Pharmacodynamics

what the drug does to the body

-related to the mechanisms of action of a drug

-related to how a drug interacts with a target tissue
; altering the activity of a cell through interactions with receptor
; altering the activity of an enzyme

-Some drugs directly to/in bacterial viruses
-Anticancer (to dna)

*most targets are protein structures: receptors on cell membranes*
-specifity (lock and key= fewer side effects)
-Endogenous substances (hormones, neurotransmitters)
-Receptor binding triggers a change within the cell or blocks receptor

-G protein (GPCR)
-Ion channels
-Nuclear receptors
-Enzymes (x2)
-Non enzyme JAK STAT

eg: epinephrine
-stimulates g protein and second messenger systems= sypathominnetic stimulation

location: cell membrane
examples: NE, Ach, muscarinic receptor

*all water soluble!

-inhibits depolarization+ no pain transduction
-most bind to voltage gated channels

Location: cell membrane

Drug examples: Ach on nicotine receptor, lidocane

-Aka steroid receptors
-most bind in cytoplasm- charge cell
-function via DNA

location: cytoplasm, nucleus

drug examples:
-estrogen, corticosteroids, thryroid hormone

2 types:
Intracellular enxymes

Transmembrane enzymes

work inside the cell where they control cell metabolism (eg respiration).

eg: insulin membrane receptor- stimulates tyrosine lenase, activate cellular glucose uptake

Signaling pathway activated by cytokines and some hormones, it provides one of the most direct routes from cell-surface receptors to gene regulation. In this pathway, cytosolic tyrosine kinases (JAKs) phosphorylate gene regulatory proteins (STATs)

*involves immunity, cell division, cell death and tumour formation

-interferons
-interleukins
-growth factors

-cellular immunity
-proligeration
-apoptosis
-differentiation

Jonas Kinase

Signal transducer and activator of transcription protein

- Receptor affinity
-Efficiancy= effectiveness
-Potency=strength

-strength of binding/length of binding
-specific, saturable, reversible

-degree to which a drug induces maximum therapeutic effect
-how well it works

how much drug is required!

eg: drug a needs 20 mg
drug b needs 10 mg

drug b has a higher potency!

-receptors
-ion channels
-enzymes
-transporters

-agonists
-antagonists

-agonists
-antagonists
-allosteric modulators
-blockers

-inhibitors
-inducers

-inhibitors
-relesors

-drug mimmics endogenous substance
-binds to receptors readily and produces very good effects

*Primary agonist*: extensively and successfully binds to existing receptor

-maximum response is smaller than that of a primary, even if all receptors are occupied
-lower efficacy

*In presence of a full agonist, partial acts as an antagonist!*

-drug blocks receptor site to prevent endogenous or endogenous like substances from binding
-no effect other than to block others from binding!

*no effiacy*

a drug that binds to a receptor and activates it
-sumatriptan
-miranes
serotonin

a drug that binds to a receptor and inhibits its function

-prpranolol: non selective
Ranitidine: histamine r. antagonist

Fluoxetine: ssri, prozac transport blocker
Omeprozole: proton pump inhibitor for GED

Flupritine: K+ channel opener, pain killer
Retigabin: K+ channel opener, antimusculant, epilepsy

Nifedipine: Ca_ channel blocker, use in BV dialation

Lidocaine: NA+ channel blocker, local anethesia (nerve)

RO28-1675: glucose kinase activator

AICAR: protein lenase stimulatory; protects from cardiac ischemia

Atovastatin: competitive inhibitor for reductase

Aspirin: inactivates COX enzyme for prostaglandin and thrombosine synthesis

Substances that bind to a cell receptor and alter the receptor's affinity for specific drugs; common allosteric modulators include guanine nucleotides, ammonium ions, calcium, and other divalent cations.

*many neurocognitive problems!*

-parkinsons, dopamine agonists
-schizophrenia

-cns disorders, depression, cognitive, memory

-median effective dose
-therapeutic index/window
-graded dose response relationship
-potency and efficiacy

-dose where 50 percent of a population has desired therapeutic ranges

the ratio between the toxic and therapeutic concentrations of a drug

LD50/ED50

Graphically visualizes differences in responses to medications in a single patient. Obtained by observing and measuring patient's response at different doses of the drug.

low doses, little change in response as dose increases- few receptors or enzymes affected; response minimal

Linear phase- sharp increase in response as dose is increased: more enzymeseceptors affected

*desired- achieves safe, therapeutic effect!*

-plateau phase- no change in response as dose increases: drug is bound to all receptors or enzymes or symptoms have all been alleviated: dose has no further effect

-effective range of a drug (and the dose) without unacceptable toxicity

-maximum intensity of response produces by a particular dose of drug
-drug with the greatest intensity of response has highest efficacy

Amount of drug necessary to elicit a biologic effect; refers to the drug's strength