DRUG

ACE inhibitors

EXAMPLES
Ramipril,
Lisinopril

USES
Hypertension
Heart Failure
Post MI

Beta-Blockers

Calcium
Channel
Blockers

Atenolol,
Propanolol

Hypertension
Angina
Arrhythmias
Stable heart failure

Dihydropines
Amlodipine,
Phenyalkylamin
es Verapamil,
Benzthiazepine
sDiltiazem
Bendrofluazide,
hydrochlorothiazi
de

Hypertension
Angina
Supraventricular
arrhythmia
(Phenylalkylamines
only)

Vasodilation
block cellular entry of Ca+ by
preventing opening of
voltage-gated L-type and Ttype calcium channels

Hypertension
Combined with loop
for Heart Failure

Loop Diuretics

Frusemide,
Bumetanide

Potassiumsparing
diuretics

Spironolactone,
Amiloride

Hypertension (but
less effective than
thiazides used
when renal
impairment or
resistant to multiple
drug Tx)
Heart Failure
Secondary
Hypertension
Severe heart Failure

Thiazide
Diuretics

MECHANISM
Block ATIATII by binding to
the site on the enzyme that
normally accommodates the
terminal leucine of ATI.
Inhibits vasoconstriction.

SIDE EFFECTS
Hypotension
Dry cough
(increased
bradykinin)
Renal failure in pts
with bilateral renal
stenosis
block -adrenergic receptors inhibiting
Provocation of
the
asthma, heart
effects of adrenaline and nonadrenaline.
failure.
1 (heart) blockage decreases HR Cold hands
and
Bradycardia contractility, 2 (bronchial and
fatigue
vascular
smooth muscle) blockage causes
vasodilation.

Flushing, headache,
P.oedema
Phenyalkylamines
can worsen heart
failure
Gynaecomastia
Impotence

increase water excretion by

decreasing reabsorption of
Na+ and Cl- in the distal
tubule by binding to the Clsite of the electroneutral
Na+/Cl- co-transport system
and inhibiting its action
causing a decrease in blood
volume, venous return and
CO
Block Na+ resorption in
ascending loop of Henle
diuretic effect.

Hypokalaemia
Hyponatraemia
Hypotension
Gout
Type II DM

Hypokalaemia
Hyponatraemia
Hypotension
Gout

Blocks action of aldosterone

in distal convoluted tubule
diuretic effect

Hypokalaemia
Hyponatraemia
Abdominal
discomfort

Angiotensin II
receptor
antagonists

Losarten,
Valsarten

Alphaadrenorecepto
r antagonists

Doxazosin,
Prazosin

Hypertension
Alternative to ACE
inhibitor in heart
failure
Hypertension (in
addition to other
hypertensives)

Vasodilation by inhibition
at the angiotensin II receptor

Usually mild
No cough like in
ACE inhibitors

Reduces peripheral
resistance by inhibiting 1adrenoreceptor-mediated
vasoconstriction.

Postural
Hypotension
Dizziness

Fibrinolytics

Thrombolysis
Acute MI, stroke, PE

Forms a complex with, and

activates, plasminogen into
plasmin.

Nausea/vomiting
Bleeding

Antiplatelet agents
Asprin

Prevention and
treatment of MI and
stroke.

Haemorrhage

Clopidogrel

Prevention and
treatment of MI and
stroke.

Irreversibly inhibits COX and

so stops synthesis of
Thromboxane A2 from
Arachidonic Acid which leads
to platelet aggregation.
Inhibits activation of the
glycoprotein IIb/IIIa receptor
on the surface of platelets
which is required for
aggregation to occur.

Haemorrhage

Anticoagulants
Warfarin

Prophylaxis+treatme
nt DVT, PE
Prophylaxis of
embolization in AF,
Rheumatic disease +
prosthetic valves.

Blocks reduction of Vit. K

epoxide necessary for
synthesis of factors II, VII, IX
and X.

Haemorrhage

Heparin

Treatment of DVT,
PE. Prophylaxis of
DVT/PE post op.
MI.
Prevention of
cardiovascular
disease

Activates antithrombin III,

which limits blood clotting by
inactivating thrombin and
factor X.
Reversibly inhibit enzyme
HMG CoA reductase which
catalyses the rate-limiting
step in the synthesis of
cholesterol:
HMG CoAmevalonic
acidcholesterol.
This in synthesis LDL
receptors so LDL levels.
Prodrugs they decompose
to form NO which activates
guanylyl cyclase, thereby
cyclic guanosine
monophosphate (cGMP).
Protein kinase G is activated
and contractile proteins are
phosphorylated. This all
leads to Dilation of vessels.
Relaxation of smooth muscle
and vasodilation.
Activates K+ channels of
vascular smooth muscle

Haemorrhage

Myopathy (muscle
ache)
Disturbed LFTs
Abdominal pain

Statins

Nitrates

Potassium
channel
activators

Streptokinase

Atorvastatin,
Simvastatin,
Pravastatin

Glyceral trinitrate
(GTN), Isosorbide
mononitrate

Nicorandil (only
licensed one)

Prophylaxis and
Treatment of angina.
LVF

Prophylaxis of
angina

Postural
hypotension
Tachycardia
Headache
Flushing
Dizziness

Headache

causing K+ to flow out of cells

causing hyperpolarization.
This therefore inhibits influx
of Ca2+ and so inhibits
contraction.
Antiarrythmics
Class Ia

Block Na2+ channels which

increases refractory period
and in addition there is a
blockade of K+ channels
which delays repolarisation.
Block Na2+ channels but little
effect on refractory period as
K+ channels not blocked.
duration of the action
potential.

Quinidine,
Disopyramide,
Procainamide

VT
WPW

Lignocaine,
Mexiletine,
Phenytoin

Ventricular arrythmi,
especially VT

Class Ic

Flecainide

Pre-excitation AF
cardioversion of
paroxsms,AVNRT
,AVRT, WPW, AF ,
AT , NSVT (nonsustained VT)

Marked Na2+ channel

blockage refractory period,
no effect on the duration of
the action potential.

Class II

Beta blockers
(see above also)

Junctional
tachyarrhythmias,
Paroxysmal
events,AF, Flutter,
NSVT, SVTs.

rate of spontaneous
depolarisation of SA and AV
nodal tissue
conduction through AV
node

Class Ib

GI disturbances
Hypotension

Nausea and
Vomiting
CNS toxicity
Hypotension
Bradycardia
CNS toxicity
Hypotension
Proarrythmogenic
after recent MI
may increase
mortality

Provocation of
asthma, heart
failure.
Cold hands

Class III

Amiodarone,
Bretylium, Sotalol
(Beta blocker with
class III
properties)

AF, AT, AVRT,

AVNRT, WPW, NSVT

Block K+ channels so prolong

the duration of the action
potential.

Amiodarone : GI
disturbances.
Corneal
microdeposits,
throtoxicosis,
photosensitivity

Class IV

Calcium channel
blockers (see
above also)

AVRT, AVNRT,
Paroxysms

Block Ca2+ channels acts

predominantly on the AVN
and affect the plateau phase
of the action potential.

Flushing, headache
P.oedema
Phenyalkylamines
can worsen heart
failure
Gynaecomastia
Impotence
Intracellular Ca2+
overload
junctional escape
beats, junctional

Digoxin

AF
Atrial Flutter

Not strictly antiarrythmic

indirect actions on the Action
potential through stimulation
of the vagus nerve:

 automaticity of the SA
node which slows sinus rate
refractory period of the AVN
which AV conduction

Adenosine

Atropine

Supraventricular
arrythmias

Sinus bradycardia
AV block
Cardiopulmonary
resuscitation

Potent effect on SA node

producing sinus bradycardia.
Slows impulse conduction
through the AVN but has no
effect on conduction in the
ventricles.
Inhibits effect of the vagus
nerve on the heart which
rate of firing of SA node
conduction through the
AVN via blockade of
muscarinic M2 receptors.

tachycardia,
ventricular ectopic
beats, VT.
Increased vagal
activity can cause
AT with 2:1 AVN
block
GI disturbances
Neurological
disturbances
Gynaecomastia
Bradycardia and AV
block
Malaise, flushing,
headache chest
pain, bronchospasm
Rhythm
disturbances
Constipation
Reduced Bronchial
secretions

Endocrinology-Diabetes
Insulin: Is a polypeptide containing 51 amino acids arranged in two chains (A and B) linked by Disulphide bridges. A precursor
called proinsulin, is hyrdolysed inside storage granules to form insulin and a residual C-peptide. The granules store insulin as
crystals containing zinc and insulin.
Insulin Release: Glucose is the most potent stimulus for insulin with surges at meal times. The B cells possess K+ channels
that are regulated by intra cellular adenosine triphosphate (ATP) (Katp channels). When the blood glucose increases, more
glucose enters the B-cells and its metabolism results in an increase in intracellular ATP, which closes the Katp channels. The
resulting depolorization of the B-cell initiates an influx of Ca2+ ions through you voltage sensitive Ca+ channels and this
triggers insulin release.
Insulin is destroyed the GI tract so must be given subcutaneously and IV or IM in some circumstances. Injections should be
rotated within the same region to avoid lipid hypertrophy. Absorption is fastest from the abdomen and slower from the thigh.
Insulin Regimes
1) Short acting insulin mixed with intermediate acting insulin injected subcutaneous twice daily, before breakfast and
before the evening meal/
2) Injection of intermediate acting insulin to provide background level of insulin and soluble insulin three times a day.
Short Acting Insulin
Soluble Insulin Actrapid
Simple solution of insulin
IV for
(onset 30 mins, peak
hyperglycaemic
activities 2-4hrs, subsides by
emergencies.
8hrs)
Subcutaneous
If IV effects only last 30
injection
minutes.
Insulin lispro
Humalog and
Insulin analogues have a
Blood glucose
Hypoglycaemia
and Insulin
Novorapid
faster onset and shorter
control

aspart (Rapid
Acting)

Intermediate and Long Acting Insulin

(duration of action between 16-35 hours)
Semilente

(amorphous
insulin zinc)
Lente
Humulin L or

Monotard

Isophane
Insulin (NPH)

Insulatard

Biphasic fixed
mixtures

Human mixed
(short- and
intermediateacting) insulins:
These include
Humulin 20/80,
Humulin 30/70,
Humulin 50/50,
Mixtard 20/80,
Mixtard 30/70,
and Mixtard
50/50.

Human mixed
insulin analogues
(with ultra-

action than soluble insulin.

This is because they do not
self associate to form
dimmers.
Onset 20-30 minutes Peak
action 1-2 hrs Duration 3-4
hrs

Insulin auto
antibodies
Lipohypertrophy

Blood glucose
control

Suspension of amorphous
insulin zinc.

Hypoglycaemia

Blood glucose conrol

Mixture of amorphous insulin

zinc (30%) and insulin zinc
crystals (70%), the latter
prolonging the duration of
the preparation Onset of
action (2-4 hours). Peak
action (6-12hrs) (Duration 20
hrs)
A complex of protamine and
insulin. The mixture is such
that no free binding sites
remain on the proatmine.
After injection, proteolytic
enzymes degrade the
protamine and the insulin is
absorbed. The duration of
NPH is similar to that of
Lente
Onset of action (30-90
mins) Peak action (4-6 hrs)
Duration action (8-16 hrs)
Contain various proportions
of soluble isophane insulin
(e.g. 30% soluble and 70%
isophane) The soluble
component gives rapid onset
and the isophane insulin
prolongs the action.
A pre-mixed short and
intermediate-acting insulin
will start to work half an hour
after being injected, peak at
1-12 hours and last for 16-24
hours.
The ultra-short acting
insulins lispro and aspart are
also available in a biphasic

Hypoglycaemia

Hypoglycaemia

Hypglycaemia

short and
intermediateacting
properties):
These include
Humalog Mix25
(insulin lispro)
and NovoMix 30
(insulin aspart).

form which retains the rapid

onset of action (about 15
minutes) but has a duration
of action similar to that of
intermediate-acting isophane
insulins.

Ultralente

Humulin UL
Ultratard

Insulin
glargine

Lantus

A suspension of poorly
soluble insulin zinc crystals
that has a duration of up to
35 hours. The long duration
of ultra lente can lead to
insulin accumulation and
dangerous hypoglycaemia.
Onset of action (2-4 hrs)
Peak (6-23 hours)
Is soluble at acid pH. It has a
long peakless activity (11-12
hrs) and is given once a day.

Hypoglycaemia

Hyoglycaemia

Oral Anti Diabetic Drugs

Tablets are introduced when metabolic control cannot be obtained by diet and lifestyle changes alone. Choice depends on
individuals characteristics. Patients with baseline Hb1A1c 9% are les likely to achieve target HbA1c with monotherapy. Drug of
choice started at low dose, dose is increased, additional drugs are introduces in combination therapy to maximum of 2-3 drugs.
Insulin is usually introduced in combination with metformin.
Bigunides
Metformin
The exact mechanism of
Type 2 diabetes
Lactic acidosis rare
Only diabetic
action of metformin is
and limited to those
PCOS
drug that reduces
uncertain. It appears to act
with impaired liver
Non Alcoholic fatty
cardiovascular
mainly by reducing hepatic
of kidney function.
liver disease
risks.
gluconeogenesis, it also
GI upset diarrhoea,
It reduces weight.
decreases absorption of
vomiting cramps.
glucose from the
gastrointestinal tract and
increases insulin sensitivity
by increasing peripheral
utilization of glucose.]
Evidence suggests that
increased peripheral
utilization of glucose may be
due to improved insulin
binding to insulin receptors
since metformin is not
effective in patients who no
longer have any residual
insulin production.The

'average' person with type 2

diabetes has three times the
normal rate of
gluconeogenesis; metformin
treatment reduces this by
over one third.
Metformin stimulates the
hepatic enzyme AMPactivated protein kinase
(AMPK), which plays an
important role in the
metabolism of fats and
glucose. Causing weight loss.
The molecular targets with
which metformin directly
interacts remain elusive.
Metformin is not
metabolized, rather it is
primarily excreted in the
urine with an elimination
half-life of 6.2 hours
Sulphonyreas

Glitazones

Glipizide (short
half life)
Glicazide (short
half life)
Glibenclamide
(longer duration
of action)
Tolbutamide.

Rosiglitazone and
Pioglitazone

Type II diabetes
(people with ideal
weight)

Type II diabetes
given alone or in
combination with
metofrmin or
sulphonyreas in
patients who cannot
tolerate metformin
or sulphonyreas
combinations.

These drugs are indicated in

patients (especially those
near their ideal weight) in
whom diet fails to control the
hyperglycaemia. In about
30% control is not achieved
by these drugs. They
stimulate insulin release
from the pancreatic islets
and so patient must have
partially functional B-cells for
these drugs to be of use.
Slow onset maximum effect
1-2 months of treatment.
Reduce hepatic glucose
output and increase
absorption into the
peripheral tissues.
Triglycerides decline and LDL
is also reduced.
Drugs increase sensitivity to
insulin by binding to the
nuclear peroxisome
proliferator activated
receptor gamma (PPAR-y)
and by derepression,
increase transcription of

GI disturbance
Rashes
Hypoglycaemia
Hypoglycaemic
coma
Contraindicated in
severe
hyperglycaemia,
surgery and major
illness
Weight gain
Fluid retention
Contraindicated in
pregnancy

insulin sensitive genes.

a- Glucosidase
inhibitors

Acarbose

Inhibits intestinal a Flautlence

glycosidases, delaying the
Diarrhoea
digestion of starch and
Abdominal Pain
sucrose. It is taken with
meals and lowers the post
prandial increase of blood
gluocose.
Prolactinomas- oligomenorrhoea, amenoffhoea, galactorrhea, infertility, loss of libido, erectile dysfunction, osteoporosis. TRH
stimulates prolactin, Dopamine inhibits it.
Dopamine
Bromocriptine
Stimulates dopamine
Prolactinoma
Nausea
agonist drugs
(ergot derivative)
receptors
in
the
brain.
Acromegaly
Psyhchiatric
Cabergoline
Symptoms
Hypogandism
Postural
Galactorrhea
Hypotension
Fibrotic changes
which can lead to
valvular heart
disease.
Acromegaly Over secretion of GH =gigantism before puberty, acromegaly after puberty. (growth of hands feet, tightening of
rings)
Somatostatin
Somatuline
Somatostatin analogue.
Acromegaly
Gallstones
analogues
Autogel
Inhibits the production of GH.
Conratindicated in
Sandostatin LAR
liver and kidney
Ocreotide
failure, diabetes
mellitus,
Insulinoma.
Diabetes Insipidus (no ADH produced so leads to excretion of large volumes of isotonic water)
ADH analogue Desmopressin
Desmopressin is preferred to
Diabetes Insipidus
Water retention
(nasal spray,
vasopressin because it is a
Hyponatremia
tablets, or
longer acting analogue. Make
Contraindicated in
subcutaneous
sure to reduce fluid intake.
heart failure, people
injection)
using diuretics for
other conditions.
Alcoholics
Hypothyroidism tiredness and lethargy are the most common symptoms. Depression of basal metabolic rate, appetite and
cardiac output. Low output heart failure might occur. Skin is dry. Thyroid deprivation in early life leads to dwarfism and
cretinism.
Thyroxine
Levothyroxine
Administered orally is the
Hypothyroidism
Concomitant
treatment of choice.
conditions
Synthetic T4 is the sodium
worsened by
salt of levothyroxine (Lthyroxine therapy.
thryoxine). Its effects are
Heart disease, heart
delayed until the plasma
failure, infarction,
protein and tissue binding
angina, chronic lung
sites are occupied.
disease,
Treatment is assessed by
breathlessness,

