Drugs

Medi cati on
List
RATE
Pharmacology
And
Therapeutics
(Spring
Term)
Drug
Name
ATROPINE
Action
Peripherally
Acting
Muscarinic
Antagonist
–
HEART
(Antimuscarinic
Drug)

IPRATROPIUM
(bd,
td)
Peripherally
Acting
 Muscarinic
Antagonist
–

The
drugs
used
to
modify

bron c practice. hial

BRONCHI
funct io n
in TIOTROPIUM
(od) By
2.

clini cal directly

(Antimuscarinic targeting Ideally
Drug) bronchial
admi nist tissue, ered
via a
inhalation lower
because: dose
1.Drug is
directed
to required
the so
target fewer
tissue systemic
Clinically effects.
useful
 in
conditions
such
as
ASTHMA
and
COPD.
OXYBUTYNIN
TOLTERODINE
Peripherally
Acting
Muscarinic
Antagonist
–
(Antimuscarinic
Drug)

Useful
to BLADDER
modify
bladder
function.
Tolterodine
is
relatively
specific
to
bladder
β2
 receptors
than
Clinically
useful
in:
OVERACTIVE
BLADDERS reflex Lecture
Use vagus 1
After activity
myocardial which
infarction depresses
(where the
there heart
is activity/HR,
typically and
a is
lot therefore
of reversed
Reference by
P&T atropine)
Spring other
The drugs
drug (like
•
• URINARY
tightens atropine).
decreased
•
FREQUENCY
the
parasympathetic
sphincter
INCONTINENCE
control),
(increased
so
sympathetic,
decreased
However,
leakage.
these
drugs
do
not
work
on
stress
incontinence
(i.e.
 TROPICAMIDE
Peripherally Lecture
Acting 1
Muscarinic
Antagonist in
– the
EYE eye.
(Antimuscarinic
Drug)

GLAUCOMA
DILATION
OF
THE
PUPILS
Tropicamide
is
a
diagnostic
drug
which
is
designed
for
use increased
only intra-‐abdominal
P&T pressure).
Spring
ADVERSE
 EFFECTS
OF Erectile
ALL dysfunction
Bronchodilation ANTIMUSCARINIC
DRUGS (perhaps
GIVEN good
side SYSTEMICALLY:
Dry effect?)
mouth •
(most • Constipation
•
•
•‘Too
comm • Good’ onest
•
• Sphincter
sympto – m)
Centrally Decreased
Acting detrussor
activity Muscarinic
so Antagonist
increased (Antimuscarinic
urinary
Dru bladder g)
retention
BENZHEXOL
Centrally Dry
Acting Eyes
Muscarinic
Blurred
Antagonist
vision
(Antimuscarinic
Drug) Increased
intraocular
Acts
in
the
BRAIN.
Hyoscine
is
similar
to
atropine,
but
more
sedating.
Widely
Used
as Lecture
to used 1
treat in
Parkinson’s travel/sea-‐sickness
Disease (labyrinthine
P&T sedative).
Spring
HYOSCINE
 Converting the Lecture
Enzyme Angiotensin 2
(e.g. conversion
Inhibitors
LISINOPRIL) ENALAPRIL, of•
• Heart
Angiotensin angiotensin
•
Converting I • failure
•
Enzyme into
•
Post-‐myocardial
Inhibitors angiotensin
infarction
(ACE-‐Inhibitors II.
/ Diabetic
ACEI) neuropathy
Progressive
These renal
inhibit insufficiency
the
somatic Patients
form at
of high
the risk
ACE of
enzyme, cardiovascular
so disease.
prevent
Uses:
Hypertension
P&T
Spring
Side
 Effects:
Cough Hypotension
Angiotensin Urticaria
Receptor /
(e.g. Angioedema
LOSARTAN,
Angiotensin Hyperkalaemia
Receptor (Contraindications
Blockers –
(ARB/AIIA) take
Acts care
as • if
•
antagonists • the
of •

the patient
Type is,
I • or
•
Receptors may
(AT )1
be
prescribed,
rece Blockers ptor K+
angiotensin
for
This II. supplements
IRBESARTAN) prevents or
the K+
renal sparing
and diuretics
vascular which
actions may
of further
angiontensin
They
are
widely
used
in
hypertension
as
an
alternative
to
ACEI
Uses:
Similar
to
ACEI
(fewer
side
effects),
and
are
used
in
chronic
heart
II.failure

patients
who
cannot
tolerate
•
•
ACEI.
Side Hyperkalaemia
Effects: (Contraindications
Hypotension •
–
Inhibits
• take
the care
enzyme if
activity
•
•
the
of
renin, patient
so is,
conversion
• or
Antagonist of Lecture
prev ents may
• angiotensinogen 2
the
• be
into
P&T prescribed,
angiotensin
Spring K+
I
Direct supplements
Renin or
Ultimately
(e.g. prevents
K+
ALISKIREN) the
sparing
formation
diuretics
Direct of
which
Renin angiotensin
may
Antagonist II
further
increase
New
blood
class
of
K+
Alternative
agents
levels)
therapeutic
intervention
Foetal
 •
PHENYLALKYLAMINES
(e.g. Calcium
•
Verapamil) •
Cha nnel
Blockers
(CCB) •
Rate •
•
ANGINA
Slowing
Treating
Calcium •
Paroxysmal
Antagonists
SVT
Cardiac
(Tachycardia
and
originating
Smooth
Muscle
above
Actions
the
Uses:
ventricular
HYPERTENSION
tissue)
Reduce
Ca2+ Atrial
entry Fibrillation
into
cardiac
and
smooth
muscle
P&T
Spring
Unwanted
Actions: cells Lecture
Bradycardia 2
and Negative
AV inotropy
Block effects
Negative (decrease
Ionotropic contractility)
Effect: Inhibits
Verapamil AV
> Node
•
Ditiazem • Conduction
Worsening
BENZOTHIAZEPINES •
of
Calcium Heart
Channel Failure
Bloc(e.g. kers Constipation
Diltiazem)
(CC B)
Rate
Slowing
Calcium
Antagonist
Cardiac
and
Smooth
Muscle
Actions
Uses:
HYPERTENSION
Reduce
Ca2+
entry
into
cardiac
and
smooth
muscle
Unwanted
Actions:
Bradycardia
and
AV
Block
Negative
Ionotropic •
Effect: cells
Verapamil
>
Ditiazem •
• ANGINA

•
•
Worsening
• of
Heart
Failure
Constipation
 •
(e.g.
Amlodipine) DIHYDROPYRIDINES
Calcium •
Channel • ANGINA
Blockers (Dihydropyridines
(CCB) are
•
Non-‐Rate • preferred
Slowing • here)
Calcium
Antagonist
Smooth
Muscle
Actions
Only
Uses:
Inhibits
Ca2+
entry
into
vascular
smooth
muscle
cells
HYPERTENSION
Unwanted
Actions:

Beta
 Blockers
(β-‐Adrenoceptor
e.g.
Post
ATENOLOL,
Myocardial-‐Infarction
Competitive
Antagonists Cardiac
of Dysrhythmias
Beta-‐Adrenoceptors
Atenolol Chronic
– Heart
Selective Failure
β1 Hypertension
Bloc ker Also Lecture
•
Antagonists) Bisoprolol • in: 2
•
– •
BISOPROLOL, • o Thyrotoxicosis
•
Sele ctive
PROPRANOL o Glaucoma
β1
OL
blocker
o Anxiety
Propranolol
States
–
Non-‐Selective
o Migraine
β-‐Blocker
Uses:
o Prophylaxis
Angina
P&T
o Benign
Spring
Essential
Ankle
Tumour
Oedema
Mechanism
of
Action:
Competitive
antagonist
of
Beta
Adrenoceptors
Use Headache/Flushing
in
Hypertension: Palpitations
No (Reflex
longer tachycardia)
1st
line
treatment

Many
clinically
used
agents
• show
• selectivity
(e.g.
atenolol
•
• for
B1)
preferred
Effects: • They
Reduce do
cardiac not
•
output • reduce
Reduce
Unwanted
•
•
PVR
renin
Actions: release
Can by
be the
due kidney
β2
to
in• May
either
partial
•
diminish
the •
selectivity.
• NA
actions •
on • release
•
β1 by
and sympathetic
sometimes
•
•
nerves
due Lipophilic
to agents
(e.g.
ORGANIC propranolol)
(GTN) NITRATES Mechanism
exert
(e.g. and not
central
nicorandil) glyceryl fully
trinitrate sympatho-‐inhibitory
understood,
actions.
but
Mechanism B1
of antagonists
 Action:
Uses:
Angina
Stimulate
the
release
of
NO
in
smooth
muscle
cells
P&T
Spring
Worsening
of
cardiac
failure
(nitrate
based
Acute
drugs)
and Lecture
• chronic
Stimulate 2
• heart
guanylate
• failure
cyclase
(NICORANDIL)
BP
• control
• Causes
during
•
VASODILATION
anaesthesia
Effects: Bradycardia
Reduces (heart
PRELOAD •
block)
• Reduces
(venous • Bronchoconstriction
return) AFTERLOAD
Pharmacokinetics: Hypoglycaemia
(peripheral
Nitrates resistance)
(in
undergo diabetics
• Minor
extensive the
on
• Effects:
first liver.
insulin)
• Antiplatelet
pass agents,
GTN
metabolism Increased
coronary
is
risk
by artery
associated
often
Unwanted of
with given
new
Effects: vasodilators
vasodilation.
sublingually
Hypotension, onset
for
headaches of
rapid
and diabetes
angina
relief.
flushing Fatigue
Excess Longer
Use: acting
Cold
associated transdermal
extremities
with patches
and
tolerance. available
worsened
(e.g.
peripheral
GTN
artery
and
disease
isosorbide
Impotence
mononitrate)
 Anti-‐Arrhythmic
e.g. Lecture
Drug adenosine, s •
3
tachyarrhythmias Treat:
amidoarone, •
(SVT)
•
dronedarone
SUP R Short-‐lived AVENTRICULAR
ARRHY THMIA
•
action S
(20-‐30s)
the Verapamil
(CCB) •
metabolism
ADENOSINE: Safer
of
to
Used ATP.
i.v. use
to than
Acts
terminate verapamil.
on
supraventricular adenosine
P&T receptor
Spring (A )
1

Mechanism to
of hyperpolarise
Action cardiac
Adenosine tissue
is and
an slow
endogenous conduction
through
mediator AV
produced node.
by
Adverse
Effects:
Chest
pain
AMIODARONE
&
DRONEDARONE:
Used
in
supraventricular
and
ventricular
Adverse
Effects:
Amiodarone •
accumulates • Dyspnoea
•
in • (shortness
the of
body breath)
(t1/2 •
tachyarrhythmias
10-‐100d) Dizziness
• Complex
Nausea
mechanism
of
action
•
• –
probably
involves
multiple
ion
channel
block.
 Has
FIBRILLATION
a
and
Treat: number
VENTRICULAR relieves
of
the
ARRHYTHMIAS important
(Amidarone, symptoms
e.g. adverse
Dronedarone) of
flecainide, effects:
CHRONIC
Treat: lidocaine,
COMPLEX Lecture
o Photosensitive

(e.g.
and 3skin
supraventricular ventricular rashes
arrhythmias
arrhythmias) HEART
FAILURE.
o Hypo-‐
disopyramide
and
DIGOXIN Hyper-‐
and Long
thyroidism
t1/2
CARDIAC •
Cardiac of
Pulmonary
GLYCOSIDES ~40hours
fibrosis
Glycosides
P&T •
Corneal
Spring • Narrow
• deposits
therapeutic
Digoxin
slows window
Neurological
ventricular
rate
and
An
in • gastrointestinal
immune
ATRIAL •
Mechanism • disturbances
Fab
•
of (Digibind)
Action: • is
Inhibits Dronedarone
available
is
for
Na-‐K-‐ATPase
(Na/K This
Pump) results
in
the
increased
accumulation
of

intracellular
Na+,
so
increases
intracellular
Ca2+
(as

more
Na+
can
be
exchanged
out
of
the
cell
for
Ca2+
via
the
So
•
POSITIVE •
INOTROPIC Central
EFFECT. vagal
Adverse stimulation
Effects: • causes
pacemaker
(Common reduced
activity)
and • rate
severe) of
Dysrhythmias N.B.
conduction
hypokalaemia
(e.g. through
and Lecture
•
AV AV
hypomagnaesia 3
Conduction node
(usually
block, a
ectopic
P&T consequence
Spring of
IVABRADINE diuretic
use),
Use: lower
Treating the
angina threshold
in for
patients
with digoxin
normal
sinus toxicity.
rhythm.
Mechanism
of
 Action:
Blocks
If
Channel
(f-‐funny)
(an
Na-‐K
channel
important
Contraindications:
Severe
bradycardia
Adverse
Effects:
Bradycardia
•

in
•
Sick
the
Sinus
SA
Syndrome
• node)
•
• 2-‐3rd
• Slows
• degree
heart
heart
rate.
block
•
• Cardiogenic
•
Shock
Recent
MI
 CARDIAC
(e.g. effect CONTRACTION
INO Dobutamine on TROPES
and heart Dobutamine
– rate)
β1 Milrinone) Have
inotropic
adrenoceptor effects
AGONIST by
(with inhibiting
little breakdown
of

Milrinone cAMP
– in
Phosphodiesterase cardiac
inhibitors. myocytes.

Agents
that
INCREASE
THE
FORCE
OF First-‐degree
CARDIAC heart
Used block
to
treat Ventricular
acute and
heart supraventricular
failure arrhythmias
 in
some
situations
(e.g.
after
Despite
increasing cardiac
cardiac surgery
contractile inotropes
or
function, have
in
so reduced
cardiogenic/septic
far survival
shock).
all doxazosin in •
and chronic
•
heart
failure.
(clonidine,
ALPHA
moxonidine) BLOCKERS
phenoxybenzamine) (e.g.
Alpha
Blockers
–
antagonists
of
α1-‐adrenoceptors
and
SYMPATHOLYTICS
Alpha
blockers
can
be:
COMPETITIVE
e.g.
 dozazosin
P&T
Spring
Used
occasionally
in
combination
with
anti-‐hypertensives
in
Phenoxybenzamine adrenoceptor
resistant Lecture
– hypertension,
agonist) 3
combined and IRREVERSIBLE
but
with e.g.
moxonidine
routine
a use phenoxybenzamine
(imadazoline
beta-‐blocker, agonist)
has
provides inhibit
declined
since
long-‐lasting
sympathetic
Sympatholytics alpha
shown
outflow
Centrally blockade
to
from
acting in
be
the
anti-‐hypertensive catecholamine-‐secreting
associated
brain,
agents with
and
e.g. tumours
increased
occasionally
(e.g.
clonidine rates
(α *
phaeochromacytoma)
used
2
of
(*α2 as
chronic
is antihypertensive
heart
an agents.
inhibitory failure.
alpha
adrenergic
receptor)
 VASOCONSTRICTORS
e.g. Lecture
Sumitriptan •
3
•
Sumitriptan Constricts
used • some
•
in large
migrane arteries
treatment partialand
SUMITRIPTAN agonist
inhibits
Agonst of trigeminal
at 5HT1
nerve
receptors)
5HT1D transmission
Receptor
(Serotonin Used
Receptor) to
P&T treat
Spring migraine
Other attacks.
ergot Contraindication
alkaloids in
are patients
also with
used coronary
in disease.
migraine
(usually
act
as
ADRENALINE
Endogenous
catecholamine
Produced
by
the
adrenal
gland,
used
in

cardi ac
anaphylactic Lecture
arrest
shock. 3
and
P&T Histaminergic
Spring (H ),
1

Muscarinic
PROMETHAZONE Cholinergic
-‐
(M)
AN and TI-‐EMETIC
•
Dopaminergic Anti-‐emetic
Acts (D )2

as Receptors
a
competitive Potency:
antagonist H1

at >
Acts M
centrally >
(labyrinth, D 2
NTS
and
vomiting
centres)
to
block
Use
an
anti-‐emetic
in:
Motion
Sickness
(Prophylaxis,
and Disorders
during of
onset) Labyrinth
P&T (e.g.
Spring Meniere’s)

Other Hyperemesis
Uses: Gravidarium
Relief Pre
activation Lecture
of
of & 10
allergic
the Post-‐Operatively
symptoms • •
(sedative
vomiting
•
•
•
and
centre.
anti-‐muscarinic

effects
• are
•
•
also
useful)
Unwanted Onset
Effects: of
Dizziness action
•
• Tinnitus
Pharmacokinetics: 1-‐2h
•
•
Oral • Fatigue
administration • Maximum
•
METACLOPRAMIDE Sedation
effect
-‐ at Excitation
ANTI-‐EMETIC aroundin
Primarily 4h•• excess
Dopamine •
•
Receptor Duration
Convulsions
Antagonist of (children
actionmore Potency:
D2 – susceptible)
>> 24h
H 1
Antimuscarinic
>> side-‐effects
Muscarinic
Receptors
P&T • Order
Spring of
antagonistic
potency:
Anaphylactic
D emergency
2

>>
H1
>>
Night
sedation
Muscarinic

and
Receptors
insomnia
Use:
Used
to
treat
nausea
and
vomiting
associated
with:
• Uraemia
–
Severe
renal
failure

• Radiation Lecture
Sickness 10

• Gastrointestinal
Disorders

• Cancer
Chemotherapy
(high
doses)
e.g.
cisplatin

(intractable
vomiting)
 HYOSCINE

-‐
(ANTI-‐EMETIC)
Muscarinic
Receptor
Antagonist
(Anti-‐Muscarinic)
ONDANSETRON
5HT3
RECEPTOR
ANTAGONIST

Mode
of
action Mode
of
action:
• Acts
to
BLOCK
TRANSMISSION
IN
VISCERAL

AFFERENTS
and
CTZ
 Filtered • Order
Clinical
by of uses:
Carbonic antagonistic
•
the
anhydrase o Prevent
•
glomerulus, potency:
e.g. inhibitors
• ACUTE
Muscarinic
Mannitol but
are >>> renal
not
weak D2 failure
DIURETIC: diuretics. =
(by
OSMOTIC reabsorbed. H1 increase
P&T
DIURETIC They
•
Spring H2O
Osmotic • Increase
act excretion) Lecture
Diuretics the
mainly 10
are: osmolarity
on Receptors(urine
of
the production
Pharmacologically tubular
PROXIMAL • Actsceases)
inert fluid
TUBULE, centrally,
(and
to: especially
in
plasma) the o Reduce
ANHYDRAS so VESTIBULAR
• Prevent INTRA-‐CRANIAL
E reduce NUCLEI,
the PRESSURE
the
reabsorption NTS,
INHIBITOR
osmotic
of VOMITINGo Reduce
S
gradient.
HCO3-‐ CENTRESINTRA-‐OCULAR
and to PRESSURE
DIURETIC Na +
block
activation
CARBONIC of Increase
o
• H2O Plasma
e.g. reabsorption
Therefore, vomiting
Osmolarity
centres.
Acetazolamine is
they
Increased
delivery an
of increased
HCO3-‐ K+
and loss.
Na+
to
the
distal INCREASED
tubule, TUBULAR
so FLUID
OSMOLARITY
and
DECREASED

H2O
REABSORPTION
IN
THE
COLLECTING
DUCT.

Therefore,
they
INCREASE
URINE
VOLUME
(increased
H O
2
 Loop Clinical
Effects DIURETIC
Diuretics of
Uses LOOP
are Loop
• Cardiac
DIU RETICS POWERFUL Diuretics
Diuretics Failure
(e.g.
e.g. (Furosemide) that Frusemide)
• Hypertension
act
on (Initially
Frusemide a
decreased
DIURETIC Large
blood
THIAZIDES the increase
volume
ascending in decreases
e.g. limb urine
–
Bendrofluazide of volume
in
the and
the
loop Na ,
long
+

of Cl
term,
-‐

Henle. and
thiazides
K+
cause
loss
(+Ca2+
INHIBIT
(Bendroflymethiazi
Na+ and vasodilation)
de
and Mg2+
• Severe
Cl-‐ Loss)
Resistant
Reabsorption Oedema
in
the CLINICAL
• Idiopathic
ascending USES:
Hypercalciuria
limb (Stone
• OEDEMA
by Formation)
 • ALDOSTERONE DIURETIC
RECEPTOR POTASSIUM
ANTAGONISTS
SPA DIURETICS • INHIBIT RING
e.g. Na+
Spironolactone REABSORPTION
–
Amil (and oride,
therefore
Classes the
of
e.g.
o
K+
SPIRONOLACTONE
Sparing
secretion
Drugs of
Potassium K+)
in
Sparing the
early
Diuretics distal
e.g. tubule
(by
Amiloride, 5%)

Spir onolactone

+• INHIBITORS
TRIPLE
of
THERAPY:
ALDOSTERONE-‐SENSITIVE
ANTIBIOTICS
Na
+ • INCREASED
PPI TUBULAR
FLUID
(FOR OSMOLARITY
–
PEPTIC so
ULCERS
CHANNELS
 –
ANTI-‐ULCER peptic
DRUGS ulcer
• METRONIDAZOLE
– disease
(active
ANTIBIOTICS against
•A
anaerobic
Triple single
Therapy bacteria antibiotic
is
-‐ and not
sufficiently
Example protozoa) effective
1 or –
partly
‘Triple AMOXYCILLIN
Therapy’ due
is (broad to
currently spectrum the
the antibiotic) development
best – of
practice depending resistance.
in on
treating •

pattern
of THREE
local PROBLEMS
resistance. WITH
AGAINST TRIPLE
H. THERAPY:
PYLORI) • COMPLIANCE
•CLARITHROMYCIN
antibiotics
with DEVELOPMENT
•
a
OF
RESISTANCE
 PROTON •
antibiotic
PUMP efficiency
INHIBITOR possibly
(PPI) by
improves increasing
PROTEIN
PUMP gastric
e.g. pH
which
OF
OM INHIBITORS improves
GASTRIC EPRAZOLE
TREATMENT
stability
ACID
OF
and
SECRETION ANTI-‐ULCER
GASTRIC
DRUGS
ULCERS
– absorption.
INHIBITORS

Mechanism Inhibit
of basal
Triple
Action: and
Therapy
stimulated
–
gastric
Example
acid
2
secretion
• H2
from
Receptor
the
Antagonist
parietal
cell
• Clarithromycin
by
>90%
• Bismuth
 HISTAMINE
•
(H2) OF •
•• Well
PPIs
TYP RECEPTOR GASTRIC E
2 Inhibit
ACID are absorbed
ANTAGONISTS gastric
SECRETION Relapses
irreversible
e.g. RANITIDINE Unwanted
acid likely
inhibitors
effects
CIM secretion after
of are ETIDINE,
ANTI-‐ULCER by withdrawal
the rare
approximately of
H+/K+
DR DRUGS CYTOPROTECTIVE
60% treatment
ATPase UGS
– DRUGS
and • Inactive
INHIBITORS are at
less neutral
effective pH
Orally at
administered healing • As

ulcers it
than is
CYTOPROTECTIVE PPIs a
e.g. weak
SULCRAFATE base,
ANTI-‐ULCER it
DRUGS accumulates
– in
These the
drugs cannaliculi
ENHANCE
MUCOSAL of
parietal
 PROTECTION

This
is
a
polymer
containing
aluminium
hydroxide

CYTOPROTECTIVE
e.g.
BISMUTH
ANTI-‐ULCER MECHANISMS
DRUGS and/or
– BUILD
A
These and
PHYSICAL
drugs sucrose
BARRIER

ENHANCE octa-‐sulphate.
over
MUCOSAL the
PROTECTION ulcer.
Mechanism
MECHANISMS
of CYTOPROTECTIVE
DRUGS and/or
DRUGS
BUILD
Acti A on:
CHELATE PHYSICAL
BARRIER

over
the
ulcer.
 • Acquires
DRUGS CYTOPROTECTIVE a
DRUGS strong
negative
charge
CYTOPROTECTIVE in
an
e.g. acid
MISOPROSTAL Mimics
ANTI-‐ULCER the environment
DRUGS action
– of • Binds
(A locally to
stable produced positively
prostaglandin
•
prostaglandins
• Neutralises
charged
analogue) groups
acid,
to in
raises
ANTACIDS maintain large
gastric molecules
ANTI-‐ULCER the pH,
DRUGS gastroduodenal
reduces (proteins,
– mucosal glycoproteins)
ANTACIDS pepsin
barrier. resulting
Mainly activity in
salts gel-‐like
of
Al3+ complexes.
and
Mg 2+
•These
Misoprostal coat
and
may protect
the
be ulcer,
limit
co-‐prescribed (non-‐
with steroidal
oral anti-‐inflammatory
NSAIDs •Decrease
drugs),
LDL
when
to
used
some
chronically:
LIPID extent
LOWERING
Bile •However,
• NSAIDs
Acid they
block
Sequestrants increase
the
hepatic
COX
Bile synthesis
enzyme
required
Acid of
for
Sequestrants: LDL
PG

synthesis
•Therefore,
from
they
arachidonic
are
acid

DRUGS not
• Therefore,
-‐ very
there
effective
is
a
REDUCTION
in
the
natural

factors
that
inhibit
 LIPID
Mechanism
DRUGS of
LO -‐ WERING
Action: STATINS
(e.g.
Atorvastatin,
Ros Simvastatin, Statins uvastatin,
block
Pravastatin, the LIPID
HMG-‐CoA
Fluvastatin)
LO Reductase WERING
Mechanism
Enzyme FIBRATES
of
Action:

Activate
PPAR
Alpha
receptors
à

DRUGS Decrease
-‐ in
fatty

acids
and
triglycerides
 LIPID
Decreases Cholesterol
•
DRUGS cholesterol, o Anti-‐Coagulant
Synthesis
LO – WERING
LDL Pathway: NICOTINIC
o Anti-‐Platelet
and •
•
triglyceride • Geranyl
ACI D
o Anti-‐Inflammatory
pyrophosphate
levels
and
Mechanism and
•
DRUGS Shown
Farnesyl
of
increases to
– action: Pyrophosphate Other
HDL – reduce
inhibits
levels risk
effe cholesterol cts:
in
these
absorption
DRUGS are trials
– lipids
Side LIPID
involved
effects
LO WERING in include:
•
EZETIMIBE the
• modification
o Flushing
Cholesterol
LIPID of and
Ester
Hepatic
LO Transfer WERING proteins
Effects
Protein (e.g.
rho
(CETP) and
and ras)
reverse CETP
inhibitors
• These
cholesterol increase
transport HDL lipids
can
levels
(since and
Must reabsorbed.
be
activated •Reduces
by cholesterol
the levels
liver, by
secreted they 15-‐20%
into cannot
the be • May
bile broken be
down) used
in
However combination
– with
they statins
increase
blood e.g.
pressure Atorvastatin
(therefore +
increase Ezetimibe
à
mortality, Extra
and 12%
reduction
hence
are in
cholesterol
no levels
longer
used) • But
 PREVENTS ANTICOAGULANTS:
activation Mechanism
of Warfarin of
VITAMIN
K
Action:
Pharmacokinetics:
Vitamin
K
required
as
a
cofactor
in
synthesis/post-‐
translational
modification
of
Factors
VII,
IX,
X
and
II
(Thrombin)

Administration:
Binds
strongly
to
plasma
proteins
(99%
bound
to
albumin)

Results
in
a
small
volume
of
distribution.

Metabolised
by
HEPATIC
MIXED
FUNTION
CYTOCHROME

P450

Anticoagulant
activity
is
 ANTICOAGULANTS:
Irreversibly Activates Mechanism
of Heparin
inhibits Anti-‐Thrombin
and
COX-‐1 III
Acti Enzyme
Low on:
Aspirin Anti-‐Thrombin ANTIPLATELET
Molecular III
DR Weight then UGS:
INHIBITS Mechanism
Heparin InhibitsFACTOR
of the
production Xa
Acti of and on:
TXA2 Administration
(Thromboxane THROMBIN
A2) (FIIa)
in
by
binding
platelets
to
the
active
serine
However,
production sites.
of
PGI 2

by
endothelium
is LMWH
not
has
a
severely
affected similar
 •Poorly
absorbed
after
oral
administration

Clopidogrel •Therefore,
A given
pro-‐drug either:
which
inhibits o SUBCUTANEOUSLY
fibrinogen
binding o INTRAVENOUSLY
to

glycoprotein
IIb/IIIa Pharmacokinetics
Receptors.
•Immediate
ANTIPLATELET onset
DRUGS: when
given
Mechanism Intravenously
of (I.V.)

Action: Delayed
by
ANTIPLATELET about
DRUGS: 1
Mechanism hour
of if
Action: given
subcutaneously
 Administration:
•Oral
•Intravenous Administration:
(I.V.)

