Download Lecture 8

Cardiovascular Anatomy,
Physiology and Pharmacology
BS913
Lecture 8: General Pharmacology,
Pharmacokinetics and –dynamics,
Introduction to cardiovascular drugs …
Mücke Leithauser
1)
What is Pharmacology?
2)
What do you want to know /
learn about pharmacology?
3)
Why is some knowledge in
pharmacology important to you?
Learning objectives „Pharmacology“
- Describe the prescribed usage, alternative
nomenclature, dosages, adverse reactions,
cautions and common routes of administration
- Describe the pharmacological interventions
commonly used in the treatment of cardiac
disorders
- Discuss the effect of common cardiac drugs on the
body and their cellular and physiological actions.
- Understand the effect of common cardiac drugs on
physical activity, and the special considerations
related to these drugs.
What is pharmacology?
-
Pharmacology is the study of
drugs and their actions on living
organisms
-
A sound knowledge of basic
pharmaceutical principles is
essential for professionals who
interact with patients who
receive medications

1)
What is Pharmacology?
2)
What do you want to know /
learn about pharmacology?
3)
Why is some knowledge in
pharmacology important to you?
4)
Where do we start?
General principles of pharmacology
-
Drug development
-
Drug names
-
Drug categories
-
Drug actions within the body
-
Drug reactions
-
Drug interactions
-
Factors influencing drug response
Drug development
-
Long and arduous process
7 to 12 years or longer
-
New drugs need to be approved (FDA
= Food and Drug Administration and /
or similar national organisations)
-
Development of a new drug is a multiphase process
pre-FDA phase
FDA phase
Drug development
-
pre-FDA phase:
-
-
in-vitro testing using animal and
human cells
studies in live animals
FDA-phase: clinical testing
phase I:
4 - 6 weeks; 20 - 100 individuals
(“normal” volunteers or in intended
treatment population)
Drug development
-
FDA-phase: clinical testing
phase II:
more people compared to phase I
-
phase III:
more people compared to phase II;
generates more info on dosing
and safety
-
Phases I-III last 2-10 years (average 5)
Decision of (dis)approval approx. 2 yr
Phases of drug development
Drug names
Drugs are referred to in a number
of ways:
-
By the class or group of drugs
Anti-Histamins
-
By generic names
Loratadine
By proprietary (or brand)
names
Claritin
-
Drug names
GROUP
Ca-channel
blockers
ß-blockers
Generic
name
Verapamil
Proprietary
name
Cordilox
Verapamil
Securon
Propanolol Inderal
Atenolol
Tenormin
Drug categories
-
Prespription drugs:
-
-
Non-prescription drugs:
-
-
Largest category of drugs
Must be prescribed by licensed
health care provider
most drugs taken by cardiac
patients need to be prescribed
can be obtained without prescription
are drugs; may cause adverse effects
Controlled substances:
-
high potential for abuse; may cause
physical or psych. dependence
Drug actions within the body:
-
Pharmaceutical phase
-
Pharmacokinetic phase
-
Pharmacodynamic phase
Drug actions within the body:
-
Drugs act in various ways in the body
-
Solid drugs taken by mouth go
through all three phases
-
Liquid drugs and parenteral drugs
(given by injection) go through the
latter two phases
Drug actions within the body:
-
Who has ever taken medication
because of horrible headache?
Pharmaceutical phase:
-
Dissolution of the drug
-
Drugs must be in solution to be
absorbed
-
Tablets or capsules: disintegrate into
small particles and dissolve into body
fluids within the gastrointestinal tract
-
Enteric-coated tablets do not
disintegrate until reaching an
alkaline environment (small intestine)
Pharmacokinetic
phase:
Pharmacokinetic phase:
-
Refers to activities involving the drug
after it is administered
-
-
Absorption
Distribution
Metabolism
Excretion
Half-life of a drug: measure of rate at
which drug is removed from the body
Absorption
-
Follows administration
-
Process by which drug becomes
available for use in the body
-
Occurs after dissolution of solid drug
or after administration of a liquid or
parenteral drug
Absorption
-
Drug particles in GIT are moved into
body fluids
active absorption (carrier moves
drug through membrane)
passive absorption (diffusion)
pinocytosis (cells engulf drug
particle causing movement
across the cell)
-
Drug transfer to tissue sites –
absorption into body tissues
Absorption
-
Factors influencing rate of absorption
-
route of administration
solubility of drug
certain body conditions (e.g.
Lipodystrophy)
Absorption
-
Drugs most rapidly absorbed
-
intravenous application
-
intramuscular application
-
subcutaneous application
-
oral application
Distribution
-
-
Systemic circulation distributes
drugs to various body tissues / target
sites
There, drugs interact with specific
receptors
-
Some drugs travel by binding to
protein (albumin)
-
Drugs bound to protein are
pharmacologically inactive
Distribution
-
Needs to be released by protein
molecules to diffuse into tissue,
interact with receptors, produce a
therapeutic effect
-
Certain blood level must be
maintained for drug to be effective
-
If level too low: drug will not produce
desired effect
-
If level too high: toxic symptoms may
develop
Metabolism
-
Sometimes called biotransformation
-
Process of chemical reactions by
which the liver converts the drug to
inactive compounds
-
Important: patients with liver disease
may require lower dosage; frequent
liver function tests are necessary
-
Kidneys, lungs, plasma and intestinal
mucosa aid in metabolism of drugs
Excretion
-
Elimination of drugs from the body
-
After liver renders a drug inactive,
kidneys excrete inactive compounds
from the body in the urine
-
Some drugs are excreted unchanged
by the kidney without liver
involvement
Excretion
-
Important: Patients with kidney
disease may require a lower dosage;
careful monitoring of kidney
function
-
Special case “children”: immature
kidney function
Special case “older adults”: reduced
kidney function
Other ways of elimination: breast
milk, breathing, faeces
-
Half life
-
Time required for the body to
eliminate 50% of the drug
-
It takes five to six half-lives to
eliminate approximately 98% of a
drug
Half-life of a drug is the same in most
people
-
Reduced liver and kidney function
can increase half-life and by this the
risk of toxicity
Pharmacodynamic phase
-
The drug’s action and effects within
the body
-
After administration most drugs enter
the systemic circulation and expose
almost all body tissue to their
potential effects
-
All drugs produce more than one
effect in the body
-
The primary effect is the desired or
therapeutic effect
Pharmacodynamic phase
-
-
Secondary effects are all other effects
(desirable or undesirable) produced by
the drug
Most drugs have an affinity for
certain organs or tissues
-
They exert greatest action at the
cellular level in those specific areas
-
Main mechanisms of action:
alteration in cellular environment
alteration in cellular function
Pharmacodynamic phase
-
Physical alterations in cellular
environment, e.g.
Changes in osmotic pressure
Absorption (activ. charcoal)
Conditions on surface of cell
membrane (stool softener)
-
Chemical alterations in cellular
environment, e.g.
alteration of chemical
components of body fluid
(ph-change; antacids)
Pharmacodynamic phase
-
Most drugs act on body by altering
cellular function
increase or decrease of certain
physiologic function, e.g.
heart rate
blood pressure
urine output
Pharmacodynamic phase
-
Receptor-mediated drug action
Cell function alters when drug
interacts with receptor
-
Agonists: drugs bind with receptor to
produce a therapeutic response
-
Antagonists: drugs bind with receptor
and thereby prevent the action of an
agonist
Pharmacodynamic phase
-
Receptor-mediated drug effects
-
Number of available receptor sites
influences effects of a drug
-
If drug occupies only few receptors
when many are available: small effect
Drugs : a variety of reactions
-
Adverse drug reactions
-
Allergic drug reactions
-
Drug idiosyncrasy
-
Drug tolerance
-
Cumulative drug effect
-
Toxic reactions
Adverse Drug reactions:
-
Adverse drug reactions
-
Undesirable drug effects
-
May be mild, severe, life-threatening
-
Occur after first dose, several doses,
many doses
-
Sometimes predictable
-
In many cases without warning
Adverse effects:
Allergic Drug reactions:
-
Hypersensivity
-
Occurs usually after more than
one dose has been given
-
Immune system views drug as a
foreign substance (antigen)
Initiates antibody production
-
Allergic reaction must be reported to
health care provider
Allergic Drug reactions:
-
Symptoms
-
Itching skin
Rash
Breathing difficulties
Wheezing
swelling of the eyes, lips
Anaphylactic Shock:
Drug idiosyncrasy:
-
Unusual or abnormal reaction to a
drug
Drug tolerance
-
Decreased response to a drug
After taking the drug for long time
increase in dosage to maintain effect
Cumulative Drug effect:
-
In patients with liver / kidney
problems
Can lead to toxic reactions
Toxic reaction
-
If administered in large dosages
When blood concentration level
exceeds therapeutic level
sometimes antidote available
Drug interactions:
-
Drug-drug interactions
-
Drug-food interactions
Drug interactions:
-
Drug-drug interactions
-
Additive drug reaction:
1+1=2
-
Synergistic drug reaction:
1 + 1 = (>2)
-
Antagonistic drug reaction:
Drug interactions:
-
Drug-Food interactions
-
Drug taken on empty stomach:
Faster absorbed
-
Full stomach:
Slower absorbed
Drug-food complex
(tetracycline)
food as “antagonist” (vit. K
and warfarin)
-
Factors influencing drug response:
-
Age
-
Weight
-
Gender
-
Disease
-
Route of administration
Factors influencing drug response:
-
Age:
immature organ function in kids
reduced function in elderly
-
Weight: reference weight 75 lb
-
Gender: higher fat/water ratio in F
-
Disease: liver, kidney;
-
Route of administration
Factors influencing drug response:
-
Route of administration
some drugs can onlygiven by
one route
differences in appearance of
drug action
Factors influencing drug response:
Drugs used to treat cardiac
conditions: