| Flap 1 |
Flap 2 |
| Formula for maintenance dose |
Cp * CL / F ;;Cp = target plasma concentration F = bioavailibility |
| In patients with impaired renal or hepatic function, the loading dose decreases, increases or remains unchanged? Maintenance dose? |
Loading dose remains unchanged Maintenance dose decreases |
| Rate of elimination is constant (constant amount of drug is eliminated per unit time) - what order elimination? What happens to target plasma concentration? |
Zero order elimination Target plasma concentration decreases linearly with time |
| Rate of elimination is proportional to drug concentration (constant fraction of drug eliminated per unit time) - what order elimination? What happens to target plasma concentration? |
First order elimination Cp decreases exponentially with time |
| Give examples of drugs with zero order elimination |
Ethanol Phenytoin Aspirin (at high or toxic concentration) |
| Phase I metabolism ;products, what happens and how eliminated |
(reduction, oxidation, hydrolysis) yields _ slightly polar, water-soluble metabolites (often still active) not yet eliminated |
| What phase of metabolism associated with cytochrome P450 |
Phase I |
| What phase of metabolism associated with conjugation |
Phase II |
| Phase II metabolism ;products, what happens and how eliminated |
acetylation, glucoronidation, sulfation) yields Very polar, inactive metanolites (renally excreted) |
| Geriatric patients lose which phase of metabolism first? |
Phase I |
| Is it safe? Pharmacokinetics? - which phase of clinical testing of the drug |
Phase I |
| Does it work in patients?- which phase of clinical testing of the drug |
Phase II |
| Does it work? Double blind - which phase of clinical testing of the drug |
Phase III |
| What happens in phase IV of clinical testing of the drug |
Postmarketing surveillance |
| A competitive antagonist shifts agonist curve where? |
To the right |
| A noncompetitive antagonist (irreversible) shifts agonist curve where? |
Downward |
| Urine pH and drug elimination;;what is trapped |
Ionized species get trapped. |
| Urine pH and drug elimination;;Ionized species |
Ionized species get trapped. |
| Urine pH and drug elimination;;Weak acids what and Tx |
Trapped in basic environments. Treat overdose with bicarbonate. |
| Urine pH and drug elimination;;Weak bases what and Tx |
Trapped in acidic environments. Treat overdose with ;ammonium chloride. |
| Urine pH and drug elimination;;Trapped in basic environments. |
Weak acids |
| Urine pH and drug elimination;;Trapped in acidic environments. |
Weak bases |
| dose response curves and;;different antagonists |
A. A competitive antagonist shifts curve to the right, decreasing potency and ↑ EC50.;;B. A noncompetitive antago-;nist shifts the agonist curve downward, decreasing efficacy. |
| dose response curves and;;shifts curve to the right, decreasing potency and ↑ EC50. |
competitive antagonist |
| dose response curves and;;shifts the curve downward, decreasing efficacy. |
noncompetitive antago-;nist |
| dose response curves and;;in a system with spare receptors |
the EC50 is lower than the Kd, indicating that to achieve 50% of maximum effect, < 50% of the receptors must be activated. EC50: dose causing 50% of maximal effect. Kd: concentration ofdrug required to bind 50% of receptor sites. |
| dose response curves and;;different agonists |
1. The partial agonist acts on the same receptor system as the full agonist but has a lower maximal efficacy no matter the dose. ;;A partial agonist;may be more potent (as in the figure), less potent, or equally potent; potency is an independent factor. |
| dose response curves and;;may be more potent (as in the figure), less potent, or equally potent; potency is an independent factor. |
A partial agonist |
| Efficacy |
maximal EFFECT |
| Potency |
amount needed for a given EFFECT |
| amount needed for a given EFFECT |
Potency |
| maximal EFFECT |
Efficacy |
| Therapeutic index |
TILE;;LD50/ED50 |
| pre and postsynaptic nervous system neurotransmitters;;Parasymp |
ACh;(nicotinic);;ACh;(muscarinic) |
| pre and postsynaptic nervous system neurotransmitters;;Somatic |
only one ;ACh (nicotinic) |
| pre and postsynaptic nervous system neurotransmitters;;Sympathetic |
pre = ACh (nicotinic);;Ach (muscarinic)- sweat glands ;;NEα,β - Cardiac and smooth;muscle, gland cells, ;nerve terminals;;D1 - Renal vascular smooth muscle |
| nicotinic receptor mech |
ACh ligand gated Na+/K+ channels |
| muscarinic receptor mech |
ACh G- protein coupled receptors that act through 2nd messengers |
| ACh ligand gated Na+/K+ channels |
nicotinic receptor |
| ACh G- protein coupled receptors that act through 2nd messengers |
muscarinic receptor |
| G-protein-linked 2nd messengers ;give G protein and major function;;α1 Receptor |
q ;;↑ vascular smooth muscle contraction |
| G-protein-linked 2nd messengers ;give G protein and major function;;α2 Receptor |
i ;;↓ sympathetic outflow, ↓ insulin release |
| G-protein-linked 2nd messengers ;give G protein and major function;;β1 Receptor |
s ;;↑ heart rate, ↑ contractility, ↑ renin release, ↑ lipolysis, ↑ aqueous ;humor formation |
| G-protein-linked 2nd messengers ;give G protein and major function;;β2 Receptor |
s ;;Vasodilation, bronchodilation, ↑ glucagon release |
| G-protein-linked 2nd messengers ;give G protein and major function;;M1 Receptor |
q ;;CNS |
| G-protein-linked 2nd messengers ;give G protein and major function;;M2 Receptor |
i ;;↓ heart rate |
| G-protein-linked 2nd messengers ;give G protein and major function;;M3 Receptor |
q ;;↑ exocrine gland secretions |
| G-protein-linked 2nd messengers ;give G protein and major function;;D1 Receptor |
s ;;Relaxes renal vascular smooth muscle |
| G-protein-linked 2nd messengers ;give G protein and major function;;D2 Receptor |
i ;;Modulates transmitter release, especially in brain |
| G-protein-linked 2nd messengers ;give G protein and major function;;H1 Receptor |
q ;;↑ nasal and bronchial mucus production, contraction of bronchioles,pruritus, and pain |
| G-protein-linked 2nd messengers ;give G protein and major function;;H2 Receptor |
s ;;↑ gastric acid secretion |
| G-protein-linked 2nd messengers ;give G protein and major function;;V1 Receptor |
q ;;↑ vascular smooth muscle contraction |
| G-protein-linked 2nd messengers ;give G protein and major function;;V2 Receptor |
s ;;↑ H2O permeability and reabsorption in the collecting tubules of ;the kidney |
| Given the major function and G-protein class name the receptor;;q ;↑ vascular smooth muscle contraction |
α1 |
| Given the major function and G-protein class name the receptor;;i ;↓ sympathetic outflow, ↓ insulin release |
α2 |
| Given the major function and G-protein class name the receptor;;s ;↑ heart rate, ↑ contractility, ↑ renin release, ↑ lipolysis, ↑ aqueous ;humor formation |
β1 |
| Given the major function and G-protein class name the receptor;;s ;Vasodilation, bronchodilation, ↑ glucagon release |
β2 |
| Given the major function and G-protein class name the receptor;;q ;CNS |
M1 |
| Given the major function and G-protein class name the receptor;;i;↓ heart rate |
M2 |
| Given the major function and G-protein class name the receptor;;q ;↑ exocrine gland secretions |
M3 |
| Given the major function and G-protein class name the receptor;;s ;Relaxes renal vascular smooth muscle |
D1 |
| Given the major function and G-protein class name the receptor;;i ;Modulates transmitter release, especially in brain |
D2 |
| Given the major function and G-protein class name the receptor;;q ;↑ nasal and bronchial mucus production, contraction of bronchioles, |
H1 |
| Given the major function and G-protein class name the receptor;;s ;↑ gastric acid secretion |
H2 |
| Given the major function and G-protein class name the receptor;;q ;↑ vascular smooth muscle contraction |
V1 |
| Given the major function and G-protein class name the receptor;;s ;↑ H2O permeability and reabsorption in the collecting tubules of the kidney |
V2 |
| G-protein-linked 2nd messengers ;Receptor G-protein class ;;how to remember which goes with which |
α1, α2, β1, β2, M1, M2, M3, D1, D2, H1, H2, V1, V2;;"QISS (kiss) and QIQ (kick) till you're SIQ (sick) of SQS (sex)." |
| G-protein-linked 2nd messengers ;Receptor G-protein class ;;3rd messengers... for Gq |
HAVe 1 M&M (H1, α1, V1, M1, M3);;↑ Phospholipase C to IP3 (↑Ca2+) and DAG (Protein Kinase C) |
| G-protein-linked 2nd messengers ;Receptor G-protein class ;;3rd messengers... for Gs |
β1, β2, D1 H2, V2 ;;↑ Adenylcyclase (↑ATP to cAMP [ ↑ Protein kinase A]) |
| G-protein-linked 2nd messengers ;Receptor G-protein class ;;3rd messengers for... Gi |
MAD 2's (M2, α2, D2);;↓Adenylcyclase (↓ATP to cAMP [ ↑ Protein kinase A]) |
| Release of NE from a sympathetic nerve ending is modulated by;;with mech |
by NE itself, acting on presynaptic α2 autoreceptors, and by ACh, ;;angiotensin II, and other substances. |