Type II diabetes

monitoring TSH levels, which

adrenal disease.
fall to normal when optimum
Due to increase in
dose is achieved. Daily dose
oxygen demand of
100 and 150ug best take on
most tissues as well
waking.
as myocardium
Liothyronine
Is
the
sodium
salt
of
T3
and
Hypothyrioidism
See above
because it is less protein
bound, it acts more quickly
than T4. The main use of T3
is in hypothyroid coma, when
it is given with
hydrocortisone by IV
injection.
Hyperthyroidism basal metabolic rate is increased, causing heat intolerance, arrthymias and increased appetite with weight
loss. Skin is warm and moist. Tachycardia sweating and tremor. Angina and high output failure may occure. Upper eyelids are
retracted. Treatment also includeds beta blockers discussed above (Propranalol or atenolol)
Antithyroids
Carbimazole
Rapidly converted to
Hyperthyroidism
Rashes
methimazole in vivo
Agranulocytosis
Once daily doses, 40mg for 1
Patients should
month, then 30mg for 1
report a sore
month, 20mg for 1 month
throat!
and then 10 mg daily until
reassessed.. Onset of action
3-4 weeks
Thionamides
Possess a thiocarbamide
Hyperthyroidism
?
group that is essential for
immunosuppressive
their activity. They prevent
the synthesis of thyroid
hormones by competitively
inhibiting the peroxidise
catalysed reactions
necessary for iodine
organification. They also
block the coupling of
iodotyrosine especially
diiodothyronine formation.
Onset of action 3-4 weeks
Propylthiouracil
Reserved for patients
Hyperthyroidism
?immunosupressive
intolerant of carbimazole.
Also inhibits the peripheral
deiodination of t4
Iodides
Have poorly understood
Hyperthyroidism
Skin rashes
actions on the thyroid. They
Nausea
inhibit organification and and
Vomiting
hormone release. In addition
Allergic reaction.
iodide decreases the size
and vascularity of the
hyperplastic gland, effects
which are useful in

preparation of patients for

thyroidectomy. They inhibit
hormone release quickly (2-7
days) is a valuabe treatment
for thyrotoxic crisis. Cannot
be used in long term
because its antithyroid
action tends to diminish.
Primary Hypoadrenalism: Addisons disease Normally! Glucocorticoids mainly cortisol are produced in the cells of the zona
fasiculata and zona reticularis. The release of cortisol is controlled by negative feedback mechanism involving the hypothalamus
and anterior pituitary. Low plasma cortisol levels results in the release of ACTH. Which stimulates coritsol synthesis and release
by activiating adenlyl cyclise. Cyclic adenosine monophosphate (cAMP) then activates protein kinase A, which phoshoporylates
and increases the activity of cholesterylester hydrolase, the rate limiting step in steroid synthesis. Alodosterone release is
effected by ACTH, but Renin release is more important influence. The steroids are examples of gene active hormones. The
steroid diffuses into the cells. In the absence of cortisol the receptor is inactivated by a heat shot protein (hsp 90). Cortisol
triggers the release of hsp90 and the activated receptor SR enters the nucleus where it stimulates or inhibits the production or
proteins, which then produce the characteristic actions of the hormone.
Coritcothrophin releasing hormone (CRH) is a 41 amino acid polypeptide whose action is enhanced by arginine avasopressin
(ADH). It is produced in the hypothalamus and reaches the adenopophysis in the hypothalamus-hypophsyial portal system
where it stimulates the production of corticotrophin.
ACTH is process from large molecular weight precursor, pro-opiomelanocortin (POMC) present in corticotroph cells of the
adenohypophosis, its main action is to stimulate the synthesis and release of cortisol.
Cortisol
Hydrocortisone
Immediate management.
Addisons
Moon face
If acutely sick!
Striae
Take blood cortisol glucose
Fat redistribution
urea and electrolytes. Give
Hirsutsim
hydrocortisone 100mg as IV
Infection
bolus. Give saline infusion
Proximal muscle
litre initially over 4-6 hours.
wasting
Correct hypoglycaemia iwth

Bruising
IV bolus of 20% glucose.

Synthetic
Aldosterone

Fludrocortisone

Addisons

Cushings Syndrome Excess production of cortisol

Continue with with IM

hydrocortisone 100mg 6
hourly.
Long term
Hydrocortisone orally
10mg on waking, 5mg at
lunch and evening (dose
varies)
Fludrocortisone 0.1-0.2mg
per day.
Synthetic mineralcorticoid
derivative of aldosterone.
Plasme rennin acitivity
should be measured 2 hours
after the flurdrocortisone
dose and maintained in the
normal range.

Hypertension
Oedema
Peptic ulcers
Mood changes
GI upset
Glaucoma

Ketoconazole

Well absorbed orally, wide

spectrum anti fungal drug
which has adrenal
suppression effects
Metirapone
Metyrapone blocks cortisol
Cushings
synthesis by inhibiting
steroid 11-hydroxylase.
Mitotane
Unknown mechanism of
Cushings
action but inhibits adrenal
Adrenal adenoma
steroidal action
Hyperparathyroidism and Malignancy account for 90% of Hypercalcaemia
Rehydration
IV Saline
Hydration must be
Hypercalcaemia
maintained with IV
intravenous saline. This
will prevent severe
hypercalcaemia. Once
volume status is normal use
bisphosphonates
Bisphosphona
Alendronate
Bind to hyrdoxyapatite
Hypercalcaemia
tes
Etidronate
crystals and reduce bone
resorption.
Hypocalaemia Commonest cause is Vit D deficiency
Calcium
Calcica
Hypocalaemia
Supplements
Osteocare
Vitamin D
analogue

Recombinant
PTH analogue

Ergocalciferol Vit
D2
Cholecalciferol Vit
D3
Alfacalcidol
1hydroxyvitamin D
Calcitriol 1,25
Dihydroxy D
Teriparatide

Cushings
Anti fungal

Hypocalcaemia
Vit D deficiency

Vitamin D analogues allow

absorption of calcium from
the gut.

