PHL- 210

Types of Nervous System

Some anatomic and neurotransmitter features of peripheral nervous system

Efferent nerves of the peripheral nervous system

The major components of the central and peripheral nervous systems and their functional relationships. Stimuli from the

environment convey information to processing circuits within the brain and spinal cord, which in turn interpret their significance and

send signals to peripheral effectors that move the body and adjust the workings of its internal organs.

Drugs Affecting Motor Function

Mechanisms for influencing skeletal muscle tone.

Inhibition of neuromuscular transmission and electromechanical coupling

A. Drugs Acting on Motor Systems: Muscle Relaxants1. Non-depolarizing muscle relaxants (competitive antagonist)d-tubocurarine

Semi-synthetic compound. Only I.V. Competitive antagonist towards

Ach on nicotinic receptors. Onset: about 4 min. Duration: about 30 min. Antidote: acetylcholinesterase

inhibitor. Adverse effects: bronchospasm,

urticaria and hypotension.Pancuronium Synthetic compound. 5-fold more potent than d-

tubocurarine, with somewhat longer duration of action.

Not likely to cause bronchospasm, urticaria and hypotension.

Adverse effects: increased heart rate and blood pressure

Newer compounds are vecuronium, pipecuronium, alcuronium, gallamine, mivacurium, and atracurium.

2. Depolarizing muscle relaxants (agonists)

Succinylcholine (suxamethonium) Double ACh molecule. Only I.V. Synthetic compound. Agonist at endplate nicotinic

cholinoceptors, but it produces muscle relaxation due to the persistent depolarization of the endplate and adjoining membrane regions.

Duration: about 10 min. Adverse effects: hyperkalemia

(risk of cardiac arrhythmias). Prolonged muscle relaxation and apnea in patients with a genetic deficiency in pseudocholinesterase.

Used at the start of anesthesia to facilitate intubation of the patient.

Antidote: no specific antidote but the transient bradycardia can be treated by atropine. Moreover, artificial respiration, and oxygen must be readily available .

B. Drugs Acting on the Parasympathetic Nervous System

Responses to activation of the parasympathetic:

Activation of ocular parasympathetic fibers (miosis and

accommodation of near vision). ↑ Secretion of saliva and intestinal

fluids (promotes digestion of foodstuffs; transport of intestinal

contents). Allowing a decreased tidal volume

(↑ bronchomotor tone) and ↓ cardiac activity.

Wall tension is ↑ by detrusor activation with a concurrent

relaxation of sphincter tonus (micturition).

Acetyl-choline (ACh) as a transmitter: (release, effects, and degradation )

B. Drugs Acting on the Parasympathetic Nervous System During activation of the nerve membrane, Ca2+ is

thought to enter the axoplasm and to activate

protein kinases. As a result, vesicles discharge their

contents into the synaptic gap.

At the postsynaptic effector cell membrane, ACh reacts with M1 receptors on nerve

cells, e.g., in ganglia. M2 receptors mediate Ach

effects on the heart. M3 receptors mediate Ach

effects on gut and bronchi and glandular epithelia.

Released ACh is rapidly hydrolyzed and inactivated by a specific Ach-esterase, present on pre- and post-junctional membranes, or

by a less specific serum cholinesterase, a soluble enzyme present in serum

and interstitial fluid.

B. Drugs Acting on the Parasympathetic Nervous System1. Parasympathomimetics

ACh is too rapidly hydrolyzed and inactivated by AChE to be of any

therapeutic use; however, its action can be mimicked by other substances,

namely 1. Direct Parasympathomimetics as Carbachol, methacholine,

bethanechol, Pilocarpine and Arecoline (refreshing & mild stim.

betel chewing).2. Indirect Parasympathomimetics as

Esters of carbamic acid (carbamates such as physostigmine and

neostigmine) and Phosphoric acid (organophosphates such as paraoxon,

echothiophate and parathion. The rate-limiting step in ACh hydrolysis is

deacetylation of the enzyme, which takes only milliseconds, thus

permitting a high turnover rate and activity of AChE. De-carbaminoyl-ation

following hydrolysis of carbamates takes hours to days, the enzyme

remaining inhibited as long as it is carbaminoylated. Cleavage of the

phosphate residue, i.e. de-phosphoryl-ation, is practically impossible;

enzyme inhibition is irreversible.