Abciximab •30-‐60
Antagonist Pharmacokinetics:
minutes
of infusion.
•Peak
the plasma
Glycoprotein concentration
IIb/IIIa 4hours
Receptor. Pharmacokinetics:
after
a
•Rapidly
single

cleared
dose
This
•t1/2
•Inhibitory
is
12-‐18
effect
a
minutes
on
hybrid
murine/human
MONOCLONAL
platelet
not
ANTIBODY seen
which Adverse
until
is Effects:
4
licensed
for days
use •Bleeding
in
ACUTE of
regular
•May
CORONARY dosing.
potentially
SYNDROMES. be
antigenic
 Is •Serious
(THROMBOLY recombinant •Intravenous
side-‐effects
•Binds
tPA
TIC) (I.V.)
at FIBRINOLYTIC
more
(Tissue 30
therapeutic Mechanism
DRUGS avidly
Plasminogen
of minute
doses
to
Activator) infusion
COX-‐1
Acti Itthan •As on:
Alteplase
works
COX-‐2 well Administration:
Ibuprofen •
as• Typical
better Inhibit
Pharmacokinetics:
•
usual
non Indomethacin -‐ on •Binds •
NSAID selective
plasminogen
irreversibly •Rapidly
cyclo-‐oxygenase
NSAIDs
to
bound actions,
cleared REVERSIBLY
COX
(NSAID) to
enzymes they
fibrin
-‐ also
•t1/2 Inhibit
(NSAID) A
than reduce
12-‐18 both Aspirin
Non-‐ unique minutesCOX-‐1 Steroidal
Anti-‐Inflammatory onproperty platelet
and
Drugs soluble aggregation
among COX2
plasminogen
the
in
Non-‐Steroidal NSAIDs AdverseHave
Anti-‐Inflammatory the Effects:anti-‐inflammatory,
Drugs plasma Aspirin analgesic
o It
– –•Bleeding
acetylates and
and Mechanism
an antipyretic
is of
amino
acid
therefore Action actions
in
said •Aspirin
the
to inhibits
be TXA2
Celecoxib
Non-‐Steroidal
Anti-‐Inflammatory
Drugs
Anti-‐Platelet
Actions
of
Aspirin
is
due
to:

(NSAID)
Non-‐selective •

NSAIDS •Very
Mechanism
high There
•
also of
inhibit degree is
Action
of• increasing
COX-‐2 evidence
Paracetamol COX-‐1
•The that
inhibition
mechanism
Is • which COX-‐2
of inhibitors
a •
pain action
• of effectively
pose
Analgesic, Has suppresses
goo Antipyretic paracetamol
higher d
• ANTI-‐PYRETIC TXA
is 2
risk
ACTION production
analgesic by of
for unclear
cardiovascular
However, platelets
mild-‐to-‐moderate – disease
it
several than
does •Covalent
mechanisms
NOT binding
have conventional
HAVE which
been NSAIDS
ANY permanently
even
ANTI-‐ inhibits though
postulated.
INFLAMMATORY mechanism
EFFECT platelet
is
COX-‐1
Therefore, unclear.
it •The
•Relatively
most Debate
is low
likely over
not capacity
mechanism the
an to
in safety
NSAID inhibit of
 Oral Morphine
(OPIATE) –
Opiate,
as 40-‐50%
it absorbed
is into
a the
direct bloodstream
derivative Slow
of acting
the –
Poppy may
resin. take
Administration: up
to
30
minutes
to
have
an
effect

Can
be
administered
i.v.
 • Structurally Codeine
(Opiate) Administration similar
to
• Oral
morphine
Codeine
Pharmacokinetics (except
for
(Semi-‐
the Heroin
Synthetic Distribution Fentanyl
Opioid) methyl
• Very
group
(Opi oid)
LIPID in Heroin
SOLUBLE the
3’
position)
• Enters
the • Far
brain less
quicker potent
than than
morphine morphine

•Converted
• Oral
to codeine
morphine is
in about
cells 5-‐10%
the
strength
of
Metabolism
i.v.
 •
o Oral Methadone
(Opioid) resemble
Opioid morphine •
– in
Synthetic structure. Distribution
compound o The
that most
does lipid
soluble
not opioid,
therefore
generally
Administration dissipates
Naloxone into
(Opioid fat
very
Ant agonist) •
quickly.
•
•
i.v.
• administration
(Opioid o Methadone
Receptor Naloxone is
Short
commonly
acting
Antagonist) Opioid used
Receptor Used
as
Antagonist in
a
opioid
overdose
morphine/heroin
substitute
(e.g.
in
weaning
 INFLAMMATORY Prednisolone,
Fluticasone, BOWEL Glucocorticoids
– DISEASE • Increase
Budesonide the
(CD
used & expression
in IBD) of
(Glucocorticoids anti-‐inflammatory
the
) genes
TRE ATMENT
OF Derived (GCR
from acting
The cortisol as
activation a
of positive
glucocorticoid transcription
receptors factor)
can
lead
to: • Decrease
the
expression
of
pro-‐inflammatory
genes

(GCR
acting
as
a
negative
 EFFECTIVE • Reduce Mesealazine
(5-‐ Olsalazine IN ASA)
(2x ULCERATIVE synthesis These
are 5-‐ASA) COLITIS. of
all eicosanoids

type (Sulfalazine) Anti-‐inflammatory, • Reduce s

of but free it colon
NOT radical is
ami (Aminosalicylates)IMMUNOSUPPRESSIVE levels in nosalicylates
– the
ONLY • Reduce most
Mechanisms They inflammatory Liver
basic
of are cytokine form
Anti-‐Inflammatory useful production –
Actions: in c.f.
Mesalazine the • Reduce
(Not treatment leukocyte sulfasalazine)
absorbed of infiltration
as active
Colonic ulcerative
flora
Colonic colitis
Metabolised
Flora, and
by:
Small for
Site
bowel maintenance
of of
and remission

Absorption:
Olsalazine
(Sulfasalazine)
Colon Immunosuppressive
Colon Agent
Azothioprine
Mechanism
Effective of
in Immunosuppression
BOTH
• Azothioprine
CROHN’s
DISEASE is
and a
PRODRUG
activated
ULCERATIVE in
COLITIS vivo
by
gut

flora
Can to
be 6-‐MERCAPTOPURINE
used
to
induce
remission • This

in interferes
Crohn’s with
Disease purine
biosynthesis
(Treatment
•Interferes
>17
with
Weeks)
DNA
SYNTHESIS
and
CELL
May
Anti-‐TNFα
Unwanted
Effects

INFLIXMAB
(i.v.)
Adalimumab • Bone therefore
• Cell

(sc.) marrow givenadhesion

TNF suppression with molecule
Inhibitor azathioprine
Can Evidence
• Metabolised
• Should
be by that
only it
immunogenic xanthine be induces
(monoclonal oxidase
antibody) used remission
–
by in
specialists
some
Natalizumab • Care
wherepatients
Antibody must adequate
be with
agai taken resuscitation
Crohn’s nst
alpha-‐4-‐integrin to facilities
Disease
check are
•
whether available
• Generally Antibody
against there – • well
due
alpha-‐4-‐integrin is to • tolerated
a •
a RISK
co-‐
Rarely
OF(1:1000)
administration
ANAPHYLAXIS
encephalopathy
of
drugs if
• 2-‐4%
which
INHIBIT taken
XANTHINE risk in
of
OXIDASE
combination
serious
e.g. with
allopurinol side-‐effect
which other
 Cellular
•

Muscimol Mechanism
not GABA-‐ergic
of
GABAA stimulate
Agonist (I.e. Action: Transmission
GABAB
Post-‐Synaptic
• receptors
Binding
Bicuculline GABA
of etc.)
Receptor)
GABAA GABA
Antagonist (or
GABA R