Hepatic necrosis
Adrenal suppression

Nausea vomiting,
abdominal
cramping pain.
Dizzyness,
drowsyness nausea
and vomiting.

Hypernaetremia

GI upset, Erosion of
Oesophagus

Hypercalcaemia
Stomach pain
Diarrhoea
Hypercalcaemia

Stimulates bones resorption,

Kindey to re absorb calcium,

stimulates production of 1.25

Dehydroxyvit D at kidney.
Phaeochromocytoma Neoplasm of the adrenal medulla. 10% are malignant, 10% are extra-adrenal, 10%
are familial. Blockage of adreno receptors must be started first.
aPhenoxybenzami
An irreversible antagonist is
Tumours of adrenal

adrenorecepto ne
used to block the a-effects of
medulla
r antagonist
Labetalol
the large amounts of
catecholamines from
Doxazosin
Phentolamine
tumours of the adrenal
Prazosin
medulla.
Tamsulosin
Terazosin

Hypocalcaemia
Hypoparathyriodism

Dizzyness
Leg Cramps
Nausea
are bilateral, 10%
Reflex tachycardia

b-blockers

Atenolol (see

above)
Conns excess production of aldesterone
Aldosterone
Spironolactone
Conns
receptor
(see above)
Liver disease with
blockers
Eplernone
ascites

Postassium
Sparing
Diuretic

Zero Order
Kinetics

Amiloride
Triamterene

Potassium sparing
diuretic
Conns

Blocks the binding of

aldosterone to its receptor
and increases the excretion
of Na+ and decreases the
electrically coupled K+
secretion.
Decrease the luminal
membrane Na+ permeability
in the distal nephron by
combining with Na+
channels and blocking them
1:1 basis. This increases Na+
(Cl- and H2O) excretion and
decreases K+ excretion.

Severe
Hyperkaleamia
Painful
Gyanocamastia
Severe
Hyperkalaemia

Common drugs

Phenytoin,
Aspirin, Ethanol,
Theophylline,
Thiopentone
Anti-Epileptics Epilepsy is a chronic disease in which seizures result from abnormal discharge of cerebral neurones. Epilepsy
is defined as a tendency to recurrent seizures i.e. two or more seizures. Partial seizures (seizures begin focally) Simple
(consciousness not impaired) Complex (with impairment of consciousness) Beginning as a simple partial seizure and
progressing to a complex partial seizure. Impairment of consciousness at onset. Partial seizure becoming secondary
generalised. Generalised Seizures Absence Seizure Typical (petit mal) Atypical. Others Myoclonic seizure, Clonic seizure,
Tonic seizure, Tonic-clonic seizure (grand mal) Atonic seizure.
Treatment should be considered when two or more unprovoked seizures have occurred within a short period. Whenever
possible, treatment should involve only one drug.
Generalised
Lamatrogine
Lamatrogine and

Lamatrogine
Epilepsy
Sodium Valproate
Valpraote have similar
Blurred vision
mech of action as
dizziness and
Phenytoins discussed
drowsyness. Serious
below. Valproate also
skin reactions can
seems to in increase
occur especially in
GABAergi central inhibition
children.
mechanisms that may
Valproate - Nausea,
involve stimulation of
weight gain,
glutamic acid decarboxylase
bleeding tendencies
activity and/ or inhibition of
and transient hair
GABA-T activity.
loss). The main
disadvantage is that
occasional
idiosyncractic
reactions cause
sever or fatal
hepatic failiure.

Focal Epilepsy

Carbamazepine
Phenytoin

Phenytoins anticonvulsant
action is probably a result of
its ability to prevent high
frequency repetitive activity.
Phenytoin binds prerentially
to inactivated (closed) Na+
channels stabilizing them in
the inactivated state and
preventing them from
returning to the resting
closed state which they must
do before they can open
again. High freuquency
repetitive depolarisation
increases the proportion of
Na+ channels in the
inactivated state and,
because these are
susceptible to blockade by
phenytoin, the Na+ is
progressively reduced until it
is eventually insufficient to
evoke and action potential.
Neruonal transmission at
normal frequencies is
relatively unaffected by
phenytoin because a smaller
portion of the Na+ channels
are in the inactivated state.
Carbamazepine, lamotrigine,
valproate, and topiramate.
Have similar actions on
neuronal Na+ channels.

Carbamazepine is
metabolised in the
liver to
carbamzepine10,11- epoxide, an
active metabolite
that partly
contributes to both
its anti-convulsant
action and
neurotoxicity. In
contrast to
phenytion there is a
linear increase in
serum
concentration with
dosage. Mild
neurotoxic effects
are common
(nausea dizziness
drowsyness, blurred
vision and ataxia)
Agranulocytosis is a
rarer idyiosyncratic
reaction.
Phenytoin is
hyroxylated in the
liver by a saturable
enzyme system.
The rate of
metabolism varies
greatly in patients.
And up to 20 days
maybe required for
the serum level to
stabilize after
changing the dose.
Dose is increased
gradually until fits
are prevented , or
until signs of
cerebellar
disturbance occur
(nystagmus, ataxia,
involuntary
movements) One
the metabolizing
enxymes are
saturated , a small

Absence
Epilepsy in
Children

Ethosuximide
Sodium Valproate

increase in dose
may produce toxic
side blood levels of
the drug. Other
effects Gum
hypertrophy, acne,
greasy skin,
coarsening of the
facial features and
hirsutism.
EthosuximideNausea vomiting.

