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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
muscle tone.
influencing
skeletal
Inhibition of neuromuscular transmission
and electromechanical coupling
A. Drugs Acting on Motor Systems: Muscle Relaxants
1. 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).
B. Drugs Acting on the Parasympathetic Nervous System
Acetyl-choline (ACh) as a transmitter: (release, effects, and degradation )
 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 Achesterase, present on pre- and postjunctional membranes, or by a less
specific serum cholinesterase, a
soluble enzyme present in serum
and interstitial fluid.
B. Drugs Acting on the Parasympathetic Nervous System
1. 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
B. Drugs Acting on the Parasympathetic Nervous System
1. Parasympatho-mimetics
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 System
2. Parasympatho-lytics
Effects of parasympathetic stimulation (blue arrow) and blockade (red)
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).
B. Drugs Acting on the Parasympathetic Nervous System
2. Parasympatholytics ((Atropine-like drugs))
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.
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-uptake
2. Inactivated by MAO
3. Inactivated by COMT
C. Drugs Acting on the Sympathetic Nervous System
1. 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
Epinephrine (Adrenaline)
Norepinephrine (Noradrenaline)
Isoproterenol
Phenylephrine
Dobutamine
Salbutamol
Indirect-acting sympathomimetics
Cocaine
inhibit NE re-uptake
Ephedrine
facilitate NE releases
Amphetamine
All the above + slow breakdown by MAO
Receptors
α1, α2, β1, β2
α1, α2 > β1, β2
β1 and β2
α1
β1
β2
α and β
α and β
α and β
C. Drugs Acting on the Sympathetic Nervous System
1. Sympathomimetics
Clinical uses of adrenoceptor agonists
1. 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 System
2. Sympatholytics
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 drugs
They 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 System
2. 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-decarboxylase), 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 System
2. 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 System
2. 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 bloodbrain 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.
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-butylscopolamine, 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), isoproterenol, 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 Drugs
Pain 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 “coanalgesics”).
 lowering of the sensitivity of
nociceptors (antipyretic
analgesics, local anesthetics).
 interrupting nociceptive
conduction in sensory nerves
(local anesthetics).
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+).
Action of endogenous and exogenous opioids at opioid receptors
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
Opioid Tolerance
 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 Dependence
 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
 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
Withdrawal Sign
 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”
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 Nacetyl-muramyl acid).
Animal and human cells lack a cell wall.
1. Inhibitors of Cell Wall Synthesis; the β-lactam penicillins
6-amino-penicillanic acid (6-APA)
 Disrupt cell wall synthesis  Hypersensitivity.  High doses.
by inhibiting transpeptidase.  Convulsions.
 With probenecid.
 Well tolerated (0.6 - 60 g ).  t1/2 ~ 0.5 h.
 Depot forms.
 Inact. by gastric a.
 Penicillinase sens.
 Narrow margin.
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
7-aminocephalosporanic acid
 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.
1. Inhibitors of Cell Wall Synthesis;
Bacitracin and vancomycin
 Disrupt cell wall synthesis  Transpeptidase inhibitor.
by inhibiting transpeptidase.  Used in bowel inflammations
 Active only against gram- occurring as a complication
positive bacteria.
of antibiotic therapy.
 Markedly nephrotoxic.
 It is not absorbed orally.
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;
 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.
rifampin, quinolones and metronidazole
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 tRNA-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.
4. Inhibition of protein synthesis; erythromycin and
clindamycin.
 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; tetracyclines,
aminoglycosides, chloramphenicol, erythromycin and clindamycin.
Drugs for Treating Fungal infections
Denture-induced stomatitis
Oral Candidosis (Thrush)
Angular Stomatitis
 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
 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 nondeleterious to inanimate materials.
 Disinfection of floors or excrement
 Disinfection of instruments
 Skin disinfection
 Disinfection of mucous membranes
 Wound disinfection
Dentifrices
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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.
Dentifrices
Toothpaste
Tooth powder
Mouth washes