Pharmacology

Illustrated Notes

Artemisa Gogollari M.D.

Marvin Bundo M.D.
 Nitric oxid (powerful
vasodilator agent) is released

Less dilatator
effect on
arterial
Very powerful peripheral
dilatator effect on system and
veins: They relax coronaries
veins, decreasing
preload and
myocardial oxygen
consumption
 vascular afterload is
capacitance is decreased
increased afterload is
\ decreased

opening of
coronary
collateral
circulation

increase of
/ blood
Blood is circulation from
distributed to epicardium to
ischemic areas subcardium

urogenital gastrointestinal biliary system

system tract
Relaxation of :
Bronchi

moderate
decrease of
platelet
aggregation
 Cardiac C a 2 + channel
blockers (Varapamil,
Diltiazem) must be not
used with Beta-blockers.
Effect on
myocardium
A combination
Dihydropyridine
Effect on on +
smooth Beta-Blockers is
muscle in the possible.
peripheral
vasculature

In smooth muscle cells

of the systemic arterial
beds :

They block L-type calcium

channels (The L-type
calcium channel is a type
of voltage-dependent vasodilation
calcium channel. " L "
stands for long-lasting
referring to the length of
activation).
decreased
peripheral
In this way Ca does not
resistance
enter the cells, and
depolarization of cell
membrane is stopped.

In cardiac cells this means: lowering of

negative ionotropic effect. blood
pressure
 They reduce cerebral
damage after
thromboembolia

Due to their negative

They are also They are used in batmotrophic effect these
used to treat every type of drugs are used to treat
migraine angina, but are supraventricular
preferred in arrhythmias: atrial flutter,
vasospastic atrial fibrillation
angina

Nimodipine has a strong

Hypertension affinity for cerebral
vassels, and decreases
morbidity after
Raynaud subarachnoid
Syndrome hemorrhage.
 decreased
cardiac
output

Negative Negative
Ionotropic Chronotropic
effect effect decreased
need of
Main usage in typical angina. myocardium
They are used in acute myocardial infarction. for 02
Contraindication: Vasospastic angina

Risk factors modification : — s m o k i n g cessation,

treatment of hypertension and hyperlipidemia)
Prevention: ACE Inhibitors, Statins , Antiplatelet drugs

Aspirine lowers
the incidence of
cardiovascular
events
 They are rarely used
as a first choice to
treat heart failure.

Digoxin a n d
Digitoxin have
very different
pharmacokinetics
Digoxin is well
absorbed w h e n
administered
orally is
Most of Digitoxin is
distributed well in
metabolized in hepar
the organism
a n d its active metabolite
(including C N S )
is Digoxin.

Only a small percentage of Digitoxin is excreted

Digoxin is metabolized. v i a biliary system
a n d it undergoes the
Enterohepatic
Supra-
circulation
ventricular
arrhythmias
In toxic doses they can
Chronic heart cause digital toxicity
failure (gastrointestinal, C N S
and Cardiac symtoms)
In these cases the drug
should be interrupted
and
Glucose Potassium
Insulin Infusions,
Lidocaine, Atropine,
Digoxin anticorpes can
be used).
 Increased
automaticity
and excability
of Purkinje
Effect on the heart: fibers.
a. Mechanical effect (direct action
on the cardiac muscle) Positive
Inotropic effet
(Negative chronotropic,
dromotropic, batmotropic effects)
b. Effect on the electrical activity (indirect
action, vagomimetic action)
Inhibition of the sinoatrial node (decrease of
the rate of impulse generation).
By slowing down the conduction in AV node
and by increasing its refractory period, it
reduces the ventricular rate.

By inhibiting the Na,K-ATPase,

they can cause adverse effects:

Nausea, Confusion,
vomiting hallucinations,
agitation

Convulsion

Diarrhea
 Prolonging of the effective
refractory period, prolonging
of the cardiac action potential.
Administration: IV

Used as an emergency drug, to resuscitate

patients with ventricular tachycardia, w h e n
Lidocaine a n d defibrillation have failed.
 Prolonging of the
cardiac action
potential, prolonging
of the effective
refractory period,
slowing of conduction,
increase of threshold
potential, inhibition of
rapid repolarization
(phase 0)

Toxic doses can cause excessive

blocking of Na+ channels, slow
conducting and cause a wide QRS
complex.

Nausea, vomiting, diarrhea,

headache, vomiting, tinnitus,
thrombocytopenia, fever, allergic
reactions.
 It blocks Na+ channel during phase
0, shortening of the cardiac action
potential, slowing of conduction,
inhibition of depolarization phase 4. It can't be administered orally
because it undergoes first-pass.

Only for
ventricular
arrhythmias.

First choice for ventricular

tachycardia, ventricular fibrillation,
ventricular fibrillation in the setting
of an acute myocardial infarction,
cardiovascular surgery.

Hypotension, paresthesia,
tremor, nausea, hearing
disorders, eye disorders,
vertigo.
 Ventricular and
atrial arrhythmias

Second choice for stable ventricular

tachyarrhythmia in the setting of an acute
myocardial infarction

Nausea,
diarrhea, rash,
agranulocytosis.

Drug induced
Lupus
syndrome

Negative chronotropic,
bathmotropic and dromotropic
effects, prolonging of effective
refractory period

Bradycardia, hypotension,
worsening of chronic
cardiac failure, heart block.

In ventricular
and supra-
ventricular
arrhythmias. Worsening of
asthma
 By blocking Ca2 +
channel, it inhibits
the depolarization
phase.
Moderate Prolonging of the
peripheral effective refractory
vasodilation. period.

Supra-ventricular arrhythmias (Verapamil and

Adenosine are the first choice)

Attention: It can cause

cardiac arrest and severe
hypotension.

Hypotension,
bradycardia,
heart block,
low cardiac
contractility
 Prolonging of the cardiac action
potential, prolonging of the
effective refractory period, slowing
of conduction, prolonging of the
repolarization (phase 3).

T1 / 2 = very short
The drug is eliminated
in2 phases: the first
phase is short (3-10
days), and the second
phase lasts for several
phase. After
interrupting the drug,
its effect last for 1-3
months.
Administration: IV

Atrial
fibrillation
Severe
ventricular
arrhythmia

Bradycardia, Pulmonary
cardiac block fibrosis

Hepatic
damage

Deposition of the drug in the skin (blue skin),

deposition in the cornea.
 They inhibit the stimulation of the
central nervous system alpha-
adrenergic receptors and decrease
sympathetic stimulation in the blood
vessels and the heart.

Methyldopa is converted in a-
• methylnorepinephrine in the
organism (an agent similar to
norepinephrine).

Then it is accumulated in
the presynaptic vesicles
(instead of
norepinephrine).

Methyldopa is then
released in the synapse by
exocytosis.
It serves as a false
neurotransmitter,
inhibiting norepinephrine
release.

It acts only on a2 receptors.

Other centrally acting
Sympatholytics also have a similar
mechanism of action.
 Moderate and severe
hypertension.

It can be used in Chronic

hypertensive hypertension.
crisis

Hypertension in
Hepatotoxicity
pregnancy
CNS depression,
sedative effect, loss
of concentration,
confusion, vertigo

Clonidine is rarely used (risk for depression).

Hypertensive
crisis, induced
hypotension,
pulmonary
edema.

Many adverse effects (inhibition of sympathetic

and parasymphatetic system).
Rarely used.
 One of the
first choices
for chronic
Hypertension

Negative Anti-renin effect by

chronotropic blocking beta 1 receptors
and negative in the juxtaglomerular
ionotropic apparatus in the kidney
effect (inhibition of renin-
angiotensin system).

decreased
cardiac
output

Inhibition of
decreased sympathetic
They block beta 1 blood system in the
receptors in the pressure CNS.
myocardium

dilation of arterial
blood vessels

Chronic
hypertension (used
as monotherapy or
combined with
Immediate-release
other drugs)
Nifedipine can be
used for rapid blood
pressure lowering.
 They block alfa 1 and
alfa2 receptors.
They also cause reflex
tachycardia because of
this mechanism.

Hydralazine (dilation of
arterial blood vessels)
Chronic hypertension

Hypertension crisis
(especially when the
cause is
pheocromocytoma).

reflex tachycardia,
headache, sympathetic
nausea, stimulation that can
vomiting, worsen heart diseases
sweating
 Dilation of
arterial blood Hypertensive
vessels crisis (IV)

headache

sweating
hirsutism

angina tachycardia,
palpitations

Dilation of arterial
and venous blood
vessels

First choice for

hypertensive crisis
metabolic (IV).
acidosis
sudden death

hypotension,
arrhythmia,
It is also used
tachycardia,
in chronic
heart failure
 Dilation of
arterial blood
vessels
Hypertensive
crisis (IV)
Severe hypotension
that can cause acute
myocardial
infarction, ischemia,
heart failure in
patients with
ischemia

ARBs are similar

to ACEi. They are
used in resistant
hypertension or in
patients in which
ACE Inhibitors
can't be used.
 Chronic
hypertension, Chronic
resistant heart failure
hypertension

Acute
myocardial
Diabetic infarction
nephropathy,
chronic
nephropathy.

