Introduction Flashcards
Articles used in diagnosis prevention treatment mitigation of diseases
Drugs
▪️What the DRUG does to the BODY
▪️ Study of the biochemical and physiological effects of drugs
▪️Effects (MOA)
Pharmacodynamics
▪️What the BODY does to the DRUG
▪️ Study of processes a drug undergoes as it reaches and leaves the biological site of action
▪️Fate & Disposition (ADME)
Pharmacokinetics
▪️ Study of rational use of drugs in the management of diseases
▪️Clinical & Uses
Pharmacotherapeutics
CLASSIFICATION OF DRUGS
▪️ Drugs that alter the biochemical and physiological functions of the cell
▪️Biggest Class of Drugs
Functional Modifiers
CLASSIFICATION OF DRUGS
Add/Supplement endogenous compounds which are insufficient/lacking/absent
Replenishers
CLASSIFICATION OF DRUGS
Drugs that are used to confirm diagnosis of certain diseases
Diagnostic Agents
CLASSIFICATION OF DRUGS
Agents used to kill or inhibit growth cells considered as foreign to the body
Chemotherapeutic Agents
▪️Biologic site of action, “action site” or “active site”
▪️Targets a physiologic action
▪️Ex. Structural & Regulatory Proteins
Target Protein Mediated
Basic unit of the structural protein
Tubulin
Made of alpha and beta units of tubulin
Microtubules
Target Protein
Structural Proteins
▪️Target?
▪️Drugs?
▪️Target: Tubulin, Microtubules
▪️Drugs: Griseofulvin, Colchicine, Vinca, Taxanes
DRUGS THAT INHIBIT MICROTUBULES (4)
- Griseofulvin
- Colchicine
- Antimitotic Drugs (Chemo Drugs)
- Benzimidazole
▪️1st line tx for acute gout
▪️Inhibits chemotaxis of immune cells that causes inflammation
Colchicine
▪️Antifungal agent for Dermatophytosis (tinea/ringworm)
▪️Enzyme inducer
▪️Inhibit blocks fungal mitosis
Griseofulvin
Neurotoxic
Vincristine (under Vinca Alkaloid as Antimitotic/AntiCA Drugs)
Taxanes (Under Antimitotic/AntiCA Drugs)
Paclitaxel
Docetaxel
Cabazitaxel
▪️Regulates biochemical or physiological cell activity or function
▪️Ex. Voltage-Gated Ion Channels (Na, K, Ca)
Regulatory Proteins
REGULATORY PROTEINS
▪️Class I Anti-Arrhythmics
▪️Local Anesthetics (-caine)
▪️Some Anticonvulsants (Phenytoin, Carbamazepine)
Voltage-Gated Na-Channels
REGULATORY PROTEINS
▪️Class III Anti-Arrythmics (BBIDAS)
▪️Insulin Secretagogues (Sulfonylureas: Glimeperide)
Voltage-Gated K Channels
What Class Number of Anti-Arrhythmics are the ff. drugs:
Disopyramide
Quinidine
Procainamide
Class IA Anti-arrhythmics
What Class Number of Anti-Arrhythmics are the ff. drugs:
Tocainamide
Mexiletine
Lidocaine
Phenytoin
Class IB Anti-arrhythmics
What Class Number of Anti-Arrhythmics are the ff. drugs:
Moricizine
Flecainide
Propafenone
Encainide
Class IC Anti-arrhythmics
- Prolong Action Potential
- Shorten Action Potential
- No Effect on Action Potential
- Class IA Anti-Arrhythmics
- Class IB Anti-Arrhythmics
- Class IC Anti-Arrhythmics
REGULATORY PROTEIN-CHANNELS?
▪️Dihydropyridine “-dipines”
▪️Non-DHP Class IV Anti-Arrhythmics
▪️ Ex. Verapamil - cardioselective tx for arrhythymia; Diltiazem
Ca Channel Blockers
What Class Number of Anti-Arrhythmics are the ff. drugs:
Propranolol
Esmolol
Acebutolol
Class II Anti-Arrhythmics
What Class Number of Anti-Arrhythmics are the ff. drugs:
Mnemonics: BBIDAS
Bepridil
Bretylium
Ibutilide
Dofetilide
Amiodarone
Sotalol
Class III Anti-Arrhythmics
What Class Number of Anti-Arrhythmics are the ff. drugs:
Diltiazem
Verapamil
Class IV Anti-Arrhythmics
CARRIER MOLECULES (2)
- Na/K-ATPase Pump (Na-K Pump)
- H/K-ATPase Pump (Proton Pump)
CARRIER MOLECULES
▪️ found in cardiac myocytes
▪️ responsible for Ca extrusion (for contraction)
▪️Inhibitor: Cardiac Glycosides
Digoxin - Digitalis lanata
DigiToxin - Digitalis purpurea
Na/K-ATPase Pump (Na-K Pump)
CARRIER MOLECULES
▪️seen in parietal cells at the stomach
▪️HCl production
▪️Inhibitor: PPIs (-prazole)
Omeprazole -most effective in hyperacidity
H/K-ATPase Pump (Proton Pump)
Enzymes (Under Regulatory Proteins)
Inhibited by NSAIDs, Aspirin, -coxibs
Cyclooxygenase (COX)
What type of cyclooxygenase (COX) is CONSTITUTIVE enzyme responsible for platelet aggregation and gastric protection or stomach/intestine
COX-1
What type of cyclooxygenase (COX) is INDUCIBLE enzyme responsible for pain and inflammation
COX-2
Withdrawn in the market due to myocardial infraction (MI)
Rofecoxib
Enzymes (Under Regulatory Proteins)
Inhibitors: MAOI A & B Selective, Non-Selective
Monoamine oxidase (MAO)
What are MAOIs
Mnemonics: MPITS
Moclobemide
Phenelzine
Isocarboxazid
Tranylcypromine
Selegiline
Selective MAOI A (1)
Moclobemide
Selective MAOI B (2)
Selegine
Rosagiline
Non-Selective MAOI
Phenelzine
Isocarboxazid
Tranylcypromine
Metabolizes: NE, EPI, 5-HT3
MAO A
Metabolizes: Dopamine
MAO B
Diseases:
▪️↓NE
▪️↓5-HT
Clinical Depression
Diseases:
▪️↓Dopamine
Parkinsonism
Enzymes (Under Regulatory Proteins)
Inhibitor: Zileuton (Anti-asthma)
5-lipoxygenase (5-LOX)
Enzymes (Under Regulatory Proteins)
Precursor for Arachidonic Acid, in turn giving prostaglandins and leukotrienes (eicosanoids), with the action of COX and LOX respectively
Phospholipids
For cycloprotection, pain, inflammation
Prostaglandin
For bronchoconstriction
Leukotrienes
Enzymes (Under Regulatory Proteins)
Inhibitors:
▪️COMTIs “-capones”
▪️ Tolcapone
▪️ Entacapone
Catechol-O-methyltransferase (COMT)
Regulatory Proteins
▪️Channels (3)
1.Voltage-Gated Na Channels
2. Voltage-Gated K Channels
3. Ca Channel Blockers
Regulatory Proteins
▪️Carrier Molecules (2)
- Na-K-ATPase Pump
- H/K-ATPase Pump (Proton Pump)
Regulatory Proteins
▪️Enzymes (6)
- Eicosanoid Pathway
- COX
- Angiotensin-Converting Enzymes (ACE) - inhibited by (-prils) for HTN
- MAO
- Acetylcholinesterase (AChE) - inhibitor: Edrophonium
- COMT
DRUG-TARGET PROTEIN MEDIATED MECHANISM OF ACTION
Receptors (4)
- Type I (Ionotropic)
- Type 2 (Metabotropic)
- Type 3 (Enzyme/Kinase-Linked)
- Type 4 (Gene Transcription-Linked)
DRUG-TARGET PROTEIN MEDIATED MECHANISM OF ACTION (Receptors)
▪️Loc: Cell Membrane
▪️Onset: Milliseconds (ms)
▪️Mechanism: Binding of ligand to receptors associated with ion channels (Ligand Gated Ion Channels)
Type I Ionotropic Receptors
Examples of Type I Ionotropic Receptors (2)
1.GABA Receptor Complex
2. Nicotinic Receptors
(Under Type I Ionotropic Receptors)
▪️Associated with CI channels -
▪️Inhibitory NT
▪️Facilitates influx of Cl- ions = hyperpolarization
GABA Complex
GABA A Receptor
Stimulators: (2 B)
- Benzodiazepines - ↑ FREQUENCY of Cl channel opening
- Barbiturates - ↑ DURATION
(Under Type I Ionotropic Receptors)
▪️Associated with Na+ channels
▪️Excitatory
▪️Drugs: curare derivatives (-curium, -curonium)
▪️Skeletal Muscle Relaxants
Nicotinic Receptors
What Drug?
Serotonin blockers: -setron
▪️Tx. for cancer-induced nausea
Ondasetron
DRUG-TARGET PROTEIN MEDIATED MECHANISM OF ACTION (Receptors)
▪️Loc: Cell Membrane
▪️Onset: Seconds (secs.)
▪️Mechanism: Increase or decrease of secondary messengers
▪️ G-protein linked, couple receptors
▪️ 7-transmembrane spanning receptors
Type II Metabotropic Receptors
G-Receptors/ANS
▪️Under Gq (4)
- a1
- M1
- H1
- V1
G-Receptors/ANS
▪️Under Gi (3)
- a2
- M2
- Dopa 2
G-Receptors/ANS
▪️Under Gs (5)
- B1
- B2
- Dopa 1
- H2 (Histamine)
- V2 (Vasopressin)
- (-triptans) -> for migraine
- Ergot Alkaloids
- (-setrons) bind to Anti-emetics
- 5-HT1D
- 5-HT2
- 5-HT3
What Type of G-Proteins is?
▪️ Stimulates adenylyl cyclase (AC)
▪️ Increase cAMP
▪️Stimulators: Epi, NE
▪️Ex. Beta-blockers
Gs
What Beta Type Receptors
1. HEART
2. LUNGS
- B1 Receptors (Heart)
- B2 Receptors (Lungs)
SABA or LABA?
▪️Salbutamol
▪️Albuterol
▪️Terbutaline
SABA
SABA or LABA?
▪️Salmeterol
▪️Formoterol
LABA
What Type of G-Proteins is?
▪️ Inhibits adenylyl cyclase (AC)
▪️ Decrease cAMP
▪️Pre-synaptic Alpha 2 receptors
▪️Stimulators: Clonidine, Guanfacine, Guanabenz, Methyldopa
▪️Inhibitor: Yohimbine
Gi
What Type of G-Proteins is?
▪️Stimulates Phospholipase C (PLC)
▪️PLC stimulates the formation of IP3 & DAG
▪️Increase Ca ions=contraction
▪️Ex. Alpha 1, M1, M3, Post-synaptic a2 receptors
Gq
QISS-QIQ-SIQ-SQS Receptors
Mnemonics:
Kiss & kick till you’re sick of sex
QISS - Alpha 1,2 & Beta 1,2
QIQ - M1, M2, M3
SIQ - D1, D2, H1
SQS - H2, V1, V2
In what body fluid is prostaglandin derive?
Semen
DRUG-TARGET PROTEIN MEDIATED MECHANISM OF ACTION (Receptors)
▪️Loc: Cell Membrane
▪️Onset: Minutes (min.)
▪️Mechanism: Direct binding of ligand to particular receptors / Phosphorylation
▪️ Insulin Receptors - Tyrosine Kinase Linked [Effects: Stimulation of glucokinase]
▪️ Ex: Platelet-derived Growth Factor, Epidermal Growth Factor
Type III Enzyme-Linked Receptors
DRUG-TARGET PROTEIN MEDIATED MECHANISM OF ACTION (Receptors)
▪️Loc: Cytoplasm/Nucleus
▪️Onset: Hours (hrs.)
▪️Mechanism: Modulate Gene Transcription
▪️Ex: Steroid Hormones, Thyroid Hormones, Vit. D & Derivative
Type IV Gene Transcription-linked Receptor/Nuclear Receptor/Intracellular Receptor
DRUG-TARGET PROTEIN MEDIATED MECHANISM OF ACTION (Receptors)
MOA
1. Depolarization (Na, Ca) & Hyperpolarization (K, Cl)
2. 2° Messenger
3. Phosphorylation
4. Gene Expression
- Type 1Ionotropic
- Type 2 Metabotropic
- Type 3 Enzyme-linked
- Type 4 Gene Transcription-linked
NON-TARGET PROTEIN MEDIATED MECHANISM (3)
- Colligative Mechanism/Mass Effect/Physical Interaction
- Chemical Antagonism/Direct Chemical Interaction
- Counterfeit or Incorporation Mechanism
NON-TARGET PROTEIN MEDIATED
▪️Colligative Properties - dependent on the number of solute particles in a solution
▪️Mannitol - osmotic diuretic/aquaretic
Colligative Mechanism/Mass Effect
NON-TARGET PROTEIN MEDIATED
▪️Acid-Base Neutralization
● Local Antacids
- Neutralization Rxn
(Ex. Mg(OH)2, Al(OH)3, CaCO3)
▪️Chelation/Complexation (Heavy Metal + Antidote)
Chemical Antagonism /Direct Chemical Rxn
Systemic Antacids
▪️NaHCO3
▪️NH4Cl
▪️Metabolic Acidosis
▪️Metabolic Alkalosis
For Heparin Toxicity
Protamine Sulfate
For Wilson’s Disease (Cu poisoning)
Penicillamine (Cuprimine°)
For Fe3+ or hemochromatosis
Deferoxamine (Desferal°)
For Hg & As toxicity (peanut oil as vehicle)
Dimercaprol (IM) or British Anti-Lewis (BAL)
NON-TARGET PROTEIN MEDIATED
▪️Aka: Drug Incorporation
▪️ Ex: Antimetabolites
▪️Purine and pyrimidine base analogues (also used as AntiCA drugs-Flucytosine)
Counterfeit/Incorporation Mechanism
Cornerstone in colon CA chemotherapy
5-FU