THERAPEUTICS I

Class 5
Alicia E. Frederick
Cert. Pharm.
Dip. Pharm. (Hons)
B. Pharm. (Hons)
Pharm. D. Candidate
RENAL DIALYSIS

• (Chapter 30)

2
THE WORKING KIDNEY

• Filters 150L of blood per day

• Entire blood within the body filtered once

every 45 minutes

• Produces 1.5 – 2 L urine per day

LIVING WITHOUT KIDNEYS

• A person can survive with only 1 kidney

• However, no working kidneys  death
• How do we know kidney is not working?

• Options:
• Dialysis
• Transplantation
 Definitions

Dialysis is the process of removing waste products

and excess fluids from the body
Dialysis is one of the primary modalities for pts with
End Stage Renal Failure

Dialysis can do two of the principal functions of the

kidney; 1. removal of endogenous waste products 2.
maintenance of water balance
 Dialysis is the process of separating elements in a solution by diffusion across a
semipermeable membrane (diffusive solute transport) down a concentration gradient

This is the principal process for removing the end-products of nitrogen metabolism (urea,
creatinine, uric acid), and for repletion of the bicarbonate deficit of the metabolic acidosis
associated with renal failure in humans
Cont…
 Indication for dialysis;
A. Acute dialysis
Advanced renal failure with: Normal renal function:
1. Hyperkalemia 1. Poisoning
2. Fluid overload 2. Nephrotic syndrome with oedema
3. Severe metabolic acidosis (PH<2) 3. Hypercalcemia
4. Pericarditis
5. Encephalopathy
6. Pulmonary oedema
7. Peripheral neuropathy
8. Uraemic symptoms
Cont…

B. Chronic dialysis

1. ESRD with or without complications

Signs of adequate dialysis;
1. Well looking
2. Eats normal
3. Normal BP
4. No oedema
5. Normal heart size
6. HB >=10
7. Albumin >35
Hemodialysis
PROCESS OF HEMODIALYSIS

• Used 3 times a week

• Duration; 4 hrs
• Complicated, need to be done in a center
• Heparin required
• Temporary arteriovenous access
• Permanent arteriovenous access
HEMODIALYSIS

• Blood is removed from the body and pumped

by a machine outside the body into a dialyzer
(artificial kidney)

• The dialyzer filters metabolic waste products

from the blood and then returns the purified
blood to the person
HEMODIALYSIS

• The total amount of fluid returned can be

adjusted

• A person typically undergoes hemodialysis at a

dialysis center

• Dialysate is the solution used by the dialyzer

HEMODIALYSIS

• HD consists of perfusion of heparinized blood

and physiologic salt solution on opposite
sides of a semipermeable membrane

• Waste products (urea, creatinine,…ets) move

from blood into the dialysate by passive
diffusion along a concentration gradient
 ANTICOAGULATION

• Necessary to prevent blood from clotting in the

extracorporeal circuit.

• Heparin administered either by:

• intermittent bolus injections or
• an initial bolus followed by a continuous infusion.
• 2,000-unit bolus of IV heparin 3 to 5 minutes before
dialysis followed by an infusion of 1,200 units/ hour.
• Discontinue 1 hour before the end of dialysis to prevent
excessive bleeding at the end.
ANTICOAGULATION

• MONITOR
• THE TARGET ACTIVATED CLOTTING TIME
(ACT) IS 40% TO 80% ABOVE THE AVERAGE
BASELINE FOR THE DIALYSIS UNIT (E.G.,
200– 250 SECONDS, FOR NORMAL VALUES
OF 120– 150 SECONDS).

• SIGNS OF BLEEDING
ANTICOAGULATION

• For Patients at increased risk of bleeding

• recent surgery, retinopathy, gastrointestinal
bleeding, and cerebrovascular bleeding.
• “minimal-dose” heparin (tight ACT control), or
• heparin-free anticoagulation.

• LMWH are FDA approved for hemodialysis.

HEMODIALYSIS

• Diffusion rate depends on;

1. The difference between solute
concentrations in the blood and
dialysate
2. Solute characteristics
3. Dialysis filter composition
4. Blood and dialysate flow rate
Cont…

Blood from the patient is circulated through a

synthetic extracorporeal membrane and
returned to the patient. The opposite side of that
membrane is washed with an electrolyte
solution (dialysate) contain- the normal
constituents of plasma water
Cont…
Dialysate;
1. Water
2. Glucose
3. Acetate
4. Bicarbonate
5. Calcium
6. Sodium
7. Potassium
Access
ACCESS
• The access is where the needles are placed to remove blood
from the body and return it to the body after it is filtered by the
dialysis machine
• Three types of accesses exist:
• natural fistula,
• artificial grafts, and
• jugular vein catheters

• A vein and an artery are joined. Within 6 to 8 weeks, the vein

becomes much bigger and is strong enough to be used as an
access for dialysis
 ACCESS- FISTULA

• 1. During dialysis, two needles are placed into

the fistula. One needle will remove the blood
so it can be cleaned. The other needle will
return filtered blood to the body

• 2. The needles are attached by plastic tubing

to a special filter called a dialyzer (or artificial
kidney)
 ACCESS- FISTULA

• 3. A pump pushes the blood through the dialyzer.

Blood passes on one side of the filter, and solution
made by the machine passes on the other side. The
blood does not mix with the solution. Instead, the
solution pulls extra fluid and waste out of the blood
by a process called dialysis

• 4. The "clean" blood returns through the plastic

tube. It passes back into the patient's body through
the second needle
ACCESS-GRAFT

• A graft is another type of access, which is used

if a person's own veins are too small or weak
to create a fistula.

• Usually, a graft is a soft, synthetic tube that

connects to an artery at one end and a vein at
the other.
ACCESS-GRAFT

• It is placed under the skin of the arm or thigh,

like a natural vein.

• The patient's blood flows through it, like it

flows through natural veins
ACCESS- EMERGENCY

• Sometimes hemodialysis is needed right away,

and there is no time to create a fistula or graft.

• If this happens, a tube called a catheter may

be inserted into a large vein in the neck
(jugular vein), behind the collarbone
(subclavian vein) or in the groin (femoral
vein).

• The patient's blood can flow through this tube

Complications;
1. Vascular access 3. Long term
a. Thrombosis a. Cardiovascular diseases
b. infection b. Renal bone diseases
c. Aluminum disease
2. Procedure related d. Social problems
a. Decrease BP
b. Headache 4. Chronic uraemia
c. Cramps a. Anaemia
d. Fever b. Infection
c. Gonadal dysfunction
d. Increase BP
Cont…
Cont…
 Standard HD
Characteristics:
1. Low permeability (low flux)
2. Membranes are made of natural products
(cellulose)
3. Each session takes 4-5 hrs
 Rapid high efficiency HD (RHED)
Characteristics:
1. Increase clearance of low molecular weight
solutes (urea)
2. Shorter procedure time
3. Increase blood and dialysate flow rates
4. Clearance of middle and high MW solutes
including drugs is not increased
 High flux dialysis (HFD)
Characteristics:
1. Shares the advantages of RHED
2. Membrane pores are more open
3. Higher clearance rate for middle molecules
4. More expensive
5. Needs experts to avoid large rapid fluid shift
Peritoneal Dialysis
Cont…
Peritoneal Dialysis

• The dialysis membrane is the person's own

peritoneum
• The dialysis fluid provides the 'container' in which
waste products and excess water can be removed
from the body
• Dialysis membrane acts as a filter
• It keeps the dialysis fluid and the blood separate
from each other, but it allows certain substances
and water to pass through it
Peritoneal Dialysis

• During dialysis, waste toxins and excess water

pass from the blood into the dialysis fluid, and this
is drained out of the body after a few hours
• A new bag of dialysis fluid is drained in, and the
process is repeated
Peritoneal Dialysis
• PD needs to be done every day
• PD involves draining dialysis fluid out of, and into the
body (known as an exchange), and leaving dialysis
fluid in the body while dialysis takes place
• Draining fluid out usually takes around 20 minutes
and draining fluid in takes around 5-10 minutes
Peritoneal Dialysis
• The 'used' dialysis fluid, containing the water and
waste (toxins) that the kidneys would normally have
passed into the urine, is drained out of the body
• The person then needs to drain between 1.5 and 3
litres of 'new' dialysis fluid into their abdomen
Peritoneal Dialysis
• The dialysis fluid is then left inside the peritoneum to
allow dialysis to take place. The length of time it is
left there varies (between 1 and 8 hours), depending
on individual requirements and the type of PD
• There are no 'set' times to carry out the exchanges
• It is easy for people to adapt the timing of exchanges
to their own needs. For example, if a person wants to
go out for the day, they could delay the mid-day
exchange, and do two 'quick bags' (say, 3 hours apart)
after they come home
Peritoneal Dialysis

