and vomiting