College Of Medicine

PHARMACOLOGY ASSIGNMENT

SUBMITTED BY: BERNARD SINDANI KATHEWERA

REG #: 201650023644

SUBMITTED TO: MR THUBOY

SEPTEMBER 24, 2019

1. D. 5L
2. B. Usually leads to inactivation of the drug.

3. Benzyl penicillin
a. Pharmacokinetics of benzyl penicillin
i. Absorption: usually administered using the intravenous or intramuscular
injection. Initial blood levels following parenteral administration are high but
transient. Oral absorption in fasting, healthy humans is only about 15-30% as
it is very susceptible to acid-catalyzed hydrolysis.
ii. Volume of Distribution; In adults, with normal renal function, the volume of
distribution is around 0.53 - 0.67 liters per kg. The drug binds serum proteins
mainly albumin with about 45 – 68% bound.
iii. Metabolism; about 16-30% of an IM dose is metabolized to penicilloic acid,
an inactive metabolite. A small amount of drug appears to be hydroxylated
into one or more active metabolites, which are excreted via urine. In adults
with a normal renal function it has a reported half-life of 0.4-0.9hours.
iv. Elimination and clearance; The drug is eliminated by the kidneys, non-renal
clearance includes hepatic metabolism and to a lesser extent, biliary
excretion. Penicillin G has a clearance level of 560ml/min in healthy humans.

b. How Probenecid influences the pharmacokinetics of benzyl penicillin? Probenecid

has a high affinity for the tubular organic acid transporter and hence inhibits renal
tubular secretion of benzyl penicillin by blocking the its active transport, and thus
prolong duration of action of penicillin.

c. Sketch ‘’plasma concentration versus time’’ graphical representations of single

dose benzyl penicillin in the presence and in the absence of probenecid.
Plasma Concentration

Graph A
Graph A (Benzyl penicillin with Probenecid)
Graph B
Graph B (Benzyl penicillin without Probenecid)

Time(Hours)
4. Diphenhydramine
a. Presence of ammonium chloride, will make the urine to be acidic and this
promotes the ionization of the drug Diphenhydramine, that is a weak base. In an
ionized form, the drug is more polar and tubular reabsorption from the nephric
lumen back into blood circulation is minimized and consequently its clearance
through urine is enhanced.

b. Diphenhydramine being a weak base, its absorption will largely occur in the
intestines. The drug will not be largely absorbed in the stomach because of its
ionization due to acidic conditions of the stomach. Ionized drugs do not easily
cross the membrane.

5. Difference between zero-order elimination and first-order elimination of drugs.

Zero-order elimination kinetics is the elimination of a constant quantity per unit time
of the drug quantity present in the organism while first order elimination kinetics is
elimination of a constant fraction per time unit of the drug quantity present in the
organism, the elimination is proportional to the drug concentration.

Figure1. Zero-Order elimination kinetics

The plasma concentration-time
profile during the elimination
phase is linear, for example
1.2mg are eliminated every hour,
independtly of drug
concentration in the body. Order
0 elimination is rear, mostly
occurring when the elimination
system is saturated. An example
is elimination of aspirin and
phenytoin
For first order elimination, the
plasma concentration – time
profile during the elimination
phase shows an exponential
decrease in the plot with linear
axes. An example of elimination under
first order is benzyl penicillin
6. Steady state
a. Yes, it will affect the steady state.
b. This is so because, since the introduction of drug B induces the enzymes for
metabolism of drug A, more of drug A will be metabolized and this will change its
steady state concentration.
c. In order to get back to the original steady state concentration of drug A, more of
this drug should be administered or increasing the frequency of administration of
the drug to compensate more of the drug which is more and rapidly metabolized
by the introduction of drug B.
d. It will take 4.3 half-lives

References Used
1. H.P Rang, M.M Dale, J.M Ritter and R.J Flower. 2007. Rang and Dale's
Pharmacology. London: Churchill Livingstone Elsevier.
2. K.S Parsy, R.G Assomull, F.Z Khan, K.S Parsy and E.Kelly. 1999. Instant
Pharmacology. Chichester: John Wiley and Sons.
3. www.drugbank.ca
4. Richard A. Harvey. Lippincott’s Pharmacology 5th Edition. Wolters Kluwer.
Lippincott Williams & Wilkins
5. W. Blackwell. Medical Pharmacology at a Glance s8th_Edition