Absence seizures involve

oscillatory neuronal activity

between the thalamus and
the cerebral cortex. This
oscillation involves (T-type)
Ca2+ channels in the
thalamic neurones, which
produce low threshold spikes
and allow the cells to fie in
bursts. Drugs (Ethosuximide
and Valproate) that control
absences reduced this Ca2+
current dampening the
thalmacortical osciallations
that are critical in the
generation of absece
seizures.
Parkinsons Main pathology is the extensive degeneration of the dopiminergic nigrostriatal tract, but the cause of the
degeneration is usually unknown. Replacement therapy alone is not possible in parkinsons because the dopamine does not pass
the blood brain barrier. However its precursor levodopa (L-dopa), does penetrate the brain where it is decarboxylated to
dopamine. Orally administered, levodopa is largely metabolized outside the brain and so it is given with a selective
extracerebral decarboxylase inhibitor (carbidopa or benserazide). Some of the peripheral side effects of dopaminergic drugs
can be reduced with domperidone, a dopamine antagonist that does not penetrate the brain. Inhibition of the drug monoamine
oxidase B (MAOb) with selegilene potentiates the actions of levodopa. Anti-muscarincs are used for the tremor that occurs with
parkinsons.
Levodopa
Sinemat
Levodopa is the immediate
Parkinsons
Nausea and
Madopar
precursos of dopamine and is
vomiting caused by
Both these drugs
able to penetrate the brain
stimulation of the
come with
where it is converted to
CTZ.
extracerebral
dopamine. The site of the
Psych effects vivid
decarboxylase
decarboyxlation is uncertain,
dreams,
inhibitors)
but as dopa decarboxylase is
hallucinations,
no rate limiting there maybe
psychotic states
sufficient enzyme in the
and confusion.
remaining dopaminergic
Postural
nerve terminals. Another
hypotension is
possibility is that the
common.
conversion occurs in nor
Dyskinesias (jerky
adrenergic or seratonergic

terminals. Because the decarboxylase activity in these

neurones is not specific.

Dopamine
Receptor
Agonists

Pre Synaptic
Re-Uptake
inhibitor

Bromocriptine
(ergot derivative)
Ropinirole (non
ergot derivative)
Apomorphine
(very powerful
given by
parenteral
administration)

Amantadine

Parkinsons
Prolactinomas

Parkinsons

Dopamine agonists have no

advantage over levopdopa
and the adverse effects are
similar.
Used with young patients, in
particular who are given a
dopamine agonist as initial
therapy (sometimes together
with selegeline). This
strategy may slow the
development of dyskinesias
but only 50% of patients
show any beneficial response
to monotherapy with
dopamine agonists.
When patients on levodopa
therapy start to show
deterioiration dopamine
agonists are often added to
try and reduce the off
periods.
Potentiates dopamine by
preventing re-uptake in the
pre-synaptic terminals.
Moderate effect but toleranc

or dance like
movement) are an
important adverse
effect.
Long term after five
years treatment
about 50% of
patients will have
lost ground. In some
there is a gradual
recurrence of
parkinsionian
akinesia. A second
form of
deterioration is the
shortening of
duration of action of
each dose. Various
dyskinesias may
appear and, with
time rapid
oscillations in
mobility and
dyskinesias.
Nausea, psychiatric
symptoms, postural
hypotension.
Pulmonary fibrosis
and retroperitoneal
fibrosis.
Apomorphine
(highly emetogenic)
domperidone should
be given before
treatment started.

Dizzyness, Loss of
co-ordindation,
inability to sleep,
nausea,

soon develops
nervousness
Inhibits monoamine oxidase
Nausea
type B (MAO-B) there by
Heartburn
increasing dopamine. This is
Dry mouth
done by reducing the
metabolism of the dopamine
in the brain potentiating the
levdopa which can be
reduced by up to one 1/3. It
is used to reduce end of dose
akinesia.
COMT
Entacapone
Inhibbits catechol-O Parkinsons
Drowsyness
inhibitors
Benzarazide
methltransferase (COMT) and
Dizzyness
prevents peripheral
Stomach upset
conversion of Levodopa to
Diarrhoea
(inactive) 3-O-methyldopa. It
increases the plasma half life
of levodopa and increases its
action.
Antimuscarini
Benzetropine
Produce a modest
Parkinsons
Dry mouth
cs
Procyclidine
iimprovement in the early
Urinary retention
Orphenadrine
stages of parkisons disease,
and constipation.
Benzhexol
but the akinesia responsible
Effect memory and
for most of the functional
concentration.
disability responds least well.
Myaesthenia Gravis An acquired organ specific autoimmune disorder in which antibodies are directed at the post synaptic
acetycholine receptor. This results in weakness and fatiguability of skeletal muscle groups. The most commonly effected
muscles are the proximal limbs and the ocular an bulbar muscles.
Oral
Prydostigmine
Most widely used drug; it has
Myaesthenia gravis
Overdose causes a
acetycholinest
a duration of about 3-5
cholinergic crisis
erase
hours. Patients response will
with severe
determine the dose required.
weakness. Colic and
Great symptomatic drug but
diarrhoea may
does not alter the natural
occur.
history of the disease.
Motor neurone disease
Riluzole
Rilutek
Used to treat amyoptrophic
MND
Nausea
lateral sclerosis. Delays the
Fatigue
onset of ventilator
Hepatitis
dependence or tracheostomy
by 2 months.
Guillain- Barres syndrome (post-infective polyneuropathy) Inflammtory demyelinating polyradiculoneuropathy. Often follows
one to two weeks after infection or diarrhoea, which may have been mild. Campylobacter jejuni has been particularly implicated
as a cause of the diarrhoea and is associated with the most severe form. Classic presentation distal paraesthesie, often with
little sensory loss, and weakness can occure proximally, distally spreading or generalised. The symptoms ascend up lower limbs
and body over days to weeks. Facial weakness present in 50% cases. In sevre cases respiratory and bulbar involvement occurs.
IF VC drops to 1 litre of below: artificial ventilation is needed.
High dose
(IVIg)
Either high-dose intravenous
Guillen Barres
Hepatitis
Monamine
oxidase
inhibitor type
B (MAO-B)