Pilocarpine

Uses of parasympathomimetics In postoperative atonia of the bowel or bladder

(neostigmine). In myasthenia gravis to overcome the relative ACh-deficiency

at the motor endplate In de-curarization before discontinuation of anesthesia to

reverse the neuromuscular blockade caused by non-depolarizing muscle relaxants.

As antidote in poisoning with parasympatholytic drugs because it has access to AChE in the brain (physostigmine).

In the treatment of glaucoma (neostigmine, pyridostigmine, physostigmine pilocarpine paraoxon and ecothiopate):

however, their long-term use leads to cataract formation. Insecticides (parathion). Although they possess high acute

toxicity in humans, they are more rapidly degraded than is the insecticide DDT following their emission into the

environment. Tacrine (Cognex) is not an ester and interferes only with the

choline-binding site of AChE. It is effective in alleviating symptoms of dementia in some subtypes of Alzheimer’s

disease. Donepezil (Aricept), galantamine, and rivastigmine (Exelon) are newer, more selective.

B. Drugs Acting on the Parasympathetic Nervous System1. Parasympatho-mimetics

B. Drugs Acting on the Parasympathetic Nervous System2. Parasympatho-lytics

Parasympathomimetics are substances acting agonistically at the M cholinoceptor (blue arrows).

Parasympatholytics are substances acting antagonistically at the M

cholinoceptor (shown in red in the panels).

Effects of parasympathetic stimulation (blue arrow) and blockade (red)

Uses of parasympatholytics:Atropine; is used to prevent cardiac arrest and as a preanesthetic medication to prevents a possible hypersecretion of bronchial mucus, which cannot be expectorated by coughing during anesthesia.Homatropine; is used as mydriatics (for diagnostic use).Benzatropine; is used in treatment of Parkinson’s disease.Pirenzepine; is used in treatment of gastric and duodenal ulcers.Ipratropium; is used in treatment of bronchial asthma, bradycardia and heart block.N-butylscopolamine; is used in treatment of biliary & renal colic.Scopolamine; is used in treatment of motion sickness.Contraindications for parasympatholytics: Glaucoma and Prostatic hypertrophy with impaired micturition. Atropine poisoning: Peripheral (tachycardia; dry mouth; hyperthermia, flashing and constipation) and Central ( restlessness, agitation, psychic disturbances and hallucinations) effects.Treatment of Atropine poisoning, general measures (gastric lavage, cooling with ice water) or therapy with indirect parasympathomimetic as physostigmine.

B. Drugs Acting on the Parasympathetic Nervous System2. Parasympatholytics ((Atropine-like drugs))

C. Drugs Acting on the Sympathetic Nervous System

Responses to sympathetic activation CNS Eye Saliva Bronchi Sweat glands Heart Liver Intestinal tract Bladder Skeletal muscle

C. Drugs Acting on the Sympathetic Nervous System

Sympathetic Transmitter nor-epinephrine (NE also called nor-adrenaline)

Synthesis of nor-epinephrine

Releases of nor-epinephrine

Fate of nor-epinephrine

1. Neuronal re-uptake2. Inactivated by MAO3. Inactivated by COMT

C. Drugs Acting on the Sympathetic Nervous System1. Sympathomimetics

Adrenoceptors (adrenergic receptors)

Receptors

Organs

α1 Smooth muscle (blood vessels, lung, intestine, bladder, ,,,,,,,,,,,,

α2 Pre-synaptic adrenergic nerve terminals, platelets, lipocytes, smooth muscle

β1 Heart, lipocytes, brain β2 Smooth muscle and cardiac muscle

Sympathomimetics (i.e., adrenoceptor agonists)

Direct-acting sympathomimetics ReceptorsEpinephrine (Adrenaline) α1, α2, β1, β2

Norepinephrine (Noradrenaline) α1, α2 > β1, β2Isoproterenol β1 and β2

Phenylephrine α1 Dobutamine β1 Salbutamol β2

Indirect-acting sympathomimetics

Cocaine inhibit NE re-uptake α and βEphedrine facilitate NE releases α and β

Amphetamine All the above + slow breakdown by MAO

α and β

Clinical uses of adrenoceptor agonists1. Cardiovascular system cardiac arrest as adrenaline cardiogenic shock as dobutamine heart block as isoprenaline, which can be used temporarily while

electrical pacing is being arranged.

2. Anaphylactic shock (acute hypersensitivity): adrenaline is the first-line treatment

3. Respiratory system (asthma): selective β2-receptor agonists (salbutamol, formoterol)

4. Nasal decongestion: drops containing phenylephrine, oxymetazoline or ephedrine reduces mucosal blood flow and, hence, capillary pressure. Fluid exuded into the interstitial space is drained through the veins, thus shrinking the nasal mucosa. Due to the reduced supply of fluid, secretion of nasal mucus decreases.

5. Miscellaneous indications Adrenaline can be used to prolong local anaesthetic action by

delaying the removal of local anesthetic. Inhibition of premature labour (salbutamol) α2-agonists as clonidine used in hypertension, menopausal

flushing, lowering intraocular pressure and migraine prophylaxis.

C. Drugs Acting on the Sympathetic Nervous System1. Sympathomimetics

Sympatholytics (Sympathatic blockers)1. α-Sympatholytics (α-blockers) non-selective (blocks both post-synaptic and pre-synaptic α-

adrenoceptors) as phentolamine. selective α1-blockers as prazosin and terazosin. α-blockers are used in treatment of hypertension and in benign

hyperplasia of the prostate. side effects of α-blockers are postural hypotension.

2. β-Sympatholytics (β-Blockers) non-selective as propranolol. selective β1-receptors as metoprolol, acebutolol, bisoprolol. β-blockers are used in treatment of angina pectoris, tachycardia,

hypertension, glaucoma. side effects of β-blockers are congestive heart failure, bradycardia,

bronchial asthma, hypoglycemia in diabetes mellitus and sedation.

3. α and β blockers as Carvendilol; used in congestive heart failure with other drugs. The

most common side effects include dizziness, fatigue, hypotension, diarrhea, asthenia, bradycardia, and weight gain.

Labetalol; It has a particular indication in the treatment of pregnancy-induced hypertension. It is also used to treat chronic hypertension and hypertensive crisis.

4. Centrally acting anti-adrenergics drugsThey are capable of lowering transmitter output from sympathetic

neurons. Their action is hypotensive however, being poorly tolerated, they enjoy only limited therapeutic use. Examples are Clonidine, Methyldopa, Reserpine and Guanethidine.

C. Drugs Acting on the Sympathetic Nervous System2. Sympatholytics

Clonidine. Clonidine is an α2-agonist whose high lipophilicity permits rapid penetration through the blood-brain barrier. In addition, activation of pre-synaptic α2-receptors in the periphery leads to a decreased release of both nor-epinephrine (NE) and acetylcholine. Side effects. Dry mouth; rebound hypertension after abrupt cessation of clonidine therapy.

Methyldopa. It converts in the brain to α-methyl-dopamine, and then to α-methyl-NE thus competes for a portion of the available enzymatic activity (inhibition of Dopa-decarb-oxylase), so that the rate of conversion of L-dopa to NE (via dopamine) is decreased. The false transmitter α-methyl-NE can be stored; however, unlike the endogenous mediator, it has a higher affinity for α2- than for α1-receptors and therefore produces effects similar to those of clonidine. The same events take place in peripheral adrenergic neurons. Adverse effects. Fatigue, orthostatic hypotension, extrapyramidal Parkinson-like symptoms, hepatic damage, immune-hemolytic anemia.

C. Drugs Acting on the Sympathetic Nervous System2. Sympatholytics

Reserpine. It abolishes the vesicular storage of biogenic amines (NE, dopamine, serotonin = 5-HT). To a lesser degree, release of epinephrine from the adrenal medulla is also impaired. Adverse effects. Disorders of extrapyramidal motor function with development of pseudo-Parkinsonism, sedation, depression, stuffy nose, impaired libido, and impotence; increased appetite. These adverse effects have rendered the drug practically obsolete.

