BASIC PHARMACOLOGY
A. Pharmacodynamics
B. Pharmacokinetics
Pharmacotherapeutics
Basic pharmacology: stud
Def'n : drug - articles used for diagnosis, prevention, treatment, mitigation, cure of diseases
Pcol - study of drugs
Classification of drugs:
1. Functional modifiers
2. Replenishers
3. Diagnostic agents
4. Chemotherapeutic agents
Functional modifiers - alter/modify physiologic or biochem activities of cells . Body
e.g. Pain perception (drugs - analgesics & anaesthectics
Vascularization - foration of new b.v - drug: VEGF inhibitors (vascular endothelial growth
factors) - Bevacizumab (Ab that targets VEGF)
Replenishers - supplement endogenous subs. (NA, K, Insulin etc) that are ins ufficient
e.g . T1 DM / insulin requiring DM (B cells are not able to produce insulin)
Pernicious anemia - not anemia due to vit b12 def.(megaloblastic)
• Will cause vit b12 def.(autoimmune, characterized by Ab that target the parietal cells of
stomach - HCl production (achlorhydria) and intrinsic factor of castle (helps in absorption
b12 in ileum) pernicious anemia leads to megalobalstic)
• Autoimmune d/s are more common in women (hormonally related)
• Drug: Vit b12 (IM) - vit b12 def and folate def. Both present in megalo
• Note: megalo - seen with folate and b12 def. (but with b12 may neurologic deficits esp.
posterior column of spinal cord - impt in proprioception, Balance, position sense)
• Other causes of b12 def- fish tapeworm, use of PPI and H2blockers(if not supplementing
with b12 caps)
Diagnostic agents - e.g tensilon (R) - edrophonium - Dx of myasthenia gravis
• Radiopharmaceuticals - Technetium 99m sestamibi and Thallium 201 - Dx presence of
ischemia or infarction (myocardium)
• Dipyridamole , dobutamine - pharmacologic stress testing (treadmill - for MI, CAD - subject
patients to exercise then ECG before, during and after exercise) for those who cant
run(wheel chair) - stimulate the heart then check stress test
Chemotherapeutic agents - agents used to kill or inhibit the growth or reprod. Of cells or NA
considered as foreign to the body(bacteria, fungi, virus, caner cells - mutated - look diff from the
rest of the body)
a. Anti-infectives i. Antimic ii. Antiviral iii. Antiparas.
b. Antineoplastic
PHARMACODYNAMIC PRINCIPLES
Def'n : drug ------- body
Dynamics - what drugs do to body ; kinetics - what body does to drugs
, Pharmacodynamics - study of the physiologic and biochemical effects of drugs in biological
systems and the mech. By which these effects are produced (MOA)
MOA - how do drugs prod. Their effects
MECHANISMS OF DRUG ACTION
a. Target protein - mediated - target proteins are the biological sites of action "active site"
Most of them are CHON
i. Structural CHON - form the cell framework = cytoskeleton = microtubules or tubulin (impt in
cell movement e.g. blood cells ; axonal transport of NT - 'vesicular transport'
Neurons - body (NT are in vesicles here - have to be relaesed at tip of axons via vesicular trans. ,
dendrites , axon) ; separation of divided chromosomes during mitosis (mitotic spindles are
microtubules)
Drugs that inh. microtubules
a. Colchicine - 1st line for acute gout and 1st line initial tx of chronic gout
b. Griseofulvin - dermatomycosis (skin and skin appendages) - dermatophytes - strong affinity
for keratin (but this is not the target site, tubulin pa din)
c. Mitotic spindle inh - e.g Vincas - Vinorelbine; Taxols ______taxel (paclitaxel, docetaxel -
from Taxus brevifolia), estramustine
ii. Regulatory CHON - regulate cellular activ. Or functions (recognition etc)
a. Channels (voltage gated channels - detect changes in envt, so like automatic mall doors)
1. Voltage-gated Na chan. (Na chan. Blockers) -
• Class I (a,b,c) antiarrythmics
• Local anesthetics
• Some anticonvulsants
2. Voltage-gated K chan - can be blocked by:
• Class III anti-arryth
• Insulin secretagogues
3. Voltage-gated Ca chan - inh by:
• CCB (-dipine)
• We also have ligand gated channels (you need a key to open the door)- defined by receptors
e.g nicotinic rceptor bockers)
b. Carrier molecules - cell membrane CHON with specific binding sites and can undergo
conformational change
• Na-K ATPasepump - movement vs. Concn gradient - inh. By digitalis
• H-K ATPasepump (proton pump) - inh. By PPIs (benzimidazoles -Prazoles but there are some
prazoles which are not PPIs e.g. - Aripiprazole Abilify (R) which is anti-
psychotic/bipolar/mood d/o
c. Enzymes
• COX - cyclooxygenase - inh by NSAIDs
• MAO - monoamine oxidase - inh by MAOIs
Nonselective - block both MAO a & b)
T - tranylcypromine
I- Isocarboxazid
P- Phenelzine
, RIMA - revers. Inh. Of MAOa (e.g - Moclobemide)
Selective MAOb inh - Selegiline - parkinsonism
Kininase II = ACE (targeted by ACEi -pril enalapril, captopril etc)
d. Receptors - fxnal macromolecular cell components with spec. stereochemical configuration
with which a ligand interacts usually in a lock and key fashion
Ligand - any subs. That binds to a receptor
Types of receptors:
i. Type 1 receptor = ionotropic receptor
Location - cell memb ; onset - in milliseconds
"Ionotropic" - receptor that is assoc. With ligand gated chan.
• Nicotinic receptor - assoc. With Na chan.
Can be inh by by NM blockers (drugs related to CURARE (-CURIUM or -CURONIUM) -
atracurium) and ganglionic blockers
• GABAa receptor complex - assoc. With chloride chan. ; stimulated by GABA, BZD and
barbiturates
ii. Type II receptors - = 7-transmembrane spanning receptors = G-CHON linked = metabotropic
receptors
Location - cell memb ; onset - seconds
Passes the memb 7 times - G CHON - either inc. or dec. conc of metabolites (2nd messengers) -
referred to as signal transduction
G Proteins types:
• Gs - s means stimulus - stimulates adenylyl cyclases (AC) acts on ATP to convert it to
cAMP - resp. For the effects assoc. With receptor
§ e.g. B(beta)1 receptor - cardiac contraction. There are drugs that prod.
Stimulation but are not agonists (diff. Mechanisms) e.g phosphodiesterase inh.
Inh. By - beta blockers (BB) - alol and olol
Stimualte by B1- agonists - dopamine, dobutamine
§ SABA - short acting B agonist - terbutaline, salbutamol
LABA - long acting B agonist - salmeterol - ceretide (R)?
• Gi - i means inhibitory - inh AC thus dec. cAMP
§ 5-HT1A presynaptic receptor (serotonin)
Stimulated by buspirone - buspar(R)
• Gq linked - once act. Will stimulate phospholipase C (PLC)
Acts on phosphatidyl inositol-4,5-bisphosphate to produce IP3 (inositol triPO4)
and DAG(diacylglycerol)
IP3 and DAG - involved in inc. Ca2+ inside the cell and also case phosphorylation
rxn of muscles., CHON and enz. - usual source of PO4 is ATP - transferring of E
from ATP to CHON or enz thus activation (contraction!)
§ Alpha 1, muscarinic = M3 - in smooth musc.
e.g alpha 1 -agonist - NE (contraction of vascualr s.m. - vasoconstriction)
muscarinic - Ach thus bronchoconstriction or spasm)
iii. Type III = Enz - linked receptors
Location: cell memb ; onset - minutes
• Insulin receptor - tyrosine kinase-linked receptor
, Phosphorylation of CHONor enz w/ a tyrosine aa residue - Glucokinase - stimulate
glycolysis; GLUT 2 & 4 transporters (bring gluc .into cell., liver, skeletal musc. or
adipose tissues fromblood consistent w/ effect ofinsulin)
iv. Type IV = Gene transcription - linked receptors (impt in modulating gene transcription - copy
DNA template into an RNA transcript)
CTAGCTACGT (DNA)
GAUCGAUGCA(mRNA)
Location: Nucleus (cytoplasm --- translocated into nucleus) = Nuclear receptors ; Onset - hours
• Steroid receptors
§ Glucocorticosteroids (cortisol receptors)
§ Mineralocorticoid (aldosterone)
§ Sex hormones (estrogen, progesterone, testosterone receptors)
§ Vit D receptors
§ Thyroid hormone receptors
b. Non-target protein mediated
1. Colligative mech. / mass effect
e.g . Osmotic diuretic - mannitol (creates an osmotic gradient across the renal tubule
partiularly at the water-permeable region of renal tubule - imbibes water kasi it creates a
higher pressure so water goes to it)
Water reabs happens at PCT, decs LOH) al it has to do is to be in the renan tubule
2. Direct chemical interaction (chemical antagonism) - reaction of a drug with subs in the body
e.g a.hyperacidity - there is inc. in HCl (drugs: acid beutralizers - by neutralization)
b. Chelation or complexation - hemachromatosis - due to chronic Fe overload
(complications: prevent insulin secretion by pancreas, stiif heart musc.) so give Fe chelator -
Desferroxamine
c. Wilson's disease - copper overload Tx: Copper chelator - penicillamine
3. Counterfeit incorporation mech - involves analogs of Purine and Pyrimidine - can serve as
alternative pur or pyr bases during DNA replication and trancription
e.g. 5-fluorouracil - analog of uracil
DNA: CTA-GCT-A
mRNA: GAU-CGA-U ; 5-FU will replace so GAU(5FU)-CGA-U(5FU) - thus not translated to aa
thus termination! Can be used in CA cells
I. MECHANISM OF DRUG ACTION
a. Target Protein
b. Non- TP mediated
II. Drug-receptor or Drug-Target Protein Interaction
a. Characteristics of drug-receptor interaction
i. Affinity - ability to bind to receptor (ligand activity)
ii. Intrinsic activity/biological activity - ability to generate a series of biochem. Events
leading to an effect.
critical site - essential for activity
Classification of ligands based on Intrinsic activity
a. Agonist = has intrinsic activity
A. Pharmacodynamics
B. Pharmacokinetics
Pharmacotherapeutics
Basic pharmacology: stud
Def'n : drug - articles used for diagnosis, prevention, treatment, mitigation, cure of diseases
Pcol - study of drugs
Classification of drugs:
1. Functional modifiers
2. Replenishers
3. Diagnostic agents
4. Chemotherapeutic agents
Functional modifiers - alter/modify physiologic or biochem activities of cells . Body
e.g. Pain perception (drugs - analgesics & anaesthectics
Vascularization - foration of new b.v - drug: VEGF inhibitors (vascular endothelial growth
factors) - Bevacizumab (Ab that targets VEGF)
Replenishers - supplement endogenous subs. (NA, K, Insulin etc) that are ins ufficient
e.g . T1 DM / insulin requiring DM (B cells are not able to produce insulin)
Pernicious anemia - not anemia due to vit b12 def.(megaloblastic)
• Will cause vit b12 def.(autoimmune, characterized by Ab that target the parietal cells of
stomach - HCl production (achlorhydria) and intrinsic factor of castle (helps in absorption
b12 in ileum) pernicious anemia leads to megalobalstic)
• Autoimmune d/s are more common in women (hormonally related)
• Drug: Vit b12 (IM) - vit b12 def and folate def. Both present in megalo
• Note: megalo - seen with folate and b12 def. (but with b12 may neurologic deficits esp.
posterior column of spinal cord - impt in proprioception, Balance, position sense)
• Other causes of b12 def- fish tapeworm, use of PPI and H2blockers(if not supplementing
with b12 caps)
Diagnostic agents - e.g tensilon (R) - edrophonium - Dx of myasthenia gravis
• Radiopharmaceuticals - Technetium 99m sestamibi and Thallium 201 - Dx presence of
ischemia or infarction (myocardium)
• Dipyridamole , dobutamine - pharmacologic stress testing (treadmill - for MI, CAD - subject
patients to exercise then ECG before, during and after exercise) for those who cant
run(wheel chair) - stimulate the heart then check stress test
Chemotherapeutic agents - agents used to kill or inhibit the growth or reprod. Of cells or NA
considered as foreign to the body(bacteria, fungi, virus, caner cells - mutated - look diff from the
rest of the body)
a. Anti-infectives i. Antimic ii. Antiviral iii. Antiparas.
b. Antineoplastic
PHARMACODYNAMIC PRINCIPLES
Def'n : drug ------- body
Dynamics - what drugs do to body ; kinetics - what body does to drugs
, Pharmacodynamics - study of the physiologic and biochemical effects of drugs in biological
systems and the mech. By which these effects are produced (MOA)
MOA - how do drugs prod. Their effects
MECHANISMS OF DRUG ACTION
a. Target protein - mediated - target proteins are the biological sites of action "active site"
Most of them are CHON
i. Structural CHON - form the cell framework = cytoskeleton = microtubules or tubulin (impt in
cell movement e.g. blood cells ; axonal transport of NT - 'vesicular transport'
Neurons - body (NT are in vesicles here - have to be relaesed at tip of axons via vesicular trans. ,
dendrites , axon) ; separation of divided chromosomes during mitosis (mitotic spindles are
microtubules)
Drugs that inh. microtubules
a. Colchicine - 1st line for acute gout and 1st line initial tx of chronic gout
b. Griseofulvin - dermatomycosis (skin and skin appendages) - dermatophytes - strong affinity
for keratin (but this is not the target site, tubulin pa din)
c. Mitotic spindle inh - e.g Vincas - Vinorelbine; Taxols ______taxel (paclitaxel, docetaxel -
from Taxus brevifolia), estramustine
ii. Regulatory CHON - regulate cellular activ. Or functions (recognition etc)
a. Channels (voltage gated channels - detect changes in envt, so like automatic mall doors)
1. Voltage-gated Na chan. (Na chan. Blockers) -
• Class I (a,b,c) antiarrythmics
• Local anesthetics
• Some anticonvulsants
2. Voltage-gated K chan - can be blocked by:
• Class III anti-arryth
• Insulin secretagogues
3. Voltage-gated Ca chan - inh by:
• CCB (-dipine)
• We also have ligand gated channels (you need a key to open the door)- defined by receptors
e.g nicotinic rceptor bockers)
b. Carrier molecules - cell membrane CHON with specific binding sites and can undergo
conformational change
• Na-K ATPasepump - movement vs. Concn gradient - inh. By digitalis
• H-K ATPasepump (proton pump) - inh. By PPIs (benzimidazoles -Prazoles but there are some
prazoles which are not PPIs e.g. - Aripiprazole Abilify (R) which is anti-
psychotic/bipolar/mood d/o
c. Enzymes
• COX - cyclooxygenase - inh by NSAIDs
• MAO - monoamine oxidase - inh by MAOIs
Nonselective - block both MAO a & b)
T - tranylcypromine
I- Isocarboxazid
P- Phenelzine
, RIMA - revers. Inh. Of MAOa (e.g - Moclobemide)
Selective MAOb inh - Selegiline - parkinsonism
Kininase II = ACE (targeted by ACEi -pril enalapril, captopril etc)
d. Receptors - fxnal macromolecular cell components with spec. stereochemical configuration
with which a ligand interacts usually in a lock and key fashion
Ligand - any subs. That binds to a receptor
Types of receptors:
i. Type 1 receptor = ionotropic receptor
Location - cell memb ; onset - in milliseconds
"Ionotropic" - receptor that is assoc. With ligand gated chan.
• Nicotinic receptor - assoc. With Na chan.
Can be inh by by NM blockers (drugs related to CURARE (-CURIUM or -CURONIUM) -
atracurium) and ganglionic blockers
• GABAa receptor complex - assoc. With chloride chan. ; stimulated by GABA, BZD and
barbiturates
ii. Type II receptors - = 7-transmembrane spanning receptors = G-CHON linked = metabotropic
receptors
Location - cell memb ; onset - seconds
Passes the memb 7 times - G CHON - either inc. or dec. conc of metabolites (2nd messengers) -
referred to as signal transduction
G Proteins types:
• Gs - s means stimulus - stimulates adenylyl cyclases (AC) acts on ATP to convert it to
cAMP - resp. For the effects assoc. With receptor
§ e.g. B(beta)1 receptor - cardiac contraction. There are drugs that prod.
Stimulation but are not agonists (diff. Mechanisms) e.g phosphodiesterase inh.
Inh. By - beta blockers (BB) - alol and olol
Stimualte by B1- agonists - dopamine, dobutamine
§ SABA - short acting B agonist - terbutaline, salbutamol
LABA - long acting B agonist - salmeterol - ceretide (R)?
• Gi - i means inhibitory - inh AC thus dec. cAMP
§ 5-HT1A presynaptic receptor (serotonin)
Stimulated by buspirone - buspar(R)
• Gq linked - once act. Will stimulate phospholipase C (PLC)
Acts on phosphatidyl inositol-4,5-bisphosphate to produce IP3 (inositol triPO4)
and DAG(diacylglycerol)
IP3 and DAG - involved in inc. Ca2+ inside the cell and also case phosphorylation
rxn of muscles., CHON and enz. - usual source of PO4 is ATP - transferring of E
from ATP to CHON or enz thus activation (contraction!)
§ Alpha 1, muscarinic = M3 - in smooth musc.
e.g alpha 1 -agonist - NE (contraction of vascualr s.m. - vasoconstriction)
muscarinic - Ach thus bronchoconstriction or spasm)
iii. Type III = Enz - linked receptors
Location: cell memb ; onset - minutes
• Insulin receptor - tyrosine kinase-linked receptor
, Phosphorylation of CHONor enz w/ a tyrosine aa residue - Glucokinase - stimulate
glycolysis; GLUT 2 & 4 transporters (bring gluc .into cell., liver, skeletal musc. or
adipose tissues fromblood consistent w/ effect ofinsulin)
iv. Type IV = Gene transcription - linked receptors (impt in modulating gene transcription - copy
DNA template into an RNA transcript)
CTAGCTACGT (DNA)
GAUCGAUGCA(mRNA)
Location: Nucleus (cytoplasm --- translocated into nucleus) = Nuclear receptors ; Onset - hours
• Steroid receptors
§ Glucocorticosteroids (cortisol receptors)
§ Mineralocorticoid (aldosterone)
§ Sex hormones (estrogen, progesterone, testosterone receptors)
§ Vit D receptors
§ Thyroid hormone receptors
b. Non-target protein mediated
1. Colligative mech. / mass effect
e.g . Osmotic diuretic - mannitol (creates an osmotic gradient across the renal tubule
partiularly at the water-permeable region of renal tubule - imbibes water kasi it creates a
higher pressure so water goes to it)
Water reabs happens at PCT, decs LOH) al it has to do is to be in the renan tubule
2. Direct chemical interaction (chemical antagonism) - reaction of a drug with subs in the body
e.g a.hyperacidity - there is inc. in HCl (drugs: acid beutralizers - by neutralization)
b. Chelation or complexation - hemachromatosis - due to chronic Fe overload
(complications: prevent insulin secretion by pancreas, stiif heart musc.) so give Fe chelator -
Desferroxamine
c. Wilson's disease - copper overload Tx: Copper chelator - penicillamine
3. Counterfeit incorporation mech - involves analogs of Purine and Pyrimidine - can serve as
alternative pur or pyr bases during DNA replication and trancription
e.g. 5-fluorouracil - analog of uracil
DNA: CTA-GCT-A
mRNA: GAU-CGA-U ; 5-FU will replace so GAU(5FU)-CGA-U(5FU) - thus not translated to aa
thus termination! Can be used in CA cells
I. MECHANISM OF DRUG ACTION
a. Target Protein
b. Non- TP mediated
II. Drug-receptor or Drug-Target Protein Interaction
a. Characteristics of drug-receptor interaction
i. Affinity - ability to bind to receptor (ligand activity)
ii. Intrinsic activity/biological activity - ability to generate a series of biochem. Events
leading to an effect.
critical site - essential for activity
Classification of ligands based on Intrinsic activity
a. Agonist = has intrinsic activity