Selegiline

Parkinsons

immunoglobul
ins

immunoglobulins (IVIg) at
Renal failure
400mg/kg for 5 days or
plasmapheresis can be
administered, as they are
equally effective and a
combination of the two is not
significantly better than
either alone. Therapy is no
longer effective after 2
weeks after the first motor
symptoms appear, so
treatment should be
instituted as soon as
possible. IVIg is usually used
first because of its ease of
administration and safety
profile, with a total of five
daily infusions for a total
dose of 2 g/kg body weight
(.4kg each day).
Glaucomas- Mixed group of disorders that have some common features: Optic disc cupping, visual field loss and usually, raised
intraocular pressure (IOP).
Beta-Blockers
Timolol, carteolol,
Reduce aqueous secretion by
Glaucoma
Ocular irritation
betaxolol,
inhibitory action on beta
Bronchospasm
levobunolol
adrenoreceptors in the
Bradycardia
cilliary body.
Nightmares
Exacerbation of
hear failure
Muscarinic
Pilocarpine (also
Increase aqueous outflow via
Glaucoma
Ocular: Misosis
(parasympath
a differential for
trabecular meshwork by
(reduced vision in
etic)
bilateral
ciliary muscle contraction
the presence of a
simulates .
constricted
cataract) spasm of
pupils!)
accommodation,
brow ache
Systemic: Swaeting,
bradycardia, GI
disturbance
Alpha2Brimonidine,
Reduces aqueos secretion by
Glaucoma
Ocular: Iris
stimulants
Apraclonidine
selective stimulation of
darkening,
Topical
alpha2 and adrenocrecptors
conjunctival
in the ciliary body increase
hyperaemia,
outflow by the uveoscleral
eyelash growth.
route
Systemic: bitter
taste, asthma.
Carbonic
Acetazolamide
Reduce aqueous secretion by
Glaucoma
Ocular route:
Anhydrase
(systemic)
the cilliary body
irritation and allergy
Inhibitors
Dorzolamide,
Systemic route:
Brinzolamide
Malaise,

paraesthesia, urea
and electrolye
disturbance,
aplastic anaemia
Mydriatics and cycloplegics ( Used for retinal examination and objective refraction (retinoscopy)
Antimuscarini
Tropicanamide,
Eye dilation for exam Inhibit muscarinic receptors
cs
cyclopentolate,
of parasympathetic nervous
atropine.
system to paralyse papillary
sphincter and ciliary muscle.

Alphastimulant

Phenylephrine

Eye dilation for exam

Stimulates dilator muscle of

the pupil no cycloplegic
effect.

Lubricants There are a wide range

Carbomers,

hyrpmellose,
polyvinyl alcohol,
liquid paraffin
Ant-Inflammatory Agents. Most important
immnosuppressants
Corticosteroid Prednisolone,

s
betamethasone,
dexamethasone

Dry eye

Exact mechanism depends

on the agent

Antihistamines

Cromoglicate,
nedocromil,
lodoxamide.
Topical:
Antazoline,
azelastine,
levocabastine.

Ocular: Allergy,
blurred vision

drugs are corticosteroids, a Variety of other drugs are available including systemic
Suppress
Inflammation

Suppresion of broad
spectrum of inflammatory
processes (see
corticosteroids)

Mast cell
stabilisers

Ocular: Blurred
vision, glare, angle
closure glaucoma.
Systemic:
Tachycardia, dry
mouth, confusion,
tremor.
Ocular: Blurred
vision, glare, angle
closure, glaucoma,
conjunctival
blanching.
Systemic
hypertension

Allergy

Stabilise mast cells

Allergy

Block histamine receptor

Ocular: Glaucoma
(especially with
local
administration),
cataract (especially
prolonged systemic
use) exacerbation
of some
infections !!! e.g.
herpes simplex.
Systemic: Negligible
with topical use,
common and varied
with systemic
administration.
Occular: Irritation
Occular route:
Irritation
Sytemic route:
Drowsiness

Systemic
(chlorphenamine,
terfendaine,
cetirisine)
NSAIDS
Topical:
Eye inflammation
(ketorolac,
diclofenac,
fluribiprofen)
Anti-Infective agents: Topically applied antibacterial and antiviral
and antiparastic agents is much less frequent.
Antibacterials
Topical:
Bacterial Infection
Chloramphenicol,
gentamicin,
ciprofloxacin,
Neomycin, fusidic
acid.
Occassionally
intra-ocular,
systemic

Antivirals
Aciclovir, topical
Herpes simplex,
or systemic
zoster

Modulate prostaglandin
production.

Systemic: Peptic
ulceration, asthma.

drugs are very commonly prescribed. The use of antifungal

Range of activities and
specificities

Inhibits herpes virus DNA

synthesis

Vary with agent

Ocular: allergy;
corneal toxicity
common with
intensive use.
Systemic: generally
only with systemic
use.

Ocular: blurred
vision, corneal
toxicity
Systemic: Rashes:
kidney, liver and
other effects may
occur with systemic
use.
Local Anaesthetics: Major uses are to relieve pain and thereby assist with clinical examination and the facilitation of surgical
anaesthesia
Local
Topical or periBlock conduction along the
Clinical exam
Ocular: Irritation,
anaesthesia
ocular injection.
nerve fibres
corneal toxicicty.
Oxyburprocaine,
Systemic: generally
proxymetacaine.
accidental
Tetracaine,
intravascular or
lidocaine.
intrathecal
(cerebrospinal fluid)
injection. During
surgical
anaesthesia,
cardiac
arrythmmias,
respiratory
depression
Botulinum toxin: Used in the management of certain ocular motility disorders amd blepharospasm, and to induce ptosis for
corneal protection
Botulinum
Injection at site of
Prevents release of the
Motility disorder
Dependant on

toxin
Migraine
Pizotifen
Sumatriptan
Acute
Migraine
Methysergide
Long term
migraine
Urinary Tract
Infection
Trimethoprim

action

neuro-transmitter
acetycholine at
neuromuscular junctions

treatment sitee.e.g
unwanted ptosis or
double vision

Serotonin
Antagonist
5HT
Serotonin
Antagonist
5HT
Serotonin
Antagonist
5HT

Migraine

Migraine

Migraine

E.coli, proteus,
saprophiticus.