C. Drugs Acting on the Sympathetic Nervous System2. Sympatholytics

Guanethidine. It has high affinity for the axolemmal and vesicular amine transporters. It is stored instead of NE, but is unable to mimic the functions of the latter. In addition, it stabilizes the axonal membrane, thereby impeding the propagation of impulses into the sympathetic nerve terminals. Storage and release of epinephrine from the adrenal medulla are not affected, owing to the absence of a re-uptake process. The drug does not cross the blood-brain barrier. Adverse effects. Cardiovascular crises are a possible risk: emotional stress of the patient may cause sympatho-adrenal activation with epinephrine release. The resulting rise in blood pressure can be all the more marked because persistent depression of sympathetic nerve activity induces supersensitivity of effector organs to circulating catecholamines.

C. Drugs Acting on the Sympathetic Nervous System2. Sympatholytics

Somatic (motor) nerve (causes skeletal muscle contraction) The neurotransmitter is acetyl-choline (ACh). ACh is hydrolyzed by acetyl-cholin-esterase. Receptor is Nicotinic (N). Convulsant as tetanus toxin, strychnine. Centrally acting muscle relaxants as benzo-diazepines, baclofen, clonidine. Non-depolarizing muscle relaxants as curare, d-tubo-curarine, pan-curonium. Depolarizing muscle relaxants as succinyl-choline.Parasympathetic nervous system (like when you eat) The neurotransmitter is acetyl-choline (ACh). Receptors are Muscarinic (M) and Nicotinic (N) receptors. ACh is hydrolyzed by acetyl-cholin-esterase. Parasympatho-mimetics may be direct as carbachol, pilocarpine, arecoline or

indirect as physostigmine, neostigmine, paraoxon, parathion. Parasympatho-lytics as atropine, hom-atropine, benz-atropine, pirenzepine, ipr-

atropium, N-butyl-scopolamine, scopolamine. Sympathetic nervous system (like when you play football) The neurotransmitter is nor-epinephrine (NE). Receptors are α and β receptors. NE is decreased at the receptors by neuronal re-uptake, MAO or COMT. Sympatho-mimetics may be direct as epinephrine (adrenaline) nor-epinephrine

(nor-adrenaline), iso-proterenol, phenyl-ephrine, dobutamine, salbutamol or indirect as cocaine, ephedrine, amphetamine.

Sympatho-lytics as phentol-amine (post-synaptic and pre-synaptic α receptors blocker), prazosin (α1), propranolol (β1 and β2), metoprolol, acebutolol, bisoprolol (β1 > β2), carvendilol and labetalol (α and β), clonidine (pre-synaptic α2-agonist), methyldopa (act as a false transmitter α-methyl-NE), reserpine (abolishes the vesicular storage of NE), guanethidine (stored instead of NE and stabilizes the axonal membrane).

Analgesics DrugsPain sensation can be

influenced or modified as follows:

elimination of the cause of pain.

suppression of transmission of nociceptive impulses in the spinal medulla (opioids).

inhibition of pain perception (opioids, general anesthetics).

altering emotional responses to pain, i.e., pain behavior (antidepressants as “co-analgesics”).

lowering of the sensitivity of nociceptors (antipyretic analgesics, local anesthetics).

interrupting nociceptive conduction in sensory nerves (local anesthetics).

Action of endogenous and exogenous opioids at opioid receptors

Opioid Analgesics Endogenous opioids

enkephalins, β-endorphin, dynorphins.

Exogenous opioids morphone, heroin, pentazocine, pethidine, meperidine, methadone, fentanyl, noscapine, codeine, tramadol. Opioid receptors are; μ (Mu), delta (δ), Kappa

(Ƙ). Mode of action of opioids 1. hyperpolarization (↑

K+). 2. ↓ release of excitatory

transmitters and ↓ synaptic activity (↓ Ca2+).