• A four-bag regime 'fits' into a typical day

• For example,
• The first bag might be exchanged before breakfast
• The second before lunch
• The third before the evening meal
• The fourth before going to bed (leaving the fluid for
the last exchange in through the night)
Peritoneal Dialysis
• A plastic tube is permanently inserted into the
abdomen
• This tube is called a PD catheter
• It is about 30 cm (12 in) long and as wide as a pencil
• The PD catheter is placed through the lower
abdominal wall, into the peritoneal cavity
Peritoneal Dialysis
• Half of the catheter lies inside the abdomen, and half
lies outside the body
• It comes out to one side of the navel (belly button)
• The PD catheter acts as a permanent pathway into
the peritoneal cavity from outside the body
Cont…
Peritoneal Dialysis
• The catheter is usually 'left alone' for 5 days or more
after the operation before it is used for dialysis
• This allows it to 'settle in' and gives the abdominal
wound time to heal
• PD could be done at home
• Much less efficient than HD, this is why it is used
more frequent
Cont…
Dialysate;
1. Water 9. Magnesium; 1.5mEq/l
2. Glucose 10.Sodium; 132mEq/l to reduce
the movement of sodium
3. Dextrose; 1.5-4.25% from the blood by gradient
4. Acetate method
5. Bicarbonate 11.No potassium in PD

6. Calcium; 3.5 or 2.5 mEq/l 12.High osmolarity; 350-

480mOsm/L
7. Chloride; 102mEq/l (serum=280mOsm/l) to
8. Lactate; 35mEq/l provide a drawing force from
the blood into the peritonium
 PET; peritoneal equilibrium test
•Is a diagnostic test that determines the peritoneal
membrane clearance and ultrafiltration
characteristics, and quantifies the ability to transfer
solutes and water across the membrane
•PET results determine which type of PD is
appropriate for each individual
Indications;
1. DM
2. No vascular access
3. CVS unstable
4. Children
5. Old adults
6. Pts unwilling to accept blood transfusion
7. Severe anaemia
8. Severe HD related symptoms e.g disequilibrium
Contraindications;
1. Peritonea adhesion
2. Severe lung disease
3. Abdominal sepsis
4. Massive polycystics
Complications;
a. Malnutrition
b. Peritonitis:
c. 70% Gm positive cocci
d. IP antibiotic is preferred
e. vancomicin or aminoglycosides. First dose in
the first 2L exchange, scond dose at day 7
f. Gentamicin 1.5 mg/kg IP in the first 2L
exchange followed by 4-8 mg/L IP in each
exchange for 10 days
Cont…
Cont…
Cont…
SUMMARY

62
DEFINITION

Dialysis is an
artificial process
of filtering the
blood to remove
solutes and
excess fluids
from the body.
INDICATIONS FOR DIALYSIS

Acute dialysis Chronic dialysis

Advanced renal failure with: ESRD:
• Hyperkalemia • With complications
• Fluid overload • Without complications
• Severe metabolic acidosis
• Uremic symptoms
Normal renal function with:
• Poisoning
• Hypercalcemia
• Nephrotic syndrome with edema
TYPES OF DIALYSIS

Haemodialysis Peritoneal dialysis

A dialysis machine and a The peritoneum is used as a
filter when sterile dialysate
special filter called a dialyzer,
solution, rich in minerals and
are used to filter blood. To get glucose, is fed into the
blood into the dialyzer, an peritoneal cavity. The
access into a blood vessel is dialysate is left in the
peritoneal cavity for some
created with minor surgery,
time, so that it can absorb
usually to the patient’s arm. waste products. Then it is
Blood is removed from the drained out through a tube
body, cleaned and returned to the patient. and discarded.
THE DIALYSIS PROCESS:
HAEMODIALYSIS
THE DIALYSIS PROCESS:
PERITONEAL DIALYSIS
COMPLICATIONS OF DIALYSIS

Haemodialysis Peritoneal Dialysis

• Vascular access • Malnutrition
• Thrombosis, infection
• Procedural • Infection – peritonitis
•  Bp, headache, cramps, fever
• Long term • Bleeding
• CVD, renal bone disease, Al disease, social problems
• Chronic uremia • Leakage of fluid
• Anemia, infection, gonadal dysfunction,  Bp
• Scarring of the peritoneum

• Hernia of the abdomen

REFERENCES

• Applied Therapeutics: The Clinical Use of Drugs, Caroline S. Zeind &

Michael G. Carvalho, 11th Edition. LWW (December 27, 2017)
• Pharmacotherapy: A Pathophysiologic Approach, Joseph DiPiro et
al, 10th Edition. McGraw Hill / Medical (December 13, 2016)
• AK. Soyibo, Caribbean Institute of Nephrology Department of
Medicine

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