This Agonist)
is GABA-‐ergic
to
a GABA
• A Transmission
•
selective GABA-‐ergic
GABAA •
Receptors
Receptor causes Transmission
agonist an
(i.e. activation
does of
Principles the
of Cl-‐
Principles channel
of on
Principles
of the
Picrotoxin same
GABAA post-‐synaptic
Antagonist knob
Convulsants
GABAA • This
 Antagonists
Non-‐competitive
Principles
of Inhibit
Principles neurotransmitter
of release
Benzodiazepines and
and function
in
GABAA
two Binds
Antagonists ways:to
chloride
Clinically • AUTORECEPTORS
channel
used – itself
drugs (Negative
and
Feedback
(see on
the blocks
other
• the
lecture) presynaptic
action GABA-‐ergic
GABAB knob)
• of
Ago Barbiturates nist Transmission
GABA
Selective GABA-‐ergic
receptors
GABAB • HETERORECEPTORS
non-‐competitively Transmission
Baclofen –
Ago nist (I.e. (Sit Inhibits
on
Principles Pre-‐Synaptic hyperpolarisation
neurones
of
of GABA other
Receptor)
terminals
Not
e.g. used
Dopaminergic
clinically
Neurones,
Phaclofen • G-‐Protein
GABAB
linked
Antagonist
• Decreased
Cellular
Mechanism Calcium
of Conductance
Action: (i.e.
Principles Influx
of of
Principles Ca2+
of GABA-‐ergic
Saclofen decreased)
so Transmission
GABAB
decreased GABA-‐ergic
Antagonist
neurotransmitter
Transmission
Flumazenil release
Competitive
Antagonist (reduce
(most vesicular
commonly transport)
Barbiturates used)
• Increased
e.g. K+
THIOPENTON Competitive conductance, GABA-‐ergic
E Benzodiazepine
Antagonist (so Transmission
Anaesthetics efflux
Anticonvulsants of
K+
increased)
These
are • Benzodiazepine
all binding
barbiturates to
producing the
such BDZ
effects. receptor
Acts leads
on to
BDZ
Receptor enhanced
on GABA
GABAA Action
Receptor
Protein • Enhanced
GABA
Anxiolytics, Binding
Barbiturates Anxiolytics, to Sedatives
Anxiolytics, the and
e.g. GABA
Phenobarbital receptor Hypnotics
Anxiolytics, protein Sedatives
and
Anti-‐spastic (reciprocated)
Hypnotics
Sedatives
Barbiturates and
e.g. • Unwanted Hypnotics
Diazepam Side
Effects
of
Development o

of pharmacokinetics
Tolerance o and
(both tissue
Anxiolytics, tolerance)
Anxiolytics,
Sedatives
/ Dependence:
e.g. Hypnotics
Amobarbital Withdrawal Sedatives
Syndrome and
Causes:
Benzodiazepines Hypnotics
Sedatives
All § Insomnia and
benzodiazepines
act Hypnotics
§ Anxiety
at
GABAA
§ Tremor
Receptors
§ Convulsions

§ Death

Sedatives
and
Hypnotics
 Anxiolytics Used
• Wide
for
margin
severe
of Sedatives
Other and
e.g. Sedatives intractable
safety:
/ Diazepam, insomnia Hypnotics
o Overdose
Other Half-‐Life
Anxiolytics: leads
Chloridazepoxide 20-‐25
to Sedatives
Hours
prolonged and
(Librium), sleep
Nitrazepam, Other which Hypnotics
is
Anxiolytics: Side
Oxazepam
effects rousable
Advantages –
of
Sedatives/Hypnotics see o No
Benzodiazepines: respiratory
above.
depression
Hypnotics Anxiolytics, Pharmacokinetics:
e.g. Anxiolytics, Sedatives
Temazepam, Administration:
o Flumazenil and
Anxiolytics,
Oxazepam,
Chloral Anxiolytics, • Well Hypnotics
Propranolol Anxiolytics, • Mild
Hydrate absorbed Sedatives
Lorazepam, effect
P.O. and
on
(Orally)
Nitrazepam
REM Hypnotics
Buspirone Sleep
• Plasma
Sedatives
concentration and
• Do
peaks
not
at Hypnotics
induce
around
L-‐
•Hypokinesia,
rigidity Pathways
(SINAMET, & and
MADOPAR tremor Anti-‐Parkinson
–
with DOPA and
peripheral is Schziophrenic
the
inhibitors) Drugs
precursor
to
DOPA dopamine,
Bromocriptine and
Dopamine is
Replacement converted
• Start
Therapy
L-‐DOPA with
Clinical low
doses
Uses : of
Pergolide the Dopaminergic
drug, Dopaminergic
Ropinerol
and
increase
dose

to
dopamine
in
the
 Deprenyl Prevents
• Selectively
inhibits
the
MAO-‐B
breakdown Pathways
(Sel egiline) (and and
MAO of
hence

Inhibitors dopamine
inhibits
Anti-‐Parkinson
Resagiline indopamine
the and
MAO breakdown)
brain Schziophrenic
Inhibitors
Deprenyl • Predominantly Drugs
(Selegiline) acts
CNS in
Peripheral
Effects dopaminergic
Effects
Dopaminergic areas
Dopaminergic COMT
of
in
the
Tolocapone the
CNS. Pathways
periphery
and
(CNS converts
• Actions

& L-‐DOPA
are Anti-‐Parkinson
COMT to
without
3-‐0-‐methyl-‐DOPA and
peripheral Pathways
Peripheral) Schziophrenic
Pathways
Inhi bitors side
(3-‐0MD). and
Dopaminergic effects and
Drugs
3-‐0MD Anti-‐Parkinson
of
and Anti-‐Parkinson
Entacapone non- ‐
L-‐DOPA and
(Peripheral selective and
compete Schziophrenic
only) MAO-‐I’s Schziophrenic
for
Drugs
the Drugs
same
 • • Anti-‐emetic
•
Neuroleptics • effect Pathways
Site and
of
Mechanism action
of •
– Anti-‐Parkinson
‘D2-‐like’
action receptors
and
–
• Blocking Schziophrenic
dopamine
• dopamine
antagonists Drugs
receptors
Other •
• in
Actions/Side
the
Effects:
chemoreceptor
Dopaminergic
Most
neuroleptics
block
other
receptors
e.g.

trigger
zone.
5-‐HT,
thus
accounting
for
some
of
their
side
 General
Anaesthetics

Clinical
setting:
Desired
effect
Loss
of
consciousness
Suppression
of
reflex
responses
Analgesia
Muscle
relaxation
Amnesia

Drug
Induction:
propofol
(i.v.)
Maintenance:
enflurane
(inhalation)
Opioid
(e.g.
 i.v.
fentanyl)
Neuromuscular General
blocking
drugs Anaesthesia
(e.g.
Benzodiazepines
(e.g.
i.v.
midazolam) suxamethonium)
Principles
of
 Amide: Local
Anaesthetics Lidocaine
Ester:
Cocaine
/ Routes/Methods
of
Lidocaine Administration
and 1.Surface
cocaine: Anaesthesia
pharmacokinetics
Mucosal
Absorption surface
(across (mouth,
mucous bronchial
membranes) tree),
Plasma Spray
protein (powder),
binding High
Metabolism concentrations
Plasma –
half-‐life can
Lidocaine lead
(amide) to
Good systemic
70% toxicity
Hepatic
N-‐dealkylation
2
hours 2. Infiltration
Cocaine
(ester)
Good Anaesthesia
90%
Hepatic
and
plasma
Non-‐specific
esterases
1
hour
Principles
of
Local
Administration: •Cocaine:
Lidocaine Now
and only
cocaine: used
unwanted as
effects a
surface
anaesthetic
Lidocaine (in
ophthalmology)
CNS
stimulation • Lidocaine:

CNS may
Restlessness be
& administered
confusion by
Tremor any
route
Myocardial
depression Metabolism:
CVS
• Cocaine:
Metabolised
rapidly
Vasodilatation
• Lidocaine:
Reduced
BP Relatively
Increased resistant
CO to
Vasoconstriction metabolism
Increased
BP Unwanted
Euphoria
and
excitation
Cocaine
 • An Methotrexate
essential Alkylating
Cytotoxic Interfere nutrient
Age Drugs with nt
• Important
– thymidylate
(Cyt synthesis ot for oxic
ALKYLATING Inhibit nucleotide
(generation
Dru AGENTS enzymes gs synthesis
)
of
in Alkylating
DNA
pyrimidines)
Age Fluorouracil synthesis nt Methotrexate:

(Cyt otoxic • Structurally

(e.g. similar
Cytotoxic thymidylate
Dru Drugs gs) to
synthetase) folic
– Azothioprine
Alkylating acid
ALKYLATING Agent
AGENTS (Cytotoxic • Can
Drugs) substitute
Folic for
Acid: folate
Cytotoxic
Drugs Cytotoxic
–
Dru ALKYLATING gs Fluorouracil:
AGENTS Inhibit • Characteristic
purine of
synthesis pyrimidines:
Cytotoxic
Drugs
Cytotoxic
Drugs
 • Actinomycin
D Cytotoxic unwind,
Intercalates and
Drugs •
– with re-‐joins
CYTOTOXIC it
DN ANTIBODIES A –
and this
interferes allows
with proliferation
DOXORUBICI
topoisomerase to
N
II occur.
Inhibits
DNA Actinomycin
and Cytotoxic D
Drugs RNA inhibits
–
CYTOTOXIC synthesis topoisomerase
II
ANTIBODIES Topoisomerase by
II
binding
cuts
DNA
the BLEOMYCINS
in
DNA,
this
allows
way
it Cytotoxic
to Drugs
It –

has CYTOTOXIC
the
ANTIBODIES
ability
to
e.g. intercalate (oxygen
etoposide DNA derived)
and Free
inhibit
Cytotoxic radicals
Cytotoxic • cause
Drugs Drugs topoisomerase
Cytotoxic DNA
– II
strand
Drugs
PLANT breaks Metal-‐
ALKALOIDS •
Bleomycins
• are
•
active Chelating-‐
VINCA Glycopeptide • against
ALKALOIDS antibiotics non-‐dividing
•
that e.g. cells,
degrade •
Vincristine DNA since
Chelate they
m do
etals not
and Cytotoxic rely
Drugs generate on
free – cell
radicals proliferation
PLANT Cytotoxic
ALKALOIDS Problems
Drugs associated
with
PODOPHYLLOTOXINS high
HYDROXYUREA Podophyllotoxins:
damage
 e.g.
etoposide
Inhibit
DNA
synthesis
and
cause
a
cell
cycle
block
Vinca
Alkaloids:
e.g.
vincristine

Bind Cytotoxic
to Drugs
tubulin at
and
inhibit •
G2

its
polymerisation
into
Cytotoxic microtubules
Drugs –
•
this
Inhibits prevents
ribonucleotide spindle
reductase fibre
(involved
in formation
Cytotoxic
Drugs

nucleic
acid
synthesis)
 CISPLATIN • intra-‐ Cytotoxic
Drugs
strand
Interacts with
cross-‐links
Cytotoxic mitosis
Drugs • at
with –
DNA • interphase
and MISC.
causes •
Metabolically
guanine activated
•
by
PROCARBAZI Cytotoxic
Drugs cytochrome
NE • P450
Inhibits and
•
Cytotoxic
As MAO
DN Drugs
Cytotoxic • A à
and –Drugs • alkylate
DNA
RN MISC. A (at
Synthesis N7
and and
interferes O6
Prednisolone of
Fosfestrol guanine)
Tamoxifen
Cytotoxic
Drugs
Hormones Prodrug
–
a
Used
for
chemotherapy
but
are
not
technically

Hormones:
Mechanism
Glucocorticoid
Androgen
SERM
Use cytotoxic
Leukaemias
Can
&
inhibit
Prostate
tumours
Breast
in
hormone-‐sensitive lymphomascancer cancer
tissues
(e.g.
prostate,
breast)
Gonadotrophin-‐releasing
hormone
analogues
e.g.
Goserelin
Side On• Partial
General
Effects: Toxic
fast
Epilepsy
Effects
growing
Blocks cells:
• Status
• Myelotoxicity
voltage-‐gated Epilepticus
• Inhibit
Na+ cell
• Impaired
channels wound
division
Indications: Mechanism
healing
of• Cell-‐cycle
Phenytoin • specific
Action:
• Depression
(PHT) of
drugs
• Blocks
growth
affect:
voltage-‐gated
(children)
bone
Na+
marrow,
Anticonvulsant
Channels
GI
• Sterility

(Anti-‐ • Teratogenicity
Tract,
Epileptic) Epithelium,
Drug
hair
• Loss
Level
of
&
Monitoring
hair
nails,
• Useful
spermatogonia
• Nausea
and
Vomiting
Elimination
On
Half-‐Life
slow
growing
• 20
cells:
Hours
Carbamazepine • Rash
•
Blockade •
of •
•
Fever
voltage-‐gated •
•
Na+ • Gingival
•
Channels hypertrophy
•
Hypersensitivity •
•
• Folate
•
deficiency
•
•
•
• Megaloblastic
anaemia

Vitamin
•
K
deficiency
Anticonvulsant
Depression
(Anti-‐
Hirsutism
Epileptic)
Peripheral
neuropathy

Osteomalacia

Reduced
bone
density
Lamotrigine • Complex
Blocks drug
voltage-‐gated interaction
Na+ profile
channels
Drug
Interactions
•
Adverse
Drug
Anticonvulsant Reactions
• Hypersensitivity
(Anti-‐ (rash,
Epileptic) hepatitis,
nephritis)

• Dose-‐Related
(Ataxia,
dizziness,
sedation,

diplopia)

• Chronic
(Vitamin
K
Deficiency,
depression,
(Sodium) • Usually
Valproate well
Enhances tolerated
GABA
transmission • Rash
by (high
several incidence;
Adverse may
be
Drug
• severe)
mechanisms
Reac Anticonvulsant tions • Headache

• Blood
(Anti-‐Epileptic) dyscrasias

• Ataxia

• Diplopia

• Dizziness

• Sedation

• Insomnia

• Mood
disturbance
Adverse bacteria •
Severe
•
Readily
Drug absorbed hepatic
Man toxicity
Reactions in
has
the (especially
evolved in
Folate GI
specific
is tract. young
uptake
required processes
for •
patients)
Maximum
for
plasma
transporting

DN Sulphanilamide folate
concentration • Pancreatitis A/RNA
is
into
Synt (P-‐Aminobenzoicreached Encephalopathy
• Drugs hesis
the (ammonia
in Acid
both
cells. driven)
man within
and Analogue) 4-‐6
hours • Drowsiness
Bacteria
have • Tremor
(ANTI-‐
to
MICROBIAL
synthesise • Blood
Side
DRUG) folate. dyscrasias
Effects:
P-‐aminobenzoic
acid • Hair
is Mild/moderate
(do thinning
Pharmacokinetics: and
essential
not
Anti-‐Microbial hair
for
warrant
Trimethoprim loss
the
withdrawal)
synthesis
of • Weight
gain
Anti-‐Microbial

(Folate
Antagonists)

(ANTI-‐
MICROBIAL
DRUG)
Co-‐Trimoxazole Trimethoprim
Penicillin is
a
folate
Anti-‐Microbial antagonist
Anti-‐Microbial that
is
more
sensitive
(Sequential to
Blockade) Unwanted Drugs
Effects

(ANTI-‐ the
MICROBIAL dihydrofolate
reductase
DRUG)
(β-‐Lactam enzyme
Antibiotics) in
BACTERIA
than
in

(ANTI-‐ • Nausea/vomiting
MICROBIAL
man
DRUG) (IC50 Drugs
[mmol/l]
0.005
bacteria,
260
man)
Elimination

Drugs
 Elimination
at, of
or most Drugs
(β-‐lactamase close penicllins CLAVULANIC
inhibitors) to, is
ACI its mainly D
active renal Functions
by CEPHALOSPORIsite. and
occurs
NS
cova lently rapidly
(β-‐Lactam binding -‐
to Antibiotics) 90%
the tubular
β-‐ Lactamase secretion
enzyme
Reduces
(ANTI-‐ resistance
to MICROBIAL Unwanted
penicillin Effects
DRUG)
Anti-‐Microbial Relatively
e.g. free
Cephalexin from
(oral), direct
Cefuroxime toxic
and effects
Cefotaxime
Hypersensitivity
reactions
–
Anti-‐Microbial (parenteral) Pharmacokinetics
Some
cephalosporins
e.g. may
cefoperazone, be
cefotaxime given
(can orally,
cross but
BBB) most
are

given
parenterally
–
Mechanism intramuscular
(i.m.)
of or
Action intravenous

• Same (i.v.)
as
penicillins,
interfere Widely
with distributed
peptidoglycan in
the
synthesis body,
passing
• Resistance into
to the
this pleural,
group
 polycyclic TETRACYCLINES
(Drugs structure. Tetracyclines
are that
inhibit
broa d-‐spectrum
bacterial
Method Drugs
anti protein of biotics
that
synthesis) Action
have
a
• Actively
Pharmacokinetics
transported
(ANTI-‐ into
MICROBIAL bacteria
DRUG) and
interrupt
protein
synthesis.

• Competition
with
tRNA
for
the
A-‐binding
site.

• Bacteriostatic,
not
bactericidal.
 • Inhibition Anti-‐Microbial
(Drugs of
that protein •Usually
inhibit synthesis. given
• Oral orally
bacterial chloramphenicol
is
protein rapidly Drugs
and
synthesis) completely
• Can
absorbed
also
• Chloramphenicol be
(ANTI-‐ binds
to given
MICROBIAL the parenterally
50s
Subunit
DRUG) of • The
the
absorption
ribosome of
and most
inhibits preparations
Chloramphenicol from
transpeptidation.
Mechanism the
• Reaches
of maximum
concentration
Action in gut
Pharmacokinetics the
is
plasma
Anti-‐Microbial irregular
and
incomplete,
within and
2 is
improved
hours.
by
Spectrum the
 AMINOGLYCOSIDES
e.g. Method
GENTAMICIN Drugs
of
action
Pharmacokinetics
(Drugs
that
inhibit
bacterial
protein
synthesis)

(ANTI-‐
MICROBIAL
DRUG)
 •The
aminoglycosides
inhibit
(Antimycobacteri bacterial
protein
al • The
aminoglycosides
agent) are
polycations
and
highly
Anti-‐Microbial

(ANTI-‐ Drugs
MICROBIAL synthesis
by
DRUG) binding
to
the
(Antimycobacteri 30s
Subunit
al of
the
polar
agent) –
hence
are
not
absorbed
(ANTI-‐ in
the
MICROBIAL GI
tract
DRUG)
ribosome
• Given
intramuscularly
(i.m.)
ISONIAZID or
RIFAMPICIN intravenously

Mechanism • This
of causes
Action: an
 Pharmacokinetics
Anti-‐Microbial • The
Anti-‐Microbial antibacterial
activity Drugs
of
isoniazid
is
limited
to
• Readily
absorbed
from
the
GI
tract,
or
after

mycobacteria.
parenteral
injection

• It
is
bacteriostatic
on
resting
organisms,
and
can
kill
• Widely
distributed
throughout
the
tissues
and

dividing
bacteria
 • Pyrazinamide PYRAZINAMIDE
is Mechanism
of (Antimycobacteri atinactive
Mechanism
of
neutral
al Action
pH,
Acti but on
agent) • Binds NYSTATIN
tuberculostatic
to Nystatin
at
is cell
acidic
a (ANTI-‐ membrane
pH.
and
MICROBIAL interferes
poly with ene
DRUG) • It

mac is permeability rolide. Drugs

and
effective
(Anti-‐Fungal Pharmacokinetics
transport
against
Agent) functions.
the
intracellular
organism
(ANTI-‐
in
MICROBIAL • It
forms
macrophages,
DRUG)
asince
pore
after
phagocytosis
in
the
the
organism
membrane
–with
be
the
contained
hydrophilic
in
Anti-‐Microbial
Anti-‐Microbial • Oral
administration
-‐ Drugs
the
drug
is
well
absorbed

after
oral
administration

• Widely
distributed,
penetrating
well
into
the

meninges

•Excreted
through
the
kidneys
(mainly

glomerular
filtration)
 antimycotic • Miconazole
agents, is
with given Drugs
(Anti-‐Fungal a by
Agent) MICONAZOLE
broad intravenous ACYCLOVIR
infusion
spectrum for Miconazole
of
(ANTI-‐ activity. systemic
belo infections ngs
MICROBIAL
to
the DRUG) •Given
Mechanism
azol of orally e
for
Action infections
of
Drugs
grou the p
of Azoles
• GI
tract.
block
synth (Anti-‐Viral the etic
Agent) synthesis •Short Pharmacokinetics
of
ergosterol
plasma Anti-‐Microbial
(the half-‐life. Herpes
main

(ANTI-‐
sim MICROBIAL sterol plex
is in
DRUG) the Unwanted
mor fungal Effects e
cell
• Relatively
sens membrane) itive
by: infrequent
to (most
acyclovir commonly
than o Interacting
with being
other
i.v. • Zidovudine •
Anti-‐Microbial
infusion is herpes
to
results an viruses
•
20-‐
in analogue whichfold
of
plasma thymidine causehigher
concentration glandular
10-‐
•In feverThe
ZIDOVUDINE
retroviruses, or drug
such is
shingles.
Mechanism as widely
of the distributed,
Action Drugs
HIV reaching

Virus,
concentrations
it Acyclovir
in
(AZIDOTHYMIDis has the
INE, an a CSF
active small,which
AZT) but are
inhibitor
of reproducible
50%
reverse effectof
(Anti-‐Viral transcriptase against
Agent) those
enzyme. cytomegalovirus
in
(CMV) the
whichplasma
(ANTI-‐ can
MICROBIAL • It cause
DRUG) is glandular
phosphorylated fever
by
Resistance • In In
Excretion
Uses: most patients
• Excretion
patients with
the is
AIDS
therapeutic in
response the• It
to kidneys,
reduces
partly
the
zidovudine by
incidence
wanes glomerular
of
with opportunistic
filtration
long-‐term and infection
use, partly

particularly (such
by
tubular
as
secretion
in Pneumocystis
late-‐stage Carnii
disease. Side
Pneumonia)
Effects
• Local
• It • Stabilises
is inflammation
weight
known can
occur
that • Reverses
during

the HIV-‐Associated
intravenous
virus thrombocytopenia
develops injection
resistance if
to • Stabilises
there
the
HIV-‐associated
is
extravasation
drug dementia
of