Effects of opioids

Analgesic effect by inhibition of nociceptive impulse transmission and attenuation of impulse spread and inhibition of pain perception → floating sensation and euphoria → dependence

Antitussive effect by inhibition of the cough reflex. Emetic effect by stimulation of chemoreceptors but this effect

disappears with repeated use. Miosis effect by stimulating the parasympathetic portion of the

oculomotor nucleus → PPP Antidiarrheic effect through ↑ segmentation, ↓ propulsive peristalsis,

↑ tone of sphincters

Rout of administrations: orally, parenterally, epidurally or intrathecally or transdermal.

With repeated administration of opioids, their CNS effects can lose intensity (increased Tolerance). In the course of therapy, progressively larger doses are needed to achieve the same degree of pain relief.

Development of tolerance does not involve the peripheral effects as locomotor stimulation and constipation, so that persistent constipation during prolonged use may force a discontinuation of analgesic therapy.

Physiological tolerance involves changes in the binding of a drug to receptors or changes in receptor transductional processes related to the drug of action.

Person who is tolerant to morphine will also be cross-tolerant to the analgesic effect of fentanyl, heroin, and other opioids. Note that a subject may be physically dependent on heroin can also be administered another opioid such as methadone to prevent withdrawal reactions.

Methadone has advantages of being more orally effective and of lasting longer than heroin.

Methadone maintenance programs allow heroin users the opportunity to maintain a certain level of functioning without the withdrawal reactions.

Toxic effects of opioids are primarily from their respiratory depressant action and this effect shows tolerance with repeated opioid use.

Opioids might be considered “safer” in that a heroin addicts drug dosage would be fatal in a first-time heroin user.

Opioid Tolerance

Physiological dependence occurs when the drug is necessary for normal physiological functioning, this is demonstrated by the withdrawal reactions.

Withdrawal reactions are usually the opposite of the physiological effects produced by the drug.

Acute withdrawal can be easily precipitated in drug dependent individuals by injecting an opioid antagonist such as naloxone.

Acute Action Withdrawal Sign Analgesia Respiratory Depression Euphoria Relaxation and sleep Tranquilization Decreased blood pressure Constipation Pupillary constriction Hypothermia Drying of secretions Reduced sex drive Flushed and warm skin

Pain and irritability Hyperventilation Dysphoria and depression Restlessness and insomnia Fearfulness and hostility Increased blood pressure Diarrhea Pupillary dilation Hyperthermia Lacrimation, runny nose Spontaneous ejaculation Chilliness and “gooseflesh”

Opioid Dependence

Morphine antagonists and partial agonists Pure Agonist: has affinity for binding plus efficacy.

Pure Antagonist: has affinity for binding but no efficacy.

Mixed Agonist-Antagonist: produces an agonist effect at one receptor

and an antagonist effect at another.

Partial Agonist: has affinity for binding but low efficacy.

The effects of opioids can be abolished by the antagonists naloxone or

naltrexone. Given by itself, neither has any effect in normal subjects;

however, in opioid-dependent subjects, both precipitate acute

withdrawal signs.

Naloxone is effective as antidote in the treatment of opioid-induced

respiratory paralysis.

Naltrexone may be used as an adjunct in withdrawal therapy.

Buprenorphine behaves like a partial agonist/antagonist at μ-receptors.

Pentazocine is an antagonist at μ-receptors and an agonist at Ƙ-

receptors. Both are classified as “low-ceiling” opioids, because neither is

capable of eliciting the maximal analgesic effect obtained with morphine

or meperidine.

Drugs for Treating Bacterial Infections

Bacterial infection. Immune response. Infectious disease develops with inflammatory signs. Antibacterial drugs (antibiotics).

Classification of antibiotics by mechanism of action

1. Inhibition of cell-wall synthesis such as penicillins and cephalosporins.

2. Inhibition of folate synthesis such as sulfonamides and trimethoprim.

3. Inhibition of nucleic acid synthesis such as rifampin, quinolones and metronidazole.

4. Inhibition of protein synthesis such as tetracyclines, aminoglycosides, chloramphenicol, erythromycin and clindamycin.

NB. Polymyxins and tyrothricin antibiotics enhance cell membrane permeability. Due to their poor tolerability, they are prescribed only for topical use.

Antibacterial drugs (antibiotics)

Bactericidal effect. Bacteriostatic effect. Bacterial resistance: natural resistance or acquired

resistance (mutation).

Cell wall

Peptideglycan (aminosugars N-acetyl-glucosamine and N-acetyl-muramyl acid).

Animal and human cells lack a cell wall.

1. Inhibitors of Cell Wall Synthesis; the β-lactam penicillins

Disrupt cell wall synthesis by inhibiting transpeptidase.

Well tolerated (0.6 - 60 g ).

Hypersensitivity.

Convulsions. t1/2 ~ 0.5 h.

Inact. by gastric a.

Penicillinase sens.

Narrow margin.

6-amino-penicillanic acid (6-APA)

High doses. With

probenecid. Depot forms.

1. Inhibitors of Cell Wall Synthesis, the β-lactam penicillins

Advantages; Acid resistance. Penicillinase resistance. Spectrum; combination with inhibitors of penicillinase (clavulanic acid, sulbactam, tazobactam).

1. Inhibitors of Cell Wall Synthesis; the β-lactam cephalosporins

Transpeptidase inhibitors..Acid stable.Resistant to Penicillinase and β-lactamase but

Cephalosporinase sensitive. Broad-spectrum antibacterials and well tolerated by

patients. All can cause allergic reactions, some also renal injury,

and bleeding.

7-aminocephalosporanic acid

Transpeptidase inhibitor.

Used in bowel inflammations occurring as a complication of antibiotic therapy.

It is not absorbed orally.

1. Inhibitors of Cell Wall Synthesis; Bacitracin and vancomycin

Disrupt cell wall synthesis by inhibiting transpeptidase.

Active only against gram-positive bacteria.

Markedly nephrotoxic.

2. Inhibition of folate synthesis; sulfonamides & trimethoprim

DHF is made from folic acid, a vitamin that cannot be synthesized in the body, but must be taken up from exogenous sources.

THF is a co-enzyme in the synthesis of purine bases and thymidine.

Most bacteria are capable of synthesizing DHF, from p-aminobenzoic acid.

Selective interference with bacterial biosynthesis of THF can be achieved with the bacteriostatics sulfonamides and trimethoprim.

Sulfonamides act as false substrates.

Trimethoprim inhibits bacterial DHF reductase, the human enzyme being significantly less sensitive than the bacterial one.

Co-trimoxazole is a combination of trimethoprim and sulfamethoxazole.

Sulfasalazine is used to treat ulcerative colitis and terminal ileitis or Crohn’s disease.

3. Inhibition of nucleic acid synthesis; rifampin, quinolones and metronidazole

Substances that inhibit reading of genetic information at the DNA template damage the regulatory center of cell metabolism.

The gyrase catalyzes DNA opening, underwinding, and closing the DNA double strand underwinding.

Quinolones are inhibitors of bacterial gyrases.

Quinolones are used for infections of internal organs and urinary tract infections.

The bactericidal metronidazole, damage DNA by complex formation or strand breakage.

Under anaerobic conditions, metronidazole will converted to reactive metabolites that attack DNA takes place (hydroxylamine).

Rifampin inhibits the bacterial enzyme that catalyzes DNA template-directed RNA transcription (polymerase).

Rifampin acts bactericidally against mycobacteria (tuberculosis and leprosy), as well as many gram-positive and -negative bacteria.

4. Inhibition of protein synthesis; tetracyclines, aminoglycosides,

chloramphenicol, ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,. Protein synthesis means

translation into a peptide chain of a genetic message first copied (transcribed) into m-RNA.

Tetracyclines inhibit the binding of t-RNA-AA complexes. Their action is bacteriostatic and affects a broad spectrum of pathogens. Disadvantage: Inactivation by chelation of Ca2+, Mg2+, Al3+, Fe2+/3+ etc.

Aminoglycosides induce the binding of “wrong” t-RNA-AA complexes, resulting in synthesis of false proteins. Aminoglycosides are bactericidal. Their activity spectrum encompasses mainly gram-negative organisms. Disadvantage: Nephrotoxicity and Vestibular ototoxicity.

Chloramphenicol inhibits peptide synthetase. It has bacteriostatic activity against a broad spectrum of pathogens. Disadvantage: bone marrow toxicity.

Protein Synthesis Animation Video - YouTube.flv

Erythromycin suppresses advancement of the ribosome. Its action is predominantly bacteriostatic and directed against gram-positve organisms. Erythromycin is well tolerated. It is a suitable substitute in penicillin allergy or resistance.

Azithromycin, clarithromycin, and roxithromycin are derivatives with greater acid stability and better bioavailability. The compounds mentioned are the most important members of the macrolide antibiotic group, which includes josamycin and spiramycin. An unrelated action of erythromycin is its mimicry of the gastrointestinal hormone motiline (↑ interprandial bowel motility).

Clindamycin has antibacterial activity similar to that of erythromycin. It exerts a bacteriostatic effect mainly on gram-positive aerobic, as well as on anaerobic pathogens. Clindamycin is a semisynthetic chloro analogue of lincomycin, which derives from a Streptomyces species. Taken orally, clindamycin is better absorbed than lincomycin, has greater antibacterial efficacy and is thus preferred. Both penetrate well into bone tissue.

4. Inhibition of protein synthesis; erythromycin and clindamycin.

4. Inhibition of protein synthesis; tetracyclines, aminoglycosides, chloramphenicol,

erythromycin and clindamycin.

Fungi are plant-like non-photosynthetic Eukaryotes that may exist in colonies of single cells (yeast) or filamentous multicellular aggregates (molds or hyphae).

Human fungal infections have increased dramatically in incidence and severity due mainly to:

Denture wearing Cancer treatment and the HIV epidemic. Critical care accompanied by increases in the use of broad-spectrum

antimicrobials. Fungal infections can be divided into: Superficial infections (affecting skin, nails, scalp or mucous

membranes). Systemic infections (affecting deeper tissues and organs) Superficial infections caused by candida species may be treated with

topical applications of clotrimazole, miconazole, ketoconazole, nystatin, or amphotericin B.

Chronic generalized mucocutaneous candidiasis is responsive to long-term therapy with oral fluconazole, terbinafine, ketoconazole.

Many antifungal agents are quite toxic, and when systemic therapy is required these agents must often be used under strict medical supervision.

Drugs for Treating Fungal infections

Oral Candidosis (Thrush) Angular StomatitisDenture-induced stomatitis

Drugs for Treating Fungal infections

Imidazole derivatives; inhibit ergosterol synthesis. Fluconazole, itraconazole and ketoconazole are available for oral administration. May induce liver damage and inhibit steroidogenesis.

Polyene antibiotics; amphotericin B and nystatin bind with ergosterol, forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+, Cl-) leakage. Amphotericin B is poorly tolerated (chills, fever, CNS disturbances, impaired renal function, phlebitis at the infusion site).

Flucytosine; disrupts DNA and RNA synthesis. It is well tolerated.

Griseofulvin; acts as a spindle poison to inhibit fungal mitosis. The need for prolonged administration, the incidence of side effects, and the availability of effective and safe alternatives have rendered griseofulvin therapeutically obsolete.

Disinfectants and Antiseptics Disinfection = killing of

pathogens. Sterilization = killing of all

germs. Antisepsis = reduction of germ

numbers on skin and mucosal surfaces.

These can be achieved by chemical or physical means [ionizing irradiation, dry or moist heat, or superheated steam (autoclave, 120 °C) to kill microorganisms].

The basic mechanisms of action involve denaturation of proteins, inhibition of enzymes, or a dehydration.

Agents for chemical disinfection ideally should cause rapid, complete, and persistent inactivation of all germs, but at the same time exhibit low toxicity (systemic toxicity, tissue irritancy, antigenicity) and be non-deleterious to inanimate materials.

Disinfection of floors or excrement

Disinfection of instruments Skin disinfection Disinfection of mucous

membranes Wound disinfection

Dentifrices

Dentifrices are agents used along with a toothbrush to clean and polish natural teeth.

They are supplied in paste, powder, gel or liquid form. Toothpaste essential components are an abrasive, binder,

surfactant and humectant. Abrasives are insoluble particles help remove plaque and calculus

from the teeth. The additional fluoride in toothpaste has beneficial effects on the

formation of dental enamel and bones.