UTI

Amoxicillin

UTI

NOT used in
pregnancy
Use nitrofurentoin
instead or
amoxicillin
Used in pregnancy

Diazoxide
Blocks insulin release
Insulinoma

Teriparatide
PTH
analogue
Hypocalaemia

Corticosteroids Release of cortisol is controlled by negative feedback mechanism involving the hypothalamus and anterior
pitruitary. Low plasms cortisol levels result in release of ACTH which stimulates cortisol synthesis and release by activating
Adenylate cyclise. cAMP then activates protein kinase A which phosphorylates and inceases the activity of cholesterylester
hydrolase, the rate limiting step in steroid synthesis. Aldosterone release is affected by ACTH but other factors (renin
angiotensin are more important.
Steroids are examples of gene active hormones. Steroid diffuses into cells where it binds to cytoplasmic glucocorticoid
receptors. IN the absence of cortisol the receptor is inactivated by a heat shock protein. Cortisol triggers the release of hsp90
and the activated receptor enteres the nucleus where it stimulates the synthesis of proteins, which then produce the
characteristic actions of the hormone.
Corticotrophin is prcessed from a large molecular weight precursor pro opiomelanocortin (POMC) precent in the corticotroph
cells of the adenohypophysis; its main action is tto stimulate the synthesis an release of cortisol. POMC also contains the
sequences for B lipoprotein (B-LPH) and B-endorphin, which are co comittantly release into the blood. Corticotrophin is also
believed to sensitize the zone glomerulosa to other stimuli which cause aldosterone release.
Glucocorticoids:- Mechanism of actionCortisol and synthetic glucocorticoids diffuse into target cells and binds to a cytoplasmic glucocorticoid receptor that belongs to
the superfamily of steroid thyroid and retinoid receptors. The activated receptor-glucocorticoid complex enters the nucleus and
binds to the steroid respsones elements on target DNA molecules. This either induces the synthesis of mRNA or represses the
genes inhibiting transcription factors e,g, NFkB for most clinical purposes, synthetic glucocoritcoids are used because they have
a higher affinity for the receptor are less rapidly inactivated and have little or no salt retaining properties.
Effects Glucorticosteroids are essential for life their most important function being facilitating the conversion of protein to
glycogen. They inhibit protein synthesis and stimulate protein catabolism to amino acids. Gluconeogenesis glycogen deposition
and glucose release from the liver are stimulated, but peripheral glucose uptake is inhibited. During fasting they are essential

for keeping blood sugars level.

Anti Inflammtory Effects and Immunosuppresive effects. Cotricosteroids have profound anti-inflamm effects. They
suppress all phases of inflammatory response, include the early swelling , redness pain and the later proliferative changes seen
in chronic inflammtation. Inflammation is suppressed by several mechanisms
Circulating immunocompetent cells and macrophages are reduced and the formation of pro inflammatory mediators, as
prostaglandins leukatrienes and platelet activating factor is inhibited. Done by stimulating the synthesis in leucocytes of a
protein (lipocortin) that inhibits phospholipase A2. This enzyme in cell membrane is activated in damaged cells adn is
responsible for the formation of arachdonic acid. The precursor of many inflammatory mediators. Corticosteroids suppress the
genes coding for phospholipase A2, (COX2) and the interleukin-2 (IL-2) receptor. These genes are normally switched on by NFkB
but steroids induce the synthesis of IkB that binds to the NFkB and inhibits it by preventing its entry into the nucleus. They also
depress monocytemacrophages fintion and decrease T-Cells, IL1 and IL2 is inhibited.
Hydrocortison Coritcosteroid
(iI)s used orally for
Anti Inflamm
Moon face, fat to
e
replacement (ii) intra
trunk and face,
venously in shock and status
purple striae,
asthmaticus and (iii) topically
hirsutism,acne,
(e.g. ointments in eczema
infections
enemas in ulcerative colitis
Osteoporosis, bruise
skin, diabetes,
hypercalaemia,
Fluid retention,
hypokalaemia.
Prednisolone
Corticosteroid
Is the most widely used drug
Anti Inflamm
A s above
driven orally in inflammatory
and allergic diseases.
Betamethason Corticosteroid
Are very potent and have so
Anti Imflamm
As above
e and
salt-retaining actions. This
Dexamethaso
makes them especially
ne
useful for high dose therapy
in conditions, such as
cerebral oedema where
water retention would be a
disadvantage.
Beclometason Corticosteroid
Pass membranes poorly and
Anti Inflamm
As above
e and
are more active topically
Budesonide
than when given orally. They
are used in asthma and
topically in sever eczema to
provide a local anti
inflammatory action with
minimal systemic effects.
Triamcinolone Corticosteroid
Used in sever asthma and by
Anti Inflamm
As above
intra articular injection for
local inflammation of the
joints.
NSAIDS inhibit COX and inihibit prostaglandin synthesis. COX exists in tissue as constitiutive isoform (COX-1) but at sites of
inflammation cytokines stimulate the induction of a second isoform (COX-2) Inhibition of of COX-2 is thought to be responsible

for the anti-flamm effects of NSIADS. Inhibition of COX 1 is responsible for GI problems. Most current NSAIDS are COX 1
inhibitors, but selective COX 2 are on the market (Celecoxib, eterocoxib, valdecoxib) are selective COX 2 inhibitors incidence of
gastric perforation obstruction and bleeding is reduced by at least 50%.
Aspirin is long standing NSAID and anti analgesic
Paracetamol is just analgesic