Intro to Pharm Flashcards
Examples of biologics
Hormones, vaccines, interferons, monoclonal antibodies, and natural blood products
What organization overlooks complementary and alternative medicine (CAM)?
National Center for Complementary and Alternative Medicine (NCCAM)
List subgroups of the FDA:
-Center for Drug Evaluation and Research (CDER)
-Center for Biologics Evaluation and Research (CBER)
-Center for Food Safety and Applied Nutrition (CFSAP)
CDER
Determines correct use of prescription and OTC agents
keeps unsafe and ineffective drugs from being marketed
CBER
Control biologics
-Childhood Vaccine Act of 1986: authorized FDA to collect info about patients receiving vaccines
CFSAP
Control herbal products and dietary supplements
-also regulated by dietary supplemental health and education act of 1994
-can still be marketed without FDA approval (monitored after distribution by FDA)
4 phases of drug development:
Phase I: Preclinical Investigation (1-3 years)
Phase II: Clinical Investigation (2-10 years)
-clinical phase 1,2,3
Phase III: Review of New Drug Application (NDA)
-2 months to 7 years
Phase IV: postmarketing surveillance
Phase I: Preclinical Investigation
-Extensive research on human and microbial cells in lab
-cultured cells and animal studies used to determine dosages, effectiveness, adverse effects
-obtain animal pharmacology and toxicology data
Phase II: Clinical Investigation: Phase I Trials
-several months
-20-100 human volunteers with disease/condition
-trade name developed
-sub-therapeutic doses used then increased
-safety and effectiveness
-70% of drugs move onto the next phase
Phase II: Clinical Investigation: Phase II Trials
-Several months-2 years
-several dozen-300 volunteers with disease/condition
-assess effectiveness, interactions with other meds, differences in effects on diff patients
-33% move on
Phase II: Clinical Investigation: Phase III Trials
1-4 years
-several hundred-3000 volunteers
-drug now assumed to have therapeutic effect
-if no serious adverse effects, drug could be quickly approved with careful monitoring
-25-30% move onto next phase
-NDA must be submitted to move on
-IND: Investigational new drug application
Durham-Humphrey Amendment of 1951
Established two classes of drugs: prescription vs OTC
Kefauver-Harris Agreement of 1962
required all new drugs marketed in US to be safe and effective (following thalidomide)
-prescription drug advertising falls under FDA
Comprehensive Drug Abuse Prevention and Control Act of 1970
-Created five categories of controlled substances
-Drug Enforcement Agency created in 1973 to enforce
Biosimilars (“branded generics”)
aka off brand
-Need prescription to match drug name, not interchangeable with name brand
-must write new prescription to receive biosimilar from pharmacy
FDA approved vs off-label
If a drug wants FDA approval for another indication, it has to go through the FDA approval process for that indication
Three types of prescription drug advertising:
1. Product claim ads
only type of ads that name a drug and discuss its benefits and risks
-must include name of drug (brand and generic), at least one FDA approved use, most significant risks
reminder advertisements
can give name of drug, not the drug’s use
-does not contain good or bad info about the drug
-not allowed for certain prescription drugs with serious risks (black box warning)
help seeking ads
can describe disease or condition, but not recommend a specific drug treatment
-allowed to include a company’s name and tele number for more info
Check powerpoint for abbreviations (introduction to pharm)
Check powerpoint for abbreviations (introduction to pharm)
Catecholamines:
NE, E, dopamine
Somatic Nervous System: neurotransmitter/receptor type
Ach, nicotinic receptors (rapid signals compared to muscarinic G-proteins)
Describe Nicotinic receptors
Ligand-gated Ion Channels
-Na+ in and K+ out
Muscarinic Receptors:
G-coupled protein receptors
Bind Ach
Muscarinic receptors types/G proteins
M1: Gq (Gi and Gs)
M2: Gi
M3: Gq
M4: Gi
M5: Gq
Gi vs Gs
Gi inhibits adenylate cyclase (decreases cAMP)
Gs stimulates cAMP
Gq
Gq –> IP3 & DAG
IP3: travels through cytoplasm to ER and opens calcium channels
-calcium flows into cytoplasm through simple diffusion and can lead to depolarization
DAG: binds kinase C, which is activated by calcium and starts to phosphorylate target proteins (activates them)
M1 receptors with Gs (not often)
ATP loses two phosphates (I think to become cAMP) which phosphorylate target proteins
M2, M4 (M1): Purpose of Gi?
blocks attachment of adenylate cyclase
inactivate cells in organs that are less important during rest and digest
Adrenergic Receptors: What do they bind?
G-protein coupled receptors
Bind catecholamines: NE and E
Types of Adrenergic receptors
Alpha 1,2
Beta 1,2,3
-See pwpt for IMPORTANT chart (slide 4)
-See pwpt for all other adrenergic info
Cholinergic Agonists (Cholinomimetics): divisions
Direct-Acting
Indirect-Acting
Direct-Acting cholinergic agonists
Meds that act on muscarinic and/or nicatinic receptors (not equally)
Mimic Acetylcholine/parasympathetic system
Direct-Acting Cholinergic Agonists targeting Muscarinic Receptors (medications)
Bethanechol: illeus (no gut movement) –> stimulate intestinal motility AND urinary retention –> stimulate bladder contraction
-given after surgery to undo general anesthesia side effects (illeus/retention)
Methacholine: Ach degrades methacholine –> short acting (thus used to screen for Asthma, cuz it causes temporary bronchoconstriction)
Pilocarpine: Used to treat Glaucoma (high intraocular pressure) cuz it stimulates contraction of ciliary muscle and increases outflow of aqueous humor
-Sjogren Syndrome (increases salivary/lacrimal glands)
-screening for cystic fibrosis (stimulates sweat and helps to get sample)
-side note: Acetylcholinesterase degrades Ach in synaptic cleft (medications can be resistant to degredation)
Contraindications of Direct-Acting Cholinergic Agonists
Cause bronchospasm –> avoid COPD, asthma
Increased gastric secretion –> avoid PUD (peptic ulcer disease?)
Indirect-Acting Cholinergic Agonists:
Inhibit Acetylcholinesterase (degrades Acetylcholine)
-Increase and prolong Acetylcholine-mediated Muscarinic & Nicotinic effects
Carbamates:
Tertiary Amines (can cross BBB)
Quarternary Amines
Medications that are Quarternary structure (cannot cross BBB)
Edrophonium: short acting, diagnose myasthenia gravis (see pwpt) by increasing Ach and showing visible strength increase
Pyridiostigmine: longest acting (treat myasthenia gravis)
Neostigmine: Mostly used to reverse anaesthesia induced paralysis (by increasing Ach availability in synaptic cleft, thus disaplacing neuromuscular blocker off nicotinic receptors)
-Can be used to treat myasthenia gravis
Meds that are tertiary structure (can cross BBB)
Physostigmine: Antidote for anti-cholinergic overdose
Donepezil & Rivastigmine both work to increase Ach
Anticholinergic toxicity symptoms
-Blind as a Bat(blurred vision, mydriasis (pupils dilate))
-Hot as a Hare (hyperthermic)
-Mad as a Hatter (delirium, hallucinations, seizures, coma)
-Dry as a Bone (NO sweating, dry skin & mucous membranes)
-Red as a Beet (flushed skin)
-Bloated as a Bladder (urinary retention, constipation)
-Cardiac = tachycardia & HTN
Physostigmine, an acetylcholinesterase inhibitor that can treat this kind of toxicity, increases Ach and increases firing of neurons
(don’t forget that sweat glands are cholinergic despite being sympathetic)
Cholinergic Toxicity: SLUDGE
Saliva
Lacrimal
Urination
Defecation
GI
Emesis
(cholinergic toxicity = anticholinesterase poisoning)
What does Oxybutynin treat and how? (muscarinic antagonist)
Overactive bladder: targets muscarinic receptors in bladder, decrease parasympathetic, thus decreasing detrusor muscle spasms and preventing urge incontinence
Ipratropium (short-acting) & Tiotropium (long-acting)
COPD and asthma (bronchodilators)
-Inhaled, bind to muscarinic receptors on tracheal and bronchial smooth muscle
-causing smooth muscle relaxation and dilation of bronchi
Scopolamine (muscarinic antagonist)
prevents the action of acetylcholine on muscarinic receptors in the vomiting (aka prevents motion sickness)
-given after surgery
-side effects: sedation/confusion
How do muscarinic antagonists cause hyperthermia as a side effect?
Anticholinergic drugs cause hyperthermia through peripheral muscle activation, reduction in the ability of the body to lose heat and a central action if they enter the CNS (for example atropine).
???
Emax:
A measure of a medication’s efficacy (max response)
EC50:
Point at which 50% of the maximum effect is produced, marks POTENCY
-smaller the EC50, shorter it takes to reach halfway to Emax, meaning higher potency
ED50:
Effective dose given to a population so that half see an effect
Ex. question: Medication A has a higher efficacy than Medication B, but they have the same EC50. Which is more potent?
They are equally potent
What is the main contraindication for muscarinic antagonists?
Narrow angle glaucoma (since parasympathetic stimulates ciliary muscles to contract which pushes aqueous humor out, muscarinic antagonists remove this influence and allow aqueous humor to build up and increase intraocular pressure)
distribution of a drug into the system is determined by:
Blood flow to target tissues, size and polarity, presence of binding proteins
include something about atropine
Adrenergic Antagonists–> Alpha and Beta blockers:
Alpha blocker and beta blockers are two types of postsynaptic anti-adrenergic medications that prevent their respective receptors from being stimulated by catecholamines (NE and epinephrine)
Types of Alpha blockers:
Nonselective:
-Phenoxybenzamine (Dibenzyline)
-Phentolamine (Regitine)
Alpha 1 Blockers:
-Doxazosin (Cardura)
-Terazosin (Hytrin)
Types of Beta blockers:
Nonselective:
-Propranolol (Inderal)
Cardioselective:
-Atenolol (Tenormin)
-Metoprolol tartate (Lopressor)
Alpha-Beta Blockers:
-Labetalol (Trandate)
-Carvedilol (Coreg)
What happens when you block alpha 1 receptors?
Vasodilation which lowers BP
Side effects of non-selective alpha blockers:
-Vasodilation leads to hypotension
-Vasodilation in brain leads to headaches
-Vasodilation of nasal mucosa –> congestion
-Difficulty ejaculating
-Tachycardia (biological response to lowered BP)
-alpha-2 inhibition –> uncontrolled catecholamine release (no more negative feedback
-Also acts on beta receptors in the heart which can increase HR and lead to tachy and arrhythmias (???)