Drug allergy renovascular disease, aortic stenosis, pregnancy, lactation

Allergic hyperkalemia
reactions
(angioedema)
hypotension

dry cough
 A diuretic is any drug that
elevates the rate of urination
and thus provides a means of
forced diuresis.

Administered IV
Increased
because it is not
extracellular
absorbable.
water
To treat the low
output of urine, acute
renal failure (oliguric
phase, not used in
anuric phase),

ocular edema,
cerebral edema Hypertension,
Mannitol has osmotic effect. headache, nausea,
It increases the intravascular
vomiting, worsening
volume.
of cardiac diseases.
It increases water diuresis.
 It increases
renal blood
flow,
improving
glomerular
filtration.

Furosemide inhibits The Na-K-Cl It also inhibits

cotransporter (protein) in the loop of Henle Mg and Ca
(inhibiting Na, K and Cl reabsorption). reabsorption.

Pulmonary edema, edema, hypercalcemia, hyperkalemia

Acute
renal
failure
Hypertensive crisis (rarely used), chronic heart failure

Hyperurecemia, hypomagnesemia, hyponatremia, hypokalemia

Metabolic
alkalosis

Allergic
reactions
Ototoxicity
 - kidney
(proximal
tubule): it is
essential for -CNS:
bicarbonates secretion of
reabsorption bicarbonates
from the
-eye: secretion blood to the
of cerebrospinal
bicarbonates fluid
from the
blood to the
eye's aqueous
By inhibiting humor
bicarbonates
reabsorption, the
bicarbonates are Kidney stones,
massively hypokalemia
excreted in the
urine. Metabolic
acidosis
It is used for
urine
alkalization.

CNS toxicity.

Glaucoma, metabolic acidosis

Allergic
reactions,
Altitude fever, rash
sickness.
 They act in
collecting tubule,
antagonizing the
aldosterone
effect.

Spironolactone
is the only that
acts also as a
diuretic. They inhibit Na+, C1+
and H20 absorption.
Amiloride and They inhibit K+ and H
Triamterene are + excretion.
only important in
potassium
sparing.

Primary and chronic heart

secondary failure
hyperaldosteronism

hypertension Hyperkalemia

Metabolic
Ascites in acidosis
patients with
cirrhosis, Kidney stones,
Combined with acute renal
other diuretics failure.
for their
Nephrotic potassium- Gynecomastia
syndrome sparing acion
(Amiloride and
Triamterene).
 Thiazide
diuretics
Hydroclorothi
azide acts on
the distal and
proximal
tubule.
It inhibits Na
+ and C1+
reabsorption.
It stimulates
Ca2+
reabsorption.

Chronic hypertension,
chronic heart failure

metabolic
alkalosis,

kidney stones,
nephrogenic
Allergic
diabetes
reactions
insipidus
 They inhibit
thrombin by
acting with L M W inhibits
H M W has great
antithrombin. mostly factor
affinity with
Xa, but does
antithrombine III and
not have effect
it inhibits the factors
on thrombin.
IIa, IXa and Xa.

LMW
(enoxaparine,
deltaparin,
tinzaparine)
are very effective
in
thromboembolic
The rate of diseases
inactivation of
these proteases
by AT can
increase by up to
1000-fold due to
the binding of
heparin
 Venous thrombosis, thrombophilia, atrial fibrillation

Mechanic valves placement, prolonged bed rest, surgery, patients with cancer.

3. Alopecia
2. Allergic
reactions

4. Osteoporosis,
1. Hemorrhage (more spontaneous fractures
risk at elder patients or
in patients with renal
failure)
Attention with the
doses!
Partial thromboplastine
5.Transient thrombocytopenia in 2 5 % of patients and
time (PTT) should be
severe thrombocytopenia in 5% of patients.
monitored (it must be
Thrombocyte count should be monitored.
maintained 2-2.5 times
the normal control).
 Active Infective Gastrointestinal
tuberculosis endocarditis ulcer

In patients with significant

thrombocytopenia,
thrombocytopenic purpura Severe
In patients who
hypertension,
had recently eye
intracranial
or brain surgery
hemorrhage

Abortion, visceral carcinoma

Severe liver diseases, severe renal diseases
In patients
allergic to In patients who will
heparin undergo lumbar puncture.

In cases of hemorrhage: The

drug must be discontinued.

Heparin can be administered

IV or in subcutaneous way. Antidote: Protamine
sulfate (for every 100
UI heparin — 1 mg
protamine sulfate).

Continuous IV infusion : It can't be

PTT should be administered
maintained 2-2.5 times IM (risk of
the normal level during hematoma).
the infusion.
Intermittent IV infusion:
PTT is controlled after 6
hours.
 Drug onset:
after 8-12
hours

For this reason the

anticoagulant
therapy is started
with heparin+ oral
They inhibit vitamin K activation, a anticoagulants.
vitamin which is required to activate
some coagulations factors :
prothrombin, VII, IX, X.

Then heparin is
removed and oral
anticoagulants are
During pregnancy (it continued.
passes the placenta,
fetal toxicity).

Risk for hemorrhage:

Warfarin is started with the
INR can be prolonged as much as it
dose 5-10mg, then it is
represents no more than 2 5 %
continued with the dose
decrease of prothrombin activity.
5-7mg.
INR should be maintained 2.5-3.5.
It is monitored and the
The antidote is vitamin K.
dosage is adjusted the
Prothrombin time (INR).
 Prophylaxis in
patients in patients In patients
with ischemic heart who will
disease, unstable undergo
angina, acute coronary
myocardial stent
infarction (325mg placement
Aspirin

Nausea,
vomiting
Dyspepsia,
Hemorrhage,
diarrhea
leucopenia
 Extra production of
plasmin caused by
Thereby Fibrinolytics breaks down
Plasmin is produced in the blood to dissolving unwanted blood clots.
break down fibrin, the major clots once
constituent of blood thrombi. they have
fulfilled their
purpose of
stopping
bleeding.

Acute myocardial
Pulmonary infarction (effective in
embolism the first hours).
(multiple emboli)

Deep vein thrombosis,

iliofemoral thrombophlebitis
 They are almost Their half-
completely (40-75%) life range
absorbed after oral from 1 to 3
administration. hours

They inhibit the first

enzymatic step of
cholesterol synthesis
(the enzyme H M G The result is
Co A reductase).

an important reduction of
LDL cholesterol levels
They are
considered to be a moderate lowering of
the best alternative triglycerides levels
for the
antihyperlipidemic a slight increase of HDL levels
effect.
 These drugs are very
effective in lowering the
elevated LDL
cholesterol levels.

Diet, weight loss and exercise These drugs should

are also indicated in patients not be taken during
who take antihyperlipidemic pregnancy or
drugs. lactation.

Patients are advised to take H M G CoA REDUCTASE

them in the afternoon, as INHIBITORS are not
the synthesis of cholesterol combined with other
occurs during the night. antihyperlipidemic drugs.
 Increase of trygliceride
lipolysis. Inhibition of the
adipose tissue lipoprotein
lipase. Lowering of VLDL,
moderate lowering of LDL,
lowering of tryglicerides.

Hypertriglyceridemia with
high VLDL levels
Contraindicated
in patients with
hepatic and renal
diseases.
* Siiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiinir

Rash, gastrointestinal disorders, myopathy, arrhythmia.

They bind to the biliary

acids in the intestine,
inhibiting their
absorption.

Isolated LDL
elevation, primary
hypercholesterolemia,
treatment of pruritus
in patients with
cholestasis Constipation, malabsorption syndrome, gallstone,
VLDL elevation (Niacin must be added in this case).
 It also lowers
triglycerides.
To normaslise LDL
levels (as monotherapy
or combined with
statins),familial
hypercholesterolemia
and other types of
hypercholesterolemia.

Cutaneous vasodilation, hot flashes, flushing, pruritus,

rash, nausea, vomiting, hepatotoxicity hyperuricemia.

Statin + Bile acid sequestrants

In patients with familial hypercholesterolemia.

Niacin + Bile acid sequestrants

In patients with elevated LDL and
VDLD. Fibric acid derivates + Bile acid sequestrants
In patients with familial combined
Niacin + Statin hyperlipidemia, intolerant to Niacin.
In patients with familial
hypercholesterolemia.
 2.They
decrease the
excitatory
neurotransmit
ters (glutamic
acid)

3. They modify
l.They increase the the permeability
GABAergic transmission of ion channels
(inhibition of the CNS) (NA, K, Cl, Ca)
 It is the most effective drug in partial epilepsy crisis
and tonic-clonic seizures. It is also used for status
epilepticus. It is well absorbed when administered
orally or IV injected.

It modifies the It stops the

permeability of ion serotonin and
channels (Na, K, Cl) noradrenaline
release.

It increases the
GABAergic
transmission Phenytoin reduces
early acetylcholine
It increases
release after
dopamine
depolarization
reuptake

Gingival hyperplasia, allergic reactions, lymphadenopathies.

Niastagmus,
diplopia
Ataxia
 Similiar to Phenytoin. It affects Na+
channels, inhibiting norepinephrine
release and re-uptake.

First choice for partial

It is used to in epilepsy, seizures. It can be
bipolar disorders, combined with
trigeminal neuralgia Phenytoin in resistant
cases. Good oral
bioavailability.

vertigo

ataxia
aplastic anemia,
agranulocytosis. gastrointestinal
diplopia disorders

It increases
GABA's
inhibiting
effect, open Cl-
First choice in channels, and
partial blocks Ca2+
seizures and channels.
Grand mal
seizure

It is All types of seizures. Very effective in

considered febrile seizures or in preventing them.
first choice in Aggravation of infantile spasms,
children absence seizure and atonic seizure are
associated with Phenobarbital use.
 Primidone is the first choice for
complex partial seizures.

It inactivates voltage
gate Na+ channels. It
also blocks Ca2+
channels.
Used as adjuvant therapy. Studies
suggest that it can be used as
monotheraphy in partial seizures.

vertigo,
headache,
diplopia,
nausea,
allergy, Effective in
drowsiness partial
seizures, but it
can cause
aplastic
anemia and
hepatitis. It
has also been
used for
neuropatic
pain and
neuralgia in
adults.
Partial
seizures and
It block Na+ tonic-clonic
channels. Similar seizures. Non-
action with Phenytoin epileptic
and Carbamazapine. seizures
It potentiates the
GABA's effect Drowsiness, fatigue,
vertigo, paresthesia,
confusion.
 First choice in petit mal and absence seizure. It
also can be used in myoclonic seizures, atypical
absence seizures, atonic seizures, tonic seizures

In patients who take valproic

acid (increased Ethosuximide
plasma concetration because
Vertigo, the elimination is decreased)
nausea,
vomiting,
headache

Eosinophilia,
leukopenia,
thrombocytopenia,
pancytopenia, lupus
erythematosus (rare)
Abdominal
pain,
weakness,
lethargy, rash
 It stimulates GABA
synthesis and inhibits
GABA destruction.

Abdominal pain
Used in all types
of epilepsy. Most Tremor Hepatotoxicity
used in tonic-
clonic seizures Nausea,
and absence vomiting
seizures.
Sedation

Diazepam is used in status Lorazepam is Clonazepam is

epilepticus and Grand mal more effective effective in every type
seizures. In resistant cases in Grand mal of epilepsy myoclonic
myorelaxants are used. seizures. seizures, absence
Administered IV or rectally (in seizures, status
children). Not effective when epilepticus, infantile
used chronically (drug spasms.
tolerance).

Treatment of status epilepticus : Diazepam IV 20-30 mg Phenytoin IV

13-18mg/kg Phenobarbital IV 100-200mg to 400-800mg. In severe
cases, intubation+general anasthesia. In resistant cases: myorelaxants
 Lithium takes a
long time to act,
so it is preferred
that patients with
mania are
treated first with
Neuroleptics and
Benzodiazepines

After the maniac

phase is under
control, the patient is
treated with Lithium
+ Benzodiazepines

In patients with
recurrent
In patients with unipolar depression,
depression who do not respond Schizoaffective
to treatment (Lithium+SSRI disorder
or Lithium + Tricyclic (Lithium +
antidepressant) Neuroleptics)
 Confusion

Tremor Involuntary
movements,
ataxia,
dysarthria

Pregnancy: teratogenic
effect, toxic effects in the
Thyroid: Thyroid newborn
function impairment,
thyroid gland
enlargement,
Hypothyroidism

Cardiac:
Renal: Nephritic Tachycardia,
syndrome, swelling, Bradycardia
frequent urination
 In patients with Parkinson,
there is an absolute
and a relative
decrease in Dopamine
increase in
(particularly in Substanca
Acetylcholine.
Nigra)

is a Dopamine precursor (Dopamine

itself can not pass the blood brain
barrier, so L-Dopa is given instead in
patients with Parkinson).

L-Dopa has good oral bioavailability but

after passing the blood brain barrier, only
1-3 % remains unchanged, because the
most part is decarboxylated. (Dopa-
decarboxylase enzyme)

For this reason L-Dopa is often

combined with Carbidopa or
Benserazide
to inhibit peripheral Dopa
decarboxylation): This reduces
the daily dose of L-Dopa by
75%.
 L-Dopa does not stop the
progress of the disease but is
associated with an decrease
in mortality if taken in the
early stages.

Patient with Parkinson have better

results the first years of taking L-
Dopa because the daily dose is then
reduced to avoid toxic effects.

Some patients also tend to

become less sensible to the
It improves all effect of L-Dopa (the patients
clinical symptoms develop tolerance to the drug).
of Parkison (mostly So L-Dopa is less effective
Bradykinesia). after 3-4 years of usage.

hepatic tests alteration

 Intestinal:
Anorexia, nausea, vomiting
These patients must take
antacids and antiemetics.
Taking Carbidope reduces
these symptoms by 20%.

Cardiovascular:
Arrhythmias: Tachycardia,
Ventricular Extrasistole, Atrial Fibrillation
(Carbidopa reduces these symptoms)
Orthostatic Hypotension (common)
Arterial Hypotension

Neurologic:Chorea, Atheosis, Ballismus,

Distonia, Tics (in 8 0 % of patients who
take L-Dopa for a long time)
Face/Extremities chorea and atheosis are
most common.
These effects are dose depended.

Mydriasis

glaucoma

hemolysis

alteration in
blood cells
 These symptoms occur more in
Psychological:
patients who take both L-Dopa and
Depression, anxiety, nervousness,
Carbidopa
insomnia, drowsiness, confusion,
In severe cases these patients must
euphoria, delusions, hallucinations,
take antipsychotics(Risperidone,
personality disorders (because the
Cloazapine or Olanzapine).
dopamine level in the brain is elevated).

Response fluctuations: O n /
Off phenomenon (In an "off"
state, the person becomes very
stiff, slow and may even be
unable to move for a few
minutes) because there is
change in Dopaminergic
receptors sensibility.
 They
stimulate
directly the
dopaminergic
receptors.

Used as monotherapy
in cases of moderate
Parkinson.
Lower response
fluctuations, longer
" O n " periods.
Studies has shown that It improves the
Dopamine behavioral changes.
Pergolide is more effective
agonists play
than Bromcriptine. The " O n "
an important
period is longer when
role in
Pergolide is used, reducing the
Parkinson
Levodopa dose.
treatment
 Dyskinesia
Gastrointestinal Mental
disorders disorders

Cardiac
disorders

Lower "Off"
periods.

It is used as adjuvant
therapy in Parkinson
disease.

It also has
anticholinoergic
effects.
It induces
It is used only in
neurons to
the early stages of
produce more
Parkinson, because
Dopamine.
its effect is weak.
 orthostatic
hypotension convulsions

depression dyspeptic
disorders

They improve vertigo,

tremor and confusion,
muscular mental
rigidity. slowness

agitation,
delusions,
hallucinations
urinary
retention,
constipation
dry mouth
tachycardia
mydriasis arrhythmia

tachypnea
 Electrode
In case of no response to treatment: therapy
Thalamotomy

Neuroprotective agents used in

Parkinson disease:
A sedative drug reduces A hypnotic drug causes
anxiety and also has a drowsiness and sleep-
sedative effect. inducing effect.

Dose-response inhibition of the central nervous

system is typical for anxiolytic and hypnotic
drugs.
 are the most used
group for the
sedative-hypnotic
effect.

All anxiolytic and hypnotic drugs

pass the placenta barrier.

They should not be

administered during pregnancy
(because they can cause
depression of the vital functions
of the neonate).
These drugs are also delivered
in the breast milk.
 Drug absorption Lipid solubility is the
and distribution main factor that
depend on their lipid conditions the drug's
solubility delivery in the CNS
Less soluble is less soluble (is
in lipids delivered in the
the CNS
slowly).
has very high
more
lipid solubility
soluble in
(has a quick
lipids
effect).

They undergo phase I After metabolism,

reactions and then are these drugs are not
conjugated, to form effective any more
glucuronides, that are
excreted in the urine
Metabolism of these
drugs in hydrophilic
substances is
Many important for their are enzymatic
metabolites, clearance. inductors
after phase A few of them are They change the
I, are active excreted unchanged. rhythm of
(and have enzymatic
long T 1/2) activity when
used chronically
(BZD are not enzymatic (Phenobarbital in particular)
inductors)
 BZD modulate the GABA effects in
each level of the CNS (spinal cord,
hypothalamus, cerebral cortex,
cerebellum)
The GABA receptor
has specific binding
sites for GABA, BZD Benzodiazepines increase the
and for every specific frequency of channel openings
Barbiturate. (chloride channels) produced
by GABA.

This receptor (that BZD do dot

functions as chloride ion replace
channel) is activated GABA, but
from the inhibitory potentiate the
neurotransmitter, GABA GABA effect.

At high
GABA is the most concentrations,
powerful inhibitory Barbiturates act as
neurotransmitter in GABA-mimetics,
the CNS. activating directing
the chloride
channels.

Barbiturates are less Barbiturates also

selective than BZD, potentiate the GABA
because they also inhibit effect by making the
excitatory chloride channels stay
neurotransmitters (like longer open.
glutamic acid)

For this reason, Barbiturates are more potent than BZD, and can cause
general anesthesia with a strong inhibition of CNS (are also less secure)
 Sedative action: sedative
effect, anxiolytic effect,
relaxing effect (but also
psychomotor retardation and
lower cognitive functions)
Hypnotic action: shorter
light sleep phase (phase I),
longer R E M sleep, shorter
N R E M sleep
In total: better sleeping
If they are used more than
2 weeks for this purpose it
leads to drug tolerance.

Anesthetic action: Some of

these drugs can cause
anesthesia

Anxiety disorders: anxiety

attack, panic attack,
phobias, chronic anxiety

Other medications used for anxiety

or sleep disorders:
Buspirone (only anxiolytic effect)
Zolpidem ( anxiolytic and hypnotic
effect. It acts very quickly and does
not cause tolerance.
 Effect on respiration: Depression on
the respiratory center, particularly in
patients with respiratory problems.
(This is also the main cause of death
from BZD).
Circulatory collapse (by lowering heart
contraction and the vascular tonus).
Anticonvulsive effect: They are used
as Antiepileptic drugs
Diazepam, Lorazepam,
Chlonazepam, Nitrazepam (status
epilepticus)
Phenobarbital (tonic-clonic seizures)
Anterograde
Amnesia
Muscle relaxant: relaxation
of the skeletal muscles in
patients with spasticity, by
increasing presynaptic
inhibition in the spinal
cord.
When choosing a medication to treat anxiety we should consider:

1. Choosing a 2. Choosing a 3. Choosing a

drug with the drug that drug that is
highest interacts the eliminated
therapeutic less possible slowly so it 4. Choosing a
index with other can stay drug that does
drugs (due to longer in the not cause
enzymatic CNS tolerance
induction)

Anterograde
amnesia Confusion,
drowsiness

Heart and
respiratory
complications

Excessive sedation,
psychomotor
retardation and lower These drugs
cognitive functions, are often used
loss of concentration, Inability to for suicide.
loss of judgement drive Barbiturates
are more
lethal.
 Opioids are well distributed
and well delivered in the CNS.
They are metabolized to polar
glucuroinides (some of them
are active).
For example Morphine 3
glucuroinide has
neuroexcitatory effect,
Morphine 6 glucuroinide has a
more powerful anesthetic effect
than Morphine.
Most Opioids are well absorbed when
administered orally or in other ways.
Most of them undergo first pass hepatic
metabolism. For this reason they are
administered in high doses when used
orally, (except codeine and oxycodone,
and are very effective when orally
administered.
 Most of Opioids
bind to the Mu
receptors
(responsible for
analgesia,
euphoria,
respiration
depression,
dependency).

The three receptors

are more
concentrated in the Adverse effects are
posterior horn of due to the
the spinal cord and supraspinal effects
play an active role of opioids,
in the spinal (respiration
transmission of depression, nausea,
pain. For this reason vomiting, sedation.
opioids have more
effect on the spinal
cord, being
The total effect of Opioids is
responsible for
due to the contribution of the
spinal analgesia.
three receptors.

1. In the presynaptic neuron, 2. In the postsynaptic

activation of the opioid receptor neuron, activation of
decrease Ca2+ influx. This the opioid receptor
decreases release of excitatory increases the efflux of
neurotransmitters (Like K+ and decreases the
glutamate, that is the main response of the
excitatory neurotransmitter, neuron to excitatory
acetylcholine, serotonin, neurotransmitters.
substance P, noradrenaline)
 Euphoria: In same cases
Particularly when they can cause
Analgesia :
administered IV dysphoria: a
Opioids reduces
in high doses. state of
the two
Opioids reduce feeling unwell
components of
stress, anxiety and or unhappy+
pain: sensitive and
cause a well being being nervous
affective
sensation. and agitated
Sedation:
confusion, loss of
concentration,
sleep induction
(particularly in
elder patients)
Opioids+ sedative/
hypnotic agents
=deep sleep Respiratory
depression: depression
of the respiratory Myosis (punctiform
center in the CNS pupils) : this is sign of
In the alveoli Pco2 is Opioids overdose
increased, but there is
hyperventilation as
compensatory
mechanism.

Codeine is used to
stop dry cough.
This can lead to
accumulated
oropharyngeal
secretions and
obstruction of the
airways.
 Truncal rigidity (increase
of muscle tonus ) : this
leads to bad ventilation
To prevent this, Opioids
should be combined with
Myorelaxants.

Trigger zone
is activated :
Nausea and
vomiting.
Skin : Rash+pruritus
C ardiovascular:
(particulary in the
bradycardia,
neck and lips),
hypotension
because of histamine
(not very often)
is release.

Gastrointestinal:
constipation,
i nausea, voming
•

Biliary tract:
Biliary colic

Renal: Increase
Uterus: they of glomerular
can delay the filtration, anti-
delivery of diuretic effect,
the baby urinary
sphincter tone is
increased
 As an
analgesic for
severe and
intensive pain

1 .For severe acute 3. Pulmonary

pain edema (morphine
Acute myocardial or pethidine IV : to
Infarction 2 For severe chronic improve the
Fractures pain dyspnea by
Renal and Biliary Pain in patients with reducing anxiety
Colics cancer and by reducing
Post -surgery pain Opioids in these cardiac pre- and
During delivery patients can be afterload
administered as:
Lasting release
opioids, patient-
controlled analgesia,
fentanyl patch

6.Anasthesia
Opioids are often used as
premedication, before
anesthesia (for their
5.To stop
4. To stop anxiolytic and analgesic
diarrhea :
coughing : In this effect).
Loperamide,
case opioids are Also they can be used as
Diphenoxylate.
used in low doses adjuvants in anesthesia, or in
high doses, combined with
other drugs, as anesthetic
drugs.
They are used for epidural
regional anesthesia.
(Morphine injected in
epidural space or
Phentanyl + local
anesthetics at low doses )
 Nausea and
vomiting

Tolerance,
Dependence

Behavioral restlessness,
tremor, hyperactivity
Constipation, (in dysphoric reaction).
Orthostatic Respiratory Urinary
hypotension depression retention

Increased
intracranial
pressure

Itching,
Urticaria
Pregnancy

In patient with
In patient
head injury (an
with
increase of P co2
pulmonary,
leads to cerebral
cardiac or
vasodilation and to
hepatic
an increased
diseases
intracranial
pressure).
 Typical Atypical
neuroleptic neuroleptic
drugs block drugs block
Dopamine Dopamine
mostly at D1 mostly at D3,
D2 receptors. D5 receptors.

Blocking of
Dopamine
receptors in
nigrostriatal
They are five pathway
types of explains the side
effects
Dopamine
receptors in the
brain D1,D2,
In patients with psychosis there is an
D3, D4, D5.
increase of Dopamine in mesocortical
and mesolimbic pathways in the brain.
Neuroleptic Drugs block Dopamine
receptors in this pathway.
 Orthostatic
Parkinson Hypotension,
Syndrome, Impotence
tardive dystonia
dyskinesia,
Amenorrhea,
Galactorrhea,
Impotence,
Infertility

By blocking
adrenergic
receptors constipation,
urinary
By blocking retention, loss
sedation, dopamine of
confusion, receptors accommodation
weight gain , dry mouth

By blocking
Extrapyramidal
histaminenergic
effects
receptors

Involuntary
movements,
Endocrine Cardiovascular Tardive dyskinesia
effects effects
Psychological
effects

falls positive pregnancy test (because of

Hiperprolaktynemia, which is a result of
Dopamine blocking)
Amenorrhea,
Galactorrhea,
Low libido, drowsiness,
Gynekomastia insomnia, loss of
Orthostatic
concentration,
Hypotension,
confusion Dangerous
arrhythmias due to
QT prolongation
Psychiatric Indications: Schizophrenia
and other psychosis, Schizoaffective
disorder, Mania, Alzheimer (to treat
the behavioral disorders in these Not Psychiatric Indications:
patients), excessive anxiety symptoms Antiemetic effects (because
Neuroleptic drugs block Dopamine
receptor in the Chemoreceptor
trigger zone).
Itching treatment (Phenothiazine
derivatives)

Atypical neuroleptics are

used in patients with :
emotional isolation,
social isolation, loss of
motivation

Combinations:

Lithium or Valproic Sedative drugs are In most cases

Acid is added to added to neuroleptic they are
neuroleptic drugs in drugs in patients who combined with
patients with also have anxious Antiparkinson
resistant psychosis symptoms Drugs
 Convulsions

Neurologic: Parkinson
Syndrome, Dystonia,
Tardive,Dyskinesia

Hyperkinesia

Malignant neuroleptic syndrome

( muscle rigidity, fever, leukocytosis)
Psichologic: Behavioral
disorders, Pseudo
Depression, Toxic
Confusional state

These drugs are considered to

be secure used during
pregnancy, but they can have a
teratogenic effect.

Allergic reactions:
Agranulocytosis, Jaundice,
Skin rash, blood disorders.
 SSRI: They
selectively Attention
stop serotonin when a SSRI
Some of these re-uptake. is combined
They stop Most used with a MAOi.
drugs have similar
Noradrenaline and drug: (this can lead
effects on these
Serotonin re- Fluoxetine to high
neurotransmitters,
uptake (so their synaptic
but more powerful.
action lasts longer) concentrations
of serotonin).

This results in an
elevation of the
synaptic concentrations
of these
neurotransmitters.
 Depression

Depressive phase of bipolar

disorder (when suicide incidence
is very high) : Antidepressants
+Lithium
SSRI are less reported to cause
maniacal crisis, compared to
other antidepressants.
Lamotrigine has shown good
Nocturnal results in bipolar disorder.
eneuresis
Tricyclics Panic disorders
(Imipramine) Panic attacks : Imipramine
SSRI are very effective in panic
disorders.
Sometimes, benzodiazepines are
used instead because they are
better tolerated and have a
quicker effect.
But SSRI should be the first
choice (although it takes weeks for
them to have effect), because
Chronic pain
benzodiazepines cause tolerance.
Venlafaxine

Obsessive compulsive
disorder
Bulimia,
SSRI are effective:
Nervous
Fluoxetine, Fluvoxamine
Anorexia:
Fluoxetine
Social phobia Hyperkinetic
syndrome

Drugs like SSRI are the most Heterocyclics

Amitriptyline, preferred, because (3 rd generation)
Doxepin, they are tolerated are also
Trazodone, better. preferred.
Mirtazapine

SSRI do not
have sedative
effect. Safety
Amitriptyline, in overdose.
Doxepin
New antidepressant drugs are
more popular because they
are better tolerated and have
lower incidence of suicide
attempts.
1/3 of patients does not
respond to antidepressants.
In this case the antidepressant
can be combined with
MAOi are used in atypical
depression (with anxiety,
phobia, hypochondria).
is that first the patient
should take SSRI (mild and
moderate depression).
Than in severe depression
SSRI can be combined with
another antidepressant.
In some cases,
Electroconvulsive therapy is
the only possible treatment.
 They are more severe in old
patients (especially the
anticholinergic effects)

weight gain withdrawal

confusion,
syndrome
aggravation
additive
of psychosis
effects with
tremor seizures other sedative
drugs

hear
arrhythmias
conduction
defects
insomnia
drowsiness
constipation,
urinary orthostatic
retention hypotension

blurred vision

sexual
disturbances
 Sexual Orthostatic
disturbances hypotension
Sleep
disturbances Weight
gain

Venlafaxine: nausea,
somolence, sweating,
dizziness, sexual
disturbances,
hypertension, anxiety

Amoxapine: similar to tricyclics + neuroleptics adverse effects

Maprotiline: similar to tricyclics, seizures are dose related
Mitrazapine: somnolence, increased appetite, weight gain, dizziness
Trazodone, Nefazodone: drowsiness, dizziness, insomnia, nausea, agitation
Gastrointestinal
symptoms

decreased
insomnia tremor anxiety libido, sexual
dysfunction
 Salicylates and
other NSAIDs
are used to stop
the signs and
symptoms of
inflammation.

stabilize the
membrane of
lysosomes

inhibition of the
production of :
Inhibition of
chemotaxis

superoxides
Free
radicals
 COX1 is
found in the
most of the
cells of the
Most NSAIDs COX2 is found in
body, in which
are not proinflammatory
the
selective (they cells
production of
inhibit both
prostaglandins
COX1 and
helps blood
COX2 : for
circulation.
this reason
they have
many adverse
effects).

As antiagregants:
They low the
Aspirin is used as
analgesic for mild to
incidents of
moderate pain. It is not ischemic attacks,
used for severe visceral Angina pectoris,
pain, (headache, coronary
toothache, Rheumatoid thrombosis,
Arthritis or other
Acute
inflammatory diseases)
Myocardial
Infarction,
thrombosis after
bypass
intervention,
cerebral
Used for all ischemia,
inflammatory diseases, cerebral insults,
as a monotherapy or Aspirin is used cerebral vascular
combined with to prevent colon accidents
Glucocorticoids or cancer
immunosuppressors
 The first phase of
inflammation is stopped
because of the inhibition
of COX and PG
production. By inhibiting PG
erythema and
swelling production (that stimulate
diminution pain receptors). The pain
mediators (substance P,
Bradykinin) that transmit
lowering of
the pain impulse are
vassal
potentiated by PG.
permeability

Aspirin lowers By inhibiting

chemotaxis of activation of body temperature thromboxane in the
only in patients thrombocytes (which
leucocytes pro-
with high is a pro-agregant and
macrophages and inflammatory
temperature (by vasoconstrictor) This
polymorphonuclears is cells is
inhibiting PG and effect is irreversible
inhibited inhibited
IL1 in and will last 7-11 days
hypothalamus) (thrombocytes
lifespan)

Salycylism:
(vomiting,
nausea,
tinnitus,
hearing
damage

Cardiotoxicity
 As production of PG is inhibited, it
leads to low blood perfusion

Respiratory
gastric ulcer

Asthma attacks
get worse in
allergic patients

Gastrointestinal
hemorrhage (lower
and upper)
Hepatic

Hepatotoxicity
(Hepatic enzymes Renal
are elevated)

Ulcer
perforation

Renal Toxicity (low blood

perfusion in kidneys: interstitial
nephritis, low glomerular
filtration rate, papillary necrosis)
acute
peritonitis
 Prednisolone has mineral-
corticosteroid effect,
Methylprednisolone has not.
Diffeferent Glucocorticoids have different
anti-inflammatory effect, different way of
administration.

Important drugs in treating

inflammatory diseases,
allergic diseases,
hematologic diseases.

Synthetic
corticosteroids have
anti-inflammatory
imunosupresory anti-
allergy and antitoxic
effect.
 Acute adrenal
Addison disease :
insufficiency:
Hydrocortisone (dose is hydrocortisone 100 mg IV
increased in stressful
every 8 hour until the
situations) + Fludrocortisone
patient is stabilized.
for the mineralocorticoid
effect.

Prenatal lung
maturation

Diagnostic purpose:
Dexamethasone suppression test is
designed to diagnose and
differentiate among the various
types of Cushing's syndrome

Prevention of Neonatal
Respiratory Distress
Syndrome (by treating
the mother)

In case of premature delivery

Cushing Disease (hyper (before 34 weeks) betamethasone is
secretion of A C T H from preferred-it easily passes the
anterior pituitary placenta
adenoma)
Allergic Reactions: Asthma,
Seasonal allergies, Insects Collagen disorders: Lupus
stings, Contact Dermatitis,
Erythematosus,
Urticaria,
Collagenosis, Rheumatoid
Arthritis, Vacuities
Anaphylactic shock:
Prednisolone

Gastrointestinal:
Bowel Blood disorders:
inflammatory hemolytic anemia,
disease Systemic leucosis
inflammations: Acute
respiratory distress
syndrome, arthritis,
bursitis, tenosynovitis

Skin
disorders:
dermatitis,
Kidney:
Seborrhoeic
Nephrotic
dermatitis,
syndrome
dermatoses

Cerebral
Edema
Organ
transplant
Sarcoidosis
 It is better to treat the disease using
medium-acting corticosteroids. If it
is possible the corticosteroids should
be taken on alternative days.
Never interrupt the therapy
immediately, but in a gradual way.
Patients who take corticosteroids,
should be monitored for
hyperglycemia, glycosuria, sodium
and fluid retention, hypertension,
edema, hypokalemia, ulcer,
osteoporosis, subclinical infections.

Glaucoma Ulcer

Cardiac diseases,
hypertension, cardiac
failure

Psychosis
Diabetes

Infections (Tuberculosis,
varicella).

A C T H can be used to stimulate the endogen production of Cortisol.

But today ATCH (Synachten) is used only in patients who require an
increase in androgen levels.
 Insomnia, behavioral
disorders, hypomania,
depression

Eye cataract,
intraocular Edema in
hypertension, patients with
worsening of renal diseases,
glaucoma
Arterial
hypertension,
worsening of
Hyperglycemia,
chronic
worsening of
cardiac failure
diabetes
Acute
ncreatitis Increased
Osteoporosis,
appetite
spontaneous
fractures,
Peptic ulcer
aseptic
necrosis of
femoral head

Gastrointestinal
Myopathy,
hemorrhages
muscles pain and
Edema in
injuries, skin
patients with
stretch marks
renal diseases

Iatrogenic Cushing
Syndrome Adrenal failure (in case that
(Moon face, buffalo glucocorticoids are used more
hump, central and than 2 weeks, they can stop the
truncal obesity thin adrenal activity. To avoid this,
extremities, atrophic the corticosteroids should be
and thin skin, thin hair, taken on alternative days.
hair loss)
 Aldosterone
stimulates H20 and
Na+ absorption in
the collector tube
and the elimination
of K+ and H+.
Aldosterone is It is influenced by
produced by ACTH: in absence of
zona ACTH there is a
glomerulosa of decrease of 50%
adrenal cortex
Increased Aldosterone ( due to
overdose or tumors) causes
hypernatremia, hypokalemia,
alkalosis, increased blood
volume, hypertension

They contribute in
sexual maturation.
DHEA is converted in
periphery in a more
powerful androgen or
estrogen.

Suprarenal
failure at
women
 Connective tissue
diseases, Rheumautoid
arthritis, Lupus, Mixed
anti-inflammatory collagenosis, Morbus
effect+ suppression Bechetrew,
of the immune Spondylarthritis,
system Sjogren's syndrome

Many adverse effects in the blood, gastrointestinal tract, liver, kidney, skin,
reproducitve system

Therapeutic use:
autoimmune disorders,
connective tissue diseases
Very effective, less
adverse effects.
They act against gram
positive, gram negative
and some anaerobic They are very
bacteria. effective for
gram negative
bacteria.
 It inhibits the
synthesis of
bacteria's wall
(by inhibiting
peptidoglycan)

In infections by
Streptococcus, Neisseria
meningitides, beta-lactamase
negative Staphylococcus
Penicillin (bactericide):
Used for prophylaxis,
syphilis, streptococcal
angin

Respiratory
infections, otitis,
laryngitis, pharyngitis,
pneumonia, sinusitis,
Allergic reactions,
Meningitis anaphylactic shock,
gastrointestinal disorders

Urinary Convulsions in patients

infections with renal failure
 They are very
They act against They are less effective effective
gram positive on gram positive against gram
bacteria, but they bacteria and more negative
have little effect effective on gram bacteria and
on gram negative negative bacteria some of them
bacteria. compared to 1 st pass the blood
generation drugs. brain barrier.

muscular post injection pain, renal toxicity, allergic reactions

When administered Sinusitis, otitis, Meningitis.
orally, they are lower respiratory
effective against: tract infections.
urinary infections,
staphylococcal
infections, cellulitis,
soft tissue abscess, They are used in severe
soft tissue infections. gram negative infections,
Cefazolin is resistant to other antibiotics.
preferred for surgical
prophylaxis.

Ceftriaxone is the
Because they first choice for
are effective Gonorrhea
against infections.
anaerobic
bacteria they
are used also Hospital-acquired
in peritonitis, infections (combined with
community aminoglycosides) . Sepsis.
pneumonia In patient with
immunodeficiency.
 It is very nefrotoxic. Not for systemic use.
Only for topic use in the skin (pomade
combined with Neomycin or Polymyxin).
For open wounds or injuries of pleural
cavity (Bacitracin solution).

Sepsis, bacterial endocarditis, infections by Methicillin

resistant staphylococcus,
(as monotherapy or combined with cephalosporins or
aminoglycosides)
In antibiotic-associated colitis.
 Depending on the dose, they
can be bactericide or
bacteriostatic.

Specter: same as
Clarithromycin
Specter: like Very effective against
Erythromycin is Erythromycin Chlamydia, less
effective on gram + some effective against
positive bacteria, Mycobacteria. streptococcus and
corynebacterium. streptococcus.

Disadvantage:
More
It is more potent than gastrointestinal
Erythromycin. Also it has a adverse effects.
longer Tl/2=6h, so it is
administered only twice a day.
 They inhibit the synthesis of
the 50s subunit (in the
ribosomes) in bacteria.

Erythromycin is First choice First choice

the first choice for gram for
for positive cocci pharyngitis,
corynebacterium in patients pneumonia,
infections allergic to skin infections,
(diphtheria, Penicillin. soft tissue
sepsis) infections.
In community
pneumonia

In Chlamydia infections
(genital, ocular at the
newborn, respiratory). Erythromycin is also
used for prophylaxis
in patients with
valvular heart
disease before dental
procedures.
 Very effective for
gram positive and
gram negative
bacteria, anaerobic
bacteria.
Lincomycin
derivate

Aspiration
Pneumonia Female genital
infections (septic
Pneumocystis
Combined with an abort, pelvic
pneumonia in
aminoglycoside or abscess).
patients with
cephalosporin, it is HIV
used for penetrating
abdominal trauma
As prophylaxis
before dental
procedures in
patients with
valvular hear
disease

Antibiotic-associated colitis
(Clostridium dificcile)- in this
case Clindamycin should be Liver damage
Diarrhea, nausea
interrupted and
metronidazole or vancomycin
should be administered.

Rash
Neutropenia
 High Toxicity
(it is not used
anymore in
developed
countries)

Rickettsiosis, Thyphoid fever, Meningitis, ear or eye infections when locally used

Gastrointestinal
disorders: Gray baby syndrome (vomiting,
vomiting, muscle flaccidity hypothermia,
diarrhea grey skin color, circulatory
collapse).

Inhibition of bone
marrow: aplastic
anemia, leucopenia,
thrombocytopenia,
Oral and
bone marrow aplasia
vaginal
candidiasis,
dysbacteriosis
 They are very
effective on gram
negative enteric
bacteria.

Sepsis, bacteremia, endocarditis,

hospital-acquired infections,
Pseudomonas Aeruginosa
infections.

High renal toxicity: renal papillary

necrosis, interstitial nephritis,
decreased creatinine clearance,
increased aminoglycosides plasma
concentration, renal failure

In high doses:
Curare-like effect:
Chochlear damage (irreversible)-
Respiratory paralysis
more common with Neomycin,
(treated with calcium
Kanamycin, Amikacin
gluconate +
Vestibular damage (reversible) -
neostigmine)
more common with
Streptomycin, Gentamycin
 Urinary tract
infections.

Pneumocystis pneumonia,
lower respiratory tract
bronchitis and pneumonia,
upper respiratory tract
infections.

Urethritis
Intestinal
infections, Prostatitis
salmonellosis,
shigellosis, E.coli
Toxoplasmosis
infections.
infections

Urinary disorders: urine crystals

(drug precipitation), hematuria,
calculosis, renal obstructions.

Nausea,
vomiting,
Allergic reactions, diarrhea.
bone marrow
aplasia, leucopenia,
granulocytopenia,
megaloblastic
anemia.
 Atypical
pneumonia Urinary tract
infections (multi
resistant bacteria),

Urethritis,
cervicitis, Diarrhea from
shigella, salmonella
or E.coli

Soft tissue
infections,
bone and Photosensitivity
articulations
Headache,
infections
vertigo

Low toxicity
Rash

They can affect

Nausea,
cartilage growth
vomiting,
and cause
diarrhea Arrhythmia
arthropathy
(counterindicated
in patients < 18
years old). Liver damage
 They are very effective on
gram positive and gram
negative bacteria.

Brucellosis and Tularemia

(combined with
aminoglycosides)
First choice for :
— Mycoplasma Pneumonia, Cholera
—Chlamydia,
Lyme disease
—Rickettsia
—and some Spirochaetes
infections
Acne (used in
Pneumonia and low doses for
acute exacerbation a long time)
of chronic
bronchitis They are used in
patients with
peptic ulcer
(against H. Pylori)

Patients treated with tetracyclines,

should not take milk, antacids or iron To avoid
salts (because they form a chelate tetracycline,
complex with metals. deposition in
bones or yellowed
teeth, pregnant
women and
children (< 11
years old) should
not take them.
 Photosensitivity
(sun exposure is
not recommended)

Vestibular
reactions: vertigo,
nausea, vomiting, Anorexia
loss of balance

epigastic
discomfort Renal
toxicity:
Hepatotoxicity: tubular
altered liver necrosis,
function tests, tubular
toxic hepatitis acidosis, drug
symptoms, accumulation
jaundice in kidneys
(except
doxycycline)

Bone and
teeth damage
in children
(counter
indicated)
Gastrointestinal disorders: nausea,
vomiting, diarrhea (most common),
dysbateriosis, mycotic superinfections,
pseudomembranous colitis.
 Inhalation: Maximal
effect after 30 minutes.
Duration: 12 hours Duration: 3-4 hours.
They are used to treat bronchospasm (caused They also can be
by histamine release, leukotrienes , platelet administered orally
activating factor PAF) or as prophylaxis in (tablets).
asthmatic patients.

Most used : Salbutamol It is quickly

absorbed in the
Administration: gastrointestinal
Inhalation (spray) It is
tract.
metabolized
in the liver.
It also can be
administered
IV slowly
during It is
resistant conjugated
asthma and then
For acute excreted in
bronchospasm : 2 attack.
It also can be the urine.
sprays and then it T l / 2 =4-6
can be inhaled used to treat
bronchiolitis hours
every 4-6 hours.
in children.

Tolerance (chronic usage), arrhythmias.

 They relax the smooth
muscle of the bronchi and
inhibit the release of
bronchoconstrictor
substances from mastocytes.

Adrenaline has
bronchodilator
Oral, subcutaneous, inhalation (the most preferred
effect (when
route because it causes less adverse effects).
administered
subcutaneously
or inhaled).

Maximal effect after

15 minutes after
inhalation.
Duration: 60-90
minutes

Tachycardia, arrhythmia, hypertension,

worsening of angina pectoris.

Isopreterenol is a
powerful
bronchodilator.

Arrhythmia,
tachycardia
 Theophylline is
most suitable to be
used as an
antiasthmatic drug.

2. Blocking of
1. Phosphodisterase inhibitor raises adenosine
intracellular AMPc and GMPc receptors.
This mechanism explains also the Adenosine is a
cardiac stimulation. bronchoconstrictor.

Cardiovascular
system:
Bronchi:
arrhythmia,
Bronchodilation
tachycardia,
extrasystoles
Gastrointestinal
tract: increased
CNS: CNS peristaltic,
stimulant, stimulation of
awaking effect digestive
secretions and
enzymes

Asthma
attack
treatment or
prophylaxis
Severe bronchospasm (IV)
 Administration:
inhalation, parenteral

They low bronchial inflammation (by

inhibiting bronchoconstrictor mediators:
prostaglandins, thromboxane, prostacyclins,
PAF, histamine), stabilize mastocytes
membrane and have synergistic effect with
catecholamines.

In children they low bronchial

inflammation or decrease the
sensitivity of the cough reflex.

Prophylaxis in
asthma
(inhalation).

As adjuvant therapy
with Beta2-agonists or
methylxanthines. In chronic usage, due to
accumulation, typical adverse effects
of corticosteroids can be manifested.
 Bronchodilator effect by blocking
acetylcholine receptors in the bronchi.

Most used: Ipratropium (inhalation).

It can be used in high doses because it
has low solubility and can't pass the
blood brain barrier.
Indicated in patients who can't
tolerate Beta2-agonists.

It stabilizes
mastocytes
membrane by
It inhibits PAF inhibiting
in eosinophils, calcium
basophils and entering in
thrombocytes. the
mastocytes.

Asthma
Administration: inhalation
attack
(bioavailability 10%, only 1%
prevention
when administered orally).
Duration: several hours

Severe asthma attack: 0 2 ,

continuous administration
Moderate asthma attack:
of albuterol (aerosol),
Inhalation of beta2-aganonists is
prednisolone or
same effective as adrenaline
methylprednisolone (IV).
injected subcutaneously.
 Before they were the main trea
ulcer and gastric dyspepsia.

They reduce gastric acidity

and increase gastric mucosal
protection.
A single dose of antacid
(taken 1 hour after meal) can
neutralize the acid for 2
hours.

In high doses (especially when dairy products

are consumed), it can lead to hypercalcemia,
renal failure and metabolic alkalosis.

Attention: The absorption

of NaCl can worsen water
retention in patient with
chronic heart failure and
renal failure.
 They react slowly with HC1.
They are combined together,
because Aluminum causes
constipation and Magnesium
causes osmotic diarrhea.
They can interact with other
drugs, inhibiting their
absorption.

They are taken They undergo Oral

orally and are well first-pass bioavailability
abosped in the metabolism in : 50%
gastrointestinal the liver.
tract.

H2- Receptor antagonists

blocks H2 histamine receptors.
So they inhibit the basal
secretion of HC1 (inhibition of
60-70% of HC1 secretion
during the daytime, 90%
during the nightime).
They are specifically effective
in inhibiting the HC1 during
the nightime.
They have a modest impact on
HC1 secretion stimulated by
eating.
 2. Erosive esophagitis (effective in less
than 50% of patients)
Proton Pump Inhibitors are more
effective.
l.Gastroesophagal reflux disease
Patients who have symptoms like
dyspepsia or regurgitation

5. Gastrointestinal
3.Peptic ulcer hemorrhage prevention
Patients should take the drug once a day In patients with stress-
at bedtime. induced gastritis and ulcer
Effective in 80-90% of patients with
peptic ulcer without complications after
6-8 weeks of usage.
Moderate effect in patients with ulcer
caused by anti-inflammatory drugs.
If anti-inflammatory drugs must be
continued for therapeutic use, Proton
Pump Inhibitors should be added.

4. Non-ulcer dyspepsia
Dyspepsia, heartburn,
stomach burn
 headache
fatigue

diarrhea constipation

myalgia

Endocrine system: Cimetidine

inhibits the normal metabolism of
CNS: confusion,
androgens and increases prolactin
hallucinations, agitation
plasmatic level.
(especially in patients
When used chronically, they can
with hepatic and renal
cause gynecomastia, impotence in
diseases)
men and galactorrhea in women.
These effects are more
Cimetidine is an enzymatic inhibitor.
severe with Cimetidine
They are contraindicated during
(its usage is restricted).
pregnancy because they pass the
placenta.

Androgens Prolactin
 They are the most preferred drugs in treating
peptic ulcer.
They are produced in acid resistant capsules.

PPI are inactive prodrugs.

In the
stomach:

The active metabolite inhibits the H / K ATPase.

The production of HC1 stops, because H+ is not secreted anymore.

T l / 2 less than 1.5 h,

These drugs should be
taken 1 hour before
meal, because the peak
plasma concentration
must correspond with
the maximum effect of
the proton pump.
but their duration can
be up to 24h, because
PPI inhibit the proton
pump in an
irreversible way.
It takes 18 hours for a
new proton pump to
be synthetized.
 When the patient takes the drug for When the patient
the first time, not all proton pumps interrupts the drug,
are inactivated. So it takes 3-4 days its effect last 3-4
for the onset of the drug. days more.

Differently from H2- Receptor antagonists,

PPI inhibits the HC1 secretion after eating.
They inhibit the secretion of 90-98% HC1
daily secretion.
1. Gastroesophageal reflux in erosive esophagitis
The drug taken once a day stops the symptoms and 85-90%
of patients are cured.
15% of patients must take it twice a day.
2. Peptic ulcer
3.Non-ulcer dyspepsia
4. Stress-induced gastritis
5. Gastric acid hypersecretory states (Zollinger-Ellison)
6. Gastric neoplasm
 PPI are considered secure drugs.
Only in a few patients: diarrhea, headache, stomach pain

Increased risk for

enteric infections
(because HC1 is
decreased)

It covers the surface of

the ulcer or erosions,
preventing further It stimulates
damage. prostaglandins
and
bicarbonates
It is used to production.
synthetize
prostaglandin
E1.

It attaches to the proteins on the

surface of the ulcer, forming a physical
barrier against caustic damage.
It stimulates prostaglandins and
bicarbonates production.
It can be added to therapy in patients
with ulcer
 stimulate the Acetylcholine,
gastrointestinal substance P
mobility. stimulate
gastrointestinal
mobility.

Metoclopramide and In patients with

Domperidone are also gastrointestinal
Dopamine antagonists in the atony
periphery. Dopamine inhibits
mobility.
By doing so, they inhibit the
antagonist effect of Dopamine
on Acetylcholine and on the
receptors in the trigger zone
(strong antiemetic effect).

Cholinergic
stimulation,
agonists in
serotonin
receptors.
 Prevention of Gastroparesis,
vomiting paralytic ileus,
constipation

Gastroesophageal
reflux

To stimulate breast milk

production
(Domperidone)

In patients who have

problems with
gastrointestinal mobility
(vagotomy or diabetic
patients).

anxiety,
insomnia,
increased agitation,
prolactin involuntary
levels movements
 They act as
They are insoluble, lubricants.
hydrophilic substances
that absorb water and
form a mass of
emollient gel that fills
the colon and increase
mobility

If they are used

chronically they can
cause lazy bowel
syndrome ( they
damage the mesenteric
plexus)
 They are soluble , not absorbable
substances that increase the water
in the bowel.

Chronic
constipation

Flatulence, abdominal cramps,

electrolyte disorders, hypovolemia

Contraindications: In
patients with renal
damage (risk for
hypermagnesaemia)
 They are used for acute
and chronic diarrhea.

does not pass

the blood Can cause
brain barrier constipation.
and does not
have
analgesic
effect.

also does not They stop diarrhea by

have inhibiting bile acids
analgesic elimination.
effect but if Adverse effects:
used flatulence,
chronically it constipation, bowel
can cause disorders.
dependence.
 They decrease mobility
Their use is restricted and because they
can cause dependence and of their
effects on CNS.

It mimics
natural
Somatostatin
pharmacology.

It inhibits the It decreases

secretion of gastrointestinal
gastrin, glucagon, mobility and
insulin, growth gallbladder
hormone, contractions.
serotonin.

Only in rare
It inhibits It also inhibits cases it is used
gastrointestinal and the release of to treat
pancreatic some anterior diarrhea.
secretions. pituitary's
hormones.
 Before
chemotherapy
to avoid
vomiting
caused by
anxiety.
They are
neuroleptics but
also have sedative
and antiemetic
effect.

Combined with other

antiemetic drugs, they can
be used in chemotherapy
 They have a powerful antiemetic
effect by blocking serotonin
receptors in the periphery and in
the vomiting center in the brain.

In chemotherapy to
avoid nausea and
vomiting (administered
IV 30 min before
chemotherapy).
After radiation or after
surgery to avoid
vomiting.

They block H1 receptors and

M receptors of acetylcholine
Therapeutic usage: motion
sickness, vertiginous syndrome,
balance disorders,
chemiotherapy.
 Insulin in the liver:
Inhibits:
-gliogenesis
-the transformation of
fatty acids in amino acids
and keto acids
-the transformation of
amino acids in glucose
In the muscles:
Stimulates:
-protein synthesis
-amino acids transportation
-glycogen synthesis
-glucose transportation
Stimulates:
-the transformation of
glucose in glycogen
-triglycerides synthesis
In the adipose tissue:
Stimulates:
-triglycerides deposition
-transformation of
lipoproteins in triglycerides
-glucose transportation in
the cells
Aspart and Lyspro imitate the
physiological secretion of
Insulin, and are administered
just before the meal.

Regular Insulin (identic

to human insulin)
The only that can be
administered IV

NPH Insuline (It It is essential in hyperglycemic

is a mix of insulin emergencies, diabetic ketoacidosis
with protamine, or in patients with immediately
so its absorption need for insulin:
and onset is Pregnancy , surgery, infection (IV
delayed. injection).
It is combined
with Regular
Insuline or Lyspro
or Aspart
Patients take it 2-4
times a day.
 Lente Insulin. Ultralente Insulin (Human
It is a mix of semilente Insulin) : It can be
insulin 30% (quick onset) combined with multiple
and ultralente insulin 70% doses of fasting acting
(slow onset, long duration). insulin in patients with
diabetes type I.
It helps Maintenance of
Basal Plasma Glucose for
24h in these patients.

Glargine: Only once a day.

Because intermediate acting

insulin takes time to reach the
maximum effect (peak), Lispro,
Aspart or regular insulin is
added before meals.

Administration:
subcutaneous, IV (only
regular insulin), inhalation,
insulin pumps (slow release).
 Insulin
allergy,
lipodystrophy
Hypoglycemia (at the insulin
Treatment: glucose (orally), injection
glucose (parenteral), places).
glucagon, adrenaline.
 Inhibition of insulin secretion
from the pancreas, decrease of
glucagon

The second generation drugs

have less adverse effects and
drug interactions.

Renal, hepatic or hematologic adverse effects

Although they should
be used with caution in
patients with cardiac
diseases and in elderly
patients.

Contraindicated in patients with severe renal or hepatic diseases.

Repaglinide: Rapid onset (1 hour),

duration 5-8 hours

Effective in patients with

Used as monotherapy or altered postprandial
combined with Biguanides. glucose.
 Stimulation Decrease of
Inhibition of Inhibition of glucose
of glycolysis plasma
gluconeogenesi reabsorption in the
in the tissues glucagon
gastrointestinal tract
concentrations

Used as monotherapy or
combined with Insulin
secretagogues or
Thiazolidinediones in
Metformin is type 2 diabetes.
indicated in insulin
resistant-patients.

It does not cause hypoglycemia

or weight gain.

In patients with
In alcoholism.
severe hepatic or
renal disease
 Their receptors are found in the muscles, liver and adipocytes.
By increasing the transcription of some specific genes (genes
related to glucose and fats metabolism, adipocytes
Particularly in differentiation), they reduce insulin resistance.
diabetic patients, they
increase adipocytes
glucose uptake.

When used as monotherapy, they

Hepatotoxicity
have similar effects like
Biguanides or Sulfonylurea, but
delayed onset.
They can be combined with
Sulfonylurea or Insulin, but there
is risk for hypoglycemia.
Contraindicated during
pregnancy.
 By inhibiting alpha-glucosidase, they
inhibit the ability of the patient to break
down complex carbohydrates
(disaccharides and oligosaccharides) into
monosaccharides (only they can be
absorbed in the gastrointestinal tract).

Usage: Before meals

Used as monotherapy or
combined with sulfonylurea
in type 2 diabetes.

Hypoglycemia
Flatulence, when
diarrhea combined with
sulfonylurea.

Abdominal
pain Contraindicated in
patients with renal
diseases.
 They inhibit the
increased thyroid
hormones
(hyperthyroidism).

Propiltiouracil is
absorbed more quickly
so it reaches its peak
concentration after 1
hour.

Methimazole is ten In pregnancy Propiltiouracil is the

times more powerful first choice because it has more
than Propiltiouracil. affinity with plasma proteins, and it
has more difficulty passing the
placenta.

2. inhibition of MIT and

DIT coupling.
3. Propiltiouracili
inhibits T4
conversion into T3
in the periphery.

1. Inhibiton of
peroxidase (the
enzyme that is
responsible for
iodine
incorporation into
the thyroglobulin.
 Severe Severe hepatoxicity.
agranulocytosis Blood tests and liver
function tests should be
done regularly.
Arthralgia

Skin rash,
dermatitis,
lupus-like
syndrome

Although T3 is more
potent than T4

T3 is not used because its T 1 / 2 is

only one day and it should be
taken several times a day.

This would increase the risk Levothyroxine T1 / 2 = 7 days

for adverse effects. (it is taken once a day).
Primary hypogonadism: In patients
with deficient estrogen production
caused by primary ovarian
insufficiency, premature
menopause, castration,
menopause).
Treatment should be started at age
11 -13 in order to stimulate
secondary sex characteristics and
growing up processes. In this way
psychological problems can be
avoided.

Postmenopause hormone replacement

therapy: to oppose the effect of estrogen
deficiency: vasomotor symptoms, sleep
disorders, genital atrophy, osteopenia,
osteoporosis, spontaneous fractures,
acceleration of atherosclerosis, psychological
disorders.
It also reduces the risk for acute myocardial
infarct, stroke.
Estrogens and progestatins can be used to stop
ovulation in patients with severe dysmenorrhea
or to stop ovarian function in patients with
hirsutism or amenorrhea.
The lowest possible dose should be used.

The linkage of estrogens with cancer is not clear.

There is a little increased incidence of breast cancer in
patients who take estrogens for a long time.
Studies have shown that the patients who take only
estrogens, have an increased risk for endometrium
carcinoma (especially in women who take estrogens more
than 5 years).

There are reported cases

of infertility, ectopic
Other adverse effects: pregnancy, premature
delivery.
Migraine worsening

Breast pain

Vomiting

Endometrium
carcinoma,
Breast growth breast cancer,
Hyperpigmentation undiagnosed
Hypertension. hemorrhagies,
thromboembolism ,
thrombosis,
varicose veins,
hepatic diseases.
 They can used to delay premature
delivery, in women who have
difficulty to get pregnant, in women
with low basal temperature, in
If Progestatins are premenstrual syndrome.
used for a long time,
it takes the ovulation
a long time to start Dysmenorrhea,
again. Endometriosis ,
Hormone bleeding.
Women should not replacement
take them, if they are therapy and
planning pregnancy. contraception

HDL lowering, increased risk for breast cancer.

Hypertension.
 Administration
route: orally, Endometrial
parenteral, hypertrophy,
implants. thicker cervical
mucus.
Inhibition of Breast growth,
ovarian function, breast pain.
inhibition of
ovulation.

Mild or
Mild adverse effects: moderate
hemorrhage.

Vaginal infections, amenorrhea, vaginal

spotting.
Severe adverse effects:
thromboembolism, acute
Weight gain, hyperpigmentation
myocardial infarction,
cerebrovascular accidents,
gastrointestinal disorders,
depression, cancer, erythema
nodosum.

Acne
exacerbation,
hirsutism
 Effective if used until 72
hours after coitus.
Effective in 9 9 % of cases.

Nausea,
vomiting,
headache
Vertigo,
cramps.

Administration: orally (low doses),

implantable, intrauterine device,
combined with estrogen

Effective contraception
with depot
Spotting medroxyprogesterone
acetate, injectable every 3 j
months.
Inhibition of ovulation for
14 weeks.
Not suitable
in women
that want to
get pregnant
in the near
future.
 It stimulates ovulation in
women with ovulatory
dysfunction (most of them
have polycystic ovary
syndrome.
Clomifene inhibits estrogen receptors in
hypothalamus, inhibiting negative
feedback of estrogen on gonadotropin
release.

Depression,
fatigue

Nausea, Increased size

vomiting of ovaries

Breast growth
Weight gain
Frequent
urination.
Multiple
pregnancy
 It inhibits 5-
alpha
reductase,
inhibiting the
effect of
Dihydrotestoste
rone on the
prostate.

Used in patients with benign

prostatic hyperplasia.

It blocks
androgen
receptors in
target tissues.

Flutamide (used as a treatment in

women with excessive androgens).

To control sex drive in

Used in women
men with severe
with hirsutism,
hypersexuality
acne, ovarian cysts.