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Samenvatting - Physiology and Pharmacology (WBFA020-05)
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summary for the course physiology and pharmacology
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Samenvatting Physiology and PharmacologyMartina Schmidt lecture 1
- pharmacodynamics: analysis of the biological
effect
- pharmacokinetics: analysis of their ‘fate‘ in the
body
Pharmacology is mainly Characterized by: application of
pharmaceuticals (= medicinal drugs) in the treatment of
diseases
Pharmacokinetics:
administration and distribution
•Oral (self-medication)!!!
- Note: portal vein system
•Inhalation
•Topical (at a particular site)
- transdermal (patch)
- sublingual, buccal
- rectal
•Injection
(e.g. peptide hormones: insulin→ does not survive low pH)
- intravenous
- subcutaneous
- intramuscular
Polarity and charge of pharmaceuticals determine:
central effect
blood-brain barrier can be crossed (permeable)→ medicijn bevat geen lading, blood-brain barrier kan
gepasseerd worden→ central system is een gesloten compartment
peripheral effect
blood-brain barrier cannot be crossed (impermeable)→pancreas
,Plasma eiwitten:
- Albumin → hoge affiniteit voor medicijnen→ bindt medicijn→ medicijn heeft geen
fysiologisch effect meer
- Plasma eiwitten→ binden elk medicijn
- Medicijnen die niet binden aan albumin→ hebben een biologisch effect
- Alleen het niet-gebonden medicijn wordt uitgescheiden
- Buffer systeem
- Versoepeling binding
- Nadeel: andere medicijnen kunnen ook de plasma eiwitten binden
Presystemic elimination:
- Kan wenselijk zijn
- Dit bepaald hoeveel medicijn het lichaam binnendringt
- First-pass effect
Propanolol:
- Non-specific ß blocker→ gunstig voor de doorbloeding
- Kan worden toegediend wanneer het hart niet correct functioneert
- Heeft het first-pass effect
Digoxin:
- wordt gebruikt bij het behandelen van hartfalen
Atropine:
- Antagonist, competative bij specifieke receptoren van muscarin acetylcholine
- Werkt op receptoren in de ogen
Active substances: leren!
- Adrenaline:
o Agonist that binds to Beta-adrenergic receptors and alpha 1+2 adrenergic receptors
o Physiological responses due to increased cAMP after binding to Beta-adrenergic
receptors:
▪ Increased heart rate, Na+
▪ Increased cardiac contraction, Ca2+
▪ Relaxation of smooth muscles→lungs and blood vessels
▪ …
o Physiological responses due to increased calcium and diacylglycerol after binding to
Alpha1-adrenergic receptors:
▪ Contraction of smooth muscles
o Physiological responses due to reduced cAMP after binding to Alpha2-adrenergic
receptors:
▪ Suppression of neurotransmitter release
, - Propranolol:
o Non-specific beta-blocker. Which helps to control heart problems and unusual
bloodpressures. Competitive antagonist of adrenalin (suppressor of physiological
responses)
- Prazosin:
o Competitive antagonist of noradrenalin that reduces blood pressure. This
synthesized alpha1 blocker blocks the binding of norepinephrine → blood vessels
widen and blood pressure decreases.
- Nicotine:
o Agonist that binds to the Nicotinic acetylcholine receptor (ligand-gated ion channels)
o Causes sweating, contraction of skeletal muscles and stimulates the heart frequency
(tachycardia). Nicotine can enter (no charge) every part in the body (CNS and ganglia)
and they drive the input of the CNS (sympathetic activities).
- Placebo
o
- Digoxin: Oldest treatment for heart failure.
o Inhibition of Na+/K+ ATPase leading to Ca2+ influx (na+/Ca2+ exchanger)
o Digoxine vergroot de contractiekracht van het hart en verlaagt de
hartfrequentie. Daarnaast vertraagt het de geleiding over de AV-knoop
- Carbachol
o Agonist in the parasympathetic nervous system that binds to muscarinic receptors
o Physiological responses due to increased calcium and diacylglycerol when binding to
an M1 receptor
▪ Improved learning and memory
o Physiological responses due to reduced cAMP when binding to an M2 receptor
▪ Reduced heart rate (reduced Na+)
▪ Reduced cardiac contraction (reduced Ca2+)
▪ Heart rest (reduced potassium)
▪ Suppression of acetylcholine release
o Physiological responses due to increased calcium and diacylglycerol when binding to
an M3 receptor
▪ Contraction of smooth muscles
▪ Increased cAMP
▪ …
- Atropine: Competitive antagonist of muscarinic acetylcholine receptors. To relax muscles
(used in cosmetics).
o Competitive antagonist of acetylcholine. Used as a therapy for broncial
asthma
EC
Emax
EC50
, Martina Schmidt lecture 2
•Agonist (mimetic drug)
– Binding to a receptor (affinity)
– Stimulation of a cellular response (efficacy)
•Antagonist (blocker, lytic drugs)
– Binding to a receptor (affinity)
–NO cellular response
– Blockade/Suppression of the agonist effect
– Necessary: Presence of an agonist
• Agonist: acetylcholine (ACh)
→Antagonist: atropine
• Agonist: Propanolol→
Antagonist:
adrenaline/noradrenaline
Pharmaceuticals (medicinal drugs)=
competitive antagonism
Propranolol and atropine
Functional antagonism: two agonists induce an opposite
effect via activation of different receptors
- In Lung: Acetylcholine- M3 receptor- Ca2+
Adrenaline- ß2 receptor- cAMP
- Heart: Acetylcholine- M2 receptor- reduces HF
Noradrenaline- ß1 receptor- increases HF
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