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PHARMACOLOGY SHORT NOTES
GENERAL PHARMACOLOGY
DR PUSHPENDRA PUSHKAR
MBBS, MD PHARMACOLOGY
Dr Pushkar, 2023

ROUTES OF DRUG ADMINISTRATION
Dr Pushkar, 2023

• Oral route- High First pass metabolism (FPM)
• Rectal- Avoids FPM to 50%
• Transdermal route-
 Highly lipid soluble drugs
 Nitroglycerine, Nicotine, Fentanyl & Hyoscine
• Nasal route- Nafarelin (GnRH agonist), Calcitonin, Desmopressin
• Sublingual route-
 Avoids FPM
 Nitroglycerine, Isosorbide dinitrate, Nifedipine
Dr Pushkar, 2023

P/K (ABSORPTION)
• When medium is same, drugs can cross the membrane (Acidic drugs in acidic medium &
Basic drugs in basic medium)
• pH=pKa, Ionization is 50% & Unionized is 50%
• Bioavailability (B/A):
 Rate (Tmax, Cmax) & Extent (AUC) of absorption of drug site of action
 Two important determinants- Absorption & FPM
 B/A of IV drugs= 100%
• Bioequivalence:
 Two preparations (same drugs, same dose, same dosage forms)- B/A diff. <20%
• Drugs with HIGH FPM  Nitrates, Lignocaine, Propranolol, Salbutamol, Morphine
Dr Pushkar, 2023

Dr Pushkar, 2023
Cmax
Tmax
AUC

P/K (DISTRIBUTION)
• Vol. of Distribution (V)
 V=Dose administered/Plasma concentration (PC ↑ V ↓)
 Depends on Lipid solubility, Plasma Protein Binding (PPB)
 High PPB  Low V, ↑ DOA (Duration of Action), Dialysis not effective
 Chloroquine- Highest V=1300 L/Kg
• Redistribution of Drugs
 Highly lipid soluble drugs
 Thiopentone- ultra short acting IV anaesthetic
 Rapid distribution to brain  Redistribute to all tissues
Dr Pushkar, 2023

P/K (METABOLISM)
• Phase I – CYP 3A4 (Most Common, MC, enzyme)
• Phase II – Glucuronide Conjugation (MC)
• Prodrugs – Inactive drugs activated by metabolism ex. ACE Inhibitors except Captopril &
Lisinopril, PPIs, Prednisone, Levodopa
• Enzyme inducers – G (GRISEOFULVIN), P (PHENYTOIN), R (RIFAMPICIN), S (SMOKING), Cell
(CARBAMAZEPINE), Phone (PHENOBARBITONE)
• Enzyme Inhibitors – Vit (VALPROATE), K (KETOCONAZOLE), Can’t (CIMETIDINE), Cause
(CIPROFLOXACIN), Enzyme (ERYTHROMYCIN), Inhibition (INH)
Dr Pushkar, 2023
Phase I
(Oxidation,
Reduction,
Hydrolysis)
Drug
Phase II
(Conjugation)
Metabolite
I
Excretion
Metabolite II
(Inactive &
Water
soluble)

P/K (EXCRETION)
• Renal (MI), Faeces (enterohepatic circulation), Lungs (General anaesthetics, Ethanol)
• Renal
 Glomerular filtration: Heparin, insulin, dextran can’t pass (Large size/molecular mass)
 Tubular secretion: 20% by filteration, 80% by secretion
• Acidic drugs (Penicillin, Aspirin, Sulphonamides)- Organic acid transport (OAT)
• Basic drugs (Morphine, Quinine)- Organic cationic transport (OCT)
 Tubular reabsorption:
 Salicylate poisoning- Alkalisation of urine will ionize aspirin and no tubular reabsorption
• Breast milk
 Sulphonamides- Kernicterus
 Penicillin- Allergy
 Ampicillin- Diarrhoea
Dr Pushkar, 2023

KINETICS OF ELIMINATION
• Half life (t1/2): Plasma conc. reduced to half,
• t1/2 = 0.639 x V / CL
• Clearance, CL, Amount of plasma completely cleared of a drug per unit time
• CL = Rate of elimination / Plasma conc.
• First Order Kinetics (First OK): CL = Constant,
• Rate of elimination ↑ Plasma conc.(PC) ↑
• Constant fraction of drug is eliminated per unit time
• t1/2 = Constant (CL & V = Constant)
• Zero OK: Rate of elimination = Constant,
• Constant amount of drug is eliminated per unit time
Dr Pushkar, 2023

• Steady state PC of drug:
• Rate of absorption = Rate of elimination
• 4-5 t1/2= Time to reach steady state
• LD & MD
• Therapeutic drug monitoring (TDM):
• Drugs with narrow safety margin
• Not done for drugs whose effect can be
easily measured such as antihypertensives,
antidiabetics, anticoagulants
Dr Pushkar, 2023

PHARMACODYNAMICS
Dr Pushkar, 2023
• The two-state receptor model:
 In this model, receptor R can exist in active (Ra) and inactive (Ri) conformations, and drugs (L)
binding to one, the other, or both states of R can influence the balance of the two forms of R and
the net effect

AGONIST &
ANTAGONIST
Dr Pushkar, 2023
Allosteric site:
Non competitive antagonist
alters the receptor in
such a way that it is unable to
combine with the
agonist

• DRC (Log dose response curve)
• EC50 – Half (50%) of maximal response
Dr Pushkar, 2023
EC50
EC50

• Efficacy - % of Response (%R)
• Potency – EC50
• A vs B: Drug B is less potent {EC50 (B) > EC50 (A)} but
equally efficacious as drug A {%R (B) = %R (A)}.
• C vs A: Drug C is less potent {EC50 (C) > EC50 (A)} and less
efficacious than drug A {%R (C) < %R (A)}.
• Drug D is more potent {EC50 (D) < EC50 (A, B, C)} than drugs
A, B, & C, but less efficacious {%R (D) < %R (A, B)} than drugs
A & B, and equally efficacious {%R (D) = %R (C)} as drug C.
Dr Pushkar, 2023

• Therapeutic Index (TI)
• TI = LD50/ED50
Dr Pushkar, 2023

GPCR (G-PROTEIN COUPLED RECEPTOR)
• aka- 7 Transmembrane receptor
(7TM)
• L- Ligand
• G-protein: a & BY dimer
• a subunit types:
• Gs, Gi, Gq
Dr Pushkar, 2023

• AC- Adenyl cyclase
• AC converts
• ATP  cAMP
• cAMP activates PKA
(Protein Kinase A)
Dr Pushkar, 2023

Gq-PLC-DAG/IP3-Ca2+ PATHWAY
• Hormones and
growth factors
release Ca2+ from its
intracellular storage
site, the ER, via a
signaling pathway
that begins with
activation of PLC
(activated by Gq
type)
Dr Pushkar, 2023

ION CHANNELS
• Ion channels regulate the flow of Na+, K+, Ca2+,
and Cl– across the cell membrane
• Classified as
 Voltage-activated (such as voltage gated Na channel,
voltage gated K channel)
 Ligand-activated
• Ligand-gated channels in the nervous system respond
to excitatory neurotransmitters such as ACh or
glutamate (AMPA and NMDA) and inhibitory
neurotransmitters such as glycine or GABA
• The nicotinic ACh receptor at the neuromuscular
junction:
• The pentameric channel, consists of four different
subunits (2α, β, δ, γ)
• Agonist-binding sites ; αγ and αδ
• Activation allows passage of Na+ and K+ ions
Dr Pushkar, 2023

TRANSMEMBRANE ENZYME (RECEPTOR TYROSINE
KINASES)
• Include receptors for hormones
(such as insulin) and growth
factors (such as EGF)
• Binding of ligand induces
phosphorylation of multiple
tyrosine
• The phosphorylation of
tyrosine residues forms docking
sites for the large number of
signaling proteins
• The phosphorylated substrate
proteins then perform
downstream signaling function
Dr Pushkar, 2023

TRANSMEMBRANE NON ENZYME
(JAK-STAT RECEPTOR PATHWAY)
• Receptors for cytokines (such as γ-
interferon) and hormones (such as
growth hormone and prolactin)
• These receptors have no intrinsic
enzymatic activity; rather, binding of
the cytokine causes recruitment of a
separate, intracellular tyrosine kinase
termed a Jak (Janus kinase) which
binds to the cytoplasmic tails of the
receptor
• Jaks phosphorylate tyrosine residues
on the receptor, which further causes
the phosphorylation of the STAT
(signal transducer and activator of
transcription)
• The phosphorylated STAT translocate
to the nucleus and regulate
transcription.
Dr Pushkar, 2023

NUCLEAR RECEPTORS
• The glucocorticoid (G) penetrates the
cell membrane and binds to the
glucocorticoid receptor (GR) in the
cytoplasm (which remains in
association with heat shock protein 90
(HSP90) + other proteins)
• The complexed proteins (HSP90, etc)
dissociates and dimerization occurs
• The steroid bound receptor dimer
translocate to the nucleus and interacts
with specific DNA sequences called
‘glucocorticoid responsive elements’
(GREs)
• The expression of these genes is
consequently altered resulting in
promotion (or suppression) of their
transcription, which in turn modifies
cell function.
Dr Pushkar, 2023

THE PHARMACOVIGILANCE
PROGRAM OF INDIA (PVPI)
• Pharmacovigilance is the science of detection, assessment, understanding and prevention of
adverse effects or any other possible drug-related problems
• The Central Drugs Standard Control Organization (CDSCO), New Delhi, under the aegis of
Ministry of Health and Family Welfare (MOHFW) has initiated the PvPI in July 2010.
• Initially National Coordinating Centre (NCC) was AIIMS, New Delhi but it was shifted to
Indian Pharmacopoeia commission (IPC), Ghaziabad (U.P.) in April 2011.
• Adverse drug reaction Monitoring Centers (AMCs) play a vital role in PvPI. These AMCs
include MCI approved medical colleges and hospitals, autonomous institutes and even
corporate hospitals.
• AMCs are responsible for collecting the ADR (adverse drug reaction) reports from patients
and sending it to NCC via entry in a software called Vigiflow. NCC then assesses the ICSR
(individual case safety reports) by various methods of causality assessment like Naranjo
scale, and if found valid will commit to Uppsala Monitoring Centre (UMC) in Sweden.
Dr Pushkar, 2023

THANK YOU!
Dr Pushkar, 2023 References: G&G, KDT, GRG, S&S, Google images