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Physiology and Pharmacology summary
This is a very extensive summary that belongs to the course physiology and pharmacology. The summary is written in English.
[Meer zien]Voorbeeld 4 van de 80 pagina's
Voorbeeld 4 van de 80 pagina's
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EfficacyMode of administration
Safety
Medicinal
Production
Discovery
drug
Physiology and Pharmacology Distribution
Cause Patient
Maandag 13 januari 2020 Disease
Healthcare Supervision
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Pharmacodynamics and Pharmacokinetics
Pharmacokinetics (kinetics = motion)
- How the body affects the drug “What the body does to the drug”
Pharmacodynamics (dynamics = change)
How the drug affects the body “What the drug does to the body”
Plasma proteins are proteins which are available in the blood stream and they determine whether
a drug has a biological mode of action.
Physiology and pharmacology
Important!!
Active medicinal substances:
Adrenaline
Propranolol
Prazosin
Nicotine
Placebo
Digoxin
Carbacal
Atropine
Pharmacology: Treatment of diseases
- Cardiovascular system
* Heart failure
* Hypertension -> a condition when people have continuously a high blood pressure.
- Respiratory system
* Bronchial asthma
* COPD (loose lung tissue)
- Endocrine pancreas
* Diabetes mellitus
* Metabolic syndrome
Pharmaceuticals = medicinal drugs
Pharmacology already started 5000 years before Christ.
Physiology
Physiology studies how the body functions
- homeostasis
* feedback mechanisms Physiology
- Integrative physiology
- physiology/pathophysiology
Physiology studies how the body functions
Drugs, medicinal drugs, active substances – homeostasis
- The medicinal drugs that were used to treat disease until the end of the 19th century were
feedback mechanisms
natural products obtained form living and inanimate things usually dried but also fresh plants or
parts thereof – integrative physiology
- These could contain substances with a healing (therapeutic) effect but also substances with a
– physiology/pathophysiology
toxic effect
Fig. 1-1
Pagina 1 van 80
,The history of pharmacology
The beginning…
‘if you want to explain every poison well, what is nor a poison? All
substances are poison; there is none which is not a poison. The right dose
differentiates a poison and a remedy’.
From poppies to morphine
Morphine = analgesic
Codeine = cough syrup
Action via receptor = proteins
Morphine was isolated from the poppy plant. (papaver plant) -> also
Codeine, Noscapine, Papaverine (taste influencer), etc. (but not heroin)
The aims of isolating pharmaceuticals are:
- Identification of the active substance/substances
- Pharmacodynamics: analysis of biological effect (analyse van biologisch effect)
- Pharmacokinetics: analysis of their ‘fate’ in the body (analyse van hun 'lot' in het lichaam)
- Guarantee that that the dose remains exact and unchanged by using the isolated pharmacon in
treatments.
- Option of chemical synthesis of pharmaceutical with more favourable pharmacological
characteristics
- Altering the chemical structure; medicinal drugs that have a stronger effect.
Pharmacology is mainly characterized by application of pharmaceuticals (=medicinal drugs) in
treatments of diseases. and pharmacodynamics
Pharmacokinetics
( storage)
Pharmacokinetics Pharmacodynamics
Applikation = Administration Biotransformation = Biotransformation (Liver!) Rezeptoren = Receptors (proteins)
Resorption = Resorption Exkretion = Elimination (Kidneys!) Biologische Wirkung = Biological effect
Verteilung = Distribution Bindung = Binding
Speicherung = Storage
Pharmacokinetics (kinetics = motion)
- How the body affects the drug “What the body does to the drug”
- Analysis of their ‘fate’ in the body
- ADME = Absorption, Distribution, Metabolism, Excretion
- The application of the drug, its fate and turn-over.
Pharmacodynamics (dynamics = change)
- How the drug affects the body “What the drug does to the body”
- Analysis of biological effect
- Pharmacodynamics mainly study the effect of a drug on a receptors.
Pagina 2 van 80
,Pharmacokinetics: Application
Oral administration gives the most patient compliance
(therapietrouw)
All the drugs enter first the liver through the portal vein
system when you take the drugs via oral administration.
The stomach is a very terrible place because it is very
acidic and a lot of drugs don’t survive through the
stomach
The drug has to survive the passive of the liver and the
acidic condition of the stomach
Inhalation -> Respiratory system (bronchial asthma).
Very good when it is properly used, when it is not
properly used it will leads to side-effects (diabetes
mellitus) There will be a treatment specificity when the drug will be end up in the lungs and not in
the stomach, liver and other organs.
na de pauze
Pharmacokinetics: Administration and Distribution
- Oral (self medication)
* Note: portal vein system
* The liver has important and a lot of enzymes that help to metabolize food
and also drugs. Some of the enzymes are active and they can be either
responsible for the inactivation of a drug during the first pass through the
liver but there are also pro-drugs which are not activated and than the liver
enzymes can be important to activate the drug. The majority of the drugs are
inactivated in the liver.
- Inhalation -> the drug will directly go to the right place when there are lung
problems.
- Topical (at a particular site)
* transdermal (patch -> pleister/lap)
* sublingual (under the tongue), buccal (wang/in de mond) -> avoid the
passing through the liver.
* rectal
- Injection (e.g. peptide hormones: insulin) (avoid passage through the liver)
* intravenous
* subcutaneous
* intramuscular
Insulin taking orally is not possible because the stomach is very acidic and will destroy every
peptide hormone.
Pharmacokinetics: blood-tissue barriers
There are barriers in the blood system.
Polarity and charge of pharmaceuticals determine:
Central effect
blood brain barrier can be crossed (permeable). Helping us to get energy to the
brain that we need for activation of activity in the nervous system.
Peripheral effect (aan de buitenzijde van het lichaam)
blood-brain barrier cannot be crossed (impermeable)
The heart will not get too much of the drugs inside. The liver is always an open
door. This is useful because it has to metabolize a lot. The pancreas is open
and has a lot of enzymes which are secreted to transform the food. The
pancreas is a more open than the brain and the heart. To treat diseases like
Pagina 3 van 80
, Alzheimer or Parkinson you need drugs that can enter the blood-brain barrier and this is difficult.
The drug has to be either lipophilic (are able to cross the membrane) or the drug must be able to
enter a transporter which are in the blood-brain barrier. It is difficult to make drugs against brain
disorders.
Pharmacokinetics: Plasma proteins
Plasma proteins are proteins which are available in the blood stream and
they determine whether a drug has a biological mode of action.
Their are different plasma proteins (Albumin). Next to albumin their are
transporters (proteins) which can for example transport insulin,
hormones (oestrogen, testosterone etc.) (the transporters are specific for
a specific product.
- Albumin
- Affinity of the active substance for the plasma proteins is low
- Affinity for specific binding sites (receptors) is high
- For most pharmaceuticals the albumin binding sites are far from
saturated at therapeutic concentrations (binding to albumin is not
specific a lot of products can bind to albumin)
- Medicinal drug-protein complex: No effect from the medicinal drug!!
The drugs is not active. The drug can either bind to its specific receptor
but it can also bind to albumin and when the drug is bind to albumin it is
not active. Albumin makes the drug inactive.
On the left side you see that there is no plasma protein so the drug is free and the drug will be
active and have a good and immediate effect but the duration of the drug is very short and that is
unwanted.
On the right side. You see that there are plasma proteins available (albumin) so a part of the drug
binds to these plasma proteins and this inhibits the biological effect of the drug. This has not be a
negative effect. There is a less biological effect and there is a lower amount of free drug in the
plasma but the free drug is acting for a longer time. When the free drug is metabolized more drug
that is bound to the plasma proteins is liberated. So the bound drug is kind of a storage (buffer
function). There is no immediately drug effect but the duration is longer and that is good in some
cases.
Medicinal drugs that are bound to plasma proteins (albumin) are biologically inactive.
Pharmacokinetics: Biotransformation
Presystemic elimination
- First-pass effect -> can be desired in certain by steroids
- High presystemic elimination can be desirable in certain therapeutic
situations!!
* Glucocorticosteroids with treatment for asthma
* Low systemic load
Propanolol:
Is used in daily practice. This drug is used for the heart and vessel function.
It is a synthetic drug. This drug has a high first-pass effect in the liver. So a
lot of the drug is eliminated during the first-passing through the liver
- list of candidate substances
- pharmacological study, or clinical pharmacological study
biotransformation -> mainly in the liver but also a bit in the lung and
intestinal.
In case of a cortisol substance a presystemic elimination (first-pass effect) is wanted. Otherwise it
can cause diabetes mellitus etc.
Pagina 4 van